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Background: The relation between operative time and postoperative complications in liver surgery is unclear. The aim of this study is to assess the impact of operative time on the development of postoperative complications in patients who underwent minimally invasive or open liver resections of various anatomical extent and technical difficulty levels., Methods: In this retrospective cohort study, patients that underwent a right hemihepatectomy (RH), technically major resection (anatomically minor resection in segment 1, 4a, 7 or 8; TMR) or left lateral sectionectomy (LLS) between 2000 and 2022 were extracted from a multicenter database comprising the prospectively maintained databases of 31 centers in 13 countries. Minimally invasive procedures performed during the learning curve were omitted. Logistic regression models, performed separately for 9 different groups based on stratification by procedure type and allocated surgical approach, were used to assess the association between the fourth quartile of operative time (25% of patients with the longest operative time) and postoperative complications., Results: Overall, 5424 patients were included: 1351 underwent RH (865 open, 373 laparoscopic and 113 robotic), 2821 TMR (1398 open, 1225 laparoscopic and 198 robotic), and 1252 LLS (241 open, 822 laparoscopic and 189 robotic). After adjusting for potential confounders (age, BMI, gender, ASA grade, previous abdominal surgery, disease type and extent, blood loss, Pringle, intraoperative transfusions and incidents), the fourth quartile of operative time, compared to the first three quartiles, was associated with an increased risk of postoperative complications after open, laparoscopic and robotic TMR (aOR 1.35, p = 0.031; aOR 1.74, p = 0.001 and aOR 3.11, p = 0.014, respectively), laparoscopic and robotic RH (aOR 1.98, p = 0.018 and aOR 3.28, p = 0.055, respectively) and solely laparoscopic LLS (aOR 1.69, p = 0.019)., Conclusions: A prolonged operative time is associated with an increased risk of postoperative complications, although it remains to be defined if this is a causal relationship., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Laparoscopic access, a critical yet challenging step in surgical procedures, often leads to complications. Existing systems, such as improved Veress needles and optical trocars, offer limited safety benefits but come with elevated costs. In this study, a prototype of a novel technology for guiding needle interventions based on vibroacoustic signals is evaluated in porcine cadavers. The prototype consistently detected successful abdominal cavity entry in 100% of cases during 193 insertions across eight porcine cadavers. The high signal quality allowed for the precise identification of all Veress needle insertion phases, including peritoneum puncture. The findings suggest that this vibroacoustic-based guidance technology could enhance surgeons' situational awareness and provide valuable support during laparoscopic access. Unlike existing solutions, this technology does not require sensing elements in the instrument's tip and remains compatible with medical instruments from various manufacturers.

Objective: To compare the perioperative outcomes of robotic liver surgery (RLS) and laparoscopic liver surgery (LLS) in various settings., Background: Clear advantages of RLS over LLS have rarely been demonstrated, and the associated costs of robotic surgery are generally higher than those of laparoscopic surgery. Therefore, the exact role of the robotic approach in minimally invasive liver surgery remains to be defined., Methods: In this international retrospective cohort study, the outcomes of patients who underwent RLS and LLS for all indications between 2009 and 2021 in 34 hepatobiliary referral centers were compared. Subgroup analyses were performed to compare both approaches across several types of procedures: (1) minor resections in the anterolateral (2, 3, 4b, 5, and 6) or (2) posterosuperior segments (1, 4a, 7, 8), and (3) major resections (≥3 contiguous segments). Propensity score matching was used to mitigate the influence of selection bias. The primary outcome was textbook outcome in liver surgery (TOLS), previously defined as the absence of intraoperative incidents ≥grade 2, postoperative bile leak ≥grade B, severe morbidity, readmission, and 90-day or in-hospital mortality with the presence of an R0 resection margin in case of malignancy. The absence of a prolonged length of stay was added to define TOLS+., Results: Among the 10.075 included patients, 1.507 underwent RLS and 8.568 LLS. After propensity score matching, both groups constituted 1.505 patients. RLS was associated with higher rates of TOLS (78.3% vs 71.8%, P < 0.001) and TOLS+ (55% vs 50.4%, P = 0.026), less Pringle usage (39.1% vs 47.1%, P < 0.001), blood loss (100 vs 200 milliliters, P < 0.001), transfusions (4.9% vs 7.9%, P = 0.003), conversions (2.7% vs 8.8%, P < 0.001), overall morbidity (19.3% vs 25.7%, P < 0.001), and microscopically irradical resection margins (10.1% vs. 13.8%, P = 0.015), and shorter operative times (190 vs 210 minutes, P = 0.015). In the subgroups, RLS tended to have higher TOLS rates, compared with LLS, for minor resections in the posterosuperior segments (n = 431 per group, 75.9% vs 71.2%, P = 0.184) and major resections (n = 321 per group, 72.9% vs 67.5%, P = 0.086), although these differences did not reach statistical significance., Conclusions: While both produce excellent outcomes, RLS might facilitate slightly higher TOLS rates than LLS., Competing Interests: M.A.H. and M.G.B. received grants from Medtronic GmbH, Intuitive Surgical Inc., and Johnson & Johnson Medical GmbH for investigator-initiated studies. S.L.B. reported received fees from Baxter, Olympus, and Johnson & Johnson. M.S. reported received fees from Merck Serono GmbH, Bayer AG, ERBE Elektromedizin GmbH, Amgen Inc., AstraZeneca, Avateramedical GmbH, Johnson & Johnson Medical GmbH, TakedaPharmaceutical Limited, Olympus K.K., Medtronic GmbH, Intuitive Surgical Inc., Corzamedical, Baxter Int Inc. A.A.F. reported speaker’s honoraria from Bayer and Olympus. F.R. reported speakers' honoraria from Olympus. The remaining authors report no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: Patients with chronic pancreatitis (CP) as well as with pancreatic head carcinoma (CA) undergo the surgical intervention named "pylorus-preserving pancreatoduodenectomy according to Traverso-Longmire (PPPD)", which allowed a comparative analysis of the postoperative courses. The hypothesis was that patients with CA would have worse general as well as immune status than patients with CP due to the severity of the tumor disease and that this would be reflected in the more disadvantageous early postoperative outcome after PPPD. Methods : With the aim of eliciting the influence of the different diagnoses, the surgical outcome of all consecutive patients who underwent surgery at the Dept. of General, Abdominal, Vascular and Transplant Surgery at the University Hospital at Magdeburg between 2002 and 2015 (inclusion criterion) was recorded and comparatively evaluated. Early postoperative outcome was characterized by general and specific complication rate indicating morbidity, mortality, and microbial colonization rate, in particular surgical site infection (SSI, according to CDC criteria). In addition, microbiological findings of swabs and cultures from all compartments as well as preoperative and perioperative parameters from patient records were retrospectively documented and used for statistical comparison in this systematic retrospective unicenter observational study (design). Results : In total, 192 cases with CA (68.1%) and 90 cases with CP (31.9%) met the inclusion criteria of this study. Surprisingly, there were similar specific complication rates of 45.3% (CA) vs. 45.6% (CP; p = 0.97) and in-hospital mortality, which differed only slightly at 3.65% (CA) vs. 3.3% (CP; p = 0.591); the overall complication rate tended to be higher for CA at 23.4% vs. 14.4% (CP; p = 0.082). Overall, potentially pathogenic germs were detected in 28.9% of all patients in CP compared to 32.8% in CA ( p = 0.509), and the rate of SSI was 29.7% (CA) and 24.4% (CP; p = 0.361). In multivariate analysis, CA was found to be a significant risk factor for the development of SSI (OR: 2.025; p = 0.048); the underlying disease had otherwise no significant effect on early postoperative outcome. Significant risk factors in the multivariate analysis were also male sex for SSI and microbial colonization, and intraoperatively transfused red cell packs for mortality, general and specific complications, and surgical revisions. Conclusions : Based on these results, a partly significant, partly trending negative influence of the underlying disease CA, compared to CP, on the early postoperative outcome was found, especially with regard to SSI after PPPD. This influence is corroborated by the international literature.

Background: ALPPS leads to fast and effective liver hypertrophy. This enables the resection of extended tumors. Conventional ALPPS is associated with high morbidity and mortality. MILS reduces morbidity and the robot adds technical features that make complex procedures safe., Material and Methods: The MD-MILS was screened for patients who underwent rALPPS. Demographic and perioperative data were evaluated retrospectively. Ninety days postoperative morbidity was scored according to the CD classification. The findings were compared with the literature., Results: Since November 2021, five patients have been identified. The mean age and BMI of the patients were 50.0 years and 22.7 kg/m 2 . In four cases, patients suffered from colorectal liver metastases and, in one case, intrahepatic cholangiocarcinoma. Prior to the first operation, the mean liver volume of the residual left liver was 380.9 mL with a FLR-BWR of 0.677%. Prior to the second operation, the mean volume of the residual liver was 529.8 mL with a FLR-BWR of 0.947%. This was an increase of 41.9% of the residual liver volume. The first and second operations were carried out within 17.8 days. The mean time of the first and second operations was 341.2 min and 440.6 min. The mean hospital stay was 27.2 days. Histopathology showed the largest tumor size of 39 mm in diameter with a mean amount of 4.7 tumors. The mean tumor-free margin was 12.3 mm. One complication CD > 3a occurred. No patient died during the 90-day follow up., Conclusion: In the first German series, we demonstrated that rALPPS can be carried out safely with reduced morbidity and mortality in selected patients.

