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Multimodal treatment of patients with advanced pelvic malignancies (APM) is challenging and surgical expertise is usually concentrated in highly specialised centres. Given significant regional variation in APM surgery, surgical training represents a cornerstone in standardising and future-proofing of this complex therapy. The aim of this study was to describe the availability and current satisfaction levels with surgical training for APM.An online questionnaire was developed and distributed through the Redcap© platform with 32 questions addressing participant and institution demographics, and training in APM surgeries. The survey was electronically disseminated in 2021 to surgical networks across Europe including all specialities treating APM via the European Society of Surgical Oncology (ESSO). All statistical analysis were performed using R.The survey received 280 responses from surgeons across 49 countries, representing general surgery (36%), surgical oncology (30%), gynaeoncology (15%), colorectal surgery (14%) and urology (5%). Fifty-three percent of participants report performing25 APM procedures/year. Respondents were departmental chiefs (12%), consultants (34%), specialist surgeons (40%) and fellows (15%). 34% were happy/very happy with their training with 70% satisfaction about their exposure to surgical procedures. Respondents reported a lack of standardised training (72%), monitoring tools (41%) and mentorship (56%). 57% rated attended courses as useful for training, while 80% rated visiting expert centres as useful.This study has identified a learning need for improved structured training in APM, with low current satisfaction levels with exposure to APM training. Organisations such as ESSO provide an important platform for visiting expert centres, courses, and structured training.

The extent of lymphadenectomy in colon cancer (CC) is a matter of debate. One argument of extensive surgery is that it may prevent lymph node recurrence (LNR). However, the incidence of LNR after surgery for CC is unknown. Here, we performed a systematic review of the incidence of LNR after either standard (D2) surgery or extensive resection (complete mesocolic excision, CME, D3).PubMed, Embase, Web of Science, and CENTRAL were searched for studies reporting on patients with primary stage I-III CC who developed locoregional or distant LNR. Methodological quality was scored using the QualSyst tool. The difference in overall and lymph node (LN) recurrence rate between CME/D3 and standard/D2 resection was statistically evaluated using non-parametric tests. Registered with PROPERO as CRD42020203288.From an initial 12.744 records, 24 studies were included, representing 13.521 CC patients. A majority of patients had right CC (64%), stage III disease (51%), and received adjuvant chemotherapy (57%). The mean number of examined nodes ranged from 14 to 30. The median overall recurrence rate was 14% in the CME/D3 group, and 19% in the standard/D2 group (P = 0.638). The median proportion of patients with any LNR was 1.7% in the CME/D3 group, and 1.2% in the standard/D2 group (P = 0.677). The median incidence of locoregional, potentially preventable LNR was 0% in the CME/D3 group and 0.4% in the standard/D2 group (P = 0.274).The incidence of locoregional, potentially preventable LNR after surgery for CC is low (lt;1%), and is not affected by the extent of lymphadenectomy.

Background The role of recurrence-free survival (RFS) as a valid surrogate endpoint for overall survival (OS) in patients who underwent upfront surgery for colorectal liver metastases remains uncertain. The aim of the study was to compare the two survival measures in a nationwide cohort of upfront resected colorectal liver metastasis. Methods Data from patients with colorectal liver metastases without extrahepatic metastases who underwent curative surgery for liver metastases were retrieved from the Japanese nationwide database (data collection 2005–2007 and 2013–2014). RFS, OS, and survival after recurrence were estimated using the Kaplan–Meier method. The correlation (ρ) between RFS and OS was assessed using the rank correlation method combined with iterative multiple imputation, to account for censoring. As a secondary analysis, the correlation was evaluated according to adjuvant chemotherapy regimen. In sensitivity analysis, the pairwise correlation between RFS and OS was calculated. Results A total of 2385 patients with colorectal liver metastases were included. In the primary analysis, there was a moderately strong correlation between RFS and OS (ρ = 0.73, 95 per cent c.i. 0.70 to 0.76). The strength of the correlation was similar regardless of the adjuvant treatment regimen (oxaliplatin plus 5-fluorouracil: ρ = 0.72, 0.67 to 0.77; 5-fluorouracil alone: ρ = 0.72, 0.66 to 0.76; observation: ρ = 0.74, 0.69 to 0.78). The mean(s.d.) pairwise correlation coefficient between 3-year RFS and 5-year OS was 0.87(0.06). Conclusion In surgically treated patients with colorectal liver metastases, there was a moderately strong correlation between RFS and OS, which was unaffected by the treatment regimen. Further validation using a trial-level analysis is required.

