Programmed Death Ligand 1 (PD-L1) Expression in Lymphomas: State of the Art.

The interaction of programmed death-1 (PD-1) on T lymphocytes with its ligands Programmed Death Ligand 1 (PD-L1) and Programmed Death Ligand 2 (PD-L2) on tumor cells and/or tumor-associated macrophages results in inhibitory signals to the T-cell receptor pathway, consequently causing tumor immune escape. PD-L1/PD-L2 are currently used as predictive tissue biomarkers in clinical practice. Virtually PD-L1 levels expressed by tumor cells are associated with a good response to immune checkpoint blockade therapies targeting the PD-1/PD-L1 axis. These therapies restore T-cell antitumor immune response by releasing T-lymphocytes from the inhibitory effects of tumor cells. Immune checkpoint therapies have completely changed the management of patients with solid cancers. This therapeutic strategy is less used in hematological malignancies, although good results have been achieved in some settings, such as refractory/relapsed classic Hodgkin lymphoma and primary mediastinal large B-cell lymphoma. Variable results have been obtained in diffuse large B-cell lymphoma and T-cell lymphomas. Immunohistochemistry represents the main technique for assessing PD-L1 expression on tumor cells. This review aims to describe the current knowledge of PD-L1 expression in various types of lymphomas, focusing on the principal mechanisms underlying PD-L1 overexpression, its prognostic significance and practical issues concerning the evaluation of PD-L1 immunohistochemical results in lymphomas.

Nonoperative management of acute complicated diverticulitis with pericolic and/or distant extraluminal air: A systematic review.

INTRODUCTION: Colonic Diverticular Disease (CDD) is a multifactorial inflammatory disease. Acute diverticulitis (AD), with extraluminal free air (both pericolic and distant), represents about 15% of radiological scenarios and remains a therapeutic challenge for surgeons. Currently, the WSES guidelines suggest trying a conservative strategy both in the presence of pericolic and distant free extraluminal air, even if both have respectively weak recommendation based on low/very low-quality evidence. METHODS: We performed a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes guidelines. PubMed/MEDLINE, Scopus, Web of Science, and Embase databases were used to identify articles of interest. RESULTS: A total of 2380 patients with AD and extraluminal free air (both pericolic and distant) who underwent nonoperative management (NOM) were analyzed. Of the 2380 patients, 2095(88%) were successfully treated with NOM, while 285 (12%) patients failed. A total of 1574 (93.1%) patients with pericolic extraluminal free air had a successful NOM with 6.9% (117) failure rates, while 135 (71.1%) patients with distant extraluminal free air had a successful NOM with 28.9% (55) failure rates. Regarding distant recurrence, we recorded a rate of 18.3% (261/1430), while a rate of 11.3% (167/1472) was recorded for patients undergoing elective surgery. CONCLUSION: NOM for patients with AD and extraluminal free air (both pericolic and distant) seems to be feasible and safe despite a higher failure rate in the distant subgroup, which remains the most challenging clinical scenario to deal with through conservative treatment.

Outcomes before and after Implementation of the ERAS (Enhanced Recovery after Surgery) Protocol in Open and Laparoscopic Colorectal Surgery: A Comparative Real-World Study from Northern Italy.

Enhanced Recovery After Surgery (ERAS) protocols have changed perioperative care, aiming to optimize patient outcomes. This study assesses ERAS implementation effects on postoperative complications, length of hospital stay (LOS), and mortality in colorectal cancer (CRC) patients. A retrospective real-world analysis was conducted on CRC patients undergoing surgery within a Northern Italian Cancer Registry. Outcomes including complications, re-surgeries, 30-day readmission, mortality, and LOS were assessed in 2023, the year of ERAS protocol adoption, and compared with data from 2022. A total of 158 surgeries were performed, 77 cases in 2022 and 81 in 2023. In 2023, a lower incidence of postoperative complications was observed compared to that in 2022 (17.3% vs. 22.1%), despite treating a higher proportion of patients with unfavorable prognoses. However, rates of reoperations and readmissions within 30 days post-surgery increased in 2023. Mortality within 30 days remained consistent between the two groups. Patients diagnosed in 2023 experienced a statistically significant reduction in LOS compared to those in 2022 (mean: 5 vs. 8.1 days). ERAS protocols in CRC surgery yield reduced postoperative complications and shorter hospital stays, even in complex cases. Our study emphasizes ERAS' role in enhancing surgical outcomes and recovery.