Background: With the rapid development of robotic surgery, especially for the abdominal surgery, robotic pancreatic surgery (RPS) has been applied increasingly around the world. However, evidence-based guidelines regarding its application, safety, and efficacy are still lacking. To harvest robust evidence and comprehensive clinical practice, this study aims to develop international guidelines on the use of RPS., Methods: World Health Organization (WHO) Handbook for Guideline Development, GRADE Grid method, Delphi vote, and the AGREE-II instrument were used to establish the Guideline Steering Group, Guideline Development Group, and Guideline Secretary Group, formulate 19 clinical questions, develop the recommendations, and draft the guidelines. Three online meetings were held on 04/12/2020, 30/11/2021, and 25/01/2022 to vote on the recommendations and get advice and suggestions from all involved experts. All the experts focusing on minimally invasive surgery from America, Europe and Oceania made great contributions to this consensus guideline., Results: After a systematic literature review 176 studies were included, 19 questions were addressed and 14 recommendations were developed through the expert assessment and comprehensive judgment of the quality and credibility of the evidence., Conclusions: The international RPS guidelines can guide current practice for surgeons, patients, medical societies, hospital administrators, and related social communities. Further randomized trials are required to determine the added value of RPS as compared to open and laparoscopic surgery., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://hbsn.amegroups.com/article/view/10.21037/hbsn-23-132/coif). M.A.H., F.P. and H.S.H. serve as unpaid editorial board members of Hepatobiliary Surgery and Nutrition. M.G.B. acknowledges grants support to his hospital for the investigator-initiated DIPLOMA-2 randomized trial. B.K.P.G. reports grant from Intuitive Foundation and consulting fees from Transmedic, Local distributor of the Da Vinci robot. U.B. is proctor for Intuitive Surgical (pancreas surgery). The other authors have no conflicts of interest to declare., (2024 Hepatobiliary Surgery and Nutrition. All rights reserved.)

Transient receptor potential (TRP) channels are strongly associated with colon cancer development and progression. This study leveraged a multivariate Cox regression model on publicly available datasets to construct a TRP channels-associated gene signature, with further validation of signature in real world samples from our hospital treated patient samples. Kaplan-Meier (K-M) survival analysis and receiver operating characteristic (ROC) curves were employed to evaluate this gene signature's predictive accuracy and robustness in both training and testing cohorts, respectively. Additionally, the study utilized the CIBERSORT algorithm and single-sample gene set enrichment analysis to explore the signature's immune infiltration landscape and underlying functional implications. The support vector machine algorithm was applied to evaluate the signature's potential in predicting chemotherapy outcomes. The findings unveiled a novel three TRP channels-related gene signature (MCOLN1, TRPM5, and TRPV4) in colon adenocarcinoma (COAD). The ROC and K-M survival curves in the training dataset (AUC = 0.761; p = 1.58e-05) and testing dataset (AUC = 0.699; p = 0.004) showed the signature's robust predictive capability for the overall survival of COAD patients. Analysis of the immune infiltration landscape associated with the signature revealed higher immune infiltration, especially an increased presence of M2 macrophages, in high-risk group patients compared to their low-risk counterparts. High-risk score patients also exhibited potential responsiveness to immune checkpoint inhibitor therapy, evident through increased CD86 and PD-1 expression profiles. Moreover, the TRPM5 gene within the signature was highly expressed in the chemoresistance group ( p = 0.00095) and associated with poor prognosis ( p = 0.036) in COAD patients, highlighting its role as a hub gene of chemoresistance. Ultimately, this signature emerged as an independent prognosis factor for COAD patients ( p = 6.48e-06) and expression of model gene are validated by public data and real-world patients. Overall, this bioinformatics study provides valuable insights into the prognostic implications and potential chemotherapy resistance mechanisms associated with TRPs-related genes in colon cancer., Competing Interests: The authors declare that they have no conflicts of interest to report regarding the present study., (© 2024 Hu et al.)

Objectives: The unexpected global overload of the health system during COVID-19 pandemic has caused changes in management of acute appendicitis worldwide. Whereas conservative treatment was widely recommended, the appendicectomy remained standard therapy in Germany. We aimed to investigate the impact of COVID-19 pandemic on treatment routine for acute appendicitis at University Hospital of Magdeburg., Methods: Adult patients with clinical and/or radiological diagnosis of acute appendicitis were included in the single center retrospective study. Data was collected to patient demographics, treatment modality and outcomes including morbidity and length of stay. The patient data related to COVID-19 period from March 22, 2020 to December 31, 2021 (649 days) were compared to the Non-COVID-19 period from June 12, 2018 to March 21, 2020 (649 days). Subgroup analysis related to conservative or surgical treatment has been performed., Results: A total of 385 patients was included in the study, 203 (52.73 %) during Non-COVID-19 period and 182 (47.27 %) during COVID-19 period. Mean age of entire collective was 43.28 years, containing 43.9 % female patients (p=0.095). Conservative treatment was accomplished in 49 patients (12.7 % of entire collective), increasing from 9.9 % to 15.9 % during COVID-19 period (p=0.074). Laparoscopic appendicectomy was performed in 99.3 % (n=152) of operated patients during COVID-19 period (p=0.013), followed by less postoperative complications compared to reference period (23.5 % vs. 13.1 %, p=0.015). The initiation of antibiotic therapy after the diagnosis increased from 37.9 % to 53.3 % (p=0.002) during COVID-19 period regardless the following treatment modality. Antibiotic treatment showed shorter duration during pandemic period (5.57 days vs. 3.16 days, p<0.001) and it was given longer in the conservative treatment group (5.63 days vs. 4.26 days, p=0.02). The overall length of stay was shorter during COVID-19 period (4.67 days vs. 4.12 days, p=0.052) and in the conservative treatment group (3.08 days vs. 4.47 days, p<0.001). However, the overall morbidity was lower during the COVID-19 period than before (17.2 % vs. 7.7 %, p=0.005) and for conservative therapy compared to appendicectomy (2 % vs. 14.3 %, p=0.016). There was no mortality documented., Conclusions: According to our findings the COVID-19 pandemic had a relevant impact on treatment of acute appendicitis, but it was possible to maintain the traditional diagnostic and treatment pathway. Although laparoscopic appendicectomy remains a recommended procedure, the conservative treatment of uncomplicated appendicitis with excellent short-term outcome can be a safe alternative to surgery during potential new wave of COVID-19 pandemic and in the daily routine., Competing Interests: Competing interests: Authors state no conflict of interest., (© 2023 the author(s), published by De Gruyter, Berlin/Boston.)

Objectives: To investigate the influence of anastomosis on the early postoperative and long-term oncological outcomes of patients with primary colon carcinoma (CA)., Methods: All consecutive patients with the histologically diagnosed primary colon CA (design, prospective multicenter observational study) were registered with regard to patient-, diagnostic-, tumor (Tu) finding-, and treatment-related aspects using a computer-based registry with 60 items to characterize early postoperative and long-term oncological outcome., Results: Basic data : From 2010 to 2016, data from a total of 14,466 patients were documented (mean age, 72.8 [range, 22-96] years; sex ratio, m:f=7,696:6,770). - 717/14,466 patients (4.96 %) were included in a matched-pair analysis. The majority of these patients underwent elective surgery ( n =12,620 patients; 87.2 %) regardless of whether a bowel anastomosis or an ostomy was created. In emergency surgery, a bowel anastomosis was possible in a large proportion ( n =1,332 patients [72.1 %]). In contrast, in 514 patients (27.9 %) who underwent emergency surgery, an ostomy was created. Interestingly, ostomy had to be created even less frequently in patients who had undergone planned surgery ( n =366 [2.5 %]). - Early postoperative outcome : Cases of postoperative mortality were mainly due to general complications. Especially among the patients treated in an emergency situation without intestinal anastomosis, a high proportion died of their pre-existing condition (17.0 %). Patients who underwent ostomy creation or emergency surgery had a worse risk profile (incl. arterial hypertension, diabetes mellitus, and secondary cardiac or renal diseases) which led to the decision to operate without anastomosis. Furthermore, data show no matter which technique had been used, patients that had undergone surgical intervention without anastomosis were more likely to develop complications. - Long-term oncosurgical outcome : The most important factors influencing long-term survival were age, resection status, and tumor stage (according to TNM and UICC). The more advanced the tumor growth, the lower the long-term survival. Patients categorized with the same tumor stage, age, and risk factors had a better chance of survival, if they underwent elective surgical intervention and with intestinal anastomosis. Interestingly, the multivariable analysis showed that older patients and such with distant metastasis benefit from a discontinuity resection., Conclusions: The association of intraoperative and postoperative complications with increased postoperative mortality, as well as preexisting risk factors and perioperative complications is in line with findings of current studies. Furthermore, current studies also agree that older patients and such with reduced general condition benefit from discontinuity resection., Competing Interests: Competing interests: Authors state no conflict of interest., (© 2023 the author(s), published by De Gruyter, Berlin/Boston.)