Background: It currently remains unclear whether the anatomical pattern of lymph node (LN) spread differs between young (≤ 45 years, Y) and elderly (≥ 80 years, E) patients with stage III colon cancer (CC).Materials and Methods: Two groups of patients (Y and E) with stage III CC who underwent extensive (D3) lymphadenectomy at Japanese centers were retrospectively analyzed. The primary endpoint was the proportion of positive central LN. The planned sample size was at least 210 (Y) based on an expected value of 9.1% and threshold of 5%, and 230 (E) based on an expected value of 2% and threshold of 5%.Results: Two-hundred and ten Y patients and 348 E patients were identified and compared. The total number of LN harvested and the total number of invaded LN were significantly higher in group Y (median of 31.5 (3-151) vs. 21 (3-116), P Conclusions: Young stage III colon cancer patients have a higher risk of central LN invasion, suggesting a more aggressive disease biology. The presence of central LN invasion is associated with a worse outcome.

Colorectal cancer (CRC) accounts for approximately 10% of all cancer cases worldwide. Conventional treatment has relied on chemotherapy, radiation therapy and surgery with limited success for patients with metastatic CRC. Toll like receptor (TLR) agonists have garnered attention for their ability to stimulate the innate immune system and consequently stimulate production of proinflammatory cytokines and activate an antitumor T cell response. However, activation of TLRs can also result in tumorigenesis and drug resistance depending on the specific TLR and cell that is targeted. Due to these contradictory effects of TLR stimulation, a key challenge is targeting specific cells, such as the dendritic cells or macrophages, to ensure the most optimal result. Additionally, TLR agonists are small molecules that can be cleared rapidly after local administration and can result in severe systemic side effects. This demonstrates the need to develop appropriate nanoparticle delivery systems for TLR agonists that can specifically target the innate immune system as a tool to treat CRC. In this review, the challenges in designing these nanoparticles will be discussed together with the recent advances of nanoparticle formulations containing TLR agonists.

Supplementary Table S1: patient characteristics including age, sex, tumor type, and treatment

Detailed information about Material and Methods used throughout the manuscript including information about cell lines, antibodies, biochemical assays and in vitro and in vivo assays.

Supplementary Figure 1-7 on irradiation of CAF; effect of irradiated CAF on cancer cells; glutamine metabolism; proteome analysis of CM CAF; effect of recombinant IGF1 on cancer cells; effect of recombinant IGF1 on metabolism of cancer cells; schematic of in vivo set-up and Figure legends or respective figures

Preoperative radiotherapy (RT) is a mainstay in the management of rectal cancer, a tumor characterized by desmoplastic stroma containing cancer-associated fibroblasts (CAF). Although CAFs are abundantly present, the effects of RT to CAF and its impact on cancer cells are unknown. We evaluated the damage responses of CAF to RT and investigated changes in colorectal cancer cell growth, transcriptome, metabolome, and kinome in response to paracrine signals emerging from irradiated CAF. RT to CAF induced DNA damage, p53 activation, cell-cycle arrest, and secretion of paracrine mediators, including insulin-like growth factor-1 (IGF1). Subsequently, RT-activated CAFs promoted survival of colorectal cancer cells, as well as a metabolic switch favoring glutamine consumption through IGF1 receptor (IGF1R) activation. RT followed by IGF1R neutralization in orthotopic colorectal cancer models reduced the number of mice with organ metastases. Activation of the downstream IGF1R mediator mTOR was significantly higher in matched (intrapatient) samples and in unmatched (interpatient) samples from rectal cancer patients after neoadjuvant chemoradiotherapy. Taken together, our data support the notion that paracrine IGF1/IGF1R signaling initiated by RT-activated CAF worsens colorectal cancer progression, establishing a preclinical rationale to target this activation loop to further improve clinical responses and patient survival.Significance: These findings reveal that paracrine IGF1/IGF1R signaling promotes colorectal cancer progression, establishing a preclinical rationale to target this activation loop. Cancer Res; 78(3); 659–70. ©2017 AACR.

