Sutureless Repair for Open Treatment of Inguinal Hernia: Three Techniques in Comparison.

Currently, groin hernia repair is mostly performed with application of mesh prostheses fixed with or without suture. However, views on safety and efficacy of different surgical approaches are still partly discordant. In this multicentre retrospective study, three sutureless procedures, i.e., mesh fixation with glue, application of self-gripping mesh, and Trabucco's technique, were compared in 1034 patients with primary unilateral non-complicated inguinal hernia subjected to open anterior surgery. Patient-related features, comorbidities, and drugs potentially affecting the intervention outcomes were also examined. The incidence of postoperative complications, acute and chronic pain, and time until discharge were assessed. A multivariate logistic regression was used to compare the odds ratio of the surgical techniques adjusting for other risk factors. The application of standard/heavy mesh, performed in the Trabucco's technique, was found to significantly increase the odds ratio of hematomas (p = 0.014) and, most notably, of acute postoperative pain (p < 0.001). Among the clinical parameters, antithrombotic therapy and large hernia size were independent risk factors for hematomas and longer hospital stay, whilst small hernias were an independent predictor of pain. Overall, our findings suggest that the Trabucco's technique should not be preferred in patients with a large hernia and on antithrombotic therapy.

Mixed mucinous adenocarcinoma/large cell neuroendocrine carcinoma of the uterine cervix: case report and molecular characterization of a rare entity.

Mixed neuroendocrine-non-neuroendocrine carcinomas of the cervix are rare and generally aggressive diseases. They often present at an advanced stage with hematogenous or lymphatic metastases. The prognosis is poor, mostly influenced by the neuroendocrine component. Unfortunately, the rarity of the disease caused a lack of information about its pathogenesis and molecular landscape. The latest guidelines recommend a multimodal approach that usually includes radical surgery, platinum/etoposide-based chemotherapy, or chemoradiation. Here, we are presenting a case of metastatic mixed adenocarcinoma-large cell neuroendocrine carcinoma of the cervix in a 49-year-old female patient. The molecular characterization of the lesion highlighted the ubiquitous presence of human papillomavirus-18 DNA both in the adenocarcinomatous and the neuroendocrine components, suggesting a role for the virus in the pathogenesis. Moreover, a different set of mutations was detected in the two parts, thus ruling out a possible clonal evolution of the neuroendocrine component from the adenocarcinoma one. More studies are needed to clarify the molecular landscape of these rare lesions and identify putative targets for therapy.

Immune landscape and oncobiota in HPV-Associated Colorectal Cancer: an explorative study.

Worldwide more than 550,000 new patients suffering from malignant tumors are associated with human papillomaviruses (HPV) infection. However, only a small portion of patients infected progress to cancer, suggesting that other factors other than HPV may play a role. Some studies have investigated HPV infection in colorectal cancer (CRC) with discordant results; moreover, the role of HPV in CRC development is still unknown. We investigated HPV infection in 50 CRC from different regions, excluding the anal one, by immunohistochemistry (IHC), real-time PCR and RNA-seq. For each patient, we studied the tumor microenvironment in neoplastic and matched non-neoplastic samples, and we compared the tumor-infiltrating immune cell phenotypes among HPV-positive and negative samples. Finally, we compared the CRC-associated microbiota in HPV-positive and negative neoplastic samples by 16S rRNA sequencing. HPV infection was identified in 20% of CRC from the right side (caecum, ascending and transverse colon) and in 40% from the left side (descending colon and rectum). In all HPV-positive CRCs we found no expression of p53 and RB, thus suggesting HPV involvement in tumorigenesis. As far as the tumor microenvironment is concerned, in HPV-related cancers we observed a neoplastic environment with a reduced immune surveillance but an enhanced cytotoxic response by lymphocytes. HPV-positive and -negative CRC showed a different microbiota with lack of species normally found in CRC in the HPV-positive ones. Our results support the carcinogenic significance of HPV in CRC, suggesting a role of HPV in modulating the tumor immune microenvironment.

Paving the Path for Immune Enhancing Nutrition in Colon Cancer: Modulation of Tumor Microenvironment and Optimization of Outcomes and Costs.

INTRODUCTION: Published evidence suggests that immunonutrition has the potential to decrease postoperative complications and reduce length of stay in patients undergoing surgery for colorectal cancer. However, only a few studies have analyzed the effects of immunonutrition on tumor microenvironment and evaluated its prognostic impact. MATERIAL AND METHODS: This is a single center retrospective study enrolling 50 patients undergoing elective surgery for colorectal cancer managed with immunonutrition and 50 patients managed with standard nutrition for comparison. Tumor microenvironment was analyzed before (on the biopsy at the time of diagnosis) and after (on the matched surgical specimen) administration of immunonutrition. Immune function related indicators, including cytotoxic T-lymphocytes, helper T-cells, antigen presenting cells, natural killer cells, T-exhausted lymphocytes, T-regulatory cells, M1 and M2 tumor associated macrophages and PD-L1 expression were assessed by immunohistochemistry. For both groups, clinicopathological data were collected and a 5-year follow-up was available. RESULTS: We found that immunonutrition significantly activated the T-cell response against cancer, alter tumor microenvironment phenotype towards M2 polarization and inhibits the PD1/PD-L1 axis. A lower rate of postoperative complications and a shorter length of stay (p = 0.04) were observed in the immune nutrition group. Compared to standard nutrition group, patients managed wit immune nutrition showed a higher 5-year overall survival (p = 0.001). Finally, immune nutrition allowed to reduce the hospital care costs. CONCLUSIONS: Immunonutrition modulates tumor microenvironment by improving immune function and could prolong survival in patients undergoing elective surgery for colorectal cancer. Further studies are needed to optimize IN protocols and confirm their prognostic impact.