Introduction: Although the evidence is minimal, an abdominal binder is commonly prescribed after open incisional hernia repair (IHR) to reduce pain. This study aimed to investigate this common postoperative treatment., Methods: The ABIHR-II trial was a national prospective, randomized, multicenter non-AMG/MPG pilot study with two groups of patients (wearing an abdominal binder (AB) for 2 weeks during daytime vs. not wearing an AB following open IHR with the sublay technique). Patient enrollment took place from July 2020 to February 2022. The primary endpoint was pain at rest on the 14th postoperative day (POD) using the visual analog scale (VAS). The use of analgesics was not systematically recorded. Mixed-effects linear regression models were used., Results: A total of 51 individuals were recruited (25 women, 26 men; mean age 61.4 years; mean body mass index 30.65 kg/m 2 ). The per-protocol analysis included 40 cases (AB group, n = 21; No-AB group, n = 19). Neither group showed a significant difference in terms of pain at rest, limited mobility, general well-being, and seroma formation and rate. Patients among the AB group had a significantly lower rate of surgical site infection (SSI) on the 14th POD (AB group 4.8% (n = 1) vs. No-AB group 27.8% (n = 5), p = 0.004)., Conclusion: Wearing an AB did not have an impact on pain and seroma formation rate but it may reduce the rate of postoperative SSI within the first 14 days after surgery. Further trials are mandatory to confirm these findings., (© 2023. The Author(s).)

Rationale and Objectives: Sarcopenia is defined as skeletal muscle loss and can be assessed by cross-sectional imaging. Our aim was to establish the effect of sarcopenia on relevant outcomes in patients with pancreatic ductal adenocarcinoma (PDAC) in curative and palliative settings based on a large patient sample., Materials and Methods: MEDLINE library, EMBASE and SCOPUS databases were screened for the associations between sarcopenia and mortality in patients with PDAC up to March 2022. The primary endpoint of the systematic review was the hazard ratio of Sarcopenia on survival. 22 studies were included into the present analysis., Results: The included 22 studies comprised 3958 patients. The prevalence of sarcopenia was 38.7%. Sarcopenia was associated with a higher prevalence in the palliative setting (OR 53.23, CI 39.00-67.45, p<0.001) compared to the curative setting (OR 36.73, CI 27.81-45.65, p<0.001). Sarcopenia was associated with worse OS in the univariable (HR 1.79, CI 1.41-2.28, p<0.001) and multivariable analysis (HR 1.62, CI 1.27-2.07, p<0.001) in the curative setting. For the palliative setting the pooled hazards ratio showed that sarcopenia was associated with overall survival (HR 1.56, CI 1.21-2.02, p<0.001) as well as in multivariable analysis (HR 1.77, CI 1.39-2.26, p<0.001). Sarcopenia was not associated with a higher rate of post-operative complications in univariable analysis (OR 1.10, CI 0.70-1.72, p = 0.69)., Conclusion: Sarcopenia occurs in 38.7% of patients with pancreatic cancer, significantly more in the palliative setting. Sarcopenia is associated with overall survival in both settings. The assessment of sarcopenia is therefore relevant for personalized oncology. Sarcopenia is not associated with postoperative complications., (Copyright © 2022 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Background: Surgical management of splenic flexure carcinoma remains controversial., Objective: This study aimed to establish an expert international consensus on splenic flexure carcinoma management., Design: A 3-round online-based Delphi study was conducted between September 2020 and April 2021., Setting: The first round included 18 experts from 12 different countries. For the second and third rounds, each expert in the first round was asked to invite 2 more colorectal surgeons (n = 47). Out of 47 invited experts, 89% (n = 42) participated in the second and third rounds of the consensus., Interventions: A total of 35 questions were created and sent via the online questionnaire tool., Main Outcome Measures: Levels of recommendation based on voting concordance were graded as follows: more than 75% agreement was defined as strong, between 50% and 75% as moderate, and below 50% as weak., Results: There was moderate consensus on the definition of splenic flexure (55%) as 10 cm from either side where the distal transverse colon turns into the proximal descending colon. Also, experts recommended an abdominopelvic CT scan plus intraoperative exploration (moderate consensus, 72%) for tumor localization and cancer registry. Segmental colectomy was the preferred technique for the management of splenic flexure carcinoma in the elective setting (72%). Moderate consensus was achieved on the technique of complete mesocolic excision and central vascular ligation principles for splenic flexure carcinoma (74%). Only strong consensus was achieved on the surgical approach for minimally invasive surgery (88%)., Limitations: Subjective decisions are based on individual expert clinical experience and not evidence based., Conclusions: This is the first internationally conducted Delphi consensus study regarding splenic flexure carcinoma. The definition of splenic flexure remains ambiguous. To more effectively compare oncologic outcomes among different cancer registries, guidelines need to be developed to standardize each domain and avoid arbitrary definitions. See Video Abstract at http://links.lww.com/DCR/C143 ., Estandarizacin De La Definicin Y Manejo Quirrgico Del Carcinoma De Ngulo Esplnico Establecido Por Un Consenso Internacional De Expertos Utilizando La Tcnica Delphi Espacio Para Mejorar: ANTECEDENTES:El tratamiento quirúrgico del cáncer de ángulo esplénico sigue siendo controvertido.OBJETIVO:Establecer un consenso internacional de expertos sobre el manejo del cáncer del ángulo esplénico.DISEÑO:Se condujo un estudio Delphi en línea de 3 rondas entre septiembre de 2020 y febrero de 2021.ESCENARIO:La primera ronda incluyó a 18 expertos de 12 países distintos. Para la segunda y tercera rondas, a cada experto de la primera ronda se le pidió que invitara a 2 cirujanos colorrectales más de su región (n = 47). De los 47 expertos invitados, el 89% (n = 42) participó en la segunda y tercera ronda del consenso.INTERVENCIONES:Se crearon y enviaron un total de 35 preguntas a través de la herramienta de cuestionario en línea.PRINCIPALES MEDIDAS DE RESULTADO:Los niveles de recomendación basados en la concordancia de votos fueron jerarquizados de la siguiente manera: más del 75% de acuerdo se definió como fuerte, entre 50 y 75% como moderado y por debajo del 50% como débil.RESULTADOS:Hubo un consenso moderado sobre la definición de ángulo esplénico (55%) como 10 cm desde cualquier lado donde el colon transverso distal se convierte en el colon descendente proximal. Así también, los expertos recomendaron la tomografía computarizada abdominopélvica más la exploración intraoperatoria (consenso moderado, 72%) para la localización del tumor y el registro del ángulo esplénico. La colectomía segmentaria fue la técnica preferida para el tratamiento del cáncer de ángulo esplénico en el caso de ser electivo (72%). Se logró un consenso moderado sobre la técnica de escisión completa del mesocolon y los principios de ligadura vascular a nivel central para el cáncer de ángulo esplénico (74%). Solo se logró un fuerte consenso sobre el abordaje quirúrgico para la cirugía mínimamente invasiva (88%).LIMITACIONES:Decisiones subjetivas basadas en la experiencia clínica de expertos individuales y no basadas en evidencia.CONCLUSIONES:Este es el primer estudio internacional de consenso Delphi realizado sobre el cáncer de ángulo esplénico. Si bien encontramos un consenso moderado sobre las modalidades de diagnóstico preoperatorio y el manejo quirúrgico, la definición de ángulo esplénico sigue siendo ambigua. Para comparar de manera más efectiva los resultados oncológicos entre diferentes registros de cáncer, se deben desarrollar pautas para estandarizar cada dominio y evitar definiciones arbitrarias. Consulte Video Resumen en http://links.lww.com/DCR/C143 . (Traducción-Dr. Osvaldo Gauto )., (Copyright © The ASCRS 2023.)

Background: Investigation of risk factors for the presence of vancomycin-resistant enterococci (VRE) in inpatients on surgical wards and associated intensive care units of a German tertiary care hospital., Methods: A single-centre retrospective matched case-control study was performed with surgical inpatients admitted between July 2013 and December 2016. Patients with in-hospital detection of VRE later than 48 h after admission were included and comprised 116 VRE-positive cases and 116 VRE-negative matched controls. VRE isolates of cases were typed by multi-locus sequence typing., Results: ST117 was identified as the dominant VRE sequence type. Next to length of stay in hospital or on an intensive care unit and previous dialysis the case-control study revealed previous antibiotic therapy as a risk factor for the in-hospital detection of VRE. The antibiotics piperacillin/tazobactam, meropenem, and vancomycin were associated with the highest risks. After taking into account length of stay in hospital as possible confounder other potential contact-related risk factors such as previous sonography, radiology, central venous catheter, and endoscopy were not significant., Conclusions: Previous dialysis and previous antibiotic therapy were identified as independent risk factors for the presence of VRE in surgical inpatients., (© 2023. The Author(s).)

