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Purpose The Montreal classification for Crohn’s disease includes “age at diagnosis” as a parameter but few is reported about the age at surgery. The aim of this study is to evaluate the short- and long-term differences in the postoperative surgical outcome and disease behaviour, according to the age at the first surgery. Methods Patients consecutively operated for abdominal Crohn’s disease during the period 1986–2012 at our centre were systematically analysed according to their age at first surgery. In our retrospective cohort, the age at first surgery ranged from 13 to 83 years, and patients were arbitrarily divided into four groups: ≤ 19 (G1), 20–39 (G2), 40–59 (G3) and ≥ 60 (G4) years old. Results In total, 1051 patients were included with a median follow-up time of 232 months. The four groups exhibited statistically significant differences in age at diagnosis, smoke habit, time between diagnosis and surgery, disease location and behaviour, history of perianal fistula or abscess, severe malnutrition requiring total parental nutrition before surgery, type of surgery, total length of resected bowel, median duration of hospitalization, incidence of abdominal recurrences and number of surgical recurrences. G1 displays an inverse linear trend with time in the severity of clinical characteristics when compared to G4 groups. On the contrary, the incidence of short-term complications, types of abdominal recurrence and presence of concomitant perianal disease did not vary among groups. In addition, at multivariate analysis, the age at surgery and the disease location were the only independent risk factors for abdominal surgical recurrence. Conclusion Despite first surgery is extremely more frequent between 20 and 59 years, patients from G1 and G4 groups showed clinical differences and peculiarities when compared to the other age groups. The most indolent CD behaviour and occurrence of surgical recurrence was observed in patients having their first abdominal surgery in the elderly, while patients operated before the age of 19 experienced a more aggressive disease course.

Background: The treatment of the primary tumour in colorectal cancer with unresectable liver and/or lung metastases but no peritoneal carcinomatosis is still a matter of debate. In the absence of clear evidence and guidelines, our survey was aimed at obtaining a snapshot of the current attitudes and the rationales for the choice of offering resection of the primary tumour (RPT) despite the presence of untreatable metastases. Methods: An online survey was administered to medical professionals worldwide. The survey had three sections: (1) demographics of the respondent, (2) case scenarios and (3) general questions. For each respondent, an “elective resection score” and an “emergency resection score” were calculated as a percentage of the times he or she would offer RPT in the elective and in the emergency case scenarios. They were correlated to independent variables such as age, type of affiliation and specific workload. Results: Most respondents would offer palliative chemotherapy as the first choice in elective scenarios, while a more aggressive approach with RPT would be reserved for younger patients with good performance status and in emergency situations. Respondents younger than 50 years old and those with a specific workload of fewer than 40 cases of colorectal cancer per year tend to be more conservative. Conclusions: In the absence of clear guidelines and evidence, there is a lack of consensus on the treatment of the primary tumour in case of colon cancer with unresectable liver and/or lung metastases and no peritoneal carcinomatosis. Palliative chemotherapy seems to be the first option, but more consistent evidence is needed to guide this choice.

Purpose: Cannabinoids have been recently proposed as a new family of potential antitumor agents. The present study was undertaken to investigate the expression of the two cannabinoid receptors, CB1 and CB2, in colorectal cancer and to provide new insight into the molecular pathways underlying the apoptotic activity induced by their activation.Experimental Design: Cannabinoid receptor expression was investigated in both human cancer specimens and in the DLD-1 and HT29 colon cancer cell lines. The effects of the CB1 agonist arachinodyl-2'-chloroethylamide and the CB2 agonist N-cyclopentyl-7-methyl-1-(2-morpholin-4-ylethyl)-1,8-naphthyridin-4(1H)-on-3-carboxamide (CB13) on tumor cell apoptosis and ceramide and tumor necrosis factor (TNF)-α production were evaluated. The knockdown of TNF-α mRNA was obtained with the use of selective small interfering RNA.Results: We show that the CB1 receptor was mainly expressed in human normal colonic epithelium whereas tumor tissue was strongly positive for the CB2 receptor. The activation of the CB1 and, more efficiently, of the CB2 receptors induced apoptosis and increased ceramide levels in the DLD-1 and HT29 cells. Apoptosis was prevented by the pharmacologic inhibition of ceramide de novo synthesis. The CB2 agonist CB13 also reduced the growth of DLD-1 cells in a mouse model of colon cancer. The knockdown of TNF-α mRNA abrogated the ceramide increase and, therefore, the apoptotic effect induced by cannabinoid receptor activation.Conclusions: The present study shows that either CB1 or CB2 receptor activation induces apoptosis through ceramide de novo synthesis in colon cancer cells. Our data unveiled, for the first time, that TNF-α acts as a link between cannabinoid receptor activation and ceramide production.

