MSI and EBV Positive Gastric Cancer's Subgroups and Their Link With Novel Immunotherapy

Gastric cancers have been historically classified based on histomorphologic features. The Cancer Genome Atlas network reported the comprehensive identification of genetic alterations associated with gastric cancer, identifying four distinct subtypes- Epstein-Barr virus (EBV)-positive, microsatellite-unstable/instability (MSI), genomically stable and chromosomal instability. In particular, EBV-positive and MSI gastric cancers seem responsive to novel immunotherapies drugs. The aim of this review is to describe MSI and EBV positive gastric cancer's subgroups and their relationship with novel immunotherapy.</p

Detecting common copy number variants in high-throughput sequencing data by using JointSLM algorithm

The discovery of genomic structural variants (SVs), such as copy number variants (CNVs), is essential to understand genetic variation of human populations and complex diseases. Over recent years, the advent of new high-throughput sequencing (HTS) platforms has opened many opportunities for SVs discovery, and a very promising approach consists in measuring the depth of coverage (DOC) of reads aligned to the human reference genome. At present, few computational methods have been developed for the analysis of DOC data and all of these methods allow to analyse only one sample at time. For these reasons, we developed a novel algorithm (JointSLM) that allows to detect common CNVs among individuals by analysing DOC data from multiple samples simultaneously. We test JointSLM performance on synthetic and real data and we show its unprecedented resolution that enables the detection of recurrent CNV regions as small as 500 bp in size. When we apply JointSLM to analyse chromosome one of eight genomes with different ancestry, we identify 3000 regions with recurrent CNVs of different frequency and size: hierarchical clustering on these regions segregates the eight individuals in two groups that reflect their ancestry, demonstrating the potential utility of JointSLM for population genetics studies

Hepatic metastases from gastric cancer: A surgical perspective

Management of patients with hepatic metastases as the sole metastatic site at diagnosis of gastric cancer (synchronous setting) or detected during follow-up (metachronous) is controversial. The prevailing attitude in these cases is passive, leading to surgical palliation and, possibly, to chemotherapy. Authors focused this editorial in order to promote a more pragmatic attitude. They stress the importance of recognizing the good candidates to curative surgery of both gastric cancer and hepatic metastases (synchronous setting) or hepatic disease alone (metachronous disease) from those who will not benefit from surgical therapy. In fact, in adequately selected subgroup of patients surgery, especially if integrated in multimodal therapeutic strategies, may achieve unexpected 5-year survival rates, ranging from 10% to 40%. The critical revision of the literature suggests that some simple clinical criteria exist that may be effectively employed in patients selection. These are mainly related to the gastric cancer (factors T, N, G) and to the extent of hepatic involvement (factor H). Upon these criteria it is possible to adequately select about 50% of cases. In the remaining 50% of cases a critical discussion on a case-by-case basis is recommended, considering that among these patients some potential long-survivors exist, that survival is strictly influenced by the ablation of the tumor bulk and by multimodality treatments including chemotherapy and that in expert institutions this kind of surgery is performed with very low mortality and morbidity rates

PIK3CA mutation in gastric cancer and the role of microsatellite instability status in mutations of exons 9 and 20 of the PIK3CA gene

8noopenBackground. A better understanding of molecular gastric cancer (GC) entities may help in tailored treatments of that neoplasm. The PIK3CA mutation is one of the most important in many cancers. Objectives. We performed a comparison of clinical and pathological data of the PIK3CA mutation in GC patients. Material and methods. The analysis was done on 472 patients operated on in one center. Polymerase chain reaction (PCR) was used for the screening of PIK3CA (exon 9 and 20). For microsatellite instability (MSI) we used 5 quasi-monomorphic mononucleotide repeats − BAT-26, BAT-25, NR-24, NR-21, and NR-27. The clinical and pathological data was analyzed. Results. PIK3CA mutation was observed in 10 out of 472 GC patients (2.1%). Nine out of 10 were MSI (9 of 111 MSI patients – 8.1%). Half of the 10 patients had mutations in exon 9 and the other half in exon 20. A majority of patients with the PIK3CA mutation had MSI (p < 0.001). The 5-year survival of MSI patients with the PIK3CA mutation was 40% and without the mutation, 70.4% (p = 0.309). For patients with the mutation in exon 9, the 5-year survival was 0%, and for those with the mutation in exon 20, 80% (p = 0.031). The Cox proportional hazards regression analysis did not show that PIK3CA is statistically correlated with a worse overall survival. Conclusions. PIK3CA mutation in GC is a rare finding. It is strongly associated with the MSI molecular subgroup, presenting a worse outcome than other MSI patients. A completely different outcome is associated with the mutation in exon 9 compared to the mutation in exon 20, with the latter being more favorable.openPolom, Karol; Marrelli, Daniele; Roviello, Giandomenico; Pascale, Valeria; Voglino, Costantino; Vindigni, Carla; Generali, Daniele; Roviello, FrancoPolom, Karol; Marrelli, Daniele; Roviello, Giandomenico; Pascale, Valeria; Voglino, Costantino; Vindigni, Carla; Generali, Daniele; Roviello, Franc