Background & Aims: Advanced colorectal carcinoma (CRC) is characterized by a high frequency of primary immune evasion and refractoriness to immunotherapy. Given the importance of interferon (IFN)-γ in CRC immunosurveillance, we investigated whether and how acquired IFN-γ resistance in tumor cells would promote tumor growth, and whether IFN-γ sensitivity could be restored., Methods: Spontaneous and colitis-associated CRC development was induced in mice with a specific IFN-γ pathway inhibition in intestinal epithelial cells. The influence of IFN-γ pathway gene status and expression on survival was assessed in patients with CRC. The mechanisms underlying IFN-γ resistance were investigated in CRC cell lines., Results: The conditional knockout of the IFN-γ receptor in intestinal epithelial cells enhanced spontaneous and colitis-associated colon tumorigenesis in mice, and the loss of IFN-γ receptor α (IFNγRα) expression by tumor cells predicted poor prognosis in patients with CRC. IFNγRα expression was repressed in human CRC cells through changes in N-glycosylation, which decreased protein stability via proteasome-dependent degradation, inhibiting IFNγR-signaling. Downregulation of the bisecting N-acetylglucosaminyltransferase III (MGAT3) expression was associated with IFN-γ resistance in all IFN-γ-resistant cells, and highly correlated with low IFNγRα expression in CRC tissues. Both ectopic and pharmacological reconstitution of MGAT3 expression with all-trans retinoic acid increased bisecting N-glycosylation, as well as IFNγRα protein stability and signaling., Conclusions: Together, our results demonstrated that tumor-associated changes in N-glycosylation destabilize IFNγRα, causing IFN-γ resistance in CRC. IFN-γ sensitivity could be reestablished through the increase in MGAT3 expression, notably via all-trans retinoic acid treatment, providing new prospects for the treatment of immune-resistant CRC., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Study: International Multicentric Minimally Invasive Liver Resection for Colorectal Liver Metastases (SIMMILR-CRLM) was a propensity score matched (PSM) study that reported short-term outcomes of patients with CRLM who met the Milan criteria and underwent either open (OLR), laparoscopic (LLR) or robotic liver resection (RLR). This study, designated as SIMMILR-2, reports the long-term outcomes from that initial study, now referred to as SIMMILR-1. Methods: Data regarding neoadjuvant chemotherapeutic (NC) and neoadjuvant biological (NB) treatments received were collected, and Kaplan−Meier curves reporting the 5-year overall (OS) and recurrence-free survival (RFS) for OLR, LLR and RLR were created for patients who presented with synchronous lesions only, as there was insufficient follow-up for patients with metachronous lesions. Results: A total of 73% of patients received NC and 38% received NB in the OLR group compared to 70% and 28% in the LLR group, respectively (p = 0.5 and p = 0.08). A total of 82% of patients received NC and 40% received NB in the OLR group compared to 86% and 32% in the RLR group, respectively (p > 0.05). A total of 71% of patients received NC and 53% received NB in the LLR group compared to 71% and 47% in the RLR group, respectively (p > 0.05). OS at 5 years was 34.8% after OLR compared to 37.1% after LLR (p = 0.4), 34.3% after OLR compared to 46.9% after RLR (p = 0.4) and 30.3% after LLR compared to 46.9% after RLR (p = 0.9). RFS at 5 years was 12.1% after OLR compared to 20.7% after LLR (p = 0.6), 33.3% after OLR compared to 26.3% after RLR (p = 0.6) and 22.7% after LLR compared to 34.6% after RLR (p = 0.6). Conclusions: When comparing OLR, LLR and RLR, the OS and RFS were all similar after utilization of the Milan criteria and PSM. Biological agents tended to be utilized more in the OLR group when compared to the LLR group, suggesting that highly aggressive tumors are still managed through an open approach.

Creating surgical access is a critical step in laparoscopic surgery. Surgeons have to insert a sharp instrument such as the Veress needle or a trocar into the patient's abdomen until the peritoneal cavity is reached. They solely rely on their experience and distorted tactile feedback in that process, leading to a complication rate as high as 14% of all cases. Recent studies have shown the feasibility of surgical support systems that provide intraoperative feedback regarding the insertion process to improve laparoscopic access outcomes. However, to date, the surgeons' requirements for such support systems remain unclear. This research article presents the results of an explorative study that aimed to acquire data about the information that helps surgeons improve laparoscopic access outcomes. The results indicate that feedback regarding the reaching of the peritoneal cavity is of significant importance and should be presented visually or acoustically. Finally, a solution should be straightforward and intuitive to use, should support or even improve the clinical workflow, but also cheap enough to facilitate its usage rate. While this study was tailored to laparoscopic access, its results also apply to other minimally invasive procedures., (© 2022. The Author(s).)

This is a review focused on advances and current limitations of computer vision (CV) and how CV can help us obtain to more autonomous actions in surgery. It is a follow-up article to one that we previously published in Sensors entitled, "Artificial Intelligence Surgery: How Do We Get to Autonomous Actions in Surgery?" As opposed to that article that also discussed issues of machine learning, deep learning and natural language processing, this review will delve deeper into the field of CV. Additionally, non-visual forms of data that can aid computerized robots in the performance of more autonomous actions, such as instrument priors and audio haptics, will also be highlighted. Furthermore, the current existential crisis for surgeons, endoscopists and interventional radiologists regarding more autonomy during procedures will be discussed. In summary, this paper will discuss how to harness the power of CV to keep doctors who do interventions in the loop.

Purpose: To assess the influence of low skeletal muscle mass (LSMM) on post-operative complications in patients with hepatic malignancies grade (Clavien Dindo ≥ 3) undergoing resection., Methods: MEDLINE, Cochrane, and SCOPUS databases were screened for associations between sarcopenia and major post-operative complications (≥ grade 3 according to Clavien-Dindo classification) after resection of different malignant liver tumors. RevMan 5.3 software was used to perform the meta-analysis. The methodological quality of the included studies was assessed according to the QUIPS instrument., Results: The analysis included 17 studies comprising 3157 patients. Subgroup analyses were performed for cholangiocarcinoma (CCC), colorectal cancer (CRC) liver metastases, and hepatocellular carcinoma (HCC). LSMM as identified on CT was present in 1260 patients (39.9%). Analysis of the overall sample showed that LSMM was associated with higher post-operative complications grade Clavien Dindo ≥ 3 (OR 1.56, 95% CI 1.25-1.95, p < 0.001). In the subgroup analysis, LSMM was associated with post-operative complications in CRC metastases (OR 1.60, 95% CI 1.11-2.32, p = 0.01). In HCC and CCC sub-analyses, LSMM was not associated with post-operative complications in simple regression analysis., Conclusion: LSMM is associated with major post-operative complications in patients undergoing surgery for hepatic metastases and it does not influence major post-operative complications in patients with HCC and CCC., (© 2022. The Author(s).)

One of the most applied imaging methods in medicine is endoscopy. A highly specialized image modality has been developed since the first modern endoscope, the "Lichtleiter" of Bozzini was introduced in the early 19th century. Multiple medical disciplines use endoscopy for diagnostics or to visualize and support therapeutic procedures. Therefore, the shapes, functionalities, handling concepts, and the integrated and surrounding technology of endoscopic systems were adapted to meet these dedicated medical application requirements. This survey gives an overview of modern endoscopic technology's state of the art. Therefore, the portfolio of several manufacturers with commercially available products on the market was screened and summarized. Additionally, some trends for upcoming developments were collected.

Background: The COVID-19 pandemic caused a global health crisis in 2020. This pandemic also had a negative impact on standard procedures in general surgery. Surgeons were challenged to find the best treatment plans for patients with acute cholecystitis. The aim of this study is to investigate the impact of the COVID-19 pandemic on the outcomes of laparoscopic cholecystectomies performed in a tertiary care hospital in Germany., Patients and Methods: We examined perioperative outcomes of patients who underwent laparoscopic cholecystectomy during the pandemic from March 22, 2020 (first national lockdown in Germany) to December 31, 2020. We then compared these to perioperative outcomes from the same time frame of the previous year., Results: A total of 182 patients who underwent laparoscopic cholecystectomy during the above-mentioned periods were enrolled. The pandemic group consisted of 100 and the control group of 82 patients. Subgroup analysis of elderly patients (> 65 years old) revealed significantly higher rates of acute [5 (17.9%) vs. 20 (58.8%); p = 0.001] and gangrenous cholecystitis [0 (0.0%) vs. 7 (20.6%); p = 0.013] in the "pandemic subgroup". Furthermore, significantly more early cholecystectomies were performed in this subgroup [5 (17.9%) vs. 20 (58.8%); p = 0.001]. There were no significant differences between the groups both in the overall and subgroup analysis regarding the operation time, intraoperative blood loss, length of hospitalization, morbidity and mortality., Conclusion: Elderly patients showed particularly higher rates of acute and gangrenous cholecystitis during the pandemic. Laparoscopic cholecystectomy can be performed safely in the COVID-19 era without negative impact on perioperative results. Therefore, we would assume that laparoscopic cholecystectomy can be recommended for any patient with acute cholecystitis, including the elderly., (© 2022. The Author(s).)

(1) Background: Here we report on a retrospective study of an international multicentric cohort after minimally invasive liver resection (SIMMILR) of colorectal liver metastases (CRLM) from six centers. (2) Methods: Resections were divided by the approach used: open liver resection (OLR), laparoscopic liver resection (LLR) and robotic liver resection (RLR). Patients with macrovascular invasion, more than three metastases measuring more than 3 cm or a solitary metastasis more than 5 cm were excluded, and any remaining heterogeneity found was further analyzed after propensity score matching (PSM) to decrease any potential bias. (3) Results: Prior to matching, 566 patients underwent OLR, 462 LLR and 36 RLR for CRLM. After PSM, 142 patients were in each group of the OLR vs. LLR group and 22 in the OLR vs. RLR and 21 in the LLR vs. RLR groups. Blood loss, hospital stay, and morbidity rates were all highly statistically significantly increased in the OLR compared to the LLR group, 636 mL vs. 353 mL, 9 vs. 5 days and 25% vs. 6%, respectively (p < 0.001). Only blood loss was significantly decreased when RLR was compared to OLR and LLR, 250 mL vs. 597 mL, and 224 mL vs. 778 mL, p < 0.008 and p < 0.04, respectively. (4) Conclusions: SIMMILR indicates that minimally invasive approaches for CRLM that follow the Milan criteria may have short term advantages. Notably, larger studies with long-term follow-up comparing robotic resections to both OLR and LLR are still needed.