Supplementary Figures S1-S3 from Cannabinoid Receptor Activation Induces Apoptosis through Tumor Necrosis Factor α–Mediated Ceramide De novo Synthesis in Colon Cancer Cells

Background:Helicobacter pylori infection is characterized by an inflammatory infiltrate that might be an important antecedent of gastric cancer. The purpose of this study was to evaluate whether interleukin (IL)-17 inflammation is elicited by gastric T cells in Helicobacter pylori patients with gastric intestinal metaplasia and dysplasia (IM/DYS). We also investigated the serum IL-17A levels in Helicobacter pylori patients with gastric intestinal metaplasia and dysplasia, and patients with Helicobacter pylori non-atrophic gastritis (NAG). Methods: the IL-17 cytokine profile of gastric T cells was investigated in six patients with IM/DYS and Helicobacter pylori infection. Serum IL-17A levels were measured in 45 Helicobacter pylori-infected IM/DYS patients, 45 Helicobacter pylori-infected patients without IM/DYS and in 45 healthy controls (HC). Results: gastric T cells from all IM/DYS patients with Helicobacter pylori were able to proliferate in response to Helicobacter pylori and to produce IL-17A. The Luminex analysis revealed that IL-17A levels were significantly increased in Helicobacter pylori IM/DYS patients compared to healthy controls and to Helicobacter pylori gastritis patients without IM/DYS (452.34 ± 369.13 pg/mL, 246.82 ± 156.06 pg/mL, 169.26 ± 73.82 pg/mL, respectively; p < 0.01, p < 0.05). Conclusions: the results obtained indicate that Helicobacter pylori is able to drive gastric IL-17 inflammation in IM/DYS Helicobacter pylori-infected patients, and that IL-17A serum levels are significantly increased in Helicobacter pylori-infected patients with IM/DYS.

Surgery, like other fields of medicine, has not been spared by a number of unfortunate phenomena. Although our perception may point at recent times, some trends can actually be traced back to 1979. Cohen and Rothschild stated that even when medical progress is extraordinary, the path has too often been driven by overwhelming acceptance of popular albeit unproven ideas. These are referred to as bandwagons. Some of such ideas were eventually proven as valid, but more often were abandoned and/or replaced by new bandwagons. In the specific case of colorectal surgery, there are at least five currently ongoing bandwagons: 1) laparoscopic lavage of perforated colon; 2) laparoscopic ventral rectopexy; 3) stapled hemorrhoidopexy, also known as procedure for prolapse and hemorrhoids (PPH); 4) watch and wait; 5) transanal total mesorectal excision (taTME). Preventing bandwagons from taking off requires efforts at different levels: 1) innovators must constrain their self-interest of fame and rather recognize the need for establishing evidence to support their ideas; 2) new treatment modalities must be carefully weighed by sufficiently powered clinical trials prior to been implemented on patients; 3) the media should not mislead patients into the "best" treatment without reliable evidence; 4) physicians should keep in mind that the process of innovation in medicine is slow and disregard the temptation to accept at face value perhaps plausible, yet unproven ideas.