Background: The survival prognosis of patients with peritoneal metastasis (PM) of gastrointestinal (GI) cancer is generally poor and treatment consists of, according to international guidelines, systemic chemotherapy. A multimodal treatment approach, including cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy, not only proved to be beneficial mainly in colorectal cancer, but also in selected patients with gastric cancer. The authors performed systematic research of articles and ongoing clinical trials using the keywords “PIPAC” and “gastric cancer” or “colorectal cancer” in PubMed in October 2021. Key findings, such as complications rates, treatment protocols, and overall survival were summarized and illustrated in Tables and critically discussed. Summary: Twenty years ago, the technique of Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) was developed by Reymond et al. and delivered evidence to be recognized as a basic therapeutic tool in this multimodal therapy. Currently, there are several ongoing Phase II and III trials exploring the usage and efficacy of PIPAC as a neoadjuvant, adjuvant, or palliative component of treatment in patients with PM of GI cancer. Key Messages: The aim of this narrative review was to help navigate the reader throughout the most current evidence for the use PIPAC and to highlight its indication in patients with upper and lower GI cancer with PM. It also provides an outline of ongoing studies and future perspectives.

Introduction: Surgery remains essential in the curative treatment of esophageal cancer (EC), but it is known for its high morbidity and impaired health-related QoL. Minimally invasive esophagectomy (MIE) was introduced to reduce surgical trauma and improve QoL. Methods: This cross-sectional study aimed to evaluate long-term HRQoL after MIE in comparison with the general population. HRQoL assessment was based on three questionnaires: the European Organisation for Research and Treatment of Cancer (EORTC) Core 30 (QLQ-C30, version 3), the EORTC QLQ Oesophago Gastric 25 (QLQ-OG25), and the Supportive Care Needs Survey-Short Form 34 (SCNS-SF34). Results were compared to a healthy reference population. Results: One hundred and forty eligible MIE patients were identified, of whom met the inclusion criteria, and 49 completed all questionnaires. Patients reported a significantly better mean score on the global health status and QoL than the healthy reference population (71.5 ± 15.1 vs. 66.1 ± 21.7; p = 0.016). However, patients scored significantly worse about functioning (physical, role, and social) (p < 0.05), fatigue (p = 0.021), eating, dysphagia, pain and discomfort, reflux, appetite loss, weight loss, coughing, and taste (p < 0.001). Discussion/Conclusion: EC survivors can reach a high global health status and QoL at least 1 year after MIE, despite long-term functional, nutritional, and gastrointestinal complaints. Patients provided written informed consent, and the study protocol was approved by the Ethics Committee of Ghent University Hospital (identifier: ID B670201940737).

Peritoneal metastasis is an advanced cancer type which can be treated with pressurized intraperitoneal aerosol chemotherapy (PIPAC). Here, chemotherapeutics are nebulized under high pressure in the intraperitoneal (IP) cavity to obtain a better biodistribution and tumor penetration. To prevent the fast leakage of chemotherapeutics from the IP cavity, however, nebulization of controlled release formulations is of interest. In this study, the potential of the thermosensitive hydrogel Pluronic F127 to be applied by high pressure nebulization is evaluated. Therefore, aerosol formation is experimentally examined by laser diffraction and theoretically simulated by computational fluid dynamics (CFD) modelling. Furthermore, Pluronic F127 hydrogels are subjected to rheological characterization after which the release of fluorescent model nanoparticles from the hydrogels is determined. A delicate equilibrium is observed between controlled release properties and suitability for aerosolization, where denser hydrogels (20% and 25% w/v Pluronic F127) are able to sustain nanoparticle release up to 30 hours, but cannot effectively be nebulized and vice versa. This is demonstrated by a growing aerosol droplet size and exponentially decreasing aerosol cone angle when Pluronic F127 concentration and viscosity increase. Novel nozzle designs or alternative controlled release formulations could move intraperitoneal drug delivery by high pressure nebulization forward.