The following is an overview of the treatment strategies and the prognostic factors to consider in the therapeutic choice of patients characterized by solitary colorectal liver metastasis. Liver resection is the only potential curative option; nevertheless, only 25% of the patients are considered to be eligible for surgery. To expand the potentially resectable pool of patients, surgeons developed multidisciplinary techniques like portal vein embolization, two-stage hepatectomy or associating liver partition and portal vein ligation for staged hepatectomy. Moreover, mini-invasive surgery is gaining support, since it offers lower post-operative complication rates and shorter hospital stay with no differences in long-term outcomes. In case of unresectable disease, various techniques of local ablation have been developed. Radiofrequency ablation is the most commonly used form of thermal ablation: it is widely used for unresectable patients and is trying to find its role in patients with small resectable metastasis. The identification of prognostic factors is crucial in the choice of the treatment strategy. Previous works that focused on patients with solitary colorectal liver metastasis obtained trustable negative predictive factors such as presence of lymph-node metastasis in the primary tumour, synchronous metastasis, R status, right-sided primary colon tumor, and additional presence of extrahepatic tumour lesion. Even the time factor could turn into a predictor of tumour biology as well as further clinical course, and could be helpful to discern patients with worse prognosis., (© 2021. The Author(s).)

Background: Incisional hernias with apertures measuring less than 7 cm can generally be treated adequately with the laparoscopic intraperitoneal onlay-mesh (IPOM) technique. The wearing of an abdominal binder after surgery is often recommended in order to promote wound healing and prevent recurrent herniation. We carried out a multicenter, randomized pilot trial to evaluate the utility of abdominal binders., Methods: The trial was conducted from May 2019 to December 2020. Persons with a laparoscopic IPOM procedure for treatment of an incisional hernia were included in the trial and randomized preoperatively (1:1). The patients in the abdominal binder group wore an abdominal binder during the day for 14 days after surgery, while those in the control group wore no binder. The primary endpoint was pain at rest on postoperative days 1, 2, and 14, as measured on a visual analog scale. The secondary endpoints were overall subjective well-being, the rates of wound infection, recurrence, and complications, mobility, and the rate and size of postoperative seromas (on postoperative days 1, 2, and 14)., Results: Forty patients were included. Three were excluded because of conversion to an open surgical technique. The biometric and perioperative data of the abdominal binder group (n = 18) and the control group (n = 19) did not differ to any statistically significant extent. The patients in the binder group had significantly less postoperative pain (F [dfn, dfd]) 4.44, 95% confidence interval [1; 35]; p = 0.042).The patients in the binder group also had better overall subjective well-being and a higher rate of postoperative seroma formation, but these differences did not reach statistical significance. There was less limitation of mobility than in the control group; however, this difference also did not attain statistical significance., Conclusion: An abdominal binder may reduce pain after incisional hernia repair with the IPOM technique. The postoperative use of analgesic medication was not measured.

Background: Using the Ideal Development Exploration Assessment and Long-term study (IDEAL) paradigm, Halls et al. created risk-adjusted cumulative sum (RA-CUSUM) curves concluding that Pioneers (P) and Early Adopters (EA) of minimally invasive (MI) liver resection obtained similar results after fewer cases. In this study, we applied this framework to a MI Hepatic-Pancreatic and Biliary fellowship-trained surgeon (FT) in order to assess where along the curves this generation fell., Methods: The term FT was used to designate surgeons without previous independent operative experience who went from surgical residency directly into fellowship. Three phases of the learning curve were defined using published data on EAs and Ps of MI Hepatectomy, including phase 1 (initiation) (i.e., the first 17 or 50), phase 2 (standardization) (i.e., cases 18-46 or 1-50) and phase 3 (proficiency) (i.e., cases after 46, 50 or 135). Data analysis was performed using the Social Science Statistics software ( www.socscistatistics.com ). Statistical significance was defined as p < .05., Results: From November 2007 until April 2018, 95 MI hepatectomies were performed by a FT. During phase 1, the FT approached larger tumors than the EA group (p = 0.002), that were more often malignant (94.1%) when compared to the P group (52.5%) (p < 0.001). During phase 2, the FT operated on larger tumors and more malignancies (93.1%) when compared to the Ps (p = 0.004 and p = 0.017, respectively). However, there was no difference when compared to the EA. In the phase 3, the EAs tended to perform more major hepatectomies (58.7) when compared to either the FT (30.6%) (p = 0.002) or the P's cases 51-135 and after 135 (35.3% and 44.3%, respectively) (both p values < 0.001). When compared to the Ps cases from 51-135, the FT operated on more malignancies (p = 0.012), but this was no longer the case after 135 cases by the Ps (p = 0.164). There were no statistically significant differences when conversions; major complications or 30- and 90-day mortality were compared among these 3 groups., Discussion: Using the IDEAL framework and RA-CUSUM curves, a FT surgeon was found to have curves similar to EAs despite having no previous independent experience operating on the liver. As in our study, FTs may tend to approach larger and more malignant tumors and do more concomitant procedures in patients with higher ASA classifications than either of their predecessors, without statistically significant increases in major morbidity or mortality., Conclusion: It is possible that the ISP (i.e., initiation, standardization, proficiency) model could apply to other innovative surgical procedures, creating different learning curves depending on where along the IDEAL paradigm surgeons fall., (© 2020. Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Although early series focused on benign disease, minimally invasive pancreatoduodenectomy (MIPD) might be particularly suited for malignancy. Unlike their predecessors, fellowship-trained (FT) Hepatic-Pancreatic and Biliary (HPB) surgeons usually have equal skills in approaching peri-ampullary tumors (PT) either openly or via minimally invasive (MI) techniques., Method: We retrospectively reviewed a MI-HPB-FT surgeon's 10-year experience with PD. A sub-analysis of malignant PT was also done (MIPD-PT vs. OPD-PT). The primary endpoint was to assess postoperative mortality and morbidity. Secondary endpoints included operative parameters, length of hospital stay, and survival analysis. Moreover, we addressed practice pattern changes for a surgeon straight out of training with no previous experience of independent surgery., Results: From December 2007-February 2018, one MI-HPB-FT performed a total of 100 PDs, including 57 MIPDs and 43 open PDs (OPDs). In both groups, over 70% of PDs were undertaken for malignancy. Eight patients with borderline resectable pancreatic ductal cancer (PDC) were in the OPD-PT group (as compared to only 2 in the MIPD-PT group) (p = 0.07). Estimated mean blood loss and length of stay were less in the MIPD-PT group (345 mL and 12 days) as compared to the OPD-PT group (971 mL and 16 days), p < 0.001 and p = 0.007, respectively. However, the mean operative time was longer for the MIPD-PT (456 min) as compared to the OPD-PT (371 min), p < 0.001. Thirty and 90-day mortality was 2.6%/5.1% after MIPD-PT compared to 0%/3.2% after OPD-PT, respectively, p = 1. Overall 30-/90-day morbidity rates were similar at 41.0%/43.6% after MIPD-PT and 35.5%/41.9% after OPD-PT, respectively, p = 0.8 and 1. Complete resection (R0) rates were not statistically different, 97.4% after MIPD-PT compared to 87.0% after OPD-PT (p = 0.2). After MIPD and OPD for malignant PT, overall 1, 3 and 5-year survival rates, and median survival were 82.5%, 59.6% and 46.3% and 38 months as compared to 52.5%, 15.7% and 10.5% and 13 months, respectively (p = 0.01). In the MIDP-PT group, recurrence free survival (RFS) at 1, 3 and 5 years and median RFS were 69.1%, 41.9% and 33.5% and 26 months as compared to 50.4%, 6.3% and 6.3% and 13 months, in the OPD-PT group, respectively (p = 0.03)., Conclusion: FT HPB Surgeons who begin their practice with the ability to do both MI and OPD may preferentially approach resectable peri-ampullary tumors minimally invasively. This may result in decreased blood loss decreased length of hospital stays. Despite longer operative time, the improved visualization of MI techniques may enable superior R0 rates when compared to historical open controls. Moreover, combined with quicker initiation of adjuvant chemotherapeutic treatments, this may eventually result in improved survival., (© 2020. Springer Science+Business Media, LLC, part of Springer Nature.)

Importance: The incidence of early-onset colorectal cancer (younger than 50 years) is rising globally, the reasons for which are unclear. It appears to represent a unique disease process with different clinical, pathological, and molecular characteristics compared with late-onset colorectal cancer. Data on oncological outcomes are limited, and sensitivity to conventional neoadjuvant and adjuvant therapy regimens appear to be unknown. The purpose of this review is to summarize the available literature on early-onset colorectal cancer., Observations: Within the next decade, it is estimated that 1 in 10 colon cancers and 1 in 4 rectal cancers will be diagnosed in adults younger than 50 years. Potential risk factors include a Westernized diet, obesity, antibiotic usage, and alterations in the gut microbiome. Although genetic predisposition plays a role, most cases are sporadic. The full spectrum of germline and somatic sequence variations implicated remains unknown. Younger patients typically present with descending colonic or rectal cancer, advanced disease stage, and unfavorable histopathological features. Despite being more likely to receive neoadjuvant and adjuvant therapy, patients with early-onset disease demonstrate comparable oncological outcomes with their older counterparts., Conclusions and Relevance: The clinicopathological features, underlying molecular profiles, and drivers of early-onset colorectal cancer differ from those of late-onset disease. Standardized, age-specific preventive, screening, diagnostic, and therapeutic strategies are required to optimize outcomes.

