A Randomized Phase III Trial of Complete Mesocolic Excision Compared with Conventional Surgery for Right Colon Cancer: Interim Analysis of a Nationwide Multicenter Study of the Italian Society of Surgical Oncology Colorectal Cancer Network (CoME-in trial).

BACKGROUND: Although complete mesocolic excision (CME) is supposed to be associated with a higher lymph node (LN) yield, decreased local recurrence, and survival improvement, its implementation currently is debated because the evidence level of these data is rather low and still not supported by randomized controlled trials. METHOD: This is a multicenter, randomized, superiority trial (NCT04871399). The 3-year disease-free survival (DFS) was the primary end point of the study. The secondary end points were safety (duration of operation, perioperative complications, hospital length of stay), oncologic outcomes (number of LNs retrieved, 3- and 5-year overall survival, 5-year DFS), and surgery quality (specimen length, area and integrity rate of mesentery, length of ileocolic and middle-colic vessels). The trial design required the LN yield to be higher in the CME group at interim analysis. RESULTS: Interim data analysis is presented in this report. The study enrolled 258 patients in nine referral centers. The number of LNs retrieved was significantly higher after CME (25 vs. 20; p = 0.012). No differences were observed with respect to intra- or post-operative complications, postoperative mortality, or duration of surgery. The hospital stay was even shorter after CME (p = 0.039). Quality of surgery indicators were higher in the CME arm of the study. Survival data still were not available. CONCLUSIONS: Interim data show that CME for right colon cancer in referral centers is safe and feasible and does not increase perioperative complications. The study documented with evidence that quality of surgery and LN yield are higher after CME, and this is essential for continuation of patient recruitment and implementation of an optimal comparison. Trial registration The trial was registered at ClinicalTrials.gov with the code NCT04871399 and with the acronym CoME-In trial.

Clostridium difficile infection after stoma reversal surgery: a systematic review and meta-analysis of the literature.

BACKGROUND: Clostridium difficile infection (CDI) has been described in the early post-operative phase after stoma reversal. This systematic review aimed to describe the incidence of CDI after stoma reversal and to identify pre-operative variables correlated with an increased risk of infection. METHODS: A systematic review of the literature was conducted according to the PRISMA guidelines in March 2024. Manuscripts were included if reported at least one patient with CDI-associated diarrhoea following stoma reversal (colostomy/ileostomy). The primary outcome of interest was the incidence of CDI; the secondary outcome was the comparison of clinical variables (age, sex, time to stoma reversal, neo-adjuvant and adjuvant therapies after index colorectal procedure) in CDI-positive versus CDI-negative patients. A meta-analysis was performed when at least three studies reported on those variables. RESULTS: Out of 43 eligible manuscripts, 1 randomized controlled trial and 10 retrospective studies were selected, including 17,857 patients (2.1% CDI). Overall, the mean age was 64.3 ± 11.6 years in the CDI group and 61.5 ± 12.6 years in the CDI-negative group (p = 0.51), with no significant difference in sex (p = 0.34). Univariable analyses documented that the mean time to stoma reversal was 53.9 ± 19.1 weeks in CDI patients and 39.8 ± 15.0 weeks in CDI-negative patients (p = 0.40) and a correlation between neo-adjuvant and adjuvant treatments with CDI (p < 0.001). A meta-analysis was performed for time to stoma reversal, age, sex, and neo-adjuvant therapies disclosing no significant differences for CDI (stoma delay, MD 11.59; 95%CI  24.32-1.13; age, MD 0.97; 95%CI 2.08-4.03; sex, OR1.11; 95%CI 0.88-1.41; neo-adjuvant, OR0.81; 95%CI 0.49-1.35). Meta-analysis including patients who underwent adjuvant therapy evidenced a higher risk of CDI (OR 2.88; 95%CI 1.01-8.17, p = 0.11). CONCLUSION: CDI occurs in approximately 2.1% of patients after stoma reversal. Although a trend of increased delay in stoma reversal and a correlation with chemotherapy were documented in CDI patients, the use of adjuvant therapy was the only possible risk factor documented on meta-analysis. PROSPERO REGISTRATION NUMBER: CRD42023484704.

Uniportal video-assisted thoracic surgery Ivor-Lewis oesophagectomy with circular stapling anastomosis.

