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.

Biological and targeting differences between the rare KRAS A146T and canonical KRAS mutants in gastric cancer models.

BACKGROUND: Gastric cancer (GC) is the third leading cause of cancer-related death worldwide, with a poor prognosis for patients with advanced disease. Since the oncogenic role of KRAS mutants has been poorly investigated in GC, this study aims to biochemically and biologically characterize different KRAS-mutated models and unravel differences among KRAS mutants in response to therapy. METHODS: Taking advantage of a proprietary, molecularly annotated platform of more than 200 GC PDXs (patient-derived xenografts), we identified KRAS-mutated PDXs, from which primary cell lines were established. The different mutants were challenged with KRAS downstream inhibitors in in vitro and in vivo experiments. RESULTS: Cells expressing the rare KRAS A146T mutant showed lower RAS-GTP levels compared to those bearing the canonical G12/13D mutations. Nevertheless, all the KRAS-mutated cells displayed KRAS addiction. Surprisingly, even if the GEF SOS1 is considered critical for the activation of KRAS A146T mutants, its abrogation did not significantly affect cell viability. From the pharmacologic point of view, Trametinib monotherapy was more effective in A146T than in G12D-mutated models, suggesting a vulnerability to MEK inhibition. However, in the presence of mutations in the PI3K pathway, more frequently co-occurrent in A146T models, the association of Trametinib and the AKT inhibitor MK-2206 was required to optimize the response. CONCLUSION: A deeper genomic and biological characterization of KRAS mutants might sustain the development of more efficient and long-lasting therapeutic options for patients harbouring KRAS-driven GC.

Safety of laparoscopic cholecystectomy performed by trainee surgeons with different cholangiographic techniques (SCOTCH): a prospective non-randomized trial on the impact of fluorescent cholangiography during laparoscopic cholecystectomy performed by trainees.

AIMS: The identification of the anatomical components of the Calot's Triangle during laparoscopic cholecystectomy (LC) might be challenging and its difficulty may increase when a surgical trainee (ST) is in charge, ultimately allegedly affecting also the incidence of common bile duct injuries (CBDIs). There are various methods to help reach the critical view of safety (CVS): intraoperative cholangiogram (IOC), critical view of safety in white light (CVS-WL) and near-infrared fluorescent cholangiography (NIRF-C). The primary objective was to compare the use of these techniques to obtain the CVS during elective LC performed by ST. METHODS: This was a multicentre prospective observational study (Clinicalstrials.gov Registration number: NCT04863482). The impact of three different visualization techniques (IOC, CVS-WL, NIRF-C) on LC was analyzed. Operative time and time to achieve the CVS were considered. All the participating surgeons were also required to fill in three questionnaires at the end of the operation focusing on anatomical identification of the general task and their satisfaction. RESULTS: Twenty-nine centers participated for a total of 338 patients: 260 CVS-WL, 10 IOC and 68 NIRF-C groups. The groups did not differ in the baseline characteristics. CVS was considered achieved in all the included case. Rates were statistically higher in the NIR-C group for common hepatic and common bile duct visualization (p = 0.046; p < 0.005, respectively). There were no statistically significant differences in operative time (p = 0.089) nor in the time to achieve the CVS (p = 0.626). Three biliary duct injuries were reported: 2 in the CVS-WL and 1 in the NIR-C. Surgical workload scores were statistically lower in every domain in the NIR-C group. Subjective satisfaction was higher in the NIR-C group. There were no other statistically significant differences. CONCLUSIONS: These data showed that using NIRF-C did not prolong operative time but positively influenced the surgeon's satisfaction of the performance of LC.

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.

Complete mesocolic excision in comparison with conventional surgery for right colon cancer: a nationwide multicenter study of the Italian Society of Surgical Oncology colorectal cancer network (CoME-in trial). Study protocol for a randomized controlled trial.