Most surgeons are skeptical as to the feasibility of autonomous actions in surgery. Interestingly, many examples of autonomous actions already exist and have been around for years. Since the beginning of this millennium, the field of artificial intelligence (AI) has grown exponentially with the development of machine learning (ML), deep learning (DL), computer vision (CV) and natural language processing (NLP). All of these facets of AI will be fundamental to the development of more autonomous actions in surgery, unfortunately, only a limited number of surgeons have or seek expertise in this rapidly evolving field. As opposed to AI in medicine, AI surgery (AIS) involves autonomous movements. Fortuitously, as the field of robotics in surgery has improved, more surgeons are becoming interested in technology and the potential of autonomous actions in procedures such as interventional radiology, endoscopy and surgery. The lack of haptics, or the sensation of touch, has hindered the wider adoption of robotics by many surgeons; however, now that the true potential of robotics can be comprehended, the embracing of AI by the surgical community is more important than ever before. Although current complete surgical systems are mainly only examples of tele-manipulation, for surgeons to get to more autonomously functioning robots, haptics is perhaps not the most important aspect. If the goal is for robots to ultimately become more and more independent, perhaps research should not focus on the concept of haptics as it is perceived by humans, and the focus should be on haptics as it is perceived by robots/computers. This article will discuss aspects of ML, DL, CV and NLP as they pertain to the modern practice of surgery, with a focus on current AI issues and advances that will enable us to get to more autonomous actions in surgery. Ultimately, there may be a paradigm shift that needs to occur in the surgical community as more surgeons with expertise in AI may be needed to fully unlock the potential of AIS in a safe, efficacious and timely manner.

Purpose: The robotic system was introduced to overcome the technical limitations of conventional laparoscopy. For complex oncological operations, it appears to offer further advantages. With regard to hiatal hernia repair, its role has yet to be determined., Methods: All consecutive patients who received elective laparoscopic or robot-assisted hiatal hernia repair at a single institution between January 2016 and July 2020 were retrospectively evaluated. We compared both techniques with particular focus on their short-term outcome. A propensity score-matched comparison considering clinical and surgical covariates was also performed between the two groups., Results: 140 patients were included, and 55 (39.3%) underwent a robot-assisted procedure. The baseline demographics and the frequency of previous abdominal operations were comparable for both groups. The size of the hiatal hernia did not differ significantly between the groups (p = 0.06). The mean operative time was significantly longer for the robot-assisted procedure (149 vs. 125 min; p < 0.01) but decreased markedly during the study period. By contrast, no significant differences were observed in terms of conversion rate (p = 1.0) and blood loss (p = 0.25). Likewise, the postoperative morbidity was comparable for both groups (10.9 vs. 12.9; p = 0.79). The hospital length of stay was not significantly different between the laparoscopic and robotic group (4.0 vs. 3.6 days; p = 0.2). After propensity score-matching, 48 patients were identified for each group. Except for the operative time, no other significant differences were found. Thus, the results of the univariate analysis were confirmed., Conclusion: Our initial results failed to demonstrate a clear advantage of the robotic technique in patients with refractory gastroesophageal reflux disease and/or symptomatic hiatal hernias., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Objectives: Indocyanine green (ICG) is a fluorescent dye which was initially used for liver functional assessment. Moreover, it is of value for intraoperative visualization of liver segments and bile ducts or primary and secondary liver tumors. Especially in minimally invasive liver surgery, this is essential to enhance the precision of anatomical guided surgery and oncological quality. As early adopters of ICG implementation into laparoscopic and robotic-assisted liver surgery in Germany, we summarize the current recommendations and share our experiences., Methods: Actual strategies for ICG application in minimally invasive liver surgery were evaluated and summarized during a review of the literature. Experiences in patients who underwent laparoscopic or robotic-assisted liver surgery with intraoperative ICG staining between 2018 and 2020 from the Magdeburg registry for minimally invasive liver surgery (MD-MILS) were evaluated and the data were analyzed retrospectively., Results: ICG can be used to identify anatomical liver segments by fluorescence angiography via direct or indirect tissue staining. Fluorescence cholangiography visualizes the intra- and extrahepatic bile ducts. Primary and secondary liver tumors can be identified with a sensitivity of 69-100%. For this 0.5 mg/kg body weight ICG must be applicated intravenously 2-14 days prior to surgery. Within the MD-MILS we identified 18 patients which received ICG for intraoperative tumor staining of hepatocellular carcinoma (HCC), cholangiocarcinoma, peritoneal HCC metastases, adenoma, or colorectal liver metastases. The sensitivity for tumor staining was 100%. In 27.8% additional liver tumors were identified by ICG fluorescence. In 39% a false positive signal could be detected. This occurred mainly in cirrhotic livers., Conclusions: ICG staining is a simple and useful tool to assess individual hepatic anatomy or to detect tumors during minimally invasive liver surgery. It may enhance surgical precision and improve oncological quality. False-positive detection rates of liver tumors can be reduced by respecting the tumor entity and liver functional impairments., Competing Interests: Competing interests: Authors state no conflict of interest., (© 2021 Mareike Franz et al., published by De Gruyter, Berlin/Boston.)

Background: Surgery may possibly be undermined by psychologic, psychiatric and psychosomatic problems, as long as these problems interfere with a patient's capacity to cope with surgery adaptively. Recent studies have shown that interpersonal trauma, e.g. abuse or neglect, and its correlates are involved in the adaptation to surgery. This observation is heuristically coherent, given the respective traumatization is an interpersonal event occurring in a relationship. Notably, surgery inevitably leads to the violation of physical boundaries within a doctor-patient relationship. Based on the principles of psycho-traumatologic thinking, such a constellation is deemed qualified to activate posttraumatic symptoms in the traumatized., Method: The present topical review summarizes the respective findings which point to a subgroup of patients undergoing surgery, in whom difficulty bearing tension and confiding in others may cause adaptive problems relevant to surgery. Although this theorizing is empirically substantiated primarily with respect to total knee arthroplasty (TKA), a pubmed-research reveals psychopathologic distress to occur prior to surgery beyond TKA. Likewise, posttraumatic distress occurs in large numbers in the context of several operations, including cardiac, cancer and hernia surgery., Conclusion: Aspects of psychological trauma may be linked to the outcomes of general surgery, as well, e.g. biliary, hernia or appendix surgery. The mechanisms possibly involved in this process are outlined in terms of a hierarchical organization of specific anxiety and negative affect as well as in terms of psychodynamics which imply the unconscious action of psychologic defenses at their core., Implications: Not least, we encourage the screening for trauma and its correlates including defenses prior to general surgery in order to identify surgical candidates at risk of, e.g. chronic postoperative pain, before the operation., (© 2020 Walter de Gruyter GmbH, Berlin/Boston.)

Background: Incisional hernias (IH) occur in 4 to 20% of cases following abdominal surgeries, often after laparotomies. In the US, there are 4 to 5 million laparotomies performed per year, which could lead to 400.000 to 1.000.000 IHs. Therefore, this disease accounts as an important social-economic factor. Furthermore, these hernias can lead to bowel incarcerations, chronic pain, and a decrease in quality of life. To guarantee sufficient wound healing and decrease the recurrence rate, physical activity restrictions (PAR) are recommended. The standard recommendations for PAR seem to vary from 0 to 12 weeks, but the evidence remains low due to a lack of clinical trials. Conducting the study at hand, we aim to provide more evidence on this topic., Methods: The 3N6 trial will be conducted as a national multicenter prospective trial with two study groups (n = 90), where the goal is to find matched pairs within the two groups. Patients who underwent open incisional hernia repair (IHR) in sublay technique will be enrolled. A patient in the 3-week PAR group will be matched to a patient in the 6-week PAR group based on heavy lifting, male gender, BMI > 30, and large hernia >7 cm. The primary endpoint is the duration of sick leave that patients require to return to work, by comparing PAR of 6 weeks with PAR of 3 weeks. The secondary endpoints are the recurrence rate, seroma formation, and chronic pain one year after surgery and postoperative complications within 30 days using Clavien-Dindo-classification., Dissemination: The findings will be published in a peer-reviewed journal. We may also present the findings at local and/or national conferences., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Ltd on behalf of Surgical Associates Ltd.)