Introduction: The PRODIGE 7-trial investigated the additional value of Hyperthermic Intraperitoneal Chemotherapy (HIPEC) to cytoreductive surgery (CRS) for patients with colorectal peritoneal metastases (CPM). The results of PRODIGE 7 were presented at the 2018 ASCO meeting showing that 30 min oxaliplatin-based HIPEC did not improve overall survival. The current study investigated the impact of PRODIGE 7 on the worldwide practice of CRS and HIPEC. Materials and methods: CRS-HIPEC experts from 19 countries were invited through the Peritoneal Surface Oncology Group International (PSOGI) to complete an online survey concerning the current CRS-HIPEC practice in their hospital and country, and were asked to appraise the effect of PRODIGE 7. Results: The survey was completed by 18/19 experts. Although their personal opinions of CRS-HIPEC were barely influenced by PRODIGE 7, they reported a substantial impact on daily practice. This included a switch towards Mitomycin-C based HIPEC-regimens and prolongation of HIPEC perfusion time, a reduction in the number of referrals from non-HIPEC centers, a reduction in national consensus, the removal of HIPEC from national guidelines, and a reduced reimbursement rate. Conclusion: The PRODIGE 7 has had a major impact on the practice of CRS-HIPEC for CPM worldwide. HIPEC remains an attractive option with potential for control and eradication of disease and further studies into the optimal HIPEC-regimen are urgently needed. Meanwhile, given the complexity of the treatment of patients with CPM, and the proven benefits of optimal CRS, referral of patients with potentially resectable CPM to expert centers is recommended whilst the precise role of HIPEC is further evaluated. (c) 2021 Published by Elsevier Ltd.

BACKGROUND: Omentoplasty is a commonly performed procedure after abdominoperineal resection for rectal cancer, but its effectiveness to reduce pelviperineal complications is not firmly established. OBJECTIVE: To assess the impact of omentoplasty on short-term pelviperineal complications and postoperative outcomes following long-course (chemo)radiotherapy and abdominoperineal resection in patients with locally advanced and locally recurrent rectal cancer. DESIGN: Retrospective cohort study. SETTINGS: Single center. PATIENTS: All patients with locally advanced and locally recurrent rectal cancer undergoing abdominoperineal resection after neoadjuvant (chemo)radiation in a tertiary referral center between 2008 and 2020 were retrospectively reviewed. MAIN OUTCOME MEASURES: Multivariable logistic and linear regression analyses were performed to examine the association between omentoplasty and pelviperineal complications (e.g., perineal wound problems and pelvic abscesses), duration of nasogastric tube drainage and length of hospital stay. RESULTS: A total of 305 patients were analysed of which 245 underwent omentoplasty (80%). Pelviperineal complications occurred in 151 patients (50%) overall, and in 125 (51%) and 26 (43%) of patients with or without omentoplasty, respectively. Independent predictors of pelviperineal complications in multivariable analyses were smoking (OR 2.68, 95% CI 1.46 - 4.94) and high BMI (OR 1.68, 95% CI 1.00 - 2.83), but not omentoplasty (OR 1.36, 95% CI 0.77-2.40). Mean duration of nasogastric tube drainage was longer after omentoplasty (6 vs. 4 days) with a significant association in multivariable analysis (β-coefficient 1.97, 95% CI 0.35-3.59). Patients undergoing omentoplasty had a significantly longer hospital stay (14 vs. 10 days), and omentoplasty remained associated with a prolonged hospital stay after adjusting for confounding (β-coefficient 3.05, 95% CI 0.05-5.74). LIMITATIONS: Retrospective design. CONCLUSION: Omentoplasty was not associated with a reduced risk of the occurrence of short-term pelviperineal complications after abdominoperineal resection in patients undergoing long-course (chemo)radiotherapy. Furthermore, in patients undergoing omentoplasty a prolonged duration of nasogastric tube drainage and hospital stay was observed. See Video Abstract at http://links.lww.com/DCR/C124.

One in four patients with colorectal cancer, 40% of gastric cancer patients, and 60% of ovarian cancer patients will develop peritoneal metastases (PM) in the course of their disease. The outcome of patients with widespread PM remains poor with currently available treatments. Despite the relatively common occurrence of PM, little is known on the pathophysiology that drives the peritoneal metastatic cascade. It is increasingly recognized that the stromal components of the peritoneal microenvironment play an essential role in tumor progression. However, little is known about the specific interactions and components of the peritoneal tumor microenvironment, particularly with respect the immune cell population. We summarize the current knowledge of the tumor immune microenvironment (TIME) in peritoneal metastases originating from the three most common origins: ovarian, gastric, and colorectal cancer. Clearly, the TIME is highly heterogeneous and its composition and functional activity differ according to tumor type and, within the same patient, according to anatomical location. The TIME in PM remains to be explored in detail, and further elucidation of their immune contexture may allow biology driven design of novel immune modulating or immune targeting therapies.

