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Growing evidence highlights the pivotal role of RORγt-innate lymphoid cells (ILCs) in the establishment of antitumor immune response and in enhancing tumor sensitivity to immunotherapy. Noteworthy, type 3 ILCs (ILC3s) have been recently acknowledged as an important class of antigen-presenting cells (APCs) in the context of host–microorganism interactions shaping the adaptive immune response in the intestinal mucosa. Although a broad range of mouse models has led to significant progress in untangling the role of ILC3s as APCs, the outcome of major histocompatibility complex (MHC)-dependent ILC-T cell crosstalk in colorectal cancer (CRC) remains underexplored in human. Moreover, expression of MHCII is confined to ILC3 subset, endowed with lymphoid tissue-inducing properties, that adopts tissue-specific fates and functions. Intestinal microbiota could dictate the plasticity of antigen-presenting ILC3s and we here summarize our current understanding of the functions of these cells in both mouse and human CRC discussing the role of microbiota as a key modulator of their tumor-suppressive activity.

Abstract Hepatitis B virus (HBV) may integrate into the genome of infected cells and contribute to hepatocarcinogenesis. However, the role of HBV integration in hepatocellular carcinoma (HCC) development remains unclear. In this study, we apply a high-throughput HBV integration sequencing approach that allows sensitive identification of HBV integration sites and enumeration of integration clones. We identify 3339 HBV integration sites in paired tumour and non-tumour tissue samples from 7 patients with HCC. We detect 2107 clonally expanded integrations (1817 in tumour and 290 in non-tumour tissues), and a significant enrichment of clonal HBV integrations in mitochondrial DNA (mtDNA) preferentially occurring in the oxidative phosphorylation genes (OXPHOS) and D-loop region. We also find that HBV RNA sequences are imported into the mitochondria of hepatoma cells with the involvement of polynucleotide phosphorylase (PNPASE), and that HBV RNA might have a role in the process of HBV integration into mtDNA. Our results suggest a potential mechanism by which HBV integration may contribute to HCC development.

This study reports the complication and disease recurrence rates for ileocecal resection for pediatric and adult Crohn’s disease (CD) and identifies perioperative risk factors for these adverse outcomes in the two groups. Patients who underwent ileocecal resection for CD in a tertiary hospital in Italy (2010–2021) were included. Risk factors for postoperative complications and clinical and surgical disease recurrences were investigated with multivariate models. A total of 96 patients were included (children, 25%). There were no intraoperative complications. Thirty-one (32.3%) patients experienced 35 (36.5%) postoperative complications, and five (5.2%) were severe (Clavien–Dindo III–IV–V), with no intergroup difference for either overall postoperative complication rate (p = 0.257) or severe postoperative complication rate (p = 0.097). Most of these (77.1%) occurred within 30 days after surgery, especially in adults (p = 0.013). The multivariate analysis did not show risk factors for postoperative complications. Clinical and surgical recurrence rates after 5 years were 46.8% and 14.6%, respectively, with no intergroup rate differences. Clinical disease recurrence was positively correlated with previous abdominal surgery (p = 0.047) and negatively correlated with preoperative Hb levels (p = 0.046). A positive correlation was found between perianal disease and both clinical (p = 0.045) and surgical disease recurrences (p = 0.045). Urgent surgery was positively associated with surgical disease recurrence (p = 0.045). Notably, no children underwent urgent surgery in this study. In conclusion, the risk of postoperative complications among CD patients receiving ileocecal resection remains high, but most of them are nonserious. Some factors, such as urgent surgery, may increase the risk of disease recurrences.

BackgroundColorectal cancer (CRC) is considered one of the most frequent neoplasms of the digestive tract with a high mortality rate. Left hemicolectomy (LC) and low anterior resection (LAR) with minimally invasive laparoscopic and robotic approaches or with the open technique are the gold standard curative treatment.Materials and methodsSeventy-seven patients diagnosed with CRC were recruited between September 2017 and September 2021. All patients underwent a preoperative staging with a full-body CT scan. The goal of this study was to compare both types of surgeries, LC-LAR LS with Knight–Griffen colorectal anastomosis and LC-LAR open with Trans-Anal Purse-String Suture Anastomosis (the TAPSSA group), by positioning a No-Coil transanal tube (SapiMed Spa, Alessandria, Italy), in terms of postoperative complications such as prolonged postoperative ileus (PPOI), anastomotic leak (AL), postoperative ileus (POI), and hospital stay.ResultsThe patients were divided into two groups: the first with 39 patients who underwent LC and LAR in LS with Knight–Griffen anastomosis (Knight–Griffen group) and the second with 38 patients who underwent LC and LAR by the open technique with the TAPSSA group. Only one patient who underwent the open technique suffered AL. POI was 3.76 ± 1.7 days in the TAPSSA group and 3.07 ± 1.3 days in the Knight–Griffen group. There were no statistically significant differences in terms of AL and POI between the two different groups.ConclusionThe important point that preliminarily emerged from this retrospective study was that the two different techniques showed similarities in terms of AL and POI, and therefore, all the advantages reported in the previous studies pertaining to No-Coil also hold good in this study regardless of the surgical technique used. However, randomized controlled trials are needed to confirm these findings.

