Rectal sparing approach after preoperative radio - and/or Chemo-therapy (ReSARCh): a prospective, multicentre, observational study.

BACKGROUND: Rectal-sparing approaches for patients with rectal cancer who achieved a complete or major response following neoadjuvant therapy constitute a paradigm of a potential shift in the management of patients with rectal cancer, however their role remains controversial. The aim of this study was to investigate the feasibility of rectal-sparing approaches to preserve the rectum without impairing the outcomes. METHODS: This prospective, multicentre, observational study investigated the outcomes of patients with clinical stage II-III mid-low rectal adenocarcinoma treated with any neoadjuvant therapy, and either transanal local excision or watch-and-wait approach, based on tumor response (major or complete) and patient/surgeon choice. The primary endpoint of the study was rectum preservation at a minimum follow-up of two years. Secondary endpoints were overall, disease-free, local and distant recurrence-free, and stoma-free survival at three years. RESULTS: Of 178 patients enrolled in 16 centres, 112 (62.9%) were managed with local excision and 66 (37.1%) with watch-and-wait. At a median (interquartile range) follow-up of 36.1 (30.6-45.6) months, the rectum was preserved in 144 (80.9%) patients. The 3-year rectum-sparing, overall, disease-free, local recurrence-free, distant recurrence-free survival was 80.6% (95%CI 73.9-85.8), 97.6% (95%CI 93.6-99.1), 90.0% (95%CI 84.3-93.7), 94.7% (95%CI 90.1-97.2), and 94.6% (95%CI 89.9-97.2), respectively. The 3-year stoma-free survival was 95.0% (95%CI 89.5-97.6). The 3-year regrowth-free survival in the watch-and-wait group was 71.8% (95%CI 59.9-81.2). CONCLUSIONS: In rectal cancer patients with major or complete clinical response after neoadjuvant therapy, the rectum can be preserved in about 80% of cases, without compromise the outcomes.

Multiple colorectal adenomas syndrome: The role of MUTYH mutation and the polyps' number in clinical management and colorectal cancer risk.

BACKGROUND & AIMS: Multiple colorectal adenomas (MCRAs) can result from APC (AFAP) or biallelic MUTYH (MAP) mutations, but most patients are wild type and referred to as non-APC/MUTYH polyposis (NAMP). We aim to examine the risk of colorectal cancer (CRC) and the role of endoscopy in managing patients with MCRAs, with a specific focus on clinical features and genotype. METHODS: Records of MRCAs between 2000 and 2022 were retrospectively analysed. Patients were divided according to the genotype (MAP vs. NAMP) and the number of categorised polyps' burden (group 1: 10-24, group 2: 25-49, and group 3: 50-99 adenomas). Predictors of outcome were CRC-free survival (CRC-FS) and Surgery free-survival (S-FS). RESULTS: 220 patients were enrolled (NAMP n = 178(80.0%)). CRC at diagnosis was more frequent in group 3 (p = 0.01), without significant differences between the genotypes (p = 0.20). At a follow-up of 83(41-164) months, 15(7%) patients developed CRC during surveillance. CRC-FS was not correlated to genotype (p = 0.07) or polyps' number (p = 0.33), while S-FS was similar in MAP and NAMP (p = 0.22) and lower in groups 2 and 3 (p = 0.0001). CONCLUSIONS: MAP and NAMP have the same CRC risk and no difference in treatment. Endoscopic surveillance compared favorably with surgery in avoiding CRC risk, even in patients with more severe colorectal polyposis.

Nodal staging with MRI after neoadjuvant chemo-radiotherapy for locally advanced rectal cancer: a fast and reliable method.