Background and Objective: To take full advantage of decision support, machine learning, and patient-level prediction models, it is important that models are not only created, but also deployed in a clinical setting. The KETOS platform demonstrated in this work implements a tool for researchers allowing them to perform statistical analyses and deploy resulting models in a secure environment., Methods: The proposed system uses Docker virtualization to provide researchers with reproducible data analysis and development environments, accessible via Jupyter Notebook, to perform statistical analysis and develop, train and deploy models based on standardized input data. The platform is built in a modular fashion and interfaces with web services using the Health Level 7 (HL7) Fast Healthcare Interoperability Resources (FHIR) standard to access patient data. In our prototypical implementation we use an OMOP common data model (OMOP-CDM) database. The architecture supports the entire research lifecycle from creating a data analysis environment, retrieving data, and training to final deployment in a hospital setting., Results: We evaluated the platform by establishing and deploying an analysis and end user application for hemoglobin reference intervals within the University Hospital Erlangen. To demonstrate the potential of the system to deploy arbitrary models, we loaded a colorectal cancer dataset into an OMOP database and built machine learning models to predict patient outcomes and made them available via a web service. We demonstrated both the integration with FHIR as well as an example end user application. Finally, we integrated the platform with the open source DataSHIELD architecture to allow for distributed privacy preserving data analysis and training across networks of hospitals., Conclusion: The KETOS platform takes a novel approach to data analysis, training and deploying decision support models in a hospital or healthcare setting. It does so in a secure and privacy-preserving manner, combining the flexibility of Docker virtualization with the advantages of standardized vocabularies, a widely applied database schema (OMOP-CDM), and a standardized way to exchange medical data (FHIR)., Competing Interests: The authors have declared that no competing interests exist.

Purpose: Enhancer of zeste homolog 2 (EZH2) is associated with epigenetic gene silencing and aggressiveness in many tumor types. However, the prognostic impact of high EZH2 expression is controversially discussed for colorectal cancer. For this reason, we immunohistochemically analyzed EZH2 expression in 105 specimens from colon cancer patients separately for tumor center and invasion front., Methods: All sections from tissue microarrays were evaluated manually and digitally using Definiens Tissue Studio software (TSS). To mirror-image the EZH2 status at the tumor invasion front, we treated HCT116 colon cancer cells with the EZH2 inhibitor 3-Deazaneplanocin A (DZNep) and studied the growth of in ovo xenografts in the chorioallantoic membrane (CAM) assay., Results: We showed a significant decrease in EZH2 expression and the repressive H3K27me3 code at the tumor invasion front as supported by the TSS-constructed heatmaps. Loss of EZH2 at tumor invasion front, but not in tumor center was correlated with unfavorable prognosis and more advanced tumor stages. The observed cell cycle arrest in vitro and in vivo was associated with higher tumor aggressiveness. Xenografts formed by DZNep-treated HCT116 cells showed loosely packed tumor masses, infiltrative growth into the CAM, and high vessel density., Conclusion: The differences in EZH2 expression between tumor center and invasion front as well as different scoring and cutoff values can most likely explain controversial literature data concerning the prognostic value of EZH2. Epigenetic therapies using EZH2 inhibitors have to be carefully evaluated for each specific tumor type, since alterations in cell differentiation might lead to unfavorable results.

Robotic minimally invasive surgery (RMIS) has played an important role in the last decades. In traditional surgery, surgeons rely on palpation using their hands. However, during RMIS, surgeons use the visual-haptics technique to compensate the missing sense of touch. Various sensors have been widely used to retrieve this natural sense, but there are still issues like integration, costs, sterilization and the small sensing area that prevent such approaches from being applied. A new method based on acoustic emission has been recently proposed for acquiring audio information from tool-tissue interaction during minimally invasive procedures that provide user guidance feedback. In this work the concept was adapted for acquiring audio information from a RMIS grasper and a first proof of concept is presented. Interactions of the grasper with various artificial and biological texture samples were recorded and analyzed using advanced signal processing and a clear correlation between audio spectral components and the tested texture were identified., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Incisional hernias of the abdominal wall are frequent complications after laparotomy (9-20%) and often need incisional hernia repair (IHR). In order to ensure wound healing and to therefore prevent postoperative short and long term morbidity carrying an abdominal binder (AB) and physical rest is frequently advised. However, there is a lack of evidence concerning clinical effects regarding these recommendations. Hence, we conducted a survey to analyze the patient reported outcome following IHR., Methods: From December 2017 to May 2018, we conducted a survey among 270 patients who underwent open and laparoscopic IHR at two maximum care hospitals. They were interviewed about their type of operation, postoperative treatment, recommendations, and outcome., Results: 163 patients replied to the questionnaire. The average age was 63.2 ± 12 years. 74 patients were female and 89 were male. 32.6% of the patients reported an AB-induced immobility and 71.2% reported that the AB reduced pain after IHR. A prolonged period of physical rest and the use of an AB had no statistical significance on postoperative morbidity., Conclusions: Due to our findings we assume that the AB may induce immobility and reduce postoperative pain. A prolonged period of physical rest and wearing an AB does not seem to have an impact on the postoperative outcome following IHR. Therefore, a shortened duration of physical rest and wearing an AB following IHR should be taken under consideration. To reveal more evidence on this topic further clinical trials are essential.

Purpose: The investigation of the predictors of outcome after hepatic resection for solitary colorectal liver metastasis., Methods: We recruited 350 patients with solitary colorectal liver metastasis at the University Hospitals of Jena and Magdeburg, who underwent curative liver resection between 1993 and 2014. All patients had follow-up until death or till summer 2016., Results: The follow-up data concern 96.6% of observed patients. The 5- and 10-year overall survival rates were 47 and 28%, respectively. The 5- and 10-year disease-free survival rates were 30 and 20%, respectively. The analysis of the prognostic factors revealed that the pT category of primary tumour, size and grade of the metastasis and extension of the liver resection had no statistically significant impact on survival and recurrence rates. In multivariate analysis, age, status of lymph node metastasis at the primary tumour, location of primary tumour, time of appearance of the metastasis, the use of preoperative chemotherapy and the presence of extrahepatic tumour proved to be independent statistically significant predictors for the prognosis. Moreover, patients with rectal cancer had a lower intrahepatic recurrence rate, but a higher extrahepatic recurrence rate., Conclusion: The long-term follow-up of patients with R0-resected liver metastasis is multifactorially influenced. Age and comorbidity have a role only in the overall survival. More than three lymph node metastasis reduced both the overall and disease-free survival. Extrahepatic tumour had a negative influence on the extrahepatic recurrence and on the overall survival. Neither overall survival nor recurrence rates was improved using neoadjuvant chemotherapy.

Using gene markers and other patient features to predict clinical outcomes plays a vital role in enhancing clinical decision making and improving prognostic accuracy. This work uses a large set of colorectal cancer patient data to train predictive models using machine learning methods such as random forest, general linear model, and neural network for clinically relevant outcomes including disease free survival, survival, radio-chemotherapy response (RCT-R) and relapse. The most successful predictive models were created for dichotomous outcomes like relapse and RCT-R with accuracies of 0.71 and 0.70 on blinded test data respectively. The best prediction models regarding overall survival and disease-free survival had C-Index scores of 0.86 and 0.76 respectively. These models could be used in the future to aid a decision for or against chemotherapy and improve survival prognosis. We propose that future work should focus on creating reusable frameworks and infrastructure for training and delivering predictive models to physicians, so that they could be readily applied to other diseases in practice and be continuously developed integrating new data.

CDX1 and CDX2 are possibly predictive biomarkers in colorectal cancer. We combined digitally-guided (next generation) TMA construction (ngTMA) and the utility of digital image analysis (DIA) to assess accuracy, tumour heterogeneity and the selective impact of different combined intensity-percentage levels on prognosis.CDX1 and CDX2 immunohistochemistry was performed on ngTMAs covering normal tissue, tumour centre and invasive front. The percentages of all epithelial cells per staining intensity per core were analysed digitally. Beyond classical prognosis analysis following REMARK guidelines, we investigated pre-analytical conditions, three different types of heterogeneity (mosaic-like, targeted and haphazard) and influences on cohort segregation and patient selection. The ngTMA-DIA approach produced robust biomarker data with infrequent core loss and excellent on-target punching. The detailed assessment of tumour heterogeneity could - except for a certain diffuse mosaic-like heterogeneity - exclude differences between the invasive front and tumour centre, as well as detect haphazard clonal heterogeneous elements. Moreover, lower CDX1 and CDX2 counts correlated with mucinous histology, higher TNM stage, higher tumour grade and worse survival ( p  < 0.01, all). Different protein expression intensity levels shared comparable prognostic power and a great overlap in patient selection. The combination of ngTMA with DIA enhances accuracy and controls for biomarker analysis. Beyond the confirmation of CDX1 and CDX2 as prognostically relevant markers in CRC, this study highlights the greater robustness of CDX2 in comparison to CDX1. For the assessment of CDX2 protein loss, cut-points as percentage data of complete protein loss can be deduced as a recommendation.