Short-Term Outcomes in Patients Undergoing Virtual/Ghost Ileostomy or Defunctioning Ileostomy after Anterior Resection of the Rectum: A Meta-Analysis.

BACKGROUND AND OBJECTIVES: Anterior rectal resection (ARR) represents one of the most frequently performed methods in colorectal surgery, mainly carried out for rectal cancer (RC) treatment. Defunctioning ileostomy (DI) has long been chosen as a method to "protect" colorectal or coloanal anastomosis after ARR. However, DI does not rule out risks of more or less serious complications. A proximal intra-abdominal closed-loop ileostomy, the so-called virtual/ghost ileostomy (VI/GI), could limit the number of DIs and the associated morbidity. MATERIALS AND METHODS: We performed a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA) guidelines. Meta-analysis was performed by use of RevMan [Computer program] Version 5.4. RESULTS: The five included comparative studies (VI/GI or DI) covering an approximately 20-year study period (2008-2021). All included studies were observational ones and originated from European countries. Meta-analysis indicated VI/GI as significantly associated with lower short-term morbidity rates related to VI/GI or DI after primary surgery (RR: 0.21, 95% CI: 0.07-0.64, p = 0.006), fewer dehydration (RR: 0.17, 95% CI: 0.04-0.75, p = 0.02) and ileus episodes after primary surgery (RR: 0.20, 95% CI: 0.05-0.77, p = 0.02), fewer readmissions after primary surgery (RR: 0.17, 95% CI: 0.07-0.43, p = 0.0002) and readmissions after primary surgery plus stoma closure surgery (RR: 0.14, 95% CI: 0.06-0.30, p < 0.00001) than the DI group. On the contrary, no differences were identified in terms of AL after primary surgery, short-term morbidity after primary surgery, major complications (CD ≥ III) after primary surgery and length of hospital stay after primary surgery. Conclusions: Given the significant biases among meta-analyzed studies (small overall sample size and the small number of events analyzed, in particular), our results require careful interpretation. Further randomized, possibly multi-center trials may be of paramount importance in confirming our results.

Treatment of postoperative jejunal intussusception in adult with oral gastrografin after laparoscopic low rectal resection. A case report.

INTRODUCTION: Postoperative intussusception is a rare cause of intestinal obstruction in adults. Intussusception refers to a condition in which a segment of the intestine invaginates into the lumen of an adjacent segment of the intestine. PRESENTATION OF CASE: We report a case of postoperative jejunojejunal intussusception in a 42-year-old male following a laparoscopic low anterior resection for rectal cancer. In post-operative day (POD) 2 the patient showed intermittent bowel obstruction and fever. Diagnosis was established with abdominal computed tomography (CT) and enteroclysis, which led to a spontaneous reduction of the invagination. DISCUSSION: The incidence of intussusception in adults is rare condition. It represents less than 5% of all cases. In adults, transient asymptomatic enteric intussusception often resolves spontaneously without any treatment. When bowel obstruction is complete and persistent, surgery is need. Intussusception as cause of intestinal obstruction should be kept in mind in a post operative patient who develops obstructive symptoms. Early diagnosis makes the difference between surgical and others treatment. The pathogenesis and diagnosis of postoperative intussusception in the adult is discussed in the case report. CONCLUSION: The authors presented a rare cause of postoperative small bowel obstruction treated without surgery. The peculiarity of this case report is that the authors have successfully used, in an adult, conservative treatment with gastrografin, which is the treatment of choice used in children. The use of gastrografin was decisive and there were no recurrences in the follow up.