OBJECTIVES: In patients with locally advanced rectal carcinoma (LARC), negative nodal status after neoadjuvant chemoradiotherapy (nCRT) may allow for rectum-sparing protocols rather than total mesorectal excision; however, current MRI criteria for nodal staging have suboptimal accuracy. The aim of this study was to compare the diagnostic accuracy of different MRI dimensional criteria for nodal staging after nCRT in patients with LARC. MATERIALS AND METHODS: Patients who underwent MRI after nCRT for LARC followed by surgery were retrospectively included and divided into a training and a validation cohort of 100 and 39 patients, respectively. Short-, long-, and cranial-caudal axes and volume of the largest mesorectal node and nodal status based on European Society of Gastrointestinal Radiology consensus guidelines (i.e., ESGAR method) were assessed by two radiologists independently. Inter-reader agreement was assessed in the training cohort. Histopathology was the reference standard. ROC curves and the best cut-off were calculated, and accuracies compared with the McNemar test. RESULTS: The study population included 139 patients (median age 62 years [IQR 55-72], 94 men). Inter-reader agreement was high for long axis (κ = 0.81), volume (κ = 0.85), and ESGAR method (κ = 0.88) and low for short axis (κ = 0.11). Accuracy was similar (p > 0.05) for long axis, volume, and ESGAR method both in the training (71%, 74%, and 65%, respectively) and in the validation (83%, 78%, and 75%, respectively) cohorts. CONCLUSION: Accuracy of the measurement of long axis and volume of the largest lymph node is not inferior to the ESGAR method for nodal staging after nCRT in LARC. CLINICAL RELEVANCE STATEMENT: In MRI restaging of rectal cancer, measurement of the long axis or volume of largest mesorectal lymph node after preoperative chemoradiotherapy is a faster and reliable alternative to ESGAR criteria for nodal staging. KEY POINTS: • Current MRI criteria for nodal staging in locally advanced rectal cancer after chemo-radiotherapy have suboptimal accuracy and are time-consuming. • Measurement of long axis or volume of the largest mesorectal lymph node on MRI showed good accuracy for assessment of loco-regional nodal status in locally advanced rectal cancer. • MRI measurement of the long axis and volume of largest mesorectal lymph node after chemo-radiotherapy could be a faster and reliable alternative to ESGAR criteria for nodal staging.

Diagnostic accuracy of state-of-the-art rectal MRI sequences for the diagnosis of extramural vascular invasion in locally advanced rectal cancer after preoperative chemoradiotherapy: dos or maybes?

OBJECTIVES: The aim of this study was to determine the accuracy of three state-of-the-art MRI sequences for the detection of extramural venous invasion (EMVI) in locally advanced rectal cancer (LARC) patients after preoperative chemoradiotherapy (pCRT). METHODS: This retrospective study included 103 patients (median age 66 years old [43-84]) surgically treated with pCRT for LARC and submitted to preoperative contrast-enhanced pelvic MRI after pCRT. T2-weighted, DWI, and contrast-enhanced sequences were evaluated by two radiologists with expertise in abdominal imaging, blinded to clinical and histopathological data. Patients were scored according to the probability of EMVI presence on each sequence using a grading score ranging from 0 (no evidence of EMVI) to 4 (strong evidence of EMVI). Results from 0 to 2 were ranked as EMVI negative and from 3 to 4 as EMVI positive. ROC curves were drawn for each technique, using histopathological results as reference standard. RESULTS: T2-weighted, DWI, and contrast-enhanced sequences demonstrated an area under the ROC curve (AUC) respectively of 0.610 (95% CI: 0.509-0.704), 0.729 (95% CI: 0.633-0.812), and 0.624 (95% CI: 0.523-0.718). The AUC of DWI sequence was significantly higher than that of T2-weighted (p = 0.0494) and contrast-enhanced (p = 0.0315) sequences. CONCLUSIONS: DWI is more accurate than T2-weighted and contrast-enhanced sequences for the identification of EMVI following pCRT in LARC patients. CLINICAL RELEVANCE STATEMENT: MRI protocol for restaging locally advanced rectal cancer after preoperative chemoradiotherapy should routinely include DWI due to its higher accuracy for the diagnosis of extramural venous invasion compared to high-resolution T2-weighted and contrast-enhanced T1-weighted sequences. KEY POINTS: • MRI has a moderately high accuracy for the diagnosis of extramural venous invasion in locally advanced rectal cancer after preoperative chemoradiotherapy. • DWI is more accurate than T2-weighted and contrast-enhanced T1-weighted sequences in the detection of extramural venous invasion after preoperative chemoradiotherapy of locally advanced rectal cancer. • DWI should be routinely included in the MRI protocol for restaging locally advanced rectal cancer after preoperative chemoradiotherapy.