BACKGROUND Rectal cancer in adolescents and young adults (age ≤39) is increasing. Early diagnosis is a challenge in this subset of patients. OBJECTIVE This study aims to analyze the presentation pattern and outcomes of sporadic rectal cancer in adolescents and young adults. DESIGN This is a retrospective study. SETTING This study was conducted at 3 European tertiary centers. PATIENTS Data on adolescents and young adults operated on for sporadic rectal cancer (January 2008 through October 2019) were analyzed. To compare outcomes, adolescents and young adults were matched to a group of patients aged ≥40 operated on during the same period. MAIN OUTCOME MEASURES The primary outcomes measured were clinical presentation and long-term outcomes. RESULTS Sporadic rectal cancers occurred in 101 adolescents and young adults (2.4%; mean age, 33.5; range, 18-39); 51.5% were male, and a smoking habit was reported by 17.8% of patients. The rate of a family history for colorectal cancer was 25.7%, and of these patients, 24.7% were obese. Diagnosis based on symptoms was reported in 92.1% patients, and the mean time from first symptoms to diagnosis was 13.7 months. The most common symptom at diagnosis was rectal bleeding (68.8%), and 12% and 34% of the adolescents and young adults presented with locally advanced or metastatic disease at diagnosis. Consequently, 68.3% and 62.4% adolescents and young adults received neoadjuvant and adjuvant treatments. The rate of complete pathological response was 24.1%; whereas 38.6% patients had stage IV disease, and 93.1% were microsatellite stable. At a mean follow-up of 5 years, no difference in cancer-specific survival, but a lower disease-free survival was reported in adolescents and young adults (p < 0.0001) vs the matched group. Adolescents and young adults with stages I to II disease had shorter cancer-specific survival and disease-free survival (p = 0.006; p < 0.0001); with stage III disease, they had a shorter disease-free survival (p = 0.01). LIMITATIONS This study was limited by its observational, retrospective design. CONCLUSIONS The significantly delayed diagnosis in adolescents and young adults may have contributed to the advanced disease at presentation and lower disease-free survival, even at earlier stages, suggesting a higher metastatic potential than in older patients. See Video Abstract at http://links.lww.com/DCR/B537. CNCER DE RECTO EN PACIENTES ADOLESCENTES Y ADULTOS JVENES CUADRO DE PRESENTACIN CLNICA Y COMPARACIN DE DESENLACES POR CASOS EMPAREJADOS ANTECEDENTES:El cancer de recto en adolescentes y adultos jovenes (edad ≤ 39) esta aumentando. El diagnostico temprano es un desafio en este subgrupo de pacientes.OBJETIVO:Analizar el cuadro de presentacion y los desenlaces en adolescentes y adultos jovenes con cancer de recto esporadico.DISENO:Estudio retrospectivo.AMBITO:Tres centros europeos de tercer nivel.PACIENTES:Se analizaron los datos de adolescentes y adultos jovenes operados de cancer de recto esporadico (enero de 2008 - octubre de 2019). Para comparar los desenlaces se emparejo a adolescentes y adultos jovenes con un grupo de pacientes mayores de 40 anos operados en el mismo periodo de tiempo.PRINCIPALES VARIABLES ANALIZADAS:Cuadro clinico, resultados a largo plazo.RESULTADOS:Los canceres de recto esporadicos en adolescentes y adultos jovenes fueron 101 (2,4%, edad media: 33,5, rango 18-39). El 51,5% eran hombres, el 17,8% de los pacientes fumaba. El 25,7% tentia antecedentes familiares de cancer colorrectal. El 24,7% eran obesos. El diagnostico con base en los sintomas se informo en el 92,1% de los pacientes, el tiempo promedio desde los primeros sintomas hasta el diagnostico fue de 13,7 meses. El sintoma mas comun en el momento del diagnostico fue el sangrado rectal (68,8%). 12% y 34% de adolescentes y adultos jovenes presentaron enfermedad localmente avanzada o metastasica en el momento del diagnostico. Por lo tanto, el 68,3% y el 62,4% de adolescentes y adultos jovenes recibieron neoadyuvancia y adyuvancia. La tasa de respuesta patologica completa fue del 24,1%; mientras que el 38,6% estaban en estadio IV. El 93,1% eran microsatelite estable. Con una media de seguimiento de 5 anos, no se observaron diferencias en la sobrevida especifica del cancer, pero se informo una menor sobrevida libre de enfermedad en adolescentes y adultos jovenes (p

Background In colon cancer (CC), surgery remains the mainstay of treatment with curative intent. Despite several clinical trials comparing open and laparoscopic approaches, data on long-term outcomes for stage III CC are lacking. Methods This post-hoc analysis of the European PETACC8 randomized phase 3 trial included patients from 340 sites between December 2005 and November 2009, with long follow-up (median 7.56 years). Patients were randomly assigned to FOLFOX or FOLFOX+cetuximab after colonic resection. The surgical approach was left to the referring surgeon's discretion. Results Among 2555 patients included, 1796 (70.29%) were operated on by open surgery and 759 (29.71%) by laparoscopy. The 5-year OS rate was better after laparoscopic resection (85.4%, 95%CI 82.5–87.7) than after open surgery (80.2%, 95%CI 78.2–82.0; p = 0.002). The 5-year DFS rate was also better after laparoscopy (p = 0.016). However, in multivariate analysis using a propensity matching, the surgical approach was not found to be an independent prognostic factor for OS or DFS. OS (p = 0.0243) and DFS (p = 0.035) were increased after laparoscopic surgery in KRAS/BRAF WT sub-group Conclusion We showed that laparoscopic resection has comparable long-term outcomes to open surgery in patients with stage III CC. For those with RAS and BRAF WT CC, laparoscopic colectomy may favorably impact survival.