ABSTRACT: Amongst all minimally invasive oesophagectomies, uniportal video-assisted thoracic surgery (VATS) Ivor-Lewis remains the most challenging procedure due to the skills required for performing the intrathoracic anastomosis. We present an easy and safe circular stapling latero-terminal anastomosis for performing uniportal VATS Ivor-Lewis. The patient had an uneventful post-operative recovery and was disease-free 9 months after surgery.

Risk of Lymph Node Metastasis in T1b Gastric Cancer: An International Comprehensive Analysis from the Global Gastric Group (G3) Alliance.

OBJECTIVE: We sought to define criteria associated with low lymph node metastasis risk in patients with submucosal (pT1b) gastric cancer from 3 Western and 3 Eastern countries. SUMMARY BACKGROUND DATA: Accurate prediction of lymph node metastasis risk is essential when determining the need for gastrectomy with lymph node dissection following endoscopic resection. Under present guidelines, endoscopic resection is considered definitive treatment if submucosal invasion is only superficial, but this is not routinely assessed. METHODS: Lymph node metastasis rates were determined for patient groups defined according to tumor pathological characteristics. Clinicopathological predictors of lymph node metastasis were determined by multivariable logistic regression and used to develop a nomogram in a randomly selected subset that was validated in the remainder. Overall survival was compared between Eastern and Western countries. RESULTS: Lymph node metastasis was found in 701 of 3166 (22.1%) Eastern and 153 of 560 (27.3%) Western patients. Independent predictors of lymph node metastasis were female sex, tumor size, distal stomach location, lymphovascular invasion, and moderate or poor differentiation. Patients fulfilling the National Comprehensive Cancer Network guideline criteria, excluding the requirement that invasion not extend beyond the superficial submucosa, had a lymph node metastasis rate of 8.9% (53/594). Excluding moderately differentiated tumors lowered the rate to 3.4% (10/296). The nomogram's area under the curve was 0.690. Regardless of lymph node status, overall survival was better in Eastern patients. CONCLUSIONS: The lymph node metastasis rate was lowest in patients with well differentiated tumors that were ≤3 cm and lacked lymphovascular invasion. These criteria may be useful in decisions regarding endoscopic resection as definitive treatment for pT1b gastric cancer.

Minimally invasive vs. open segmental resection of the splenic flexure for cancer: a nationwide study of the Italian Society of Surgical Oncology-Colorectal Cancer Network (SICO-CNN).

BACKGROUND: Evidence on the efficacy of minimally invasive (MI) segmental resection of splenic flexure cancer (SFC) is not available, mostly due to the rarity of this tumor. This study aimed to determine the survival outcomes of MI and open treatment, and to investigate whether MI is noninferior to open procedure regarding short-term outcomes. METHODS: This nationwide retrospective cohort study included all consecutive SFC segmental resections performed in 30 referral centers between 2006 and 2016. The primary endpoint assessing efficacy was the overall survival (OS). The secondary endpoints included cancer-specific mortality (CSM), recurrence rate (RR), short-term clinical outcomes (a composite of Clavien-Dindo > 2 complications and 30-day mortality), and pathological outcomes (a composite of lymph nodes removed ≧12, and proximal and distal free resection margins length ≧ 5 cm). For these composites, a 6% noninferiority margin was chosen based on clinical relevance estimate. RESULTS: A total of 606 patients underwent either an open (208, 34.3%) or a MI (398, 65.7%) SFC segmental resection. At univariable analysis, OS and CSM were improved in the MI group (log-rank test p = 0.004 and Gray's tests p = 0.004, respectively), while recurrences were comparable (Gray's tests p = 0.434). Cox multivariable analysis did not support that OS and CSM were better in the MI group (p = 0.109 and p = 0.163, respectively). Successful pathological outcome, observed in 53.2% of open and 58.3% of MI resections, supported noninferiority (difference 5.1%; 1-sided 95%CI - 4.7% to ∞). Successful short-term clinical outcome was documented in 93.3% of Open and 93.0% of MI procedures, and supported noninferiority as well (difference - 0.3%; 1-sided 95%CI - 5.0% to ∞). CONCLUSIONS: Among patients with SFC, the minimally invasive approach met the criterion for noninferiority for postoperative complications and pathological outcomes, and was found to provide results of OS, CSM, and RR comparable to those of open resection.

Application of fluorescence-guided surgery in the acute care setting: a systematic literature review.