Objectives To assess the risk perception and the uptake of measures preventing environment-related risks in the operating room (OR) during hyperthermic intraperitoneal chemotherapy (HIPEC) and pressurized intraperitoneal aerosol chemotherapy (PIPAC). Methods A multicentric, international survey among OR teams in high-volume HIPEC and PIPAC centers: Surgeons (Surg), Scrub nurses (ScrubN), Anesthesiologists (Anest), Anesthesiology nurses (AnesthN), and OR Cleaning staff (CleanS). Scores extended from 0–10 (maximum). Results Ten centers in six countries participated in the study (response rate 100%). Two hundred and eleven responses from 68 Surg (32%), 49 ScrubN (23%), 45 Anest (21%), 31 AnesthN (15%), and 18 CleanS (9%) were gathered. Individual uptake of protection measures was 51.4%, similar among professions and between HIPEC and PIPAC. Perceived levels of protection were 7.57 vs. 7.17 for PIPAC and HIPEC, respectively (p Conclusions Experience with the current practice of safety protocols was similar during HIPEC and PIPAC. The individual uptake of protection measures was rather low. The safety perception was better for PIPAC, but the perceived level of protection remained relatively low. The willingness to obtain more information was high. Intensified, standardized training of all OR team members involved in HIPEC and PIPAC is meaningful.

The peritoneum is a common site of metastasis in advanced gastric cancer (GC). Diagnostic laparoscopy is now routinely performed as part of disease staging, leading to an earlier diagnosis of synchronous peritoneal metastasis (PM). The biology of GCPM is unique and aggressive, leading to a dismal prognosis. These tumors tend to be resistant to traditional systemic therapy, and yet, this remains the current standard-of-care recommended by most international clinical guidelines. As this is an area of unmet clinical need, several translational studies and clinical trials have focused on addressing this specific disease state. Advances in genomic sequencing and molecular profiling have revealed several promising therapeutic targets and elucidated novel biology, particularly on the role of the surrounding tumor microenvironment in GCPM. Peritoneal-specific clinical trials are being designed with a combination of locoregional therapeutic strategies with systemic therapy. In this review, we summarize the new knowledge of cancer biology, advances in surgical techniques, and emergence of novel therapies as an integrated strategy emerges to address GCPM as a distinct clinical entity.

Background PIPAC is a novel mode of intraperitoneal drug delivery for patients with peritoneal cancer (PC). PIPAC is a safe treatment with promising oncological results. Therefore, a structured training program is needed to maintain high standards and to guarantee safe implementation. Methods An international panel of PIPAC experts created by means of a consensus meeting a structured 2-day training course including essential theoretical content and practical exercises. For every module, learning objectives were defined and structured presentations were elaborated. This structured PIPAC training program was then tested in five courses. Results The panel consisted of 12 experts from 11 different centres totalling a cumulative experience of 23 PIPAC courses and 1880 PIPAC procedures. The final program was approved by all members of the panel and includes 12 theoretical units (45 min each) and 6 practical units including dry-lab and live surgeries. The panel finalized and approved 21 structured presentations including the latest evidence on PIPAC and covering all mandatory topics. These were organized in 8 modules with clear learning objectives to be tested by 12 multiple-choice questions. Lastly, a structured quantifiable (Likert scale 1–5) course evaluation was created. The new course was successfully tested in five courses with 85 participants. Mean overall satisfaction with the content was rated at 4.79 (±0.5) with at 4.71 (±0.5) and at 4.61 (±0.7), respectively for course length and the balance between theory and practice. Conclusions The proposed PIPAC training program contains essential theoretical background and practical training enabling the participants to safely implement PIPAC.

Background The ideal treatment approach for colorectal cancer (CRC) with synchronous liver metastases (SCRLM) remains debated. We performed a network meta-analysis (NMA) comparing the ‘bowel-first’ approach (BFA), simultaneous resection (SIM), and the ‘liver-first’ approach (LFA). Methods A systematic search of comparative studies in CRC with SCRLM was undertaken using the Embase, PubMed, Web of Science, and CENTRAL databases. Outcome measures included postoperative complications, 30- and 90-day mortality, chemotherapy use, treatment completion rate, 3- and 5-year recurrence-free survival, and 3- and 5-year overall survival (OS). Pairwise and network meta-analysis were performed to compare strategies. Heterogeneity was assessed using the Higgins I2 statistic. Results One prospective and 43 retrospective studies reporting on 10 848 patients were included. Patients undergoing the LFA were more likely to have rectal primaries and a higher metastatic load. The SIM approach resulted in a higher risk of major morbidity and 30-day mortality. Compared to the BFA, the LFA more frequently resulted in failure to complete treatment as planned (34% versus 6%). Pairwise and network meta-analysis showed a similar 5-year OS between LFA and BFA and a more favorable 5-year OS after SIM compared to LFA (odds ratio 0.25–0.90, p = 0.02, I2 = 0%), but not compared to BFA. Conclusion Despite a higher tumor load in LFA compared to BFA patients, survival was similar. A lower rate of treatment completion was observed with LFA. Uncertainty remains substantial due to imprecise estimates of treatment effects. In the absence of prospective trials, treatment of stage IV CRC patients should be individually tailored.