Tumor-associated macrophages (TAMs) may be noticed in gastric carcinomas (GC), but their clinicopathological significance has not been yet explored. From a histological review of 400 cases of tubular/papillary adenocarcinomas, 24 cases of stage I–II gastric adenocarcinomas with intraglandular and stromal TAMs were identified. Their clinicopathological features were compared with 72 pT-matched as well as stage-matched control cases of adenocarcinomas without TAMs. TAMs present in GC cases were present either in glands or in neoplastic stroma, showing an immunoreactivity for CD68 and CD80; sometimes, they were organized in mature granulomas with occasional giant cells. Therefore, the stained TAMs were reminiscent of a specific polarized macrophage M1 phenotype; however, in any case of our cohort, no M2 phenotype macrophages were documented by CD 163 and CD 204 immunostainings. Statistically, no significant differences in age, gender, tumor location, size, and lymphovascular and perineural invasion between the case group with TAMs and pT- as well as stage-matched controls were reported; furthermore, the case group showed lower frequency of lymph node metastasis (p = 0.02). In addition, a significantly different clinical course and overall survival rate were also observed in gastric adenocarcinomas with M1 TAMs (p = 0.02) in comparison to controls. These results suggest that tumor-associated M1 macrophages are related to a quite indolent growth and a better prognosis of patients with this peculiar variant of gastric adenocarcinomas.

BackgroundTo prospectively evaluate the diagnostic accuracy of magnetic resonance imaging (MRI) for the planning of surgical treatment of deep pelvic endometriosis.Materials and MethodsFrom January 2020 to December 2021, we evaluated 72 patients with symptoms characteristic of endometriosis to plan appropriate surgical treatment. Sensitivity (Se), specificity (Sp), positive and negative predictive values (VPP/VPN), and the accuracy of MRI for the detection of deep pelvic endometriosis were calculated.ResultsSeventy-two patients (mean age, 35.5 years; range, 20–46 years) suspected of having pelvic endometriosis were recruited. Pelvic endometriosis was confirmed at pathologic examination in 56 (77.7%) of 72 patients. A total of 22 (39.3%) of 56 patients were subjected to video laparoscopy (VLS), and 16 (72.2%) of 22 were treated by surgery. Se, Sp, VPP, and VPN in intestinal endometriosis diagnosis were, respectively, 100%, 93.3%, 100%, and 87.5%, and diagnostic accuracy was 95.4%. MRI Se in ureteral endometriosis diagnosis was 50%, Sp 100%, VPP 100%, VPN 78%, and diagnostic accuracy 82%. MRI Se in endometrioma diagnosis was 92.3%, Sp 100%, VPP 100%, VPN 90%, and diagnostic accuracy 95.4%. MRI Se in rectum-vaginal septum (SRV) endometriosis diagnosis was 80%, Sp 100%, VPP 100% VPN 85.7%, and diagnostic accuracy 91%. The MRI Se in the diagnosis of endometriosis involving ULS was 100%, Sp 92.8%, VPP 89%, VPN 100%, and diagnostic accuracy 95.4%. Complete concordance results in a 100% accuracy for all calculated values in diagnosing bladder endometriosis localizations.ConclusionMR imaging demonstrates high accuracy in detecting deep pelvic endometriosis in specific locations. It allows the localization of deep pelvic lesions with highly fibrotic components that are hardly recognizable with other imaging methods and not visible with VLS.

Abstract Background Colorectal cancer (CRC) is the most common tumor of the gastrointestinal tract. Anastomotic leak (AL) and prolonged postoperative ileus (PPOI) are two important complications of colorectal surgery. In this observational retrospective study, we evaluated the positive effects of transanal tube No Coil® in patients with CRC undergoing low anterior resection (LAR) and left hemicolectomy (LC). Methods Thirty-eight cases and forty controls resulted eligible for the final sample. No Coil® placement (SapiMed Spa, Alessandria, Italy) was considered an inclusion criteria for the case group. No Coil® was placed immediately after the end of surgical treatment. Results PPOI was significantly more frequent in the control group. AL was evident in 1 patient (2.6%) of cases and 3 patients (7.5%) of controls. No statistical difference was found in AL occurrence between groups. POI days and AL resulted associated with hospital stay. POI days were negatively associated with No Coil placement and positively with AL. Conclusion With our preliminary data, we suggest that No Coil® placement can be considered as a valuable procedure assisting colorectal surgery, but further studies are required to confirm and enlarge actual evidence.

