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Malignant pleural mesothelioma (MPM) is a malignancy associated with asbestos exposure and is typically categorized as an orphan disease. Recent developments in immunotherapy with anti-PD-1 and anti-CTLA-4 antibodies, specifically with agents nivolumab and ipilimumab, have demonstrated an improvement in overall survival over the previous standard chemotherapy leading to their FDA-approval as first-line therapy for unresectable disease. For quite some time, it has been known that these proteins are not the only ones that function as immune checkpoints in human biology, and the hypothesis that MPM is an immunogenic disease has led to an expanding number of studies investigating alternative checkpoint inhibitors and novel immunotherapy for this malignancy. Early trials are also supporting the notion that therapies that target biological molecules on T cells, cancer cells, or that trigger the antitumor activity of other immune cells may represent the future of MPM treatment. Moreover, mesothelin-targeted therapies are thriving in the field, with forthcoming results from multiple trials signaling an improvement in overall survival when combined with other immunotherapy agents. The following manuscript will review the current state of immune therapy for MPM, explore the knowledge gaps in the field, and discuss ongoing novel immunotherapeutic research in early clinical trials.

Objective: The stability and composition of intestinal flora plays a vital role in human wellbeing throughout life from as early as birth. Over the past 50 years, several studies have been conducted to evaluate the effect of probiotic administration in pediatric gastroenterology. This document aims to provide a recommendation score on probiotic utilization in pediatric gastroenterology, together with a review of current knowledge concerning its benefits, tolerability, and safety., Study Design: Published literature was selected without study design restriction: clinical guidelines, meta-analyses, randomized controlled trials (RCTs), cohort studies, outcomes research and case-controlled studies were selected using the following MESH-validated terms: probiotics, diarrhea, acute diarrhea, antibiotic-associated diarrhea, traveler's diarrhea, bacterial diarrhea, nosocomial diarrhea, prophylactic diarrhea, Helicobacter pylori infection, colic, infantile colic, necrotizing enterocolitis (NEC), inflammatory bowel disease, constipation, and allergy. Once the validity and the quality of results were evaluated, a recommendation score and level of evidence were assigned for pediatric gastrointestinal-related conditions, according to the updated Evidence-Based Medicine guidelines: 1a for systematic review (SR) of RCTs, 1b for individual RCT, 1c for SR and individual RCT, 2a for SR of cohort studies, 2b for individual cohort studies, 2c for outcomes research, and 3a for SR of case-control studies., Results and Conclusions: The Latin American Expert group consensus recommends the use of the following probiotics for pediatric gastrointestinal conditions: prevention of acute infectious diarrhea (AID): 1b for Bifidobacterium lactis, Lactobacillus rhamnosus GG (LGG), and L. reuteri; prevention of nosocomial diarrhea: 1 b for B. lactis Bb12, B. bifidum, LGG and Streptococcus thermophiles; treatment of AID: 1a for LGG and S. boulardii, 1b for L. reuteri; prevention of antibiotic-associated diarrhea: 1b for LGG and S. boulardii; prevention of traveler's diarrhea: 1b for S. boulardii; prevention of infantile colic: 1a for L. reuteri DSM 17938; treatment of infantile colic: 1b for L. reuteri DSM 17938; prevention of NEC: 1a for B. breve, mixtures of Bifidobacterium and Streptococcus, LGG, L. acidophilus and L. reuteri DSM 17938; induction and maintenance of remission in ulcerative colitis: 1b for VSL#3; improving symptoms of irritable bowel syndrome: 2c for LGG and VSL#3.