Complete mesocolic excision with central vascular ligation, or simply CME, includes the sharp dissection along the mesocolic visceral and parietal layers, with the ligation of the main vessels at their origins. To date, there is low evidence on its safety and efficacy. This is a study-protocol of a multicenter, randomized, superiority trial in patients with right-sided colon cancer. It aims to investigate whether the complete mesocolic excision improves the oncological outcomes as compared with conventional right hemicolectomy, without worsening early outcomes. Data on efficacy and safety of complete mesocolic excision are available only from a large trial recruiting eastern patients and from a low-volume single-center western study. No results on survival are still available. For this reason, complete mesocolic excision continues to be a controversial topic in daily practice, particularly in western world. This new nationwide multicenter large-volume trial aims to provide further data on western patients, concerning both postoperative and survival outcomes.

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.

Personalized therapeutic strategies in HER2-driven gastric cancer.

BACKGROUND: Trastuzumab is the only approved targeted therapy in patients with HER2-amplified metastatic gastric cancer (GC). Regrettably, in clinical practice, only a fraction of them achieves long-term benefit from trastuzumab-based upfront strategy. To advance precision oncology, we investigated the therapeutic efficacy of different HER2-targeted strategies, in HER2 "hyper"-amplified (≥ 8 copies) tumors. METHODS: We undertook a prospective evaluation of HER2 targeting with monoclonal antibodies, tyrosine kinase inhibitors and antibody-drug conjugates, in a selected subgroup of HER2 "hyper"-amplified gastric patient-derived xenografts (PDXs), through the design of ad hoc preclinical trials. RESULTS: Despite the high level of HER2 amplification, trastuzumab elicited a partial response only in 2 out of 8 PDX models. The dual-HER2 blockade with trastuzumab plus either pertuzumab or lapatinib led to complete and durable responses in 5 (62.5%) out of 8 models, including one tumor bearing a concomitant HER2 mutation. In a resistant PDX harboring KRAS amplification, the novel antibody-drug conjugate trastuzumab deruxtecan (but not trastuzumab emtansine) overcame KRAS-mediated resistance. We also identified a HGF-mediated non-cell-autonomous mechanism of secondary resistance to anti-HER2 drugs, responsive to MET co-targeting. CONCLUSION: These preclinical randomized trials clearly indicate that in HER2-driven gastric tumors, a boosted HER2 therapeutic blockade is required for optimal efficacy, leading to complete and durable responses in most of the cases. Our results suggest that a selected subpopulation of HER2-"hyper"-amplified GC patients could strongly benefit from this strategy. Despite the negative results of clinical trials, the dual blockade should be reconsidered for patients with clearly HER2-addicted cancers.

The Italian version of the LARS score: cross-cultural adaptation and validation. An Italian Society of Surgical Oncology-Colorectal Cancer Network (SICO-CCN) collaborative study.

PURPOSE: The LARS score is an internationally well-accepted questionnaire to assess low anterior resection syndrome, but currently there is no formally validated Italian version. The purpose of this study was to test the reliability and validity of the Italian version among Italian patients submitted to sphincter-sparing surgery for rectal cancer. METHODS: The English version of the LARS score was translated into Italian following the forward-and-back translation process. A total of 147 patients filled out our version. Among them, 40 patients answered the questionnaire twice for the test-retest reliability phase. The validity of the LARS score was tested using convergent and discriminant validity indicators by correlating the EORTC QLQ-C30 and QLQ-CR29 questionnaires. The LARS score capability to differentiate groups of patients with different demographic or clinical features was also assessed. RESULTS: The test-retest reliability was excellent in 87.5% of patients, remained in the same LARS category in both tests. The convergent validity phase showed a relevant relationship of the LARS score with the EORTC domains, which was significant for 7 of 15 EORTC QLQ-C30 subscales, and for 14 of 29 EORTC QLQ-CR29 subscales. The LARS score was able to discriminate patients who received radiotherapy (p = 0.0026), TME vs. PME (p = 0.0060), tumour site at < 10 cm from the anal verge (p = 0.0030) and history of protective stoma (p < 0.0001). CONCLUSION: The Italian version of the LARS score is a valid and reliable tool for measuring LARS in Italian patients after SSS for rectal cancer.

Primary Aorto-Duodenal Fistula in Association with Chronic Ischemic Enteritis: A Case Report.