Treatment and Prognosis of Fibrolamellar Hepatocellular Carcinoma: a Systematic Review of the Recent Literature and Meta-analysis.

BACKGROUND: Fibrolamellar hepatocellular carcinoma (FL-HCC) is a rare disease and current efforts are focused on the prognosis and on the development of efficient and specific treatments. This study aimed to review the latest evidence regarding FL-HCC treatment and prognosis. METHODS: A systematic review of the literature over the past 10 years regarding FL-HCC, and meta-analysis of 1-, 3-, and 5-year overall survival (OS) comparing FL-HCC and conventional HCC were performed. RESULTS: Overall, 1567 articles were screened, of them 21 were selected for the systematic review, and 6 for meta-analysis. Twenty-one studies included a total of 2168 patients with FL-HCC, with a median age ranging from 11 to 56 years. The majority of patients underwent surgical resection or liver transplantation. After a median follow-up ranging from 24 to 58 months, 1-year OS was 67-100% and 5-year OS was 28-65%. A total of 743 patients with FL-HCC and 163,472 with conventional HCC were included in the meta-analysis. There was a significantly improved 1-, 3-, and 5-years OS in the FL-HCC group compared to the conventional HCC group, although high heterogeneity was found. When excluding population-based studies, and including 96 FL-HCC and 221 conventional HCC patients, the heterogeneity was low, and the meta-analysis showed a significantly longer 1-year OS in patients with FL-HCC than conventional HCC; however, there were no differences at 3- and 5-years OS. CONCLUSIONS: Surgical resection for FL-HCC is currently the only curative treatment available. FL-HCC is plagued by high-recurrence rates and poor long-term outcomes which may be related to the absence of specific treatment for advanced and recurrent disease.

Prognostic value of major pathological response following neoadjuvant therapy for non resectable pancreatic ductal adenocarcinoma.

BACKGROUND: The aim of this study is to evaluate the impact of major pathological response on overall survival (OS) in borderline resectable and locally advanced pancreatic ductal adenocarcinoma following neoadjuvant treatment, and to identify predictors of major pathological response. METHODS: Patients surgically resected following neoadjuvant treatment between 2010 and 2020 at the Pederzoli Hospital were retrospectively analyzed. Pathologic response was assessed using the College of American Pathologists (CAP) score, and major pathological response was defined as CAP 0-1. OS was estimated and compared using the Kaplan-Meier method and log-rank test. A logistic and Cox regression model were performed to identify predictors of major pathologic response and OS. RESULTS: Overall, 200 patients were included in the study. A major and complete pathological response were observed in 52(26.0%) and 15(7.3%) patients respectively. The 1-, 3-, 5-year OS was 92.7, 67.2, and 41.7%, and 71.0, 37.4, and 20.8% in patients with or without major pathologic response respectively (log-rank test p < 0.001). Major pathologic response was confirmed as independent predictor of OS (OR 0.50 95%CI 0.29-0.88, p = 0.01). Post-treatment CA19-9 normalization (OR 4.20 95%CI 1.14-10.35, p = 0.02) and radiological post-treatment tumor residual size<25 mm (OR 2.71 95%CI 1.27-5.79, p = 0.01) were found to be independent predictors of major pathologic response. CONCLUSION: Patients experienced a major pathological response after neoadjuvant treatment have an increased survival, and major pathologic response is an independent predictor of OS. A normal CA19-9 value and radiological tumor size at restaging are confirmed to be independent predictors of major pathologic response.