Abstract Background Since its first documentation, a novel coronavirus (SARS-CoV-2) infection has emerged worldwide, with the consequent declaration of a pandemic disease (COVID-19). Severe forms of acute respiratory failure can develop. In addition, SARS-CoV-2 may affect organs other than the lung, such as the liver, with frequent onset of late cholestasis. We here report the histological findings of a COVID-19 patient, affected by a tardive complication of acute ischemic and gangrenous cholecystitis with a perforated and relaxed gallbladder needing urgent surgery. Case presentation A 59-year-old Caucasian male, affected by acute respiratory failure secondary to SARS-CoV-2 infection was admitted to our intensive care unit (ICU). Due to the severity of the disease, invasive mechanical ventilation was instituted and SARS-CoV-2 treatment (azithromycin 250 mg once-daily and hydroxychloroquine 200 mg trice-daily) started. Enoxaparin 8000 IU twice-daily was also administered subcutaneously. At day 8 of ICU admission, the clinical condition improved and patient was extubated. At day 32, patient revealed abdominal pain without signs of peritonism at examination, with increased inflammatory and cholestasis indexes at blood tests. At a first abdominal CT scan, perihepatic effusion and a relaxed gallbladder with dense content were detected. The surgeon decided to wait and see the evolution of clinical conditions. The day after, conditions further worsened and a laparotomic cholecystectomy was performed. A relaxed and perforated ischemic gangrenous gallbladder, with a local tissue inflammation and perihepatic fluid, was intraoperatively met. The gallbladder and a sample of omentum, adherent to the gallbladder, were also sent for histological examination. Hematoxylin-eosin-stained slides display inflammatory infiltration and endoluminal obliteration of vessels, with wall breakthrough, hemorrhagic infarction, and nerve hypertrophy of the gallbladder. The mucosa of the gallbladder appears also atrophic. Omentum vessels also appear largely thrombosed. Immunohistochemistry demonstrates an endothelial overexpression of medium-size vessels (anti-CD31), while not in micro-vessels, with a remarkable activity of macrophages (anti-CD68) and T helper lymphocytes (anti-CD4) against gallbladder vessels. All these findings define a histological diagnosis of vasculitis of the gallbladder. Conclusions Ischemic gangrenous cholecystitis can be a tardive complication of COVID-19, and it is characterized by a dysregulated host inflammatory response and thrombosis of medium-size vessels.

Relatively little research has examined sex differences among people affected by obesity. The aim of this study is to assess the relationship between negative emotions and eating behaviors, taking into account the role of biological sex. The final sample consists of 200 candidates for bariatric surgery, 62 males (31%) and 138 females (69%), aged from 18 to 60 years (M = 40.71; SD = 11.30). Participants were screened with the Binge Scale Questionnaire (BSQ) and individually evaluated with the Eating Disorder Inventory (EDI) and the Profile of Mood States (POMS). Correlations were calculated by splitting the sample by sex. Analyses of the relationship between negative emotions and eating behavior showed a large number of correlations in the sample of women and few correlations in men. The differences between women and men with obesity suggest the need for a different theoretical construct that explains the differentiated mechanisms of functioning and lays the foundations for specific therapeutic paths.

This study reports the outcomes of an enhanced recovery after surgery (ERAS) protocol in pediatric inflammatory bowel disease (IBD) surgery. Children who underwent surgery for IBD at two academic referral centers from January 2016 to June 2021 were included. Preoperative counseling, early enteral feeding (Impact®, Nestlé Health Science, and early mobilization were all part of the ERAS protocol. The outcomes (timing of first defecation, postoperative complications, and length of hospital stay (LOS)) were compared to traditional perioperative regimens (non-ERAS group). Thirty-three children who had 61 abdominal surgeries for IBD were included. Forty (65.5%) surgical procedures were included in the non-ERAS group, and 21 (34.5%) were included in the ERAS group. The postoperative complication rate was significantly lower in the ERAS group than in the non-ERAS group (29.6% vs. 55%, p = 0.049). The first defecation occurred earlier in the ERAS group than in the non-ERAS group (p < 0.001). There was no significant intergroup difference in the LOS. The implementation of ERAS in pediatric IBD surgery resulted in better outcomes than traditional perioperative care, especially in terms of postoperative complication rate and bowel function recovery. Further pediatric studies are needed to validate these findings and support ERAS application in children.