Whether tumour side affects the anatomical extent and distribution of lymph node metastasis in colon cancer is unknown. The impact of tumour side on the anatomical pattern of lymphatic spread in colon cancer was assessed.Patients with stage III colon cancer from a Japanese multi-institutional database who underwent extensive (D3) lymphadenectomy, which is similar in concept to complete mesocolic excision with central venous ligation, were divided into groups with right- and left-sided tumours. Based on location, mesenteric lymph nodes were categorized as paracolic (L1), intermediate (L2) or central (L3). The Kaplan-Meier method was used to evaluate disease-free survival (DFS) and overall survival (OS), and multivariable Cox models were used to evaluate the association between anatomical lymph node level, metastatic pattern and outcome.A total of 4034 patients with stage III colon cancer (right 1618, left 2416) were included. Unadjusted OS was worse in patients with right colon cancer (hazard ratio 1·23, 95 per cent c.i. 1·08 to 1·40; P = 0·002), but DFS was similar. Right-sided tumours more frequently invaded L3 nodes than left-sided lesions (8·5 versus 3·7 per cent; P 0·001). The proportion of patients with a skipped pattern of lymphatic spread was higher in right than in left colon cancer (13·7 versus 9·0 per cent; P 0·001). In multivariable analysis, invasion of L3 nodes was associated with worse OS in left but not in right colon cancer. The presence of skipped metastasis was associated with worse DFS in left, but not right, colon cancer.There are significant differences in the pattern of lymph node invasion between right- and left-sided stage III colon cancer, and in their prognostic significance, suggesting that tumour side may dictate the operative approach.Se desconoce si la lateralidad del tumor influye en la extensión anatómica y en la distribución de las metástasis en los ganglios linfáticos (lymph node metastasis, LN) en el cáncer de colon. Se evaluó el impacto de la lateralidad del tumor en el patrón anatómico de diseminación linfática en el cáncer de colon. MÉTODOS: Los pacientes con cáncer de colon en estadio III recogidos en una base de datos japonesa multicéntrica, que se sometieron a una linfadenectomía ampliada (D3), conceptualmente similar a la escisión completa del mesocolon con ligadura venosa central, se dividieron en cáncer de colon del lado derecho y cáncer de colon del lado izquierdo. Según la ubicación, las LN mesentéricas se clasificaron como paracólicas (L1), intermedias (L2) o centrales (L3). Se utilizó el método de Kaplan-Meier para evaluar la supervivencia libre de enfermedad (disease-free survival, DFS) y la supervivencia global (overall-survival, OS), y se utilizaron modelos de Cox multivariados para evaluar la asociación entre el nivel L y el patrón metastásico con el resultado.Se incluyeron 4.034 pacientes con cáncer de colon en estadio III (cáncer de colon derecho: n = 1.618, cáncer de colon izquierdo: n = 2.416). La OS no ajustada fue peor en el cáncer de colon derecho (cociente de riesgos instantáneos, hazard ratio, HR 1,23, i.c. del 95%: 1,08-1,4; P = 0,002), pero la DFS fue similar. La afectación de los ganglios L3 fue más frecuente en pacientes con cáncer de colon derecho que izquierdo (8,5% versus 3,7%, P 0,001). En el cáncer de colon derecho, la proporción de pacientes con patrón de diseminación linfática discontinuo, con salto entre niveles, fue mayor en comparación con el cáncer de colon izquierdo (13,7% versus 9%; P 0,001). En el análisis multivariante, la invasión de los ganglios L3 se asoció con una peor OS en el cáncer de colon izquierdo, pero no en el cáncer de colon derecho. La presencia de metástasis discontinuas se asoció con una peor DFS en el cáncer de colon izquierdo, pero no en el cáncer de colon derecho. CONCLUSIÓN: Existen diferencias significativas en el patrón de invasión de los LN entre el cáncer de colon derecho e izquierdo en estadio III, así como en su importancia pronóstica, lo que sugiere que la lateralidad del tumor puede determinar el abordaje quirúrgico.

