Biliary complications after adult-to-adult living-donor liver transplantation: An international multicenter study of 3633 cases.

In living-donor liver transplantation, biliary complications including bile leaks and biliary anastomotic strictures remain significant challenges, with incidences varying across different centers. This multicentric retrospective study (2016-2020) included 3633 adult patients from 18 centers and aimed to identify risk factors for these biliary complications and their impact on patient survival. Incidences of bile leaks and biliary strictures were 11.4% and 20.6%, respectively. Key risk factors for bile leaks included multiple bile duct anastomoses (odds ratio, [OR] 1.8), Roux-en-Y hepaticojejunostomy (OR, 1.4), and a history of major abdominal surgery (OR, 1.4). For biliary anastomotic strictures, risk factors were ABO incompatibility (OR, 1.4), blood loss >1 L (OR, 1.4), and previous abdominal surgery (OR, 1.7). Patients experiencing biliary complications had extended hospital stays, increased incidence of major complications, and higher comprehensive complication index scores. The impact on graft survival became evident after accounting for immortal time bias using time-dependent covariate survival analysis. Bile leaks and biliary anastomotic strictures were associated with adjusted hazard ratios of 1.7 and 1.8 for graft survival, respectively. The study underscores the importance of minimizing these risks through careful donor selection and preoperative planning, as biliary complications significantly affect graft survival, despite the availability of effective treatments.

Liberal use of veno-arterial extracorporeal membrane oxygenation in combined sequential heart-liver transplantation.

Combined heart-liver transplantation (CHLT) is a rarely though increasingly performed procedure with evolving indications. Despite CHLT being performed at only a handful of centers, the use of intraoperative mechanical circulatory support to optimize hemodynamics and facilitate dual-organ transplantation varies widely. At our center, we liberally utilize veno-arterial extracorporeal membrane oxygenation (V-A ECMO) when a veno-venous shunt is anticipated to be insufficient in mitigating the hemodynamic perturbations associated with liver reperfusion. In this series, we describe our experience with V-A ECMO in sequential (heart-first) CHLT and demonstrate highly favorable outcomes with this strategy.

Novel Benchmark for Adult-to-Adult Living-donor Liver Transplantation: Integrating Eastern and Western Experiences.

OBJECTIVE: To define benchmark values for adult-to-adult living-donor liver transplantation (LDLT). BACKGROUND: LDLT utilizes living-donor hemiliver grafts to expand the donor pool and reduce waitlist mortality. Although references have been established for donor hepatectomy, no such information exists for recipients to enable conclusive quality and comparative assessments. METHODS: Patients undergoing LDLT were analyzed in 15 high-volume centers (≥10 cases/year) from 3 continents over 5 years (2016-2020), with a minimum follow-up of 1 year. Benchmark criteria included a Model for End-stage Liver Disease ≤20, no portal vein thrombosis, no previous major abdominal surgery, no renal replacement therapy, no acute liver failure, and no intensive care unit admission. Benchmark cutoffs were derived from the 75th percentile of all centers' medians. RESULTS: Of 3636 patients, 1864 (51%) qualified as benchmark cases. Benchmark cutoffs, including posttransplant dialysis (≤4%), primary nonfunction (≤0.9%), nonanastomotic strictures (≤0.2%), graft loss (≤7.7%), and redo-liver transplantation (LT) (≤3.6%), at 1-year were below the deceased donor LT benchmarks. Bile leak (≤12.4%), hepatic artery thrombosis (≤5.1%), and Comprehensive Complication Index (CCI ® ) (≤56) were above the deceased donor LT benchmarks, whereas mortality (≤9.1%) was comparable. The right hemiliver graft, compared with the left, was associated with a lower CCI ® score (34 vs 21, P < 0.001). Preservation of the middle hepatic vein with the right hemiliver graft had no impact neither on the recipient nor on the donor outcome. Asian centers outperformed other centers with CCI ® score (21 vs 47, P < 0.001), graft loss (3.0% vs 6.5%, P = 0.002), and redo-LT rates (1.0% vs 2.5%, P = 0.029). In contrast, non-benchmark low-volume centers displayed inferior outcomes, such as bile leak (15.2%), hepatic artery thrombosis (15.2%), or redo-LT (6.5%). CONCLUSIONS: Benchmark LDLT offers a valuable alternative to reduce waitlist mortality. Exchange of expertise, public awareness, and centralization policy are, however, mandatory to achieve benchmark outcomes worldwide.