Impact of DNA mismatch repair proteins deficiency on number and ratio of lymph nodal metastases in colorectal adenocarcinoma.

BACKGROUND: Approximately 15 % of colorectal adenocarcinomas (CRCs) are characterized by an altered expression of DNA mismatch repair (MMR) proteins (i.e. MMR deficiency [MMRd]). Lymph node ratio (LNR) represents one of the most important prognostic markers in non-advanced CRCs. No significant data are available regarding LNR distribution depending on MMR status. PURPOSE OF THE STUDY: The aim of the present work was to compare pathological and clinical characteristics of MMRd tumors versus MMR proficient (MMRp) cases. Particular attention was paid to how these molecular sub-groups relate to the LNR. MATERIALS AND METHODS: A mono-Institutional series of 1037 consecutive surgically treated stage I-IV CRCs were retrospectively selected and data were obtained from pathological reports. Cases were characterized for MMR/MSI status by means of immunohistochemistry or for microsatellite instability (MSI) analysis. RESULTS: MMRd/MSI tumors (n = 194; 18.7 %) showed significant differences in comparison to MMRp lesions for sex (female prevalence 50.5 % vs 40.7 %; p = 0.013), age (74.2 vs 69.2; p < 0.001), location (right side; p < 0.001), diameter (larger than MMRp; p < 0.001), growth pattern (expansive pattern of growth; p < 0.001), peri- (p = 0.0002) and intra-neoplastic (p = 0.0018) inflammatory infiltrate, presence of perineural invasion (p < 0.001), stage (lower stage at presentation; p < 0.001), grade (higher prevalence of high-grade tumors; p < 0.001), and LNR (lower; p < 0.001). CONCLUSIONS: MMRd/MSI tumors are a distinct molecular CRC subtype characterized by a significantly lower LNR in comparison to MMRp lesions. These data further support the prognostic impact of MMRd/MSI status in early-stage CRCs.

Rectal Sparing Approaches after Neoadjuvant Treatment for Rectal Cancer: A Systematic Review and Meta-Analysis Comparing Local Excision and Watch and Wait.

Local Excision (LE) or Watch and Wait (WW) for patients with complete clinical response or near-complete clinical response after neoadjuvant chemoradiotherapy (nCRT) were proposed to avoid morbidity and impairment of quality of life after rectal resection. The aim of this study is to perform a systematic review of the literature, and to compare rectal-sparing approaches, in terms of rectum-preservation rate, local control, and distant recurrences. A systematic review and meta-analysis were performed of studies published until July 2022 (PROSPERO, registration CRD42022341480), and the quality of evidence was assessed using a GRADE approach. Seven retrospective studies and one prospective trial were included. In six studies, patients were treated with standard long-course nCRT, and in two with Total Neoadjuvant Therapy (TNT). Overall, there were 213 and 188 patients in WW and LE group, respectively, and no difference was found between WW and LE when considering rectum-preservation rate (OR 0.80 95%CI 0.31-2.01, p = 0.63), local disease (OR 1.60 95%CI 0.75-3.42, p = 0.22), locoregional failure (OR 0.85 95%CI 0.20-3.66, p = 0.83) and distant recurrence (OR 0.76 95%CI 0.37-1.55, p = 0.45). Studies directly comparing WW and LE are still lacking, even though no differences between WW and LE in terms of rectum-preservation, local control, and distant recurrences have been found.

Robotic Resection of Giant Duodenal Hamartoma After 18Fluorodeoxyglucose Positron Emission Tomography Magnetic Resonance Imaging (18FDG PET-MRI).