Robot-assisted laparoscopic vs open gastrectomy for gastric cancer: Systematic review and meta-analysis

AIM To evaluate the potential effectiveness of robot-assisted gastrectomy (RAG) in comparison to open gastrectomy (OG) for gastric cancer patients. METHODS A comprehensive systematic literature search using PubMed, EMBASE, and the Cochrane Library was carried out to identify studies comparing RAG and OG in gastric cancer. Participants of any age and sex were considered for inclusion in comparative studies of the two techniques independently from type of gastrectomy. A meta-analysis of short-term perioperative outcomes was performed to evaluate whether RAG is equivalent to OG. The primary outcome measures were set for estimated blood loss, operative time, conversion rate, morbidity, and hospital stay. Secondary among postoperative complications, wound infection, bleeding and anastomotic leakage were also analysed. RESULTS A total of 6 articles, 5 retrospective and 1 randomized controlled study, involving 6123 patients overall, with 689 (11.3%) cases submitted to RAG and 5434 (88.7%) to OG, satisfied the eligibility criteria and were included in the meta-analysis. RAG was associated with longer operation time than OG (weighted mean difference 72.20 min; P < 0.001), but with reduction in blood loss and shorter hospital stay (weighted mean difference -166.83 mL and -1.97 d respectively; P < 0.001). No differences were found with respect to overall postoperative complications (P = 0.65), wound infection (P = 0.35), bleeding (P = 0.65), and anastomotic leakage (P = 0.06). The postoperative mortality rates were similar between the two groups. With respect to oncological outcomes, no statistical differences among the number of harvested lymph nodes were found (weighted mean difference -1.12; P = 0.10). CONCLUSION RAG seems to be a technically valid alternative to OG for performing radical gastrectomy in gastric cancer resulting in safe complications

Data on the quality of life after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal malignancies: does it concern patients with gastric cancer?

AbstractIntroduction.So far there are no reports devoted exclusively to the quality of life after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in metastatic gastric cancer. Current literature concerning this issue was, thus, reviewed in order to: 1) search for such data concerning metastatic gastric cancer; 2) assess if the latest reviews evenly pertain to all peritoneal surface malignancies; and 3) conclude if they are a reliable source of data for patients with metastatic gastric cancer.Materials and Methods.The electronic PubMed/MEDLINE and EMBASE databases were retrieved for studies concerning the influence of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy on quality of life in patients with metastatic gastric cancer and regardless of initial diagnosis. The data on the number of patients with particular tumours were analysed and the results were presented in the form of a table.Results.Approximately half of all patients encompassed by the reviews had a form of primary peritoneal surface malignancies. Within peritoneal metastases, the most numerous were colorectal (21-24%) and ovarian cancers (5-15%). Gastric cancers and sarcomas were the smallest defined subgroups (4% each).Conclusions.The promising outcomes in quality of life after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in primary peritoneal surface malignancies might differ from rarely reported ones in metastatic gastric cancer. The problem needs further, gastric cancer-devoted investigations

2-Dimensional ultra-high performance liquid chromatography and DMT-MM derivatization paired with tandem mass spectrometry for comprehensive serum N-glycome characterization.