Purpose: Surgical retained foreign objects (RFOs) have significant morbidity and mortality. They are associated with approximately $1.5 × 10(9) annually in preventable medical costs. The detection accuracy of radiographs for RFOs is a mediocre 59%. The authors address the RFO problem with two complementary technologies: a three-dimensional (3D) gossypiboma micro tag, the μTag that improves the visibility of RFOs on radiographs, and a computer aided detection (CAD) system that detects the μTag. It is desirable for the CAD system to operate in a high specificity mode in the operating room (OR) and function as a first reader for the surgeon. This allows for fast point of care results and seamless workflow integration. The CAD system can also operate in a high sensitivity mode as a second reader for the radiologist to ensure the highest possible detection accuracy., Methods: The 3D geometry of the μTag produces a similar two dimensional (2D) depiction on radiographs regardless of its orientation in the human body and ensures accurate detection by a radiologist and the CAD. The authors created a data set of 1800 cadaver images with the 3D μTag and other common man-made surgical objects positioned randomly. A total of 1061 cadaver images contained a single μTag and the remaining 739 were without μTag. A radiologist marked the location of the μTag using an in-house developed graphical user interface. The data set was partitioned into three independent subsets: a training set, a validation set, and a test set, consisting of 540, 560, and 700 images, respectively. A CAD system with modules that included preprocessing μTag enhancement, labeling, segmentation, feature analysis, classification, and detection was developed. The CAD system was developed using the training and the validation sets., Results: On the training set, the CAD achieved 81.5% sensitivity with 0.014 false positives (FPs) per image in a high specificity mode for the surgeons in the OR and 96.1% sensitivity with 0.81 FPs per image in a high sensitivity mode for the radiologists. On the independent test set, the CAD achieved 79.5% sensitivity with 0.003 FPs per image in a high specificity mode for the surgeons and 90.2% sensitivity with 0.23 FPs per image in a high sensitivity mode for the radiologists., Conclusions: To the best of the authors' knowledge, this is the first time a 3D μTag is used to produce a recognizable, substantially similar 2D projection on radiographs regardless of orientation in space. It is the first time a CAD system is used to search for man-made objects over anatomic background. The CAD system for the μTags achieved reasonable performance in both the high specificity and the high sensitivity modes.

Background: This study evaluated operative outcomes and ergonomics for a magnetic camera (MAGS) used in conjunction with percutaneous instruments [percutaneous surgical set (PSS)] compared with single-site laparoscopic (SSL) and conventional laparoscopic (LAP) cholecystectomy techniques., Methods: Four surgical trainees each performed three porcine cholecystectomies using three randomized techniques including MAGS/PSS, SSL, and LAP. The operative outcomes, procedure-specific ratings (1-5 scale; 1 = superior), workload (1-10 scale; 1 = superior), and global impressions (1-10 scale; 10 = superior) were recorded. Comparisons used analysis of variance (ANOVA) on ranks (Kruskal-Wallis), and p values lower than 0.05 were considered significant., Results: The operative outcomes were similar except for significantly higher blood loss with SSL (16.3 ± 10.3) versus LAP (2.8 ± 1.5; p < 0.05) but not with MAGS/PSS (4.8 ± 3.8). Several inadvertent tissue-damaging events occurred with SSL but not with MAGS/PSS or LAP. The incision was significantly shorter with MAGS/PSS (29.3 ± 2.8 mm) and SSL (29.3 ± 2.5 mm) than with LAP (48.0 ± 3.6 mm; p < 0.05). Compared with SSL (3.6 ± 0.5), the procedure-specific ratings significantly favored MAGS/PSS (2.8 ± 0.4) and LAP (1.7 ± 0.2; p < 0.05). Ergonomics and technical challenges both were rated significantly inferior with SSL (4.3 ± 1.0 and 3.8 ± 0.5, respectively) versus LAP (1.5 ± 0.6 and 2.0 ± 0.8, respectively; p < 0.05) but not with MAGS/PSS (2.5 ± 1.0 and 3.0 ± 0.8, respectively). Both MAGS/PSS (4.5 ± 0.5) and SSL (4.8 ± 1.0) were associated with a significantly greater workload than LAP (2.5 ± 0.6; p < 0.05). Global impression ratings were significantly higher for LAP (8.7 ± 1.3) versus SSL (5.8 ± 2.0; p < 0.05) but not for MAGS/PSS (7.1 ± 1.8). Cosmesis was significantly better with MAGS/PSS (9.5 ± 0.6) versus LAP (6.5 ± 2.4; p < 0.05) but not with SSL (8.8 ± 1.3)., Conclusion: The MAGS/PSS technique allows better triangulation and fewer technical difficulties than SSL and better cosmesis than LAP. Further development of these devices is warranted.