Brunner's gland hamartoma is a rare duodenal lesion. Resection for benign neoplasms of the duodenum should be considered in case of malignant potential or in case of symptomatic lesions. An accurate preoperative staging is mandatory in order to allow minimally invasive surgical approach, and to avoid under- or overtreatment. Endoscopic ultrasonography (EUS), Computed tomography (CT) scan, Magnetic Resonance Imaging (MRI) and PET/CT are techniques widely used for gastrointestinal tumor staging. We report a case of a 41-year-old female presenting a giant lesion of the second portion of the duodenum. Pathological examination of multiple forceps biopsies was inconclusive for histological characterization of the lesion. After a clinical staging including Esophagusgastroduodenoscopy, EUS, and CT scan, a Hybrid 18FDG PET/MRI was performed to assess the malignant potential of the lesion and the relation between polyp base and Vater's papilla. After multidisciplinary meeting, the patient underwent robotic transduodenal excision. The post-operative course was uneventful, and the patient was discharged on post-operative day 5. Final pathologic report consists in a histologically of Brunner's Glands Hamartoma. This is the first report on the role of 18FDG PET/MRI in staging and planning treatment of bulky low malignant duodenal lesion. An accurate staging with 18FDG PET/MRI could be very useful in the planning the management of duodenal lesion with uncertain malignant potential in order to avoid under- and overtreatment.

Molecular Determinants of Peritoneal Dissemination in Gastric Adenocarcinoma.

BACKGROUND: Peritoneal dissemination represents a poor prognostic indicator in gastric cancer. Despite a comprehensive molecular characterization of this disease, no peritoneal dissemination-specific signature has been identified, limiting the tailoring of the surgical and oncological treatments. In this review, we outline the available literature focusing on the role of the different molecular pathways involved in the acquisition of peritoneal metastatic dissemination. SUMMARY: According to our results, several molecular determinants are associated with peritoneal carcinomatosis and are involved in several cellular and molecular carcinogenetic processes. However, a comprehensive understanding of the complex molecular landscape of gastric carcinosis is still lacking. KEY MESSAGES: More efforts should be made toward the integration of molecular and histologic data to perform a risk prediction assessment of peritoneal dissemination based on molecular profiling and histological evaluation.

Obesity may not be related to pathologic response in locally advanced rectal cancer following neoadjuvant chemoradiotherapy.

Background: The aim of this study is to evaluate the correlation between body mass index (BMI) and body fat composition (measured with radiological fat parameters (RFP)) and pathological response after neoadjuvant chemoradiotherapy for locally advanced rectal cancer patients. The secondary aim of the study was to assess the role of BMI and RFP on major surgical complications, overall survival (OS), and disease-free survival (DFS). Methods: All patients who underwent surgical resection following nCRT between 2005 and 2017 for mid-low rectal cancer were retrospectively collected. Visceral fat area (VFA), superficial fat area (SFA), visceral/superficial fat area ratio (V/S), perinephric fat thickness (PNF), and waist circumference (WC) were estimated by baseline CT scan. Predictors of pathologic response and postoperative complications were investigated using logistic regression analysis. The correlations between BMI and radiologic fat parameters and survival were investigated using the Kaplan-Meier method and log-rank test. Results: Out of 144 patients included, a complete (TRG1) and major (TRG1+2) pathologic response was reported in 32 (22%) and 60 (45.5%) cases, respectively. A statistically significant correlation between BMI and all the RFP was found. At a median follow-up of 60 (35-103) months, no differences in terms of OS and DFS were found considering BMI and radiologic fat parameters. At univariable analysis, neither BMI nor radiologic fat parameters were predictors of complete or major pathologic response; nevertheless, VFA, V/S>1, and BMI were predictors of postoperative major complications. Conclusions: We found no associations between BMI and body fat composition and pathological response to nCRT, although VFA, V/S, and BMI were predictors of major complications. BMI and RFP are not related to worse long-term OS and DFS.

COVID-19 free pathways decrease postoperative complications in patients undergoing elective colorectal surgery.