Combined heart and liver transplantation in a patient supported by left ventricular assist device (LVAD) with propionic acidemia.

Propionic acidemia (PA) is a rare inherited metabolic disease due to inborn errors of metabolism. PA results in the accumulation of abnormal organic acid metabolites in multiple systems, mainly the central nervous system and the heart. Cardiac complications include dilated cardiomyopathy (DCM) and carry a 40-50% increased mortality risk. Liver transplantation (LT) is required in PA patients when medical treatment fails and may prevent or slow down the cardiomyopathy progression. However, severe heart disease may be a serious contraindication to LT. We present a complicated case of a PA patient, supported with a Left Ventricular Assist Device, who underwent a heart and Liver transplant. PA patients are at increased risk for metabolic acidosis during surgery, with increased anion gap and hyperammonemia. A strict multi-disciplinary approach is needed to prevent and treat metabolic decompensation. The patient had a successful heart and liver transplant after a strict treatment protocol in the pre, intra, and post-operative periods. His case highlights the complexity of PA patients and the increased risk for metabolic decompensation during surgery and provides an insight into how to manage such complicated patients.

Ex Vivo Liver Resection and Autotransplantation: Should It be Used More Frequently?

OBJECTIVE: We herein advocate for more extensive utilization of ex vivo resection techniques for otherwise unresectable liver tumors by presenting the largest collective American experience. BACKGROUND: Advanced in situ resection and vascular reconstruction techniques have made R0 resection possible for otherwise unresectable liver tumors. Ex vivo liver resection may further expand the limits of resectability but remains underutilized due to concerns about technical complexity and vascular thrombosis. However, we believe that the skillset required for ex vivo liver resection is more widespread and the complications less severe than widely assumed, making ex vivo resection a more attractive option in selected case. METHODS: We retrospectively analyzed 35 cases performed by surgical teams experienced with ex vivo liver resections (at least 4 cases) between 1997 and 2021. RESULTS: We categorized malignancies as highly aggressive (n=18), moderately aggressive (n=14), and low grade (n=3). All patients underwent total hepatectomy, vascular reconstruction and resection in hypothermia on the backtable, and partial liver autotransplantation. Overall survival was 67%/39%/28%, at 1/3/5 years, respectively, with a median survival of 710 days (range: 22-4824). Patient survival for highly aggressive, moderately aggressive, and low-grade tumors was 61%/33%/23%, 67%/40%/22%, and 100%/100%/100% at 1/3/5 years, respectively, with median survival 577 days (range: 22-3873), 444 days (range: 22-4824), and 1825 days (range: 868-3549). CONCLUSIONS: Ex vivo resection utilizes techniques commonly practiced in partial liver transplantation, and we demonstrate relatively favorable outcomes in our large collective experience. Therefore, we propose that more liberal use of this technique may benefit selected patients in centers experienced with partial liver transplantation.

Ex Vivo Resection and Autotransplantation for Conventionally Unresectable Tumors - An 11-year Single Center Experience.