The physical microenvironment of cancer is characterized by elevated stiffness and tissue pressure, the main component of which is the interstitial fluid pressure (IFP). Elevated IFP is an established negative predictive and prognostic parameter, directly affecting malignant behavior and therapy response. As such, measurement of the IFP would allow to develop strategies aimed at engineering the physical microenvironment of cancer. Traditionally, IFP measurement required the use of invasive methods. Recent progress in dynamic and functional imaging methods such as dynamic contrast enhanced (DCE) magnetic resonance imaging and elastography, combined with numerical models and simulation, allows to comprehensively assess the biomechanical landscape of cancer, and may help to overcome physical barriers to drug delivery and immune cell infiltration. Here, we provide a comprehensive overview of the origin of elevated IFP, and its role in the malignant phenotype. Also, we review the methods used to measure IFP using invasive and imaging based methods, and highlight remaining obstacles and potential areas of progress in order to implement IFP measurement in clinical practice.

Peritoneal carcinomatosis from appendiceal goblet cell carcinoma (A-GCC) is a rare and aggressive form of appendiceal tumor. Cytoreductive surgery (CRS) and hyperthermic intra peritoneal chemotherapy (HIPEC) was reported as an interesting alternative regarding survival compared to surgery without HIPEC and/or systemic chemotherapy. Our aim was to evaluate the impact of CRS and HIPEC for patients presenting A-GCC through an international registry.A prospective multicenter international database was retrospectively searched to identify all patients with A-GCC tumor and peritoneal metastases who underwent CRS and HIPEC through the Peritoneal Surface Oncology Group International (PSOGI). The post-operative complications, long-term results, and principal prognostic factors were analyzed.The analysis included 83 patients. After a median follow-up of 47 months, the median overall survival (OS) was 34.6 months. The 3- and 5-year OS was 48.5% and 35.7%, respectively. Patients who underwent complete macroscopic CRS had a significantly better survival than those treated with incomplete CRS. The 5-year OS was 44% and 0% for patients who underwent complete, and incomplete CRS, respectively (HR 9.65, p 0.001). Lymph node involvement and preoperative chemotherapy were also predictive of a worse prognosis. There were 3 postoperative deaths, and 30% of the patients had major complications.CRS and HIPEC may increase long-term survival in selected patients with peritoneal metastases of A-GCC origin, especially when complete CRS is achieved. Ideally, randomized control trials or more retrospective data are needed to confirm CRS and HIPEC as the gold standard in this pathology.

Objectives Safe implementation and thorough evaluation of new treatments require prospective data monitoring and standardization of treatments. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a promising alternative for the treatment of patients with peritoneal disease with an increasing number of suggested drug regimens. The aim was to reach expert consensus on current PIPAC treatment protocols and to define the most important research topics. Methods The expert panel included the most active PIPAC centers, organizers of PIPAC courses and principal investigators of prospective studies on PIPAC. A comprehensive literature review served as base for a two-day hybrid consensus meeting which was accompanied by a modified three-round Delphi process. Consensus bar was set at 70% for combined (strong and weak) positive or negative votes according to GRADE. Research questions were prioritized from 0 to 10 (highest importance). Results Twenty-two out of 26 invited experts completed the entire consensus process. Consensus was reached for 10/10 final questions. The combination of doxorubicin (2.1 mg/m2) and cisplatin (10.5 mg/m2) was endorsed by 20/22 experts (90.9%). 16/22 (72.7%) supported oxaliplatin at 120 with potential reduction to 90 mg/m2 (frail patients), and 77.2% suggested PIPAC-Ox in combination with 5-FU. Mitomycin-C and Nab-paclitaxel were favoured as alternative regimens. The most important research questions concerned PIPAC conditions (n=3), standard (n=4) and alternative regimens (n=5) and efficacy of PIPAC treatment (n=2); 8/14 were given a priority of ≥8/10. Conclusions The current consensus should help to limit heterogeneity of treatment protocols but underlines the utmost importance of further research.