Background: To reduce the exposition risk to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in surgical patients more prone to develop serious forms of Coronavirus disease 2019, a reorganization that previewed the creation "COVID-19-free" hospitals or units was pursued. The aim of this study was to quantify the effect of clear pathways to reduce the risk of SARS-Cov-2 transmission, on postoperative complications. Methods: Data of all consecutive patients undergoing surgical procedure for colorectal diseases, between November 2019 and July 2020 in two Italian referral centers, were retrospectively analyzed. Patients were divided into two groups: the ones underwent surgical procedures during the period before the pandemic from November 2019 to March 2020 (Group 1) (before-COVID), and those who underwent surgical procedure from April to July 2020 during the pandemic (Group 2) (during-COVID pandemic). Results: Overall, 264 patients were collected, 168 (63.4%) in Group 1 and 96 (36.4%) Group 2. Preoperative characteristics were similar between groups; during the pandemic there was a higher proportion of patients who underwent surgical procedures for malignancy compared with the period before the pandemic (92.7% vs 72%; p = 0.001). Patients in Group 2 had a lower rate of postoperative general complications (21.9% vs 34.5%; p = 0.03) and a lower rate of surgical complications (14.6% vs 25%; p = 0.05). No difference in term of medical complications, infections, and intraoperative complications were found. Minimally invasive approach (OR 0.46; 95% CI 0.04-0.83; p = 0.01) and isolation of patients (OR, 0.18; 95% CI, 0.04-0.83; p = 0.03) were independently associated with lower risk of postoperative complications. Conclusion: In this cohort study COVID-19-free pathways were significantly associated with low rate of postoperative morbidity in patients undergoing colorectal elective surgery.

Contrast-Enhanced CT Texture Analysis in Colon Cancer: Correlation with Genetic Markers.

Background: The purpose of the study was to determine whether contrast-enhanced CT texture features relate to, and can predict, the presence of specific genetic mutations involved in CRC carcinogenesis. Materials and methods: This retrospective study analyzed the pre-operative CT in the venous phase of patients with CRC, who underwent testing for mutations in the KRAS, NRAS, BRAF, and MSI genes. Using a specific software based on CT images of each patient, for each slice including the tumor a region of interest was manually drawn along the margin, obtaining the volume of interest. A total of 56 texture parameters were extracted that were compared between the wild-type gene group and the mutated gene group. A p-value of <0.05 was considered statistically significant. Results: The study included 47 patients with stage III-IV CRC. Statistically significant differences between the MSS group and the MSI group were found in four parameters: GLRLM RLNU (area under the curve (AUC) 0.72, sensitivity (SE) 77.8%, specificity (SP) 65.8%), GLZLM SZHGE (AUC 0.79, SE 88.9%, SP 65.8%), GLZLM GLNU (AUC 0.74, SE 88.9%, SP 60.5%), and GLZLM ZLNU (AUC 0.77, SE 88.9%, SP 65.8%). Conclusions: The findings support the potential role of the CT texture analysis in detecting MSI in CRC based on pre-treatment CT scans.

Predictors of Metastatic Lymph Nodes at Preoperative Staging CT in Gastric Adenocarcinoma.