BACKGROUND AND AIMS: Ex vivo surgery may provide a chance at R0 resection for conventionally unresectable tumors. However, long-term outcomes have not been well documented. In this study, we analyze our 11-year outcomes to define its role. STUDY DESIGN: We retrospectively analyzed 46 consecutive patients who underwent ex vivo surgery at our institution 2008-2019. RESULTS: The types of tumors were: carcinoma (n = 20), sarcoma (n = 20) and benign to low grade tumor (n = 6). The type of ex vivo surgery was chosen based on tumor location and vascular involvement. The most commonly performed procedure was ex vivo hepatectomy (n = 18), followed by ex vivo resection and intestinal autotransplantation (n = 12), ex vivo Whipple procedure and liver autotransplantation (n = 8) and multivisceral ex vivo procedure (n = 7). Twenty-three patients (50%) are currently alive with median follow-up of 4.0-years (11 months-11.8 years). The overall survival was 70%/59%/52%, at 1-/3-/5-years, respectively. Patient survival for benign to low grade tumors, sarcoma, and carcinoma was 100%/100%/100%, 65%/60%/50%, and 65%/45%/40%, at 1-/3-/5-years, respectively. Ninety-one percent patients had R0 resection, and 57% had no recurrence to date with median follow-up of 3.1-years. Two patients (4.3%) died within 30 days due to sepsis and gastroduodenal artety (GDA) stump blowout. Two additional patients died between 30 and 90 days due to sepsis. Perioperative mortality in the last 23 consecutive cases was limited to 1 patient who died of sepsis between 30 and 90 days. CONCLUSIONS: For a selected group of patients with conventionally unresectable tumors, ex vivo surgery can offer effective surgical removal with a reasonably low perioperative mortality at experienced centers.

Trinational Study Exploring the Early Impact of the COVID-19 Pandemic on Organ Donation and Liver Transplantation at National and Unit Levels.

BACKGROUND: The coronavirus disease (COVID-19) pandemic is stressing healthcare services to an unprecedented extent. There is anecdotal evidence of reduction in organ donation and transplantation activity across the world. METHODS: The weekly organ donation and liver transplant numbers over a 3-month period (Feb 17, 2020, till May 17, 2020) for the United States, United Kingdom, and India were compared with their previous year's activity. Liver transplant activity in 6 centers from these countries with varying local COVID-19 caseload was also compared. RESULTS: The COVID-19 pandemic has led to a significant contraction in organ donation and liver transplantation in all 3 countries. Peak reduction ranged from 25% in the United States to over 80% in the United Kingdom and India. The reduction was different for deceased donor and living donor liver transplantation and varied between centers within a country. There was early evidence of recovery of deceased donation in the United States and United Kingdom and resumption of living donor liver transplantation activity in India toward the end of the study period. A number of policy changes were undertaken at national and transplant center levels to ensure safe transplantation despite significant redirection of resources to combat the pandemic. CONCLUSIONS: There was a substantial reduction in organ donation and liver transplantation activity across the 3 countries with signs of recovery toward the end of the study period. Multiple factors including COVID-19 severity, stress on resources and influence of regulatory agencies and local factors are responsible for the reduction and recovery.

Bariatric surgery prior to living donor nephrectomy: a solution to expand the living donor kidney pool - a retrospective study.

Most transplant centers decline morbidly obese people for living kidney donation. Their inclusion in the living donor pool after weight loss and reversal of comorbidities by bariatric surgery could reverse the downward living donation trend. We investigated whether bariatric surgery in the morbidly obese altered their candidacy for donation, complicated their subsequent donor nephrectomy, and impacted their early postoperative outcomes in a series of 22 donors who had bariatric surgery 0.7-22 years prior to laparoscopic living donor nephrectomy. Eighteen would have been excluded from donation prior to bariatric surgery based on a body mass index (BMI) > 40. Seventeen reached a BMI < 35 after bariatric surgery. One had hypertension that resolved after bariatric surgery. Prior bariatric surgery did not influence port placement and laterality of donor nephrectomy. None required open conversion or blood transfusion. In an exploratory comparison with 37 donors with a BMI 35-40, length of stay and warm ischemic time were shorter, blood loss and postoperative complications were similar, and operative time was longer. We therefore advocate the consideration of bariatric surgery in preparation for donation in morbidly obese people since it positively alters their candidacy without major impact on the subsequent living donor nephrectomy and early outcomes.