Objective: Up to 30% of pediatric patients with Crohn's disease (CD) require surgery. The aim of the study was to evaluate long-term health-related quality of life (HRQoL) outcome in children with CD who have had ileocolonic resection.Materials and methods: This was a retrospective cross-sectional study on all pediatric patients who had undergone surgery for CD between January 2015 and December 2017 in the Pediatric Surgery and Gastroenterology Units of the University Hospital of Messina. Surgical treatment was represented by laparoscopic ileocecal resection with latero-lateral anastomosis. Patients were asked to fill in a modified version of the IMPACT III questionnaire made up of 15 closed questions before and after surgery. The questionnaire was scored on a five-point scale with 5 reporting “not a problem” and 1 “a very severe problem.” The total score ranged from 15 (worst HRQoL) to 75 (best HRQoL). Frequency of relapses, reoperations, complications during follow-up, and postoperative bowel function were also studied.Results: Data were obtained in 10 patients (9 males), who underwent surgery at a median age of 13.5 years (range 13–18), after a median post-diagnosis period of 2.5 years (range 0–8). Preoperative scores were low in all 4 domains of the questionnaire. Postoperatively, HRQoL measures improved significantly (p < 0.05) about symptoms, school attendance, social and emotional functioning. Overall, nearly all patients were completely satisfied with the surgical outcome.Conclusions: HRQoL is low in CD children referred for possible operation, and surgery may positively affect the overall HRQoL. Collecting HRQoL data provides insight into the impact of treatment on children health status.

Background: Mast cells (MCs) contain proangiogenic factors, in particular tryptase, associated with increased angiogenesis in several tumours. With special reference to pancreatic cancer, few data have been published on the role of MCs in angiogenesis in both pancreatic ductal adenocarcinoma tissue (PDAT) and adjacent normal tissue (ANT). In this study, density of mast cells positive for c-Kit receptor (MCDP-c-KitR), density of mast cells positive for tryptase (MCDPT), area of mast cells positive for tryptase (MCAPT), and angiogenesis in terms of microvascular density (MVD) and endothelial area (EA) were evaluated in a total of 45 PDAT patients with stage T2–3N0–1M0. Results: For each analysed tissue parameter, the mean ± standard deviation was evaluated in both PDAT and ANT and differences were evaluated by Student’s t-test (p ranged from 0.001 to 0.005). Each analysed tissue parameter was then correlated to each other one by Pearson t-test analysis (p ranged from 0.01 to 0.03). No other correlation among MCDP-c-KitR, MCDPT, MCAPT, MVD, EA and the main clinical–pathological characteristics was found. Conclusions: Our results suggest that tissue parameters increased from ANT to PDAT and that mast cells are strongly associated with angiogenesis in PDAT. On this basis, the inhibition of MCs through tyrosine kinase inhibitors, such as masitinib, or inhibition of tryptase by gabexate mesylate may become potential novel antiangiogenetic approaches in pancreatic cancer therapy.

Multiple endocrine neoplasia (MEN)-1 syndrome is a rare disorder, due to the loss of function of the tumor suppressor menin. It consists of the association of two or more endocrine tumors, often presenting in a familial setting, being inherited in an autosomal dominant fashion. The most frequent manifestations of MEN-1 syndrome are primary hyperparathyroidism, followed by pituitary adenomas (mainly prolactinomas) and gastrointestinal neuroendocrine tumors, but several other associated conditions have been reported. Herein we describe the case of a male patient, affected by sporadic MEN-1, diagnosed with primary hyperparathyroidism, TSH-secreting pituitary adenoma and bilateral adrenal hyperplasia causing Cushing’s syndrome, due to a de novo MEN-1 gene mutation. The patient has been successfully treated with first generation somatostatin analog Octreotide LAR (30 mg every 28 days) -with stabilization of the known neuroendocrine lesions and shrinkage of the pituitary adenoma- and with bilateral adrenalectomy. The patient is still regularly followed-up at our Endocrine Unit, and his clinical conditions are stable.

OBJECTIVE To assess a new bloodless technique using radiofrequency energy for segmental liver resection of hepatic tumors.SUMMARY BACKGROUND DATA Liver resection remains a formidable surgical procedure; safe performance requires a high level of training and skill. Intraoperative blood loss during liver resection remains a major concern because it is associated with a higher rate of postoperative complications and shorter long-term survival.METHODS From January 2000 to June 2001, 15 patients with various hepatic tumors were operated on using radiofrequency energy to remove the tumor in its entirety. Radiofrequency energy was applied along the margins of the tumor to create “zones of necrosis” before resection with a scalpel.RESULTS No blood transfusions were required. The mean blood loss during resection was 30 ± 10 mL. No mortality or morbidity was observed. The median postoperative stay was 8 days (range 5-9). No liver recurrence was detected in patients undergoing resection with this technique during follow-up periods ranging from 2 to 20 months.CONCLUSIONS Segmental and wedge liver resection assisted by radiofrequency is safe. This novel technique offers a new method for transfusion-free resection. [ABSTRACT FROM AUTHOR]