The purpose of the present article was to present the series operated by a Liver Transplant Group of the interior of the State of Sao Paulo, Brazil. Sixty patients were transplanted from May 2001 to May 2007. Thirty percent of the patients had alcoholic cirrhosis. 18.3% had C virus-induced cirrhosis, 10% had C virus- and alcohol-induced cirrhosis, 6% had B virus-induced cirrhosis, 13.3% had cryptogenic cirrhosis, 8.3% autoimmune cirrhosis, 13.3% had familial amyloidotic polyneuropathy (FAP), and 13.3% had hepatocellular carcinomas. The series was divided by a chronological criterion into two periods: A (n = 42) and B (n = 18) with the latter group operated based upon the Model for End-stage Liver Disease (MELD) criterion. Sixty-nine percent were men. Age ranged from 14 to 66 years. Period A included 12% Child A: 59.2%, Child B; 24%, Child C; and 4.8%, FAP. Period B comprises 22.2% Child A: 11.1%, Child B: 33.3%, Child C: and 33.3%, FAP. MELD scores ranged from 8 to 35 for period A and from 14 to 31 for period B. Intraoperative mortality was 2/42 patients for period A and 0/18 for period B, overall postoperative mortality was 40% including for period A, 35% among Child B and C patients, and 5% among FAP and Child A patients (P < .05) and 16.6% for period B among 11.1% Child B patients and 5.5% FAP patients; 3.3% of patients required retransplantation due to hepatic artery thrombosis. Real postoperative survival was 60% during period A and 83.3% during period B, with an overall survival rate of 67% for the two periods. The present results show levels of postoperative mortality, (especially during period B), and survival rates similar to those reported by several other centers in Brazil.

The objective of the present study was to analyze hepatic mitochondrial function in patients with familial amyloidotic polyneuropathy (FAP) undergoing cadaveric donor orthotopic liver transplantation. From February 2005 to May 2007, eight patients with FAP, ranging in age from 34 to 41 years and with Model for End-Stage Liver Disease scores ranging from 24 to 29. Underwent orthotopic transplantation using a liver from a deceased donor by the piggyback method. Immediately before beginning the recipient hepatectomy in a patient with FAP, a biopsy was obtained for analysis of mitochondrial function (FAP group). The control group consisted of 15 patients undergoing hepatic surgery to treat small tumors of the liver. Mitochondrial respiration was determined on the basis of oxygen consumption by energized mitochondria using a polarographic method. The membrane potential of the mitochondria was determined spectrofluorometrically. Data were analyzed statistically by the Mann-Whitney test, with the level of significance set at 5%. State 3 and 4 values, respiratory control ratio, and membrane potential were 47 +/- 8 versus 28 +/- 10 natoms O/min/mg protein (P < .05); 14 +/- 3 vs 17 +/- 7 nat.O/min/mg.prot.mit. (P > .05); 3.6 +/- .5 vs 1.7 +/- 0.7 (P < .05); and 135 +/- 5.2 vs 135 +/- 6 mV (P > .05) for control versus FAP patients, respectively, demonstrating a decreased energy status of the liver in FAP.

Objective: Evaluation of feasibility and efficacy of left resection of the pancreas with preservation of the splenic vessels and spleen as a laparoscopic procedure., Background: Laparoscopic technique is used less often on the pancreas than on other organs. The most common indications are enucleation of endocrine-active tumors and distal resections for benign primary pancreatic lesions. An important premise of these operations is atraumatic removal of as little of the pancreas as possible and the preservation of the spleen and its main vessels., Methods: Five patients aged 16 to 56 years, all female, underwent laparoscopic left resection of the pancreas with preservation of the splenic vessels and the spleen. There were 4 cases of benign epithelial tumors of the pancreas and 1 case of a left-sided adrenal cyst, which pre- and intraoperatively gave the impression of a pancreatic cystadenoma., Results: In all 5 cases, the laparoscopic procedure was completed with preservation of the splenic vessels and the spleen itself. No patient required blood transfusion, and there was only 1 postoperative fluid collection at the site of the tumor resection, which was drained percutaneously on the fourth postoperative day., Conclusion: Distal pancreas resection can be performed as a laparoscopic procedure, with the usual advantages that this techniques has for the patient. Optimal closure of the cut edge of the pancreas and the preservation of the spleen and its main vessels are the most important aspects of this operation.