Synthesis and evaluation of antimicrobial, antitubercular and anticancer activities of 2-(1-benzoyl-1H-benzo[d]imidazol-2-ylthio)-N-substituted acetamides.

BACKGROUND: The study describes the synthesis, characterization, in vitro antimicrobial and anticancer evaluation of a series of 2-(1-benzoyl-1H-benzo[d]imidazol-2-ylthio)-N-substituted acetamide derivatives. The synthesized derivatives were also assessed for in vitro antitubercular activity against Mycobacterium tuberculosis H37Rv. The compounds found active in in vitro study were assessed for their in vivo antitubercular activity in mice models and for their inhibitory action on vital mycobacterial enzymes viz, isocitrate lyase, pantothenate synthetase and chorismate mutase. RESULTS: Compounds 8, 9 and 11 emerged out as excellent antimicrobial agents in antimicrobial assays when compared to standard antibacterial and antifungal drugs. The results of anticancer activity displayed that majority of the derivatives were less cytotoxic than standard drugs (tamoxifen and 5-fluorouracil) towards MCF7 and HCT116 cell lines. However, compound 2 (IC50 = 0.0047 µM/ml) and compound 10 (IC50 = 0.0058 µM/ml) showed highest cytotoxicity against MCF7 and HCT116 cell lines, respectively. The results of in vivo antitubercular activity revealed that a dose of 1.34 mg/kg was found to be safe for the synthesized compounds. The toxic dose of the compounds was 5.67 mg/kg while lethal dose varied from 1.81 to 3.17 mg/kg body weight of the mice. Compound 18 inhibited all the three mycobacterial enzymes to the highest level in comparison to the other synthesized derivatives but showed lesser inhibition as compared to streptomycin sulphate. CONCLUSIONS: A further research on most active synthesized compounds as lead molecules may result in discovery of novel anticancer and antitubercular agents.

Impact of IgG2 high molecular weight species on neonatal Fc receptor binding assays.

A cell-based assay and a solution neonatal Fc receptor (FcRn) binding assay were implemented for the characterization of an IgG2 antibody after observation that different product lots exhibited unexpected differences in FcRn binding in the cell-based format with membrane-bound FcRn. The experiments described here suggest that the apparent differences observed in the FcRn binding across different product lots in the cell-based format can be attributed to the different levels of the higher order high molecular weight species (HMWs) in them. A strong correlation between FcRn binding in the cell-based format and the percentage (%) higher order HMWs suggests that small amounts (∼0.1%) of the latter could cause the enhanced apparent FcRn binding (% relative binding ranging from 50 to 100%) in the format. However, when the binding was assessed with recombinant FcRn in soluble form, avidity effects were minimal and the assay format exhibited less sensitivity toward the differences in higher order HMWs levels across product lots. In conclusion, a solution-based assay may be a more appropriate assay to assess FcRn binding of the dominant species of an Fc-fusion protein or monoclonal antibody if minor differences in product variants such as higher order HMWs are shown to affect the binding significantly.

Increasing body mass index portends abbreviated survival following pancreatoduodenectomy for pancreatic adenocarcinoma.