PURPOSE: Fluorescence-based imaging has found application in several fields of elective surgery, but there is still a lack of evidence in the literature about its use in emergency setting. The present review critically summarizes currently available applications and limitations of indocyanine green (ICG) fluorescence in abdominal emergencies including acute cholecystitis, mesenteric ischemia, and trauma surgery. METHODS: A systematic review was performed according to the PRISMA statement identifying articles about the use of ICG fluorescence in the management of the most common general surgery emergency. Only studies focusing on the use of ICG fluorescence for the management of acute surgical conditions in adults were included. RESULTS: Thirty-six articles were considered for qualitative analysis. The most frequent disease was occlusive or non-occlusive mesenteric ischemia followed by acute cholecystitis. Benefits from using ICG for acute cholecystitis were reported in 48% of cases (clear identification of biliary structures and a safer surgical procedure). In one hundred and twenty cases that concerned the use of ICG for occlusive or non-occlusive mesenteric ischemia, ICG injection led to a modification of the surgical decision in 44 patients (36.6%). Three studies evaluated the use of ICG in trauma patients to assess the viability of bowel or parenchymatous organs in abdominal trauma, to evaluate the perfusion-related tissue impairment in extremity or craniofacial trauma, and to reassess the efficacy of surgical procedures performed in terms of vascularization. ICG injection led to a modification of the surgical decision in 50 patients (23.9%). CONCLUSION: ICG fluorescence is a safe and feasible tool also in an emergency setting. There is increasing evidence that the use of ICG fluorescence during abdominal surgery could facilitate intra-operative decision-making and improve patient outcomes, even in the field of emergency surgery.

Development of the PERI-Gastric (PEritoneal Recurrence Index) and PERI-Gram (Peritoneal Recurrence Index NomoGRAM) for predicting the risk of metachronous peritoneal carcinomatosis after gastrectomy with curative intent for gastric cancer.

BACKGROUND: A model that quantifies the risk of peritoneal recurrence would be a useful tool for improving decision-making in patients undergoing curative-aim gastrectomy for gastric cancer (GC). METHODS: Five Italian centers participated in this study. Two risk scores were created according to the two most widely used pathologic classifications of GC (the Lauren classification and the presence of signet-ring-cell features). The risk scores (the PERI-Gastric 1 and 2) were based on the results of multivariable logistic regressions and presented as nomograms (the PERI-Gram 1 and 2). Discrimination was assessed with the area under the curve (AUC) of receiver operating curves. Calibration graphs were constructed by plotting the actual versus the predicted rate of peritoneal recurrence. Internal validation was performed with a bootstrap resampling method (1000 iterations). RESULTS: The models were developed based on a population of 645 patients (selected from 1580 patients treated from 1998 to 2018). In the PERI-Gastric 1, significant variables were linitis plastica, stump GC, pT3-4, pN2-3 and the Lauren diffuse histotype, while in the PERI-Gastric 2, significant variables were linitis plastica, stump GC, pT3-4, pN2-3 and the presence of signet-ring cells. The AUC was 0,828 (0.778-0.877) for the PERI-Gastric 1 and 0,805 (0.755-0.855) for the PERI-Gastric 2. After bootstrap resampling, the PERI-Gastric 1 had a mean AUC of 0.775 (0.721-0.830) and a 95%CI estimate for the calibration slope of 0.852-1.505 and the PERI-Gastric 2 a mean AUC of 0.749 (0.693-0.805) and a 95%CI estimate for the slope of 0.777-1.351. The models are available at www.perigastric.org . CONCLUSIONS: We developed the PERI-Gastric and the PERI-Gram as instruments to determine the risk of peritoneal recurrence after curative-aim gastrectomy. These models could direct the administration of prophylactic intraperitoneal treatments.

Risk factors for anastomotic leakage after anterior resection for rectal cancer (RALAR study): A nationwide retrospective study of the Italian Society of Surgical Oncology Colorectal Cancer Network Collaborative Group.