Laparoscopic near-total splenectomy: a single-center experience of a standardized procedure.

Background: Near-total splenectomy (NTS) represents an innovative and effective surgery technique for spleen disease, reducing the risk of severe infections and thromboembolic events after total splenectomy. The authors reported a laparoscopic near-total splenectomy (LNTS) surgical experience following the optimal results of the open approach, describing a standardized and effective minimally invasive technique with the purpose of preserving a minimal residual spleen.Material and methods: From November 2006 to September 2016, 15 patients with splenic and hematologic disease underwent LNTS, according to a laparoscopic procedure developed by the authors. The end criterion was to conserve a remanent spleen of 10-15 cm3 in size.Results: Patient age ranged between 18 and 59 years. Mean operative time was 70 ± 20 min. Mean hospital stay was 3.46 (range 3-7) days. One complication occurred during the surgery for a lesion of the inferior polar artery with need of a total splenectomy. No conversion to open surgery was necessary.Conclusions: LNTS is a safe and effective technique for the management of splenic and hematologic disease with a low intra- and post-operative complication rate, and it can minimize the late sequelae of secondary splenectomy. However, it requires further studies with more cases to evaluate its role.

Correction to: Next-generation sequencing analysis of receptor-type tyrosine kinase genes in surgically resected colon cancer: identification of gain-of-function mutations in the RET proto-oncogene.

In the publication of this article [1], there is an error in Fig. 7. The minus and plus signals are inverted which impairs understanding of the results described.

Next-generation sequencing analysis of receptor-type tyrosine kinase genes in surgically resected colon cancer: identification of gain-of-function mutations in the RET proto-oncogene.

BACKGROUND: Improvement in genetic characterization of Colon Cancer (CC) patients is required to propose new potential targets, since surgical resection coupled to chemotherapy, presents several limits such as cancer recurrence and drug resistance. Targeted therapies have more efficacy and less toxicity than standard treatments. One of the most relevant cancer-specific actionable targets are receptor tyrosine kinases (RTKs) whose role in CC need to be better investigated. METHODS: We have analysed 37 CC patients using the Ion AmpliSeq™ Comprehensive Cancer Panel (CCP). We have confirmed the somatic nature of RET variants through Sanger sequencing and assessed RET activation status and protein expression by immunofluorescence and western-blot analyses. We have used RET mutant expression vectors to evaluate the effect of selected mutations in HEK293 cells by performing proliferation, migration and clonogenic assays. RESULTS: Among the 409 cancer-related genes included in the CCP we have focused on the RTKs. Overall, we have observed 101 different potentially damaging variants distributed across 31 RTK genes in 28 patients. The most frequently mutated RTKs were FLT4, ROS1, EPH7, ERBB2, EGFR, RET, FGFR3 and FGFR4. In particular, we have identified 4 different somatic variants in 10% of CC patients in RET proto-oncogene. Among them, we have demonstrated that the G533C variant was able to activate RET by promoting dimer formation and enhancing Y1062 phosphorylation. Moreover, we have demonstrated that RET G533C variant was able to stimulate anchorage-dependent proliferation, migration and clonogenic cell survival. Notably, the effects induced by the RET G533C variant were abolished by vandetanib. CONCLUSIONS: The discovery of pathogenic variants across RTK genes in 75% of the CC patients under analysis, suggests a previously underestimated role for RTKs in CC development. The identification of a gain-of-function RET mutation in CC highlights the potential use of RET in targeted therapy.

Intraoperative cholangiography during cholecystectomy in sequential treatment of cholecystocholedocholithiasis: To be, or not to be, that is the question A cohort study.