BACKGROUND: Primary aorto-duodenal fistula (PADF) is a rare but life-threatening condition that should be taken into account when considering upper gastrointestinal bleeding in elderly patients with history of abdominal aortic aneurysm. Unfortunately, its diagnosis is often unsuspected until surgery or at postmortem. PRESENTATION OF CASE: We report a case of a 69 years old man with massive gastrointestinal bleeding secondary to a primary aortic duodenal fistula without a history of abdominal aortic aneurysm and with a misleading diagnosis of chronic ischemic enteritis. Repeated endoscopies and a prior CT angiography failed to document a proper diagnosis. Finally, the aorto-duodenal fistula was identified with a further abdominal CT angiography. Despite a prompt endovascular treatment with aortic endoprosthesis placement, the patient died due to a severe hemorrhagic shock consequent to the massive blood loss. DISCUSSION: Primary aorto-duodenal fistula represents a very rare (<0.1% of incidence) cause of severe upper gastrointestinal bleeding most often leading to patient's death for hemorrhagic shock. It is frequently associated to aortic atherosclerosis. Its prompt diagnosis with endoscopy and CT angiography is very often difficult and almost never immediate. Furthermore, these exams may be misleading. In case of massive upper GI bleeding without a certain diagnosis in patients with severe aortic atherosclerosis, laparotomy with careful inspection of the distal duodenum is strongly recommended for aortic repair and bowel suture. CONCLUSIONS: The diagnosis of PADF should be taken into account in patients with upper gastrointestinal bleeding associated with aortic atherosclerosis with strong suspect of penetrating ulcer.

Segmental Colonic Resection Is a Safe and Effective Treatment Option for Colon Cancer of the Splenic Flexure: A Nationwide Retrospective Study of the Italian Society of Surgical Oncology-Colorectal Cancer Network Collaborative Group.

BACKGROUND: Global experience with splenic flexure cancer is limited because of its low incidence. Both limited (segmental) and extended resections are performed, because agreement on which is the adequate procedure has not been reached. OBJECTIVE: The purpose of this study was to investigate whether segmental resection is as safe and effective as extended resection. DESIGN: This nationwide retrospective cohort study included all consecutive resections of splenic flecure cancer between January 2006 and December 2016 using data from the National Colorectal Cancer Network of the Italian Society of Surgical Oncology following the guidelines set out in the STROBE statement. SETTING: Data were obtained for 31 Italian Referral Centers for Colorectal Surgery. PATIENTS: A total of 1304 patients were submitted to resection of the splenic flexure (n = 791, 60.7%) or extended procedures (extended right and left colectomies; n = 513, 39.3%). MAIN OUTCOME MEASURES: We evaluated Clavien-Dindo ≥3 postoperative complications and oncological (number of lymph nodes removed, length of free proximal and distal margins, rate of R0 resections) and survival outcomes. RESULTS: The 2 arms were well balanced in regard to sex, BMI, ASA and Eastern Cooperative Oncology Group scores, and disease stage. Limited resection was performed more frequently using a minimally invasive approach (62.1% vs 50.9%, p < 0.001) and with shorter operation times than extended procedures (165 vs 189 minutes, p < 0.001), but the same Clavien-Dindo ≥3 postoperative complications (6.44% vs 6.43%, p = 0.99), 30-day mortality (0.63% vs 0.38%), oncological outcomes, and survival rates (5-year overall survival 0.84 vs 0.83, 5-year progression-free survival 0.85 vs 0.84). LIMITATIONS: There are limitations inherent to the retrospective nature of the study and a potential lack of consistency in treatment across centers over time. Indications as to why a specific operation was chosen were based mostly on surgeons' beliefs. CONCLUSIONS: Segmental resection is a safe and effective treatment option for cancer of the splenic flexure. See Video Abstract at http://links.lww.com/DCR/B307. LA RESECCIÓN DE COLON SEGMENTARIA ES UNA OPCIÓN DE TRATAMIENTO SEGURA Y EFICAZ PARA EL CÁNCER DE COLON DE LA FLEXIÓN ESPLÉNICA: UN ESTUDIO RETROSPECTIVO A NIVEL NACIONAL DE LA SOCIEDAD ITALIANA DE ONCOLOGÍA QUIRÚRGICA - GRUPO COLABORATIVO RED DE CÁNCER COLORRECTAL: La experiencia global con el cáncer de flexión esplénica es limitada debido a su baja incidencia. Se realizan resecciones limitadas (segmentarias) y extendidas, ya que no se ha llegado a un acuerdo sobre cuál es el procedimiento adecuado.El propósito de este estudio fue investigar si la resección segmentaria es tan segura y efectiva como la resección extendida.Este estudio de cohorte retrospectivo a nivel nacional incluyó todas las resecciones consecutivas de cáncer de flecura esplénica entre enero de 2006 y diciembre de 2016 utilizando datos de la Red Nacional de Cáncer Colorrectal de la Sociedad Italiana de Oncología Quirúrgica siguiendo las pautas establecidas en la declaración STROBE.Se obtuvieron datos para 31 centros de referencia italianos para cirugía colorrectal.Un total de 1304 pacientes fueron sometidos a resección de la flexión esplénica (n = 791, 60.7%) o procedimientos extendidos (colectomías extendidas derecha e izquierda; n = 513, 39.3%).Evaluamos Clavien-Dindo ≥3 complicaciones postoperatorias y oncológicas (número de ganglios linfáticos extirpados, longitud de márgenes proximales y distales libres, tasa de resecciones R0) y resultados de supervivencia.Los dos brazos estaban bien equilibrados en cuanto a sexo, IMC, ASA y puntajes ECOG, y etapa de la enfermedad. La resección limitada se realizó con mayor frecuencia utilizando un enfoque mínimamente invasivo (62.1% versus 50,9%, p < 0.001) y con tiempos de operación más cortos que los procedimientos extendidos (165 min versus 189 min, p <0.001), pero el mismo Clavien-Dindo ≥3 complicaciones postoperatorias (6,44% versus 6,43%, p = 0.99), mortalidad a los 30 días (0,63% versus 0,38%), resultados oncológicos y tasas de supervivencia (5-y OS 0,84 versus 0,83, 5-PFS 0,85 versus 0,84).Existen limitaciones inherentes a la naturaleza retrospectiva del estudio y una posible falta de consistencia en el tratamiento entre centros a lo largo del tiempo. Las indicaciones de por qué se eligió una operación específica se basaron principalmente en crieterios de los cirujanos.La resección segmentaria es una opción de tratamiento segura y efectiva para el cáncer de la flexión esplénica. Consulte Video Resumen en http://links.lww.com/DCR/B307. (Traducción-Dr. Adrian Ortega).