A national survey on the current status of minimally invasive gastric practice on behalf of GIRCG.

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

Peripancreatic paraganglioma: Lesson from a round table.

We described the case of a peripancreatic paraganglioma (PGL) misdiagnosed as pancreatic lesion. Surgical exploration revealed an unremarkable pancreas and a large well-defined cystic mass originating at the mesocolon root. Radical enucleation of the mass was performed, preserving the pancreatic tail. Histologically, a diagnosis of PGL was rendered. Interestingly, two previously unreported mutations, one affecting the KDR gene in exon 7 and another on the JAK3 gene in exon 4 were detected. Both mutations are known to be pathogenetic. Imaging and cytologic findings were blindly reviewed by an expert panel of clinicians, radiologists, and pathologists to identify possible causes of the misdiagnosis. The major issue was lack of evidence of a cleavage plane from the pancreas at imaging, which prompted radiologists to establish an intra-parenchymal origin. The blinded revision shifted the diagnosis towards an extra-pancreatic lesion, as the pancreatic parenchyma showed no structural alterations and no dislocation of the Wirsung duct. Ex post, the identified biases were the emergency setting of the radiologic examination and the very thin mesocolon sheet, which hindered clear definition of the lesion borders. Original endoscopic ultrasonography diagnosis was confirmed, emphasizing the intrinsic limit of this technique in detecting large masses. Finally, pathologic review favored a diagnosis of PGL due to the morphological features and immonohistochemical profile. Eighteen months after tumor excision, the patient is asymptomatic with no disease relapse evident by either radiology or laboratory tests. Our report strongly highlights the difficulties in rendering an accurate pre-operative diagnosis of PGL.

Surgeon-Pathologist Team Approach Dramatically Affects Lymph Nodes Detection and Improves Patients' Short-Term Outcome.

The downstaging of gastric cancer has recently gained particular attention in the field of gastric cancer surgery. The phenomenon is mainly due to an inappropriate sampling of lymph nodes during standard lymphadenectomy. Hence, collection of the maximum number of lymph nodes is a critical factor affecting the outcome of patients. None of the techniques proposed so far have demonstrated a real efficiency in increasing the number of identified lymph nodes. To harvest the maximum number of lymph nodes, we designed a protocol for on-site macroscopic evaluation and sampling of lymph nodes according to the Japanese Gastric Cancer Association protocol. The procedure was carried out by a surgeon/pathologist team in the operating room. We enrolled one hundred patients, 50 of whom belonged to the study group and 50 to a control group. The study group included patients who underwent lymph node dissection following the proposed protocol; the control group encompassed patients undergoing standard procedures for sampling. We compared the number and maximum diameter of lymph nodes collected in both groups, as well as some postoperative variables, the 30-day mortality and the overall survival. In the study group, the mean number of lymph nodes harvested was higher than the control one (p = 0.001). Moreover, by applying the proposed technique, we sampled lymph nodes with a very small diameter, some of which were metastatic. Noticeably, no difference in terms of postoperative course was identified between the two groups, again supporting the feasibility of an extended lymphadenectomy. By comparing the prognosis of patients, a better overall survival (p = 0.03) was detected in the study group; however, to date, no long-term follow-up is available. Interestingly, patients with metastasis in node stations number 8, 9, 11 or with skip metastasis, experienced a worse outcome and died. Based on our preliminary results, the pathologist/surgeon team approach seems to be a reliable option, despite of a slight increase in sfaff workload and technical cost. It allows for the harvesting of a larger number of lymph nodes and improves the outcome of the patients thanks to more precise staging and therapy. Nevertheless, since a higher number of patients are necessary to confirm our findings and assess the impact of this technique on oncological outcome, our study could serve as a proof-of-concept for a larger, multicentric collaboration.

A look towards the clonal origin of metastatic pulmonary carcinosarcoma: Report of a patient with an unexpected long-term survival.

INTRODUCTION: Pulmonary carcinosarcoma is a rare histological subtype of non-small cell lung cancer, defined by the combination of epithelial and mesenchimal elements. Prognosis is usually dismal, with a median survival of about 6 months. The use of immunotherapy by blockade of PD1/PD-L1 immune checkpoint signaling has been shown to improve patients' survival. However, local aggressiveness and distant metastases are frequent. Spread to the gastrointestinal tract is seldom reported. The genetic landscape of the disease has only recently begun to emerge, pointing at TP53, KRAS, EGFR and MET as the most common mutated genes. CASE DESCRIPTION: We describe the case of a metastatic patient with 37 months overall survival, treated by an aggressive multimodal approach combining surgery, chemotherapy, radiotherapy and immunotherapy. To shed new light on the molecular basis for sarcomatoid component in lung carcinoma, we performed next generation sequencing analysis of the squamous and sarcomatoid component by the two sites. We demonstrated a clonal origin and hypermutability of the sarcomatous elements that may account for the good response to immunotherapy. Moreover, we identified some mutations involving TP53 and EGFR genes, targetable by already available drugs. CONCLUSIONS: We depicted a model of how a squamous cell carcinoma can differentiate during its natural history into sub-clonal populations with different features and may ultimately result in a neoplasm (i.e. pulmonary carcinosarcoma) showing clonal heterogeneity. Our data might contribute to a better understanding of the pathogenesis and molecular mechanisms of this rare tumor and open new ways for a more tailored approach.