Body composition profiles influence the prognosis of several types of cancer; however, the role of body composition in patients with locally advanced gastric cancer (LAGC) after neoadjuvant treatment (NT) has not been well characterized.A total of 213 patients with LAGC who underwent gastrectomy after NT at a high-volume institution from southern China were comprehensively evaluated for primary analysis. Additionally, 170 and 77 patients from Western China and Italy, respectively, were reviewed for external validation. The skeletal muscle index (SMI), skeletal muscle radiodensity (SMD), and the subcutaneous as well as the visceral adiposity index were assessed from clinically acquired CT scans at diagnosis and preoperatively.Overall, none of the body composition parameters significantly changed after NT. The pre-NT skeletal muscle radiodensity (SMD) and change in SMI (ΔSMI) were both significantly lower in the patients with poor response (tumor regression50%; mean SMD: 43.5 vs 46.5, P = 0.003; mean ΔSMI: -1.0 vs 2.2, P 0.001), and the cutoff values were calculated according to the Youden index as 43.7 and 1.2, respectively. Based on these 2 parameters, a novel model, the Skeletal Muscle Score (SMS), was proposed to predict the pathological response (AUC = 0.764 alone and = 0.822 in combination with the radiological response). Moreover, patients with an SMI loss1.2 had a significantly prolonged drainage tube removal time (mean: 10.0 vs 8.2, P = 0.003) and postoperative hospital stay (mean: 11.1 vs 9.8, P = 0.048), as well as a significantly higher rate of postoperative complications (30.9% vs 16.7%, P = 0.015). In the multivariate analysis, SMI loss1.2 independently predicted poor overall survival (HR: 1.677, 95% CI 1.040-2.704, P = 0.034) and recurrence-free survival (HR: 1.924, 95% CI 1.165-3.175, P = 0.011). ΔSMI was also significantly associated with pathological response, surgical outcomes, and survival in the 2 external cohorts (P all 0.05).For LAGC, the pre-NT SMD and ΔSMI could accurately predict the pathological response after NT. An SMI loss1.2 is closely associated with poorer outcomes and may indicate the need more supportive treatment.

The sporadic parathyroid pathology of surgical interest is primarily limited to lesions that are the cause of hormonal hyperfunction (primary hyperparathyroidism). In recent years, parathyroid surgery has evolved significantly, and numerous minimally invasive parathyroidectomy techniques have been developed. In this study, we describe a single-center and well-documented case series of sporadic primary hyperparathyroidism, surgically treated by a single operator in the Endocrine Surgery Unit of the Surgical Clinic of the University of Florence-Careggi University Hospital, recorded and updated in a dedicated database that embraces the entire evolutionary timeframe of parathyroid surgery. From January 2000 to May 2020, 504 patients with a clinical and instrumental diagnosis of hyperparathyroidism were included in the study. The patients were divided into two groups, based on the application of intraoperative parathyroid hormone (ioPTH). The analysis shows that the use of ioPTH with the rapid method could be ineffective in helping surgeons in primary operations, especially when ultrasound and scintiscan are concordant. The advantages obtained by not using intraoperative PTH are not only economic. In fact, our data shows shorter operating and general anesthesia times and hospital stays, having an important impact on patient biological commitment. Furthermore, the significant reduction in operating time makes it possible to almost triple the volume of activity in the same unit of time available, with an undeniable advantage for the reduction of waiting lists. In recent years, minimally invasive approaches have allowed surgeons to reach the best compromise between invasiveness and aesthetic results.

At the end of the Bronze Age, technical improvements have made possible the rise of the first generation of major sea powers around the Mediterranean realm, such as Etruria in Italy. The Etruscan coast was fringed by large lagoons, of which only one survives today: the lagoon of Orbetello. This peculiar lagoon is held between two sand spits that connect the former island of Argentario to the mainland. A third sand spit lies in the middle of the lagoon, and supports the Etruscan city of Orbetello. Archeological investigations suggest that the lagoon was connected to the sea through a natural outlet until the 9th century BCE, when an integrated management plan of the lagoon was implemented to optimize fishing. Subsequent closure of the natural outlet implies that lagoon management heavily subsequently relied on man-made openings to maintain the lagoon connected to the sea and nearby rivers. Today, three canals connect the lagoon to the sea. Management plans were implemented in the late 20th Century to fight a massive phase of eutrophication driven by excess release of fertilizers. Eutrophication as responsible for extensive fish kills, and to the release of mercury in the water column. Little is known about lagoon management and the evolution of the city before the 17th century CE, but it is clear that the wealth of the city of Orbetello and the health of its lagoon have been strongly correlated over the past three millennia. To track this coevolution, we conducted a coring campaign coupled to sub-bottom imaging in the very shallow (2) lagoon. iXblue Echoes 10 000 sub-bottom profiler reveals individual layers that can be traced across the lagoon, allowing stratigraphic correlations between cores, and highlighting the environmental significance of the sedimentary facies. Architecture of the deposits reveals a pronounced transgression of the lagoon over its shallowly inward-dipping margins since Antiquity. This led to the flooding of an array of regularly-spaced Roman farms along its southern shorelines, and to a more important flooding of Etruscan structures. Lagoon level rise was driven by a combination of regional sea level rise and fluctuations in the hydraulic balance of the lagoon, controlled by the opening and closure of canals. Sub-bottom imaging reveals buried structures tentatively interpreted as docks and canals used for navigation and salinity control. Sediment analyses under XRF scanning, Rock Eval, and hyperspectral imaging reveals that sedimentation is marked by an alternation of black, shelly organic silty clays and decimeter-thick layers of broken shells. Radiocarbon dating indicates that the cores capture up to five millennia of sedimentation. Ongoing analysis of mercury and phosphorus content, ostracods and pollen assemblages, and chromatic pigments in the organic fractions are expected to document the links between sediment facies, eutrophication and salinity crises, and the rise and demise of land and lagoon management through the past three millennia. A sub-bottom profiling campaign in June 2022 is aimed at mapping the observed structure. Further coring is planned near putative man-made structures next Fall.