BACKGROUND: Body mass index (BMI), a common surrogate marker for grading obesity, does not differentiate between metabolically active visceral fat and the relatively inert subcutaneous fat. We aim to determine the utility of BMI as a prognostic marker for the impact of obesity on outcomes and survival following pancreatoduodenectomy for pancreatic adenocarcinoma. METHODS: From a database of over 1,000 patients who had undergone pancreatoduodenectomy, 228 patients with a diagnosis of pancreatic adenocarcinoma were identified. Demographic data including BMI and perioperative parameters-operative time, estimated blood loss, length of stay, survival, nodal status, and American Joint Committee on Cancer stage-were obtained. Data are presented as median. RESULTS: One hundred ninety-two patients had a BMI less than or equal to 29 and 36 patients had a BMI greater than or equal to 30 (24 vs. 34, P < .001). Median age was 70 and the majority of the patients (52%) were male and the 2 groups of patients did not differ in this regard. A significantly greater number of obese patients had positive nodes (69% vs. 62%, P < .05) and this was associated with a worse survival (14 vs. 18 months, P < .05). CONCLUSIONS: For patients with pancreatic adenocarcinoma undergoing pancreatoduodenectomy, obesity does not impact operative complexity or length of stay but results in a shortened survival. Therefore, we conclude that BMI is an important prognostic marker that portends an abbreviated survival following pancreatoduodenectomy for pancreatic adenocarcinoma.

Margin status impacts survival after pancreaticoduodenectomy but negative margins should not be pursued.

Negative margins are the goal with pancreaticoduodenectomy for pancreatic adenocarcinoma. Thereby, margins are assessed intraoperatively with frozen section analysis and negative margins are pursued. This study was undertaken to determine the impact of margin status with pancreaticoduodenectomy for pancreatic adenocarcinoma and the value of extending resections to achieve negative margins. The intraoperative frozen section analysis and final margins for 448 patients undergoing pancreaticoduodenectomy for pancreatic adenocarcinoma were assessed and their impact on survival was determined. Median data are presented. Two hundred ninety-eight (67%) patients had negative margins (R0), an additional 110 (25%) patients had microscopically positive and macroscopically negative margins (R1), and an additional 40 (9%) patients had initially positive microscopic margins, which became negative with further resection (R1 → R0). R0 resections were more likely to have smaller tumors, earlier T grade, earlier N grade, lower American Joint Committee on Cancer stage, and less frequent extrapancreatic extension (P ≤ 0.03 for each). Survival was better with R0 resections than R1 resections (20 vs 12 months, P < 0.001); extending resections to achieve negative margins (i.e., R1 → R0) did not improve survival beyond R1 resections (14 vs 12 months, P = 0.19). Survival after pancreaticoduodenectomy is disappointing. Patients with initial negative margins do best. Positive microscopic margins reflect more aggressive tumor-specific factors and lead to abbreviated survival even with extended resections to achieve negative margins (i.e., R1 → R0). With an initial positive margin, pursuing negative margins does not improve survival and, thereby, negative margins should not be "chased."

Comparison of Markers and Functional Attributes of Human Adipose-Derived Stem Cells and Dedifferentiated Adipocyte Cells from Subcutaneous Fat of an Obese Diabetic Donor.

Objective: Adipose tissue is a robust source of adipose-derived stem cells (ADSCs) that may be able to provide secreted factors that promote the ability of wounded tissue to heal. However, adipocytes also have the potential to dedifferentiate in culture to cells with stem cell-like properties that may improve their behavior and functionality for certain applications. Approach: ADSCs are adult mesenchymal stem cells that are cultured from the stromal vascular fraction of adipose tissue. However, adipocytes are capable of dedifferentiating into cells with stem cell properties. In this case study, we compare ADSC and dedifferentiated fat (DFAT) cells from the same patient and fat depot for mesenchymal cell markers, embryonic stem cell markers, ability to differentiate to adipocytes and osteoblasts, senescence and telomerase levels, and ability of conditioned media (CM) to stimulate migration of human dermal fibroblasts (HDFs). Innovation and Conclusions: ADSCs and DFAT cells displayed identical levels of CD90, CD44, CD105, and were CD34- and CD45-negative. They also expressed similar levels of Oct4, BMI1, KLF4, and SALL4. DFAT cells, however, showed higher efficiency in adipogenic and osteogenic capacity. Telomerase levels of DFAT cells were double those of ADSCs, and senescence declined in DFAT cells. CM from both cell types altered the migration of fibroblasts. Despite reports of ADSCs from a number of human depots, there have been no comparisons of the ability of dedifferentiated DFAT cells from the same donor and depot to differentiate or modulate migration of HDFs. Since ADSCs were from an obese diabetic donor, reprogramming of DFAT cells may help improve a patient's cells for regenerative medicine applications.