Background. The aim of this study was to identify the most accurate computed-tomography (CT) dimensional criteria of loco-regional lymph nodes (LNs) for detecting nodal metastases in gastric cancer (GC) patients. Methods. Staging CTs of surgically resected GC were jointly reviewed by two radiologists, considering only loco-regional LNs with a long axis (LA) ≥ 5 mm. For each nodal group, the short axis (SA), volume and SA/LA ratio of the largest LN, the sum of the SAs of all LNs, and the mean of the SA/LA ratios were plotted in ROC curves, taking the presence/absence of metastases at histopathology for reference. On a per-patient basis, the sums of the SAs of all LNs, and the sums of the SAs, volumes, and SA/LA ratios of the largest LNs in all nodal groups were also plotted, taking the presence/absence of metastatic LNs in each patient for reference. Results. Four hundred and forty-three nodal groups were harvested during surgery from 107 patients with GC, and 173 (39.1%) were metastatic at histopathology. By nodal group, the sum of the SAs showed the best Area Under the Curve (AUC), with a sensitivity/specificity of 62.4/72.6% using Youden's index with a >8 mm cutoff. In the per-patient analysis, the sum of the SAs of all LNs in the loco-regional nodal groups showed the best AUC with a sensitivity/specificity of 65.6%/83.7%, using Youden's index with a >39 mm cutoff. Conclusion. In patients with GC, the sum of the SAs of all the LNs at staging CT is the best predictor among dimensional LNs criteria of both metastatic invasion of the nodal group and the presence of metastatic LNs.

Prognostic significance of additional histologic features for subclassification of pathological T3 colon cancer.

BACKGROUND: Additional histologic features of T3 colon cancer, such as tumour depth invasion beyond muscularis propria and elastic lamina invasion (ELI), have taken interest for a more accurate staging. METHODS: Patients with pT3 and pT4a (control group) colon adenocarcinoma were retrospectively collected from our institutional database. The study group was divided according to depth of tumour invasion < 5 mm and ≥ 5 mm, and into ELI - and ELI + . Chi-square test was used to compare the clinicopathological characteristics. OS and DFS were estimated using Kaplan-Meier method and compared with the log-rank test. Univariable and multivariable Cox proportional hazard models were employed to assess the effect on OS and DFS. RESULTS: Out of 290 pT3 tumours, 168 (58%) had a depth of tumour invasion < 5 mm and 122 (42%) ≥ 5 mm. The 5-year OS and DFS were 85.2, 68.7 and 60.9%, and 81.4, 73.9 and 60.1% in pT3 < 5 mm, pT3 ≥ 5 mm, and pT4a respectively (p = 0.001, p = 0.072). Considering ELI - (n = 157, 54%) and ELI + (n = 133, 46%), the 5-year OS and DFS were 78.9, 76.7, and 60.9%, and 75.5, 81.5, and 60.1% in ELI - , ELI + and pT4a respectively (p = 0.955, p = 0.462). At multivariable analysis, the depth of invasion was found to be an independent predictive factor for OS (HR 2.04, 95%CI 1.28-3.24, p = 0.003) and DFS (HR 1.98, 95%CI 1.24-3.18, p = 0.004), while ELI did not result a prognostic factor for OS nor DFS. CONCLUSION: In pT3 colon cancer, depth of tumour invasion ≥ 5 mm is an independent risk factor for OS and DFS, whereas ELI did not result a prognostic factor affecting OS nor DFS.

The impact of anastomotic leak on long-term oncological outcomes after low anterior resection for mid-low rectal cancer: extended follow-up of a randomised controlled trial.

PURPOSE: The impact of anastomotic leaks (AL) on oncological outcomes after low anterior resection for mid-low rectal cancer is still debated. The aim of this study was to evaluate overall survival (OS), disease-free survival (DFS), and local and distant recurrence in patients with AL following low anterior resection. METHODS: This is an extension of a multicentre RCT (NCT01110798). Kaplan-Meier method and the log-rank test were used to estimate and compare the 3-, 5-, and 10-year OS and DFS, and local and distant recurrence in patients with and without AL. Predictors of OS and DFS were evaluated using the Cox regression analysis as secondary aim. RESULTS: Follow-up was available for 311 patients. Of them, 252 (81.0%) underwent neoadjuvant chemoradiotherapy and 138 (44.3%) adjuvant therapy. AL occurred in 63 (20.3%) patients. At a mean follow-up of 69.5 ± 31.9 months, 23 (7.4%) patients experienced local recurrence and 49 (15.8%) distant recurrence. The 3-, 5-, and 10-year OS and DFS were 89.2%, 85.3%, and 70.2%; and 80.7%, 75.1%, and 63.5% in patients with AL, and 88.9%, 79.8% and 72.3%; and 83.7, 74.2 and 62.8%, respectively in patients without (p = 0.89 and p = 0.84, respectively). At multivariable analysis, AL was not an independent predictor of OS (HR 0.65, 95%CI 0.34-1.28) and DFS (HR 0.70, 95%CI 0.39-1.25), whereas positive circumferential resection margins and pathological stage impaired both. CONCLUSIONS: In the context of modern multimodal rectal cancer treatment, AL does not affect long-term OS, DFS, and local and distant recurrence in patients with mid-low rectal cancer.