AIM: Anastomotic leakage after restorative surgery for rectal cancer shows high morbidity and related mortality. Identification of risk factors could change operative planning, with indications for stoma construction. This retrospective multicentre study aims to assess the anastomotic leak rate, identify the independent risk factors and develop a clinical prediction model to calculate the probability of leakage. METHODS: The study used data from 24 Italian referral centres of the Colorectal Cancer Network of the Italian Society of Surgical Oncology. Patients were classified into two groups, AL (anastomotic leak) or NoAL (no anastomotic leak). The effect of patient-, disease-, treatment- and postoperative outcome-related factors on anastomotic leak after univariable and multivariable analysis was measured. RESULTS: A total of 5398 patients were included, 552 in group AL and 4846 in group NoAL. The overall incidence of leaks was 10.2%, with a mean time interval of 6.8 days. The 30-day leak-related mortality was 2.6%. Sex, body mass index, tumour location, type of approach, number of cartridges employed, weight loss, clinical T stage and combined multiorgan resection were identified as independent risk factors. The stoma did not reduce the leak rate but significantly decreased leak severity and reoperation rate. A nomogram with a risk score (RALAR score) was developed to predict anastomotic leak risk at the end of resection. CONCLUSIONS: While a defunctioning stoma did not affect the leak risk, it significantly reduced its severity. Surgeons should recognize independent risk factors for leaks at the end of rectal resection and could calculate a risk score to select high-risk patients eligible for protective stoma construction.

Enterotomy Closure after Minimally Invasive Distal Gastrectomy with Intracorporeal Anastomosis: A Multicentric Study.

INTRODUCTION: Despite progressive improvements in technical skills and instruments that have facilitated surgeons performing intracorporeal gastro-jejunal and jejuno-jejunal anastomoses, one of the big challenging tasks is handsewn knot tying. We analysed the better way to fashion a handsewn intracorporeal enterotomy closure after a stapled anastomosis. METHODS: All 579 consecutive patients from January 2009 to December 2019 who underwent minimally invasive partial gastrectomy for gastric cancer were retrospectively analysed. Different ways to fashion intracorporeal anastomoses were investigated: robotic versus laparoscopic approach; laparoscopic high definition versus three-dimensional versus 4K technology; single-layer versus double-layer enterotomies. Double-layer enterotomies were analysed layer by layer, comparing running versus interrupted suture; the presence versus absence of deep corner suture; and type of suture thread. RESULTS: Significantly lower rates of bleeding (p = 0.011) and leakage (p = 0.048) from gastro-jejunal anastomosis were recorded in the double-layer group. Barbed suture thread was significantly associated with reduced intraluminal bleeding and leakage rates both in the first (p = 0.042 and p = 0.010) and second layer (p = 0.002 and p = 0.029). CONCLUSIONS: Double-layer sutures using barbed suture thread both in first and second layer to fashion enterotomy closure result in lower intraluminal bleeding and anastomotic leak rates.

3D pelvimetry and biometric measurements: a surgical perspective for colorectal resections.

PURPOSE: Male sex, high BMI, narrow pelvis, and bulky mesorectum were acknowledged as clinical variables correlated with a difficult pelvic dissection in colorectal surgery. This paper aimed at comparing pelvic biometric measurements in female and male patients and at providing a perspective on how pelvimetry segmentation may help in visualizing mesorectal distribution. METHODS: A 3D software was used for segmentation of DICOM data of consecutive patients aged 60 years, who underwent elective abdominal CT scan. The following measurements were estimated: pelvic inlet, outlet, and depth; pubic tubercle height; distances from the promontory to the coccyx and to S3/S4; distance from S3/S4 to coccyx's tip; ischial spines distance; pelvic tilt; offset angle; pelvic inlet angle; angle between the inlet/sacral promontory/coccyx; angle between the promontory/coccyx/pelvic outlet; S3 angle; and pelvic inlet to pelvic depth ratio. The measurements were compared in males and females using statistical analyses. RESULTS: Two-hundred patients (M/F 1:1) were analyzed. Out of 21 pelvimetry measurements, 19 of them documented a significant mean difference between groups. Specifically, female patients had a significantly wider pelvic inlet and outlet but a shorter pelvic depth, and promontory/sacral/coccyx distances, resulting in an augmented inlet/depth ratio when comparing with males (p < 0.0001). The sole exceptions were the straight conjugate (p = 0.06) and S3 angle (p = 0.17). 3D segmentation provided a perspective of the mesorectum distribution according to the pelvic shape. CONCLUSION: Significant differences in the structure of pelvis exist in males and females. Surgeons must be aware of the pelvic shape when approaching the rectum.