Transduodenal ampullectomy for ampullary adenomas: a safe and effective procedure with long-term salutary outcomes.

With widespread use of endoscopy, ampullary adenomas are more frequently identified, many of which are not amenable to endoscopic resection. Pancreatoduodenctomy is curative for these lesions but carries high morbidity. The purpose of this study was to determine the safety and efficacy of transduodenal ampullectomy for these lesions. Data were collected on 32 patients who underwent transduodenal ampullectomy from 2002 to 2010. The median age of patients was 64 years. Adenomas were found because of abdominal pain in 34 per cent, jaundice in 22 per cent, and incidentally on endoscopic screening in 16 per cent and on computed tomography scan of the abdomen in 9 per cent. All patients had a preoperative diagnosis of premalignant disease; 6 per cent required intraoperative conversion to pancreaticoduodenectomy after frozen section evaluation documented carcinoma. Of ampullectomies, 97 per cent had clear margins. Follow-up was 28 months. Four (13%) patients developed recurrent disease at 4 years, 2 years, 1.5 years, and 4 months; all had clear margins at ampullectomy and underwent subsequent pancreaticoduodenectomy with invasive malignancy in a single patient. After preoperative biopsy documenting premalignant disease, malignancy at ampullectomy is unusual. Recurrence is uncommon but occurs even with clear margins necessitating diligent follow-up; even with diligent follow-up, recurrence can be malignant.

Obesity portends increased morbidity and earlier recurrence following liver transplantation for hepatocellular carcinoma.

BACKGROUND: Obesity has been associated with poor oncologic outcomes following pancreatoduodenectomy for pancreatic cancer. However, there is a paucity of evidence on the impact of obesity on postoperative complications, oncologic outcome and survival in patients with hepatocellular carcinoma (HCC) undergoing orthotopic liver transplantation (OLT). METHODS: From a database of over 1000 patients who underwent OLT during 1996-2008, 159 patients with a diagnosis of HCC were identified. Demographic data, body mass index (BMI), perioperative parameters, recurrence and survival were obtained. Complications were grouped according to Clavien-Dindo grading (Grades I-V). RESULTS: There were increased incidences of life-threatening complications in overweight (58%) and obese (70%) patients compared with the non-obese patient group (41%) (P < 0.05). Furthermore, the incidence of recurrence of HCC was doubled in the presence of overweight (15%) and obesity (15%) compared with non-obesity (7%) (P < 0.05). Time to recurrence also decreased significantly. Differences in mean ± standard deviation survival in the overweight (45 ± 3 months) and obese (41 ± 4 months) groups compared with the non-obese group (58 ± 6 months) did not reach statistical significance. CONCLUSIONS: These findings indicate that BMI is an important surrogate marker for obesity and portends an increased risk for complications and a poorer oncologic outcome following OLT for HCC.

Qualification of a homogeneous cell-based neonatal Fc receptor (FcRn) binding assay and its application to studies on Fc functionality of IgG-based therapeutics.

The Fc region of IgG-based molecules plays an important role in determining their in vivo pharmacokinetic profile by its pH-dependent binding to the neonatal Fc receptor (FcRn) which is expressed on the endothelial cells lining blood vessels. By virtue of this pH-specific interaction with IgG-Fc, FcRn mediates IgG homeostasis in human adults by maintaining serum IgG levels, and also transfers maternal IgGs from mother to fetus via the placenta. The Fc-FcRn interaction is also critical for keeping IgG-based therapeutic molecules in circulation thereby enhancing their serum half life. A homogeneous cell-based flow cytometric FcRn binding assay was established to characterize the Fc-FcRn interaction