BACKGROUND: Choledocholithiasis occurs in 10-15% of patients with cholecystolithiasis. Despite the existence of many therapeutic options for the treatment of cholecystocholedocholithiasis, a sequential treatment in which pre-operative ERCP is combined with intraoperative cholangiography (IOC) and laparoscopic cholecystectomy (LC), is the most commonly accepted strategy. However, use of IOC in the "splitting treatment" of cholecystocholedocholithiasis is controversial. The aim of the present study is to investigate the utility of IOC in detecting residual stones in patients undergoing LC in the sequential treatment of common biliary duct or gallbladder stones. METHODS: Patients were recruited retrospectively among those who underwent IOC during LC, performed as second stage in the sequential treatment for cholecystocholedocholithiasis between 2010 and 2016. Demographic and clinical data were obtained from CPT codes at Ospedale Monaldi A.O.R.N dei Colli Naples, Italy. Data obtained from all pre-operative ERCP analyses were recorded, including cholangiogram findings and performance of sphincterotomy. Statistical analysis was carried out using the IBM SPSS Statistic 19.0 software package. RESULTS: Between January 2010 and December 2016 575 patients (343 males, 242 females) underwent IOC during LC for symptomatic cholecystitis due to cholelithiasis. Among patients accrued for the study, 143 underwent preoperative ERCP for suspicion of common biliary duct stones. At the time of pre-operative ERCP, 123 were found to have common biliary duct stones while 20 (15%) presented negative ERCP. Complete removal of stones was accomplished in 119 patients. Among these patients, 13 had residual common biliary duct stones diagnosed by IOC (11%). Two patients underwent laparoscopic bile duct revision and, last, two patients were referred for ERCP at a later point. It is of note that all patients who presented residual stones by IOC had undergone pre-operative sphincterotomy. CONCLUSION: This study demonstrates that IOC is particularly effective in detecting residual stones in patients undergoing LC in sequential treatment of common biliary duct and/or gallbladder stones, and may be used on a routine basis in the sequential treatment of cholecystocholedocholithiasis.

Irreversible electroporation for locally advanced pancreatic cancer through a minimally invasive surgery supported by laparoscopic ultrasound.

INTRODUCTION: Pancreatic cancer is one of the most lethal cancers worldwide, with 5-years survival rate as low as 6%. The majority of pancreatic cancer patients present locally advanced or metastatic disease at diagnosis. Typically, patients affected by locally advanced pancreatic cancer (LAPC) do not undergo radical surgery but are treated with focal ablative therapies. However, a high rate of morbidity due to the heat sink effect has limited the application of ablative techniques on a routine basis in LAPC patients. Irreversible electroporation (IRE) has proved to be a new method of LAPC ablation. PRESENTATION OF THE CASE: A 69-year-old woman affected by LAPC with good response to systemic chemotherapy with FOLFIRINOX and residual 35 mm mass in the neck of the pancreas underwent to IRE through a minimally invasive surgical approach under laparoscopic ultrasound guide. The post-operative course was uneventful and the patient was discharged after 5 days. Six months after surgery she had no evidence of distant or recurrent disease. DISCUSSION: IRE has previously shown promising results in the treatment of LAPC, with relatively acceptable morbidity rates and improvement of survival. We report on the application of IRE through a minimally invasive surgical approach supported by laparoscopic ultrasound. CONCLUSION: In conclusion, we propose a novel technical approach that combines the benefits of IRE on the treatment of patients affected by LAPC with the advantages of laparoscopic surgery.

A New Robot-assisted Billroth-I Reconstruction: Details of the Technique and Early Results.

BACKGROUND: Laparoscopic surgery for gastric tumor is considered a demanding procedure because of lymph node dissection and reconstruction. Billroth-I (B-I) reconstruction after laparoscopic distal gastrectomy is commonly performed extracorporeally because of the complexity of an intracorporeal procedure. Robotic surgery overcomes some limitations of laparoscopy, allowing to reproduce the basic maneuvers of open surgery. We describe a new technique to perform robotic B-I anastomosis. METHODS: Between January 2012 and February 2015, 5 patients underwent distal gastrectomy with intracorporeal B-I-stapled anastomosis. Patient demographics, tumor characteristics, histopathologic features, and perioperative data were analyzed. RESULTS: Median operative time was 170 minutes (145 to 180 min). There were no conversions. Contrast swallow was routinely performed on the third postoperative day. Median postoperative hospitalization was 7 days (range: 6 to 8). No major complications or mortality were observed. CONCLUSIONS: Robotic distal gastrectomy with intracorporeal B-I anastomosis is a safe and promising technique in selected cases of gastric tumors.