The learning curve of TaTME for mid-low rectal cancer: a comprehensive analysis from a five-year institutional experience.

BACKGROUND: Transanal total mesorectal excision (TaTME) was introduced in 2009 as a dedicated approach for the treatment of mid-low rectal cancer. We aimed to describe and discuss the learning curve for 121 consecutive TaTME procedures performed by the same team. METHODS: The primary outcome was the number of operations required to decrease the mean operative time (mOT). The secondary outcomes were the number of operations required to decrease the major complication (MC) rate, the anastomotic leakage (AL) rate, the clinical anastomotic failure rate, and the reoperation rate. A cumulative sum (CUSUM) curve analysis was used to identify the inflection points. As an integrative analysis, Bernoulli CUSUM curves, risk-adjusted CUSUM curves based on the observed-expected outcomes, and CUSUM curves targeting results reported in the literature were created. RESULTS: Seventy-one cases were needed to overcome the OT learning curve sufficiently to reach mastery. The MC and reoperation rates started to decrease after the 54th case and further decreased after the 69th case. The AL rate started to decrease after the 27th case and remained stable at 5-5.1%. The comparison between the different phases of the learning curves confirmed these turning points. CONCLUSIONS: TaTME had a learning curve of 71 cases for the mOT, 55-69 cases for MCs and reoperation, and 27 cases for AL. According to our results, attention should be paid during the first part of the learning curve to avoid an increased rate of MCs and AL.

The gut microbiota and colorectal surgery outcomes: facts or hype? A narrative review.

BACKGROUND: The gut microbiota (GM) has been proposed as one of the main determinants of colorectal surgery complications and theorized as the "missing factor" that could explain still poorly understood complications. Herein, we investigate this theory and report the current evidence on the role of the GM in colorectal surgery. METHODS: We first present the findings associating the role of the GM with the physiological response to surgery. Second, the change in GM composition during and after surgery and its association with colorectal surgery complications (ileus, adhesions, surgical-site infections, anastomotic leak, and diversion colitis) are reviewed. Finally, we present the findings linking GM science to the application of the enhanced recovery after surgery (ERAS) protocol, for the use of oral antibiotics with mechanical bowel preparation and for the administration of probiotics/synbiotics. RESULTS: According to preclinical and translational evidence, the GM is capable of influencing colorectal surgery outcomes. Clinical evidence supports the application of an ERAS protocol and the preoperative administration of multistrain probiotics/synbiotics. GM manipulation with oral antibiotics with mechanical bowel preparation still has uncertain benefits in right-sided colic resection but is very promising for left-sided colic resection. CONCLUSIONS: The GM may be a determinant of colorectal surgery outcomes. There is an emerging need to implement translational research on the topic. Future clinical studies should clarify the composition of preoperative and postoperative GM and the impact of the GM on different colorectal surgery complications and should assess the validity of GM-targeted measures in effectively reducing complications for all colorectal surgery locations.

A detailed analysis of the recurrence timing and pattern after curative surgery in patients undergoing neoadjuvant therapy or upfront surgery for gastric cancer.

BACKGROUND AND OBJECTIVES: The aim of this study was to determine whether the administration of neoadjuvant therapy (NAD) affects the incidence, timing, and pattern of recurrence in patients treated by curative gastrectomy. METHODS: Sixty-nine patients undergoing NAD and R0 gastrectomy were compared with 198 patients undergoing upfront surgery using the propensity score matching (PSM) method. Disease-free survival (DFS), disease-specific survival (DSS), and progression-free survival (PFS) analyses were conducted with a log-rank test and Cox regression. Risk factors for recurrence were assessed by logistic regression. RESULTS: Among 69 patients with NAD, 28 (40.6%) experienced recurrence, and signet-ring cell (SRC) carcinoma was the only factor independently associated with recurrence. In the whole sample, NAD did not influence DFS, DSS, rate of recurrence, or PFS. After PSM, the variables associated with DFS were cN1, type of gastrectomy, the presence of SRCs, and the presence of lymphovascular invasion. Variables independently associated with recurrence were cN1, type of gastrectomy, and the presence of SRCs. CONCLUSIONS: NAD had no impact on DFS, DSS, or the pattern of recurrence in any patients with gastric cancer. To define a better treatment strategy, future studies should focus on subtypes that do not respond to the current neoadjuvant regimens.