Italian Research Group for Gastric Cancer (GIRCG), during the 2013 annual Consensus Conference to gastric cancer, stated that laparoscopic or robotic approach should be limited only to early gastric cancer (EGC) and no further guidelines were currently available. However, accumulated evidences, mainly from eastern experiences, have supported the application of minimally invasive surgery also for locally advanced gastric cancer (AGC). The aim of our study is to give a snapshot of current surgical propensity of expert Italian upper gastrointestinal surgeons in performing minimally invasive techniques for the treatment of gastric cancer in order to answer to the question if clinical practice overcome the recommendation. Experts in the field among the Italian Research Group for Gastric Cancer (GIRCG) were invited to join a web 30-item survey through a formal e-mail from January 1st, 2020, to June 31st, 2020. Responses were collected from 46 participants out of 100 upper gastrointestinal surgeons. Percentage of surgeons choosing a minimally invasive approach to treat early and advanced gastric cancer was similar. Additionally analyzing data from the centers involved, we obtained that the percentage of minimally invasive total and partial gastrectomies in advanced cases augmented with the increase of surgical procedures performed per year (p = 0.02 and p = 0.04 respectively). It is reasonable to assume that there is a widening of indications given by the current national guideline into clinical practice. Propensity of expert Italian upper gastrointestinal surgeons was to perform minimally invasive surgery not only for early but also for advanced gastric cancer. Of interest volume activity correlated with the propensity of surgeons to select a minimally invasive approach.

BACKGROUND Transanal endoscopic microsurgery (TEM) and Transanal endoscopic operation (TEO) have been initially described for local excision of rectal adenomas and selected cases of rectal carcinomas. In the past decade, however, several new indications raised, and others could raise in the future. The aim of this review was to evaluate, both in the literature and in our personal experience, the use of TEM and TEO for nonconventional applications, different from rectal tumors. METHODS We conducted a systematic review of published papers and we selected articles reporting patients who underwent endoscopic surgery for other medical reason than polyp cancer resection, with TEM or TEO. PubMed, MEDLINE, EMBASE and bibliographies of the selected studies were searched for articles in English published up to May 2020 to identify all relevant articles. We excluded articles reporting TEM and TEO used for classical indications. We finally report our experience of non-conventional use of TEO in 5 patients with different diseases. RESULTS The research revealed 800 papers and among them we selected 52 articles for a total of 697 patients. Of all patients, only 52 had intraoperative or postoperative complications, with only 10 patients requiring major surgery. CONCLUSIONS Our study suggest that TEM and TEO may be valid alternatives to traditional surgery in situations other than its classical indication. These findings can positively impact on the care of patients, who could benefit from less invasive surgical procedures associated with lower morbidity.

This study aimed to evaluate the presence of superficial peritoneal endometriosis (SUP) in women referred to emergency surgery for right iliac fossa (RIF) pain and undergoing an appendectomy, considering which factors may be useful to suspect and identify endometriosis.An observational case-control study was conducted on a group (n = 149) of fertile age women. After surgery, Group A was selected upon the diagnosis of endometriosis (n = 34); Group B (n = 115) represented the controls. Demographics, comorbidities and clinical findings were registered and analysed.Appendicitis of various grades of severity was diagnosed in all patients, but SUP was also identified in 23%, of which 14.7% also presented with endometriosis of the appendix. Women in Group A reported chronic pelvic pain, dysmenorrhoea, dyspareunia and oral contraceptive use more frequently. At multivariate analysis, factors associated with endometriosis were: age40 years, autoimmune disorders, multiple allergies, abdominal chronic pain, associated gynaecological pain symptoms, Alvarado score ≤6, and inconclusive ultrasound findings.The incidental finding of SUP in fertile age women presenting with an acute RIF pain and undergoing emergency surgery is a relevant observation. Clinical history and symptoms should guide surgeons in performing a correct diagnosis and in referring the patient to the gynaecology specialist.

Crohn’s disease (CD) patients are generally considered at high risk of post-operative complications with respect to non-CD patients. The primary endpoint of this study is to compare early major complications rates between CD and colon cancer (CC) patients undergoing mini-invasive ileo-colic resections or right hemicolectomies. The secondary endpoint is to evaluate the role of pre-operative medication with anti-TNF as a possible risk factor for post-operative complications. An observational retrospective study was carried on patients who underwent mini-invasive ileocolic resections for CD and right hemicolectomies for CC at Digestive Surgery Unit and IBD Unit, Careggi Univeristy Hospital, from January 1, 2008, to June 1, 2019. Data collected included demographic and clinical informations, pre-operative anti-TNF use, major complications and mortality. Hundred and thirty-three mini-invasive ileocolic resections for CD and 131 mini-invasive right hemicolectomies for CC were included. Early major post-operative complications rates were 4.5% for CD patients and 3% for CC patients (p = 0.535). Anastomotic leak rates were 1.5% in both groups. There was no significant difference in mean length of stay; while, mean operation time was significantly longer in CD patients (p