Surgical approach to right colon cancer: From open technique to robot. State of art.

This work is a topic highlight on the surgical treatment of the right colon pathologies, focusing on the literature state of art and comparing the open surgery to the different laparoscopic and robotic procedures. Different laparoscopic procedures have been described for the treatment of right colon tumors: Totally laparoscopic right colectomy, laparoscopic assisted right colectomy, laparoscopic facilitated right colectomy, hand-assisted right colectomy, single incision laparoscopic surgery colectomy, robotic right colectomy. Two main characteristics of these techniques are the different type of anastomosis: Intracorporeal (for totally laparoscopic right colectomy, single incision laparoscopic surgery colectomy, laparoscopic assisted right colectomy and robotic technique) or extracorporeal (for laparoscopic assisted right colectomy, laparoscopic facilitated right colectomy, hand-assisted right colectomy and open right colectomy) and the different incision (suprapubic, median or transverse on the right side of abdomen). The different laparoscopic techniques meet the same oncological criteria of radicalism as the open surgery for the right colon. The totally laparoscopic right colectomy with intracorporeal anastomosis and even more the single incision laparoscopic surgery colectomy, remain a technical challenge due to the complexity of procedures (especially for the single incision laparoscopic surgery colectomy) and the particular right colon vascular anatomy but they seem to have some theoretical advantages compared to the other laparoscopic and open procedures. Data reported in literature while confirming the advantages of laparoscopic approach, do not allow to solve controversies about which is the best laparoscopic technique (Intracorporeal vs Extracorporeal Anastomosis) to treat the right colon cancer. However, the laparoscopic techniques with intracorporeal anastomosis for the right colon seem to show some theoretical advantages (functional, technical, oncological and cosmetic advantages) even if all studies conclude that further prospective randomized trials are necessary. Robotic technique may be useful to overcome the problems related to inexperience in laparoscopy in some surgical centers.

Preoperative Predictive Factors of Successful Weight Loss and Glycaemic Control 1 Year After Gastric Bypass for Morbid Obesity.

BACKGROUND: Gastric bypass (GBP) is one of the most effective surgical procedures to treat morbid obesity and the related comorbidities. This study aimed at identifying preoperative predictors of successful weight loss and type 2 diabetes mellitus (T2DM) remission 1 year after GBP. METHODS: Prospective longitudinal study of 771 patients who underwent GBP was performed at four Italian centres between November 2011 and May 2013 with 1-year follow-up. Preoperative anthropometric, metabolic and social parameters, the surgical technique and the previous failed bariatric procedures were analyzed. Weight, the body mass index (BMI), the percentage of excess weight lost (% EWL), the percentage of excess BMI lost (% BMIL) and glycated haemoglobin (HbA1c) were recorded at follow-up. RESULTS: Univariate and multivariate analysis showed that BMI <50 kg/m(2) (p = 0.006) and dyslipidaemia (p = 0.05) were predictive factors of successful weight loss. Multivariate analysis of surgical technique showed significant weight loss in patients with a small gastric pouch (p < 0.001); the lengths of alimentary and biliary loops showed no statistical significance. All diabetic patients had a significant reduction of HbA1c (p < 0.001) after surgery. BMI ≥ 50 kg/m(2) (p = 0.02) and low level of preoperative HbA1c (p < 0.01) were independent risk factors of T2DM remission after surgery. CONCLUSIONS: This study provides a useful tool for making more accurate predictions of best results in terms of weight loss and metabolic improvement.