18F-FDG-PET/MRI texture analysis in rectal cancer after neoadjuvant chemoradiotherapy.

OBJECTIVE: Reliable markers to predict the response to neoadjuvant chemoradiotherapy (nCRT) in locally advanced rectal cancer (LARC) are lacking. We aimed to assess the ability of 18F-FDG PET/MRI to predict response to nCRT among patients undergoing curative-intent surgery. METHODS: Patients with histological-confirmed LARC who underwent curative-intent surgery following nCRT and restaging with 18F-FDG PET/MRI were included. Statistical correlation between radiomic features extracted in PET, apparent diffusion coefficient (ADC) and T2w images and patients' histopathologic response to chemoradiotherapy using a multivariable logistic regression model ROC-analysis. RESULTS: Overall, 50 patients were included in the study. A pathological complete response was achieved in 28.0% of patients. Considering second-order textural features, nine parameters showed a statistically significant difference between the two groups in ADC images, six parameters in PET images and four parameters in T2w images. Combining all the features selected for the three techniques in the same multivariate ROC curve analysis, we obtained an area under ROC curve of 0.863 (95% CI, 0.760-0.966), showing a sensitivity, specificity and accuracy at the Youden's index of 100% (14/14), 64% (23/36) and 74% (37/50), respectively. CONCLUSION: PET/MRI texture analysis seems to represent a valuable tool in the identification of rectal cancer patients with a complete pathological response to nCRT.

A nomogram to predict overall survival and disease-free survival after curative-intent gastrectomy for gastric cancer.

An individual prediction of DFS and OS may be useful after surgery for gastric cancer to inform patients and to guide the clinical management. Patients who underwent curative-intent resection for gastric cancer between January 2010 and May 2020 at a single Italian institution were identified. Variables associated with OS and DFS were recorded and analysed according to univariable and multivariable Cox models. Nomograms predicting OS and DFS were built according to variables resulting from multivariable Cox models. Discrimination ability was calculated using the Harrell's Concordance Index. Overall, 168 patients underwent curative-intent resection. Nomograms to predict OS were developed including age, tumor size, tumor location, T stage, N stage, M stage and post-operative complications, while nomogram to predict DFS includes Lauren classification, and lymph node ratio (LNR). On internal validation, both nomograms demonstrated a good discrimination with a Harrell's C-index of 0.77 for OS and 0.71 for DFS. The proposed nomogram to predict DFS and OS after curative-intent surgery for gastric cancer showed a good discrimination on internal validation, and may be useful to guide clinician decision-making, as well help identify patients with high-risk of recurrence or with a poor estimated survival.

Definition and management of colorectal polyposis not associated with APC/MUTYH germline pathogenic variants: AIFEG consensus statement.

An expert consensus panel convened by the Italian Association for Inherited and Familial Gastrointestinal Tumors (Associazione Italiana per lo Studio della Familiarità ed Ereditarietà dei Tumori Gastrointestinali, AIFEG) reviewed the literature and agreed on a number of position statements regarding the definition and management of polyposis coli without an identified pathogenic mutation on the APC or MUTYH genes, defined in the document as NAMP (non-APC/MUTYH polyposis).