Ex vivo testing is a fundamental step in the development of new medical devices; indeed without it, it is impossible to proceed with in vivo tests. At the University of Florence, a robotic tool for microwave thermal ablation is under development. Up to now, the thermoablation tests for the validation of the tool were carried out on non-perfused ex vivo livers, providing results that inevitably differ from those obtainable with an in vivo liver. The aim is to design, and consequently create, a compact and transportable system which allows to perfuse a swine liver with physiological solution and heparin. This device should also allow the organ to be transported from the explantation place to the laboratory, keeping it under normothermal condition. The perfusor was designed to simulate the physiological flow within the liver in the most realistic way possible. The design, construction, and optimization of the perfusor have been addressed using the physiological values of hepatic flow and pressure identified in the literature, neglecting in the first instance any load losses. Therefore, open circuit tests were conducted, validated through perfusion tests on freshly explanted pig liver; during these tests, the surface temperature of the organ was recorded using an infrared camera, and the fluid temperature was verified using an immersion probe. The perfusion test showed a good alignment with the open circuit tests, demonstrating the validity of the simplifications adopted to treat the complex vascular structure of the liver.

Resectable gastric or gastroesophageal (G/GEJ) cancer is a heterogeneous disease with no defined molecularly based treatment strategy. Unfortunately, nearly half of patients experience disease recurrence despite standard treatments (neoadjuvant and/or adjuvant chemotherapy/chemoradiotherapy and surgery). In this review, we summarize the evidence of potential tailored approaches in perioperative treatment of G/GEJ cancer, with a special focus on patients with human epidermal growth factor receptor-2(HER2)-positive and microsatellite instability-high (MSI-H) tumors. In patients with resectable MSI-H G/GEJ adenocarcinoma, the ongoing INFINITY trial introduces the concept of non-operative management for patients with complete clinical-pathological-molecular response, and this could be a novel and potential practice changing strategy. Other pathways involving vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), claudin18 isoform 2 (CLDN18.2), and DNA damage repair proteins are also described, with limited evidence until now. Although tailored therapy appears to be a promising strategy for resectable G/GEJ cancer, there are several methodological issues to address: inadequate sample size for pivotal trials, underestimation of subgroup effects, and choice of primary endpoint (tumor-centered vs. patient-centered endpoints). A better optimization of G/GEJ cancer treatment allows maximizing patient outcomes. In the perioperative phase, although caution is mandatory, times are changing and tailored strategies could introduce new treatment concepts. Overall, MSI-H G/GEJ cancer patients possess the characteristics to be the subgroup that could receive the most benefit from a tailored approach.

Indocyanine green (ICG) lymphography can be performed to obtain realtime fluorescent images of the thoracic duct (TD). The injection of ICG into the inguinal nodes usually is ultrasound-guided. Our hypothesis was to simplify the ICG administration until making it executable by unqualified personnel without ultrasound guidance.From October 2019 to October 2021 we enroled 18 patients. ICG was injected with a 25 Gauge needle in the subcutaneous tissue of the inguinal region bilaterally 14-16 h before surgery.The TD was visualised in every case considered. The easy switching between fluorescence and white light visualization facilitated the identification and dissection of the TD avoiding involuntary injuries.The simplified ICG administration to identify TD during oesophagectomy is easy to perform, does not require specifically trained staff, is not time demanding and has comparable results to the procedure performed under ultrasound guide.

Background: The laparoscopic approach in gastric cancer surgery is being increasingly adopted worldwide. However, studies focusing specifically on laparoscopic gastrectomy with D2 lymphadenectomy are still lacking in the literature. This retrospective study aimed to compare the short-term and long-term outcomes of laparoscopic versus open gastrectomy with D2 lymphadenectomy for gastric cancer. Methods: The protocol-based, international IMIGASTRIC (International study group on Minimally Invasive surgery for Gastric Cancer) registry was queried to retrieve data on patients undergoing laparoscopic or open gastrectomy with D2 lymphadenectomy for gastric cancer with curative intent from January 2000 to December 2014. Eleven predefined, demographical, clinical, and pathological variables were used to conduct a 1:1 propensity score matching (PSM) analysis to investigate intraoperative and recovery outcomes, complications, pathological findings, and survival data between the two groups. Predictive factors of long-term survival were also assessed. Results: A total of 3033 patients from 14 participating institutions were selected from the IMIGASTRIC database. After 1:1 PSM, a total of 1248 patients, 624 in the laparoscopic group and 624 in the open group, were matched and included in the final analysis. The total operative time (median 180 versus 240 min, p &lt, 0.0001) and the length of the postoperative hospital stay (median 10 versus 14.8 days, p &lt, 0.0001) were longer in the open group than in the laparoscopic group. The conversion to open rate was 1.9%. The proportion of patients with in-hospital complications was higher in the open group (21.3% versus 15.1%, p = 0.004). The median number of harvested lymph nodes was higher in the laparoscopic approach (median 32 versus 28, p &lt, 0.0001), and the proportion of positive resection margins was higher (p = 0.021) in the open group (5.9%) than in the laparoscopic group (3.2%). There was no significant difference between the groups in five-year overall survival rates (77.4% laparoscopic versus 75.2% open, p = 0.229). Conclusion: The adoption of the laparoscopic approach for gastric resection with D2 lymphadenectomy shortened the length of hospital stay and reduced postoperative complications with respect to the open approach. The five-year overall survival rate after laparoscopy was comparable to that for patients who underwent open D2 resection. The types of surgical approaches are not independent predictive factors for five-year overall survival.