Background: The influence of neoadjuvant radiochemotherapy (RCT) on programmed death-ligand 1 (PD-L1) expression, a predictive marker for programmed cell death protein 1 (PD-1) inhibitor therapy, was studied on tumour and inflammatory cells in rectal adenocarcinoma patients along with its prognostic value., Methods: PD-L1 immunohistochemistry was performed on tissue microarrays of 103 pre-RCT biopsies and 159 post-RCT surgical specimens (central tumour, invasive front and normal tissue) of 199 patients. In 63 patients, both samples were available. Proportion and maximum intensity of PD-L1-positive (PD-L1+) cells were evaluated., Results: RCT increased the proportion of PD-L1-expressing cancer cells from 2.1% to 7.8% in the central tumour (p < 0.001) or 9.3% in the invasive front (p < 0.001). Cancer cell PD-L1 on its own could not predict prognosis. High PD-L1 expression on pre-RCT inflammatory cells (maximum intensity: p = 0.048) and post-RCT invasive front inflammatory cells (p = 0.010) correlated with improved no evidence of disease survival. In multivariate analysis, the combination of low PD-L1 in cancer and inflammatory cells was an independent negative prognostic marker for overall survival (OS) pre-RCT (Cox's proportional hazard ratio 0.438, p = 0.045) and in the invasive front post-RCT (Cox's proportional hazard ratio 0.257, p = 0.030)., Conclusion: Neoadjuvant RCT is associated with an increased PD-L1 expression in rectal adenocarcinoma patients, which should prompt clinical trials combining radiotherapy and PD-1/PD-L1 pathway blockade. Combined low PD-L1 expression on tumour and inflammatory cells is an independent negative prognostic marker for OS in RCT of rectal adenocarcinoma., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Introduction: There is continuing controversy over the significance of prognostic factors in sporadic desmoid-type fibromatosis (DF). Further, only limited data is available in the literature concerning second recurrence in patients with recurrent DF. The purpose of this study was to identify prognostic factors influencing recurrence-free survival (RFS) and to determine rates of local recurrence (LR) in patients with primary and recurrent DF., Methods: Fifty-three consecutive patients with DF who underwent surgery at a single institution were identified. As a result of strict exclusion criteria, a homogeneous cohort of thirty-two patients who received macroscopically complete resection was included in this study and split into a primary (PG) and recurrent disease (RG) group. Clinicopathological parameters and immunohistochemical markers were retrospectively and independently analyzed in both groups., Results: The local recurrence rate was 35% for the PG and 33% for the RG. The PG's calculated median time to relapse was 17 months, and the RG's was 29 months. The estimated 1-, 5-, and 8-year RFS rates for the PG were 75%, 64%, and 55% while the corresponding RFS rates for the RG were 69%, 69%, and 52%, respectively. In primary disease, extraabdominal tumor location was the only significant adverse prognostic factor associated with worse RFS (p = 0.008). Whereas in recurrent disease, age ≥40 yrs (p = 0.022) and R0 margin status (p = 0.049) correlated with a significantly better outcome., Conclusion: Recurrence in primary and recurrent DF is characterized by different predictive factors and benefits from distinct therapeutic strategies. Immunohistochemical markers are valuable tools in the diagnosis of DF, although have limited potential in predicting the outcome., (Copyright © 2016 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.)

Purpose: There is a sound theoretical basis but little clinical evidence substantiating the benefits of concurrent chemoradiotherapy with two-drug chemotherapy for locally advanced soft tissue sarcomas. Our five-year data on the feasibility and effectiveness of neoadjuvant chemoradiotherapy with systemically effective doses of adriamycin and ifosfamide combined is presented here., Patients and Methods: Between 2000 and 2011, 53 patients with UICC (2010) stage I (n=1, 1.9%), II (n=12, 22.7%) or III (n=40, 75.5%) nonmetastatic soft tissue sarcoma received neoadjuvant chemoradiotherapy with ifosfamide (1.5 g/m(2)/day, d1-5, q28) and doxorubicin (50mg/m(2)/day, d3, q28) plus concurrent radiotherapy with a target dose of 50-64 Gy (median 60 Gy). The treatment of 34 patients (64.2%) was combined with hyperthermia., Results: At five years, the local control rate was 89.9% (± 5.7%), distant metastasis-free survival 66.6% (± 7.6%), and survival 83.3% (± 6%). The R0 resection rate was 81.1%. Radiotherapy was completed as planned in all patients and chemotherapy in 42/53 (70.2%). Grades III (n=21, 29.6%) and IV (n=18, 34%) leukopenia was the main acute adverse event. All acute and chronic non-hematologic toxicities were moderate., Conclusion: Neoadjuvant chemoradiotherapy for soft tissue sarcoma is associated with good feasibility, manageable acute and late toxicities, and high local efficacy., (Copyright © 2015 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Purpose: There is an increasing need to identify molecular markers, which can be used to prognosticate patient populations in gastric cancer. Whereas a significant number have been identified, very few have been characterized in the context of their ability to discriminate between young and old age groups in which a survival difference clearly exists., Material/methods: In this study, using immunohistochemistry, we evaluated three markers with proven involvement in gastric cancer. The p53 tumor suppressor, the cell adhesion glycoprotein epithelial cadherin (CDH1) and the caudal-related homeobox transcription factor (CDX2) all of these have important roles in the aetiopathogenesis and/or progression of gastric cancer., Results: After adjustments for TNM stage, tumor grade, histopathological characteristics (Lauren classification), we found significant differences in the expression of these proteins, particularly E-cadherin and CDX2 between young and elderly patients. However, these differences did not amount to a significant difference in survival., Conclusions: This study demonstrates that the protein expression of p53, CDH1 and CDX2 significantly discriminates young patients with gastric cancer who have a better prognostic outlook from older patients, but this difference in expression does not contribute to a survival benefit., (Copyright © 2014 Medical University of Bialystok. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.)

Background: The necessity to translate eligibility criteria from free text into decision rules that are compatible with data from the electronic health record (EHR) constitutes the main challenge when developing and deploying clinical trial recruitment support systems. Recruitment decisions based on case-based reasoning, i.e. using past cases rather than explicit rules, could dispense with the need for translating eligibility criteria and could also be implemented largely independently from the terminology of the EHR's database. We evaluated the feasibility of predictive modeling to assess the eligibility of patients for clinical trials and report on a prototype's performance for different system configurations., Methods: The prototype worked by using existing basic patient data of manually assessed eligible and ineligible patients to induce prediction models. Performance was measured retrospectively for three clinical trials by plotting receiver operating characteristic curves and comparing the area under the curve (ROC-AUC) for different prediction algorithms, different sizes of the learning set and different numbers and aggregation levels of the patient attributes., Results: Random forests were generally among the best performing models with a maximum ROC-AUC of 0.81 (CI: 0.72-0.88) for trial A, 0.96 (CI: 0.95-0.97) for trial B and 0.99 (CI: 0.98-0.99) for trial C. The full potential of this algorithm was reached after learning from approximately 200 manually screened patients (eligible and ineligible). Neither block- nor category-level aggregation of diagnosis and procedure codes influenced the algorithms' performance substantially., Conclusions: Our results indicate that predictive modeling is a feasible approach to support patient recruitment into clinical trials. Its major advantages over the commonly applied rule-based systems are its independency from the concrete representation of eligibility criteria and EHR data and its potential for automation.

Background and Objectives: Despite its dwindling occurrence, gastric cancer remains a leading cause of cancer related mortality worldwide. Molecular determinants of prognosis that impact survival are being sought out as a means to facilitate rational clinical decision-making and enhance patient management. In this study, we evaluated three molecules implicated in gastric carcinogenesis and demonstrated that the differential expression of cyclooxygenase-2 (COX-2) and the viral oncogene homolog Src proteins could explain the differences in survival observed in patients older and younger than 50 years of age., Methods: We evaluated 5-year survival in a cohort of 423 gastric cancer patients using chronological age as a variable. Additionally, we assessed the protein expression of three molecules (COX-2, TFF1, Src) implicated in the pathogenesis of gastric cancer using immunohistochemistry., Results: We found that patients younger than 50 years of age had a better 5-year survival rate in all tumor stages. We found that the expression of COX-2 and Src correlated significantly with survival in this group without any significant impact attributable to TFF1., Conclusions: Our study demonstrates that young gastric cancer patients have a better prognostic outlook that could in part be explained by the differential expression of COX-2 and Src., (© 2013 Wiley Periodicals, Inc.)

Introduction: Because of the potential benefit of robotics in pancreatic surgery, we review our experience at two minimally invasive pancreatic surgery centers that utilize a robotically controlled laparoscope holder to see if smaller robots that enable the operating surgeon to maintain contact with the patient may have a role in the treatment of pancreatic disease., Methods: From March 1994 to June 2011, a total of 200 laparoscopic pancreatic procedures utilizing a robotically controlled laparoscope holder were performed., Results: A total of 72 duodenopancreatectomies, 67 distal pancreatectomies, 23 enucleations, 20 pancreatic cyst drainage procedures, 5 necrosectomies, 5 atypical pancreatic resections, 4 total pancreatectomies, and 4 central pancreatectomies were performed. Fourteen patients required conversion to an open approach and eight a hand-assisted one. A total of 24 patients suffered a major complication. Sixteen patients developed a pancreatic leak and 19 patients required reoperation. Major complications occurred in 14 patients and pancreatic leaks occurred in 13 patients. Ten patients required conversion to a lap-assisted or open approach and six patients required reoperation., Conclusions: Currently, a robotically assisted approach using a camera holder seems the only way to incorporate some of the benefits of robotics in pancreatic surgery while maintaining haptics and contact with the patient.

The tumor necrosis factor (TNF) gene is an immediate early gene, rapidly transcribed in a variety of cell types following exposure to a broad range of pathogens and signals of inflammation and stress. Regulation of TNF gene expression at the transcriptional level is cell type- and stimulus-specific, involving epigenetic mechanisms or miRNAs. A better knowledge of the molecular mechanisms that control TNF gene regulation and TNF signalling will provide deeper understanding of the initiation and development of apoptotic and inflammatory processes triggered by TNF cytokine in the gut. The described efforts to embed TNF in clinical treatment regiments reflect its attractive effectiveness in killing tumor cells. Whether the described strategies will achieve the success of incorporating TNF in lower gastrointestinal tract therapy for inflammatory diseases and cancer remains to be determined.