Glycosylation is a prominent co- and post-translational modification which contributes to a variety of important biological functions. Protein glycosylation characteristics, particularly N-glycosylation, are influenced by changes in one's pathological state, such as through the presence of disease, and as such, there is great interest in N-glycans as potential disease biomarkers. Human serum is an attractive source for N-glycan based biomarker studies as circulatory proteins are representative of one's physiology, with many serum proteins containing N-glycosylation. The difficulty in comprehensively characterizing the serum N-glycome arises from the absence of a biosynthetic template resulting in great structural heterogeneity and complexity. To help overcome these challenges we developed a 2-dimensional liquid chromatography platform which utilizes offline weak anion exchange (WAX) chromatography in the first dimension and hydrophilic interaction liquid chromatography (HILIC) in the second dimension to separate N-glycans by charge, corresponding to degree of sialylation, and size, respectively. Performing these separations offline enables subsequent derivatization with 4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM) for sialic acid linkage determination and the identification of sialic acid linkage isomers. Subsequent tandem mass spectrometry analysis revealed the identification of 212 complete and partial N-glycan structures including low abundant N-glycans containing acetyl and sulphate modifications. The identifications obtained through this platform were then applied to N-glycans released from a set of stage 3 gastric cancer serum samples obtained from patients before (pre-op) and after (post-op) tumour resection to investigate how the serum N-glycome can facilitate differentiation between the two pathological states

Transanal hemorrhoidal dearterialization (THD) for hemorrhoidal disease: An Italian single-institution 5-year experience analysis and updated literature review

Background: Hemorrhoidal disease is a highly prevalent, chronic disorder that usually compromise patients' quality of life. Despite recent advances in pharmacologic and surgical therapeutic options, a clear treatment "gold standard" is lacking. Our aim is to analyze the outcomes following Transanal Hemorrhoidal Dearterialization (THD) procedure. MethodsPatients who failed conservative treatment and underwent THD Doppler between 2017 and 2021 were enrolled. Follow-up interviews (consisting of clinical examination, Visual Analog Scale for pain-VAS, Vaizey incontinence score, Hemorrhoid Severity Score) were administered 1 week, 2 weeks, 1 month and 6 months after surgery. ResultsForty-seven out of 75 patients were male, and the mean age was 50 (+/- 17.9) years. Hemorrhoids were classified as Goligher's degree II in 25 cases, III in 40 and IV, simple irreducible without ischemic changes, in 10. The mean operative time was 35 (28-60) minutes, and most procedures were performed with epidural anesthesia (80%). No intraoperative complications occurred, and 73 patients (97.3%) were discharged within post-operative day 1. Early post-operative pain and bleeding occurred in 37.3% and 8% of patients, respectively. No patients experienced anal incontinence and severe symptoms at 6 months after surgery. The overall success rate was 97.3%. ConclusionsTHD is safe and effective in hemorrhoidal disease at degree II if bleeding, III, and IV without ischemic changes, both as a first intervention and on recurrence. Physician and patient need to understand each other's expectations, weight the risks and benefits, and customize the treatment

Gastric duplication presenting as partial gastric outlet obstruction

Abstract We present a very rare case of gastric duplication treated with complete excision with two surgical procedures. We decided to report our case to share our experience that confirm the difficult of preoperative/intraoperative diagnosis of gastric duplication in a pediatric patient. Finally we reviewed the literature to date

Conversion gastrectomy for stage IV unresectable gastric cancer: a GIRCG retrospective cohort study

Background: The aim of this study is to report the experience with conversion surgery from six Gruppo Italiano Ricerca Cancro Gastrico (GIRCG) centers, focusing our analysis on factors affecting survival and the risk of recurrence. Methods: A retrospective, multicenter cohort study was performed in patients who had undergone conversion gastrectomy between 2005 and 2017. Data were extracted from a GIRCG database including all metastatic gastric cancer patients submitted to surgery. Only stage IV unresectable tumors/metastases which became resectable after chemotherapy were included in this analysis. Results: Forty-five resected M1 patients were included in the analysis. Reasons for being deemed unresectable at diagnosis were peritoneal involvement (PCI &gt; 6) (n = 38, 84.4%), distant metastatic nodes (n = 3, 6.6%) and extensive liver involvement (n = 4, 8.8%). Median follow-up was 25&nbsp;months (IQR 9-50). Median overall survival from surgery was 15&nbsp;months and 1-, 3- and 5-year survivals were 57.2, 36.1 and 24%, respectively. Median progression-free survival was 12&nbsp;months with 1- and 3-year survival of 46.4 and 33.9%, respectively. At cox regression analysis the only independent prognostic factor for OS was the presence of more than one type of metastasis (HR 4.41, 95% CI 1.72\u201311.3, p = 0.002). A positive microscopic resection margin was the only risk factor for recurrence (HR 5.72, 95% CI 1.04\u201331.4, p = 0.045). Conclusions: Unresectable stage IV GC patients could benefit from radical surgery after chemotherapy and achieve long survivals. The main prognostic factor for these patients was the presence of more than one type of extra-gastric metastatic involvement