BACKGROUND The COVID-19 epidemic became a challenge for Emergency Departments (ED) and a remarkable reduction in surgical emergencies has been widely noticed. The aim of the present study was to evaluate the impact of the pandemic period in the need of surgical emergencies. METHODS Between January 1, and May 31, 2020 all the consecutive general surgery emergencies performed by the Unit Hospital Emergency Surgery of the Careggi University (Florence, Italy) were prospectively recorded and compared to the same period of 2019. Demographic and clinical data were recorded and analyzed. RESULTS The number of surgical procedures decreased only in the month of March 2020 (compared to 2019), while in April the total numer of emergency surgical procedures was similar. Only appendectomy, complicated hernia repair and colonic resection were significantly reduced (40%, 48% and 33% respectively). The number of small intestine excision, cholecystectomy and lysis of peritoneal adhesions remained stable throughout the entire period. No statistically significant differences were found considering age, sex, Emergency Surgery Score, mortality, ICU postoperative admission and time between admission and surgery, even when analyzed with multivariate analysis for every single surgical procedure, suggesting a comparable disease severity and comorbility patterns. Mortality in COVID patients was 25%, compared to 7% of no-covid patients. CONCLUSIONS The COVID-19 pandemic has caused major changes in daily clinical practice, especially in areas such as Emergency. This has led to a temporary reduction and changes in the flow of patients to the emergency room, with implications also for emergency surgical activities.

Background: the neoplastic B cells of the Helicobacter pylori-related low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma proliferate in response to H. pylori, however, the nature of the H. pylori antigen responsible for proliferation is still unknown. The purpose of the study was to dissect whether CagY might be the H. pylori antigen able to drive B cell proliferation. Methods: the B cells and the clonal progeny of T cells from the gastric mucosa of five patients with MALT lymphoma were compared with those of T cell clones obtained from five H. pylori–infected patients with chronic gastritis. The T cell clones were assessed for their specificity to H. pylori CagY, cytokine profile and helper function for B cell proliferation. Results: 22 of 158 CD4+ (13.9%) gastric clones from MALT lymphoma and three of 179 CD4+ (1.7%) clones from chronic gastritis recognized CagY. CagY predominantly drives Interferon-gamma (IFN-γ) and Interleukin-17 (IL-17) secretion by gastric CD4+ T cells from H. pylori-infected patients with low-grade gastric MALT lymphoma. All MALT lymphoma-derived clones dose dependently increased their B cell help, whereas clones from chronic gastritis lost helper activity at T-to-B-cell ratios greater than 1. Conclusion: the results obtained indicate that CagY drives both B cell proliferation and T cell activation in gastric MALT lymphomas.

Chemotherapy is still widely used as a coadjutant in gastric cancer when surgery is not possible or in presence of metastasis. During tumor evolution, gatekeeper mutations provide a selective growth advantage to a subpopulation of cancer cells that become resistant to chemotherapy. When this phenomenon happens, patients experience tumor recurrence and treatment failure. Even if many chemoresistance mechanisms are known, such as expression of ATP-binding cassette (ABC) transporters, aldehyde dehydrogenase (ALDH1) activity and activation of peculiar intracellular signaling pathways, a common and universal marker for chemoresistant cancer cells has not been identified yet. In this study we subjected the gastric cancer cell line AGS to chronic exposure of 5-fluorouracil, cisplatin or paclitaxel, thus selecting cell subpopulations showing resistance to the different drugs. Such cells showed biological changes, among them, we observed that the acquired chemoresistance to 5-fluorouracil induced an endothelial-like phenotype and increased the capacity to form vessel-like structures. We identified the upregulation of thymidine phosphorylase (TYMP), which is one of the most commonly reported mutated genes leading to 5-fluorouracil resistance, as the cause of such enhanced vasculogenic ability.