D1-plus vs D2 nodal dissection in gastric cancer: a propensity score matched comparison and review of published literature.

BACKGROUND: The results of D1-plus lymphadenectomy following gastric resection are seldom investigated. The aim of this study was to compare results of D1-plus vs D2 resections and to provide a literature review. METHODS: Patients who underwent upfront R0 gastrectomy for adenocarcinoma from 2000 to 2016 in three Institutions were selected using propensity scores and categorized according to lymphadenectomy. Statistical analyses were performed for the nodal harvest (LNH) and survival. Published literature comparing D1-plus and D2 was reviewed and analyzed according to PICO and PRISMA guidelines. RESULTS: Two matched groups of 93 D1-plus and 93 D2 resections were selected. LNH was significantly greater in D2 vs D1-plus dissections (mean 31.2 vs 27.2, p 0.04), however LNH distribution was similar. The cumulative incidence curves for overall survival, disease free and disease specific events did not report significant differences, however Cox regression analysis disclosed that total gastrectomies (HR 1.8; 95% 1.0-2.9), advanced stages (HR 5.9; 95% 3.4-10.3) and D1-plus nodal dissection (HR 2.1; 95% 1.26-3.50) independently correlated with disease free survival. Literature review including 297 D1-plus and 556 D2 lymphadenectomies documented LNH in favor of D2 sub-group (SMD -0.772; 95%CI -1.222- -0.322). CONCLUSION: D2 provided greater LNH than D1-plus dissections; prospective studies should aim to investigate long-term survival of D1-plus lymphadenectomy.

Ratio-based staging systems are better than the 7th and 8th editions of the TNM in stratifying the prognosis of gastric cancer patients: A multicenter retrospective study.

BACKGROUND: The current and the previous editions of the tumor-node-metastasis (TNM) system for gastric cancer (GC; TNM8 and TNM7) have a high risk of stage-migration bias when the node count after gastrectomy is suboptimal. Hence, they are possibly not the optimal staging systems for GC patients. This study aims to compare the TNM with two systems less affected by the stage-migration bias, namely, the lymph nodes ratio (LNR) and the log odds of positive lymph nodes (LODDS), to assess which one is the best in stratifying the prognosis of GC patients. METHODS: The sample study included 1221 GC patients. Two 7-cluster staging systems based on the combination of pT categories and LNR and LODDS categories (TLNR and TLODDS) were compared with the two last editions of TNM, using the Akaike information criteria, the Bayesian information criteria, and the receiver operating characteristic (ROC) curve graphs. Further validation on an independent sample of 251 patients was carried out. RESULTS: The univariable and multivariable analyses and the ROC curves detected an advantage of the TLNR and TLODDS systems over the TNM. The TLNR and TLODDS showed the best accuracy both in the subgroup of patients with ≥16 nodes examined. The results were confirmed in the validation analysis. CONCLUSIONS: TLNR and TLODDS staging systems should be considered a valid implementation of the TNM for the prognostic stratification of GC patients. If these results are confirmed in further studies, the future implementation of the TNM should consider the introduction of the LNR or the LODDS along with the number of metastatic nodes.

Prognostic Indicators in Stage IV Surgically Treated Gastric Cancer Patients: A Retrospective Multi-Institutional Study.

INTRODUCTION: The role of gastric resection in treating metastatic gastric adenocarcinoma is controversial. In the present study, we reviewed the short- and long-term outcomes of stage IV patients undergoing surgery. METHODS: A retrospective review was conducted that assessed patients undergoing elective surgery for incurable gastric carcinoma. Short- and long-term results were evaluated. RESULTS: A total of 122 stage IV gastric cancer patients were assessed. Postoperative mortality was 5.7%, and the overall rate of complications was 35.2%. The overall survival rate at 1 and 3 years was 58 and 19% respectively; the median survival was 14 months. Improved survival was observed for the factors age less than 60 years (p = 0.015), site of metastases (p = 0.022), extended lymph node dissection (p = 0.044), absence of residual disease after surgery (p = 0.001), and administration of adjuvant chemotherapy (p = 0.016). Multivariate analysis showed that residual disease and adjuvant chemotherapy were independent prognostic factors. CONCLUSIONS: The results of this study suggest that surgery combined with systemic chemotherapy in selected patients with stage IV gastric cancer can improve survival.

Telocytes are the physiological counterpart of inflammatory fibroid polyps and PDGFRA-mutant GISTs.

PDGFRA mutations in the gastrointestinal (GI) tract can cause GI stromal tumour (GIST) and inflammatory fibroid polyp (IFP). Hitherto no cell type has been identified as a physiological counterpart of the latter, while interstitial Cajal cells (ICC) are considered the precursor of the former. However, ICC hyperplasia (ICCH), which strongly supports the ICC role in GIST pathogenesis, has been identified in germline KIT-mutant settings but not in PDGFRA-mutant ones, challenging the precursor role of ICC for PDGFRA-driven GISTs. Telocytes are a recently described interstitial cell type, CD34+/PDGFRA+. Formerly considered fibroblasts, they are found in many organs, including the GI tract where they are thought to be involved in neurotransmission. Alongside IFPs and gastric GISTs, GI wall "fibrosis" has been reported in germline PDGFRA-mutants. Taking the opportunity offered by its presence in a germline PDGFRA-mutant individual, we demonstrate that this lesion is sustained by hyperplastic telocytes, constituting the PDGFRA-mutant counterpart of germline KIT mutation-associated ICCH. Moreover, our findings support a pathogenetic relationship between telocyte hyperplasia and both IFPs and PDGFRA-mutant GISTs. We propose the term "telocytoma" for defining IFP, as it conveys both the pathogenetic (neoplastic) and histotypic ("telocytary") essence of this tumour, unlike IFP, which rather evokes an inflammatory-hyperplastic lesion.

Transanal Total Mesorectal Excision vs Laparoscopic Total Mesorectal Excision in the Treatment of Low and Middle Rectal Cancer: A Propensity Score Matching Analysis.

BACKGROUND: Transanal total mesorectal excision is a novel and promising technique in the treatment of low and middle rectal cancer. OBJECTIVE: This study aimed to compare the safety and feasibility of transanal total mesorectal excision versus laparoscopic total mesorectal excision. DESIGN: This was a retrospective study using propensity score matching analysis. SETTINGS: This study was conducted in a single high-volume university hospital. PATIENTS: Patients with low and middle rectal cancer who underwent total mesorectal excision with curative intent between 2007 and 2017 were recruited. INTERVENTIONS: Laparoscopic total mesorectal excision and transanal total mesorectal excision had been performed. MAIN OUTCOME MEASURES: Intraoperative, pathological, and 30-day postoperative outcomes were compared between the transanal and laparoscopic groups. RESULTS: Overall, 105 patients were selected from the whole sample of 316 patients with rectal cancer. After propensity score matching analysis, 46 patients for each group were compared. Laparoscopic total mesorectal excision was associated with a higher conversion rate to open surgery (19.6% vs 0%, p = 0.002). Transanal total mesorectal excision showed a longer distal resection margin (15 mm vs 25 mm; p < 0.001), and similar results regarding the completeness of mesorectal excision and circumferential resection margin involvement, compared to laparoscopy. There were no statistically significant differences between the 2 groups in terms of postoperative complications. LIMITATIONS: The study was limited by its retrospective design and the small size of the sample. CONCLUSIONS: Transanal total mesorectal excision is a safe and feasible technique that results in a high-quality rectal cancer resection specimen and favorable 30-day postoperative outcomes.

Fatal Case of Metformin-Associated Lactic Acidosis Associated With Temporary Ileostomy: A Case Report.

BACKGROUND: Metformin is considered a first choice for oral treatment of patients with type 2 diabetes in the absence of contraindications. Colorectal cancer is the second most frequent cancer among the general population; low anterior resections and temporary diverting ileostomies are commonly performed in this population. As the incidence of type 2 diabetes increases, the use of metformin in patients with both type 2 diabetes and an ileostomy will most likely increase as well. CASE: We present the case of a patient affected by colorectal cancer who developed a severe metformin-associated lactic acidosis (MALA) after creation of a temporary ileostomy to protect a low colorectal anastomosis. High-volume output from his ileostomy led to significant fluid loss and electrolyte imbalance, his condition was complicated by MALA, resulting in death. CONCLUSION: The population of ileostomy patients who also have type 2 diabetic and taking metformin is at risk for MALA. High stomal output can lead to dehydration, with a loss of fluids and electrolytes and metformin could aggravate this condition, potentiating the risk of MALA.