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.

Predicting Postoperative Length of Stay in Patients Undergoing Laparoscopic Right Hemicolectomy for Colon Cancer: A Machine Learning Approach Using SICE (Società Italiana di Chirurgia Endoscopica) CoDIG Data.

The evolution of laparoscopic right hemicolectomy, particularly with complete mesocolic excision (CME) and central vascular ligation (CVL), represents a significant advancement in colon cancer surgery. The CoDIG 1 and CoDIG 2 studies highlighted Italy's progressive approach, providing useful findings for optimizing patient outcomes and procedural efficiency. Within this context, accurately predicting postoperative length of stay (LoS) is crucial for improving resource allocation and patient care, yet its determination through machine learning techniques (MLTs) remains underexplored. This study aimed to harness MLTs to forecast the LoS for patients undergoing right hemicolectomy for colon cancer, using data from the CoDIG 1 (1224 patients) and CoDIG 2 (788 patients) studies. Multiple MLT algorithms, including random forest (RF) and support vector machine (SVM), were trained to predict LoS, with CoDIG 1 data used for internal validation and CoDIG 2 data for external validation. The RF algorithm showed a strong internal validation performance, achieving the best performances and a 0.92 ROC in predicting long-term stays (more than 5 days). External validation using the SVM model demonstrated 75% ROC values. Factors such as fast-track protocols, anastomosis, and drainage emerged as key predictors of LoS. Integrating MLTs into predicting postoperative LOS in colon cancer surgery offers a promising avenue for personalized patient care and improved surgical management. Using intraoperative features in the algorithm enables the profiling of a patient's stay based on the planned intervention. This issue is important for tailoring postoperative care to individual patients and for hospitals to effectively plan and manage long-term stays for more critical procedures.

A pragmatic approach improves the clinical management of stage IV gastric cancer: Comparison between the Meta-Gastro results and the GIRCG's retrospective series.

INTRODUCTION: The Italian Research Group for Gastric Cancer developed a prospective database about stage IV gastric cancer, to evaluate how a pragmatic attitude impacts the management of these patients. MATERIALS AND METHODS: We prospectively collected data about metastatic gastric cancer patients thanks to cooperation between radiologists, oncologists and surgeons and we analyzed survival and prognostic factors, comparing the results to those obtained in our retrospective study. RESULTS: Three-hundred and eighty-three patients were enrolled from 2018 to September 2022. We observed a higher percentage of laparoscopic exploration with peritoneal lavage in the prospective cohort. In the registry only 3.6 % of patients was submitted to surgery without associated chemotherapy, while in the retrospective population 44.3 % of patients were operated on without any chemotherapy. At univariate and multivariate analyses, the different metastatic sites did not show any survival differences among each other (OS 20.0 vs 16.10 vs 16.7 months for lymphnodal, peritoneal and hepatic metastases, respectively), while the number of metastatic sites and the type of treatment showed a statistical significance (OS 16,7 vs 13,0 vs 4,5 months for 1, 2 and 3 different metastatic sites respectively, p < 0.001; 24,2 vs 12,0 vs 2,5 months for surgery with/without chemotherapy, chemotherapy alone and best supportive treatment respectively, p < 0.001). CONCLUSIONS: Our data highlight that the different metastatic sites did not show different survivals, but survival is worse in case of multiple localization. In patients where a curative resection can be achieved, acceptable survival rates are possible. A better diagnostic workup and a more accurate staging impact favorably upon survival.

Textbook Outcome in Colorectal Surgery for Cancer: An Italian Version.

Background/Objectives: The textbook outcome (TO) is a composite tool introduced to uniform surgical units and regulate surgical quality and outcomes. A patient is considered TO only if all predetermined items are met. In colorectal surgery, TO represents a new tool that can achieve important results given the prevalence of colorectal cancers. However, at present, there is a lack of uniformity in the TO's definition. This study utilized the Delphi process to define an Italian version of the TO in colorectal cancer. Methods: The survey consisted of two rounds of online questionnaires submitted to an expert panel in colorectal oncological surgery, renowned academic surgeons, who had attended multiple scientific conferences and who were authors of papers on this specific topic. Five main topics with 26 questions were investigated through an online modified Delphi method. Items with almost 75% agreement achieved consensus. Results: Twenty-eight Italian experts were selected and participated in the two rounds. The Italian version of the textbook outcome in colorectal surgery was defined as the presence of 90-day postoperative survival, negative margins and at least 12 lymph nodes, a minimally invasive approach, ostomy fashioning if preoperatively planned, postoperative complication < Clavien-Dindo 3b, at least 10 ERAS items, no readmission, proper CHT and RT regimens, complete colonoscopy after or before surgery and Tumor Board Evaluation. Conclusions: The textbook outcome in colorectal cancer patients is a quality instrument providing a complete overview of the care of such patients, from diagnosis to treatment. We hereby propose an Italian version of the TO with outcomes chosen by an expert panel.

International External Validation of Risk Prediction Model of 90-Day Mortality after Gastrectomy for Cancer Using Machine Learning.

BACKGROUND: Radical gastrectomy remains the main treatment for gastric cancer, despite its high mortality. A clinical predictive model of 90-day mortality (90DM) risk after gastric cancer surgery based on the Spanish EURECCA registry database was developed using a matching learning algorithm. We performed an external validation of this model based on data from an international multicenter cohort of patients. METHODS: A cohort of patients from the European GASTRODATA database was selected. Demographic, clinical, and treatment variables in the original and validation cohorts were compared. The performance of the model was evaluated using the area under the curve (AUC) for a random forest model. RESULTS: The validation cohort included 2546 patients from 24 European hospitals. The advanced clinical T- and N-category, neoadjuvant therapy, open procedures, total gastrectomy rates, and mean volume of the centers were significantly higher in the validation cohort. The 90DM rate was also higher in the validation cohort (5.6%) vs. the original cohort (3.7%). The AUC in the validation model was 0.716. CONCLUSION: The externally validated model for predicting the 90DM risk in gastric cancer patients undergoing gastrectomy with curative intent continues to be as useful as the original model in clinical practice.

Robotic Rectal Resection for Rectal Cancer in Elderly Patients: A Systematic Review and Meta-Analysis.

Rectal cancer is estimated to increase due to an expanding aging population, thus affecting elderly patients more frequently. The optimal surgical treatment for this type of patient remains controversial because they are often excluded from or underrepresented in trials. This meta-analysis aimed to evaluate the feasibility and the safety of robotic surgery in elderly patients (>70 years old) undergoing curative treatment for rectal cancer. Studies comparing elderly (E) and young (Y) patients submitted to robotic rectal resection were searched on PubMed, Embase, and the Cochrane Library. Data regarding surgical oncologic quality, post-operative, and survival outcomes were extracted. Overall, 322 patients underwent robotic resection (81 in the E group and 241 in the Y group) for rectal cancer. No differences between the two groups were found regarding distal margins and the number of nodes yielded (12.70 in the E group vs. 14.02 in the Y group, p = 0.16). No differences were found in conversion rate, postoperative morbidity, mortality, and length of stay. Survival outcomes were only reported in one study. The results of this study suggest that elderly patients can be submitted to robotic resection for rectal cancer with the same oncologic surgical quality offered to young patients, without increasing postoperative mortality and morbidity.

Clinical outcomes of patients with complicated post-operative course after gastrectomy for cancer: a GIRCG study using the GASTRODATA registry.

Gastrectomy for gastric cancer is still performed in Western countries with high morbidity and mortality. Post-operative complications are frequent, and effective diagnosis and treatment of complications is crucial to lower the mortality rates. In 2015, a project was launched by the EGCA with the aim of building an agreement on list and definitions of post-operative complications specific for gastrectomy. In 2018, the platform www.gastrodata.org was launched for collecting cases by utilizing this new complication list. In the present paper, the Italian Research Group for Gastric Cancer endorsed a collection of complicated cases in the period 2015-2019, with the aim of investigating the clinical pictures, diagnostic modalities, and treatment approaches, as well as outcome measures of patients experiencing almost one post-operative complication. Fifteen centers across Italy provided 386 cases with a total of 538 complications (mean 1.4 complication/patient). The most frequent complications were non-surgical infections (gastrointestinal, pulmonary, and urinary) and anastomotic leaks, accounting for 29.2% and 17.3% of complicated patients, with a median Clavien-Dindo score of II and IIIB, respectively. Overall mortality of this series was 12.4%, while mortality of patients with anastomotic leak was 25.4%. The clinical presentation with systemic septic signs, the timing of diagnosis, and the hospital volume were the most relevant factors influencing outcome.

Oligometastatic Gastric Cancer: Clinical Data from the Meta-Gastro Prospective Register of the Italian Research Group on Gastric Cancer.

BACKGROUND: Interest in the field of metastatic gastric cancer has grown in recent years, and the identification of oligometastatic patients plays a critical role as it consents to their inclusion in multimodal treatment strategies, which include systemic therapy but also surgery with curative intent. To collect sound clinical data on this subject, The Italian Research Group on Gastric Cancer developed a prospective multicentric observational register of metastatic gastric cancer patients called META-GASTRO. METHODS: Data on 383 patients in Meta-Gastro were mined to help our understanding of oligometastatic, according to its double definition: quantitative/anatomical and dynamic. RESULTS: the quantitative/anatomical definition applies to single-site metastases independently from the metastatic site (p < 0.001) to peritoneal metastases with PCI ≤ 12 (p = 0.009), to 1 or 2 hepatic metastases (p = 0.024) and nodal metastases in station 16 (p = 0.002). The dynamic definition applies to a percentage of cases variable according to the metastatic site: 8%, 13.5 and 23.8% for hepatic, lymphatic and peritoneal sites, respectively. In all cases, the OS of patients benefitting from conversion therapy was similar to those of cases deemed operable at diagnosis and operated after neoadjuvant chemotherapy. CONCLUSIONS: META-GASTRO supports the two-fold definition of oligometastatic gastric cancer: the quantitative/anatomical one, which accounts for 30% of our population, and the dynamic one, observed in 16% of our cases.