Highlights • Caustic ingestion represents a drama for patients and doctors. • Emergency treatment is hard and needs experienced team. • Despite is mainly related to suicide attempt our goal is to guarantee the patient’s survival. • This report represents a prompt management with II step reconstruction. • Multi-disciplinary approach with high competency represents the only possibility to manage a so complex situation., Introduction Ingestion of caustic substances is a life-threatening medical emergency with high morbidity and mortality rate. Case report We present a case report of young patient who presents to our department secondary to ingestion of caustic substances was submitted to multi-visceral resection surgery having saved his life after a long and complex multidisciplinary management. Conclusion An aggressive surgical approach allows successful initial treatment of extended caustic injuries. Early surgical treatment is essential to improve the prognosis in these patients and refer the patient to large and experienced hospital represents the main goal to guarantee a surviving chance.

Background: Several meta-analyses have tried to defi ne the role of minimally invasive approaches. However, further evidence to get a wider spread of these methods is necessary. Current studies describe minimally invasive surgery as a possible alternative to open surgery but deserving further clarifi cation. However, despite the increasing interest, the difficulty of planning prospective studies of adequate size accounts for the low level of evidence, which is mostly based on retrospective experiences. A multi-institutional prospective study allows the collection of an impressive amount of data to investigate various aspects of minimally invasive procedures with the opportunity of developing several subgroup analyses. A prospective data collection with high methodological quality on minimally invasive and open gastrectomies can clarify the role of diff erent procedures with the aim to develop specifi c guidelines. Methods and analysis: a multi-institutional prospective database will be established including information on surgical, clinical and oncological features of patients treated for gastric cancer with robotic, laparoscopic or open approaches and subsequent follow-up. The study has been shared by the members of the International study group on Minimally Invasive surgery for GASTRIc Cancer (IMIGASTRIC) The database is designed to be an international electronic submission system and a HIPPA protected real time data repository from high volume gastric cancer centers. Ethics: This study is conducted in compliance with ethical principles originating from the Helsinki Declaration, within the guidelines of Good Clinical Practice and relevant laws/regulations. Trial registration number: NCT02751086

Funding Information: The authors are grateful to the Birmingham Surgical Trials Consortium at the University of Birmingham for the use of their servers for secure online data collection. Disclosure: The authors declare no conflict of interest.

Tailored treatments for metastatic colorectal cancer (mCRC) have not yet completely evolved due to the variety in response to drugs. Therefore, artificial intelligence has been recently used to develop prognostic and predictive models of treatment response (either activity/efficacy or toxicity) to aid in clinical decision making. In this systematic review, we have examined the ability of learning methods to predict response to chemotherapy alone or combined with targeted therapy in mCRC patients by targeting specific narrative publications in Medline up to April 2022 to identify appropriate original scientific articles. After the literature search, 26 original articles met inclusion and exclusion criteria and were included in the study. Our results show that all investigations conducted on this field have provided generally promising results in predicting the response to therapy or toxic side-effects. By a meta-analytic approach we found that the overall weighted means of the area under the receiver operating characteristic (ROC) curve (AUC) were 0.90, 95% C.I. 0.80–0.95 and 0.83, 95% C.I. 0.74–0.89 in training and validation sets, respectively, indicating a good classification performance in discriminating response vs. non-response. The calculation of overall HR indicates that learning models have strong ability to predict improved survival. Lastly, the delta-radiomics and the 74 gene signatures were able to discriminate response vs. non-response by correctly identifying up to 99% of mCRC patients who were responders and up to 100% of patients who were non-responders. Specifically, when we evaluated the predictive models with tests reaching 80% sensitivity (SE) and 90% specificity (SP), the delta radiomics showed an SE of 99% and an SP of 94% in the training set and an SE of 85% and SP of 92 in the test set, whereas for the 74 gene signatures the SE was 97.6% and the SP 100% in the training set.

BACKGROUND Pelvic organ prolapse (POP) etiology is a combination of anatomical, physiological, genetic, lifestyle, and reproductive factors determine pelvic floor dysfunction. POP is very common across all ages women worldwide and has become an increasing socioeconomic problem with public health consequences, with symptoms that could lead to a significant decrease in quality of life. METHODS This study retrospectively analyzes a small case series of our initial experience of laparoscopic vaginal suspension with mesh focusing on the technical aspects of the technique. Although sacrocolpopexy and sacrohysteropexy are the most performed surgical techniques, they are associated with serious complications. Laparoscopic vaginal suspension appears reproducible and safe to learn. RESULTS Between November 2017 and January 2020, fifteen patients underwent laparoscopic vaginal suspension for pelvic organ prolapse repair. Despite the small number, for a minimally invasive skilled surgeon, we notice a significative reduction of the learning curve to become proficient in this procedure. CONCLUSIONS The diagnosis and management of pelvic organ prolapse are further complicated by what is considered "successful" treatment. Laparoscopic vaginal suspension is a feasible surgical procedure for one-stage treatment of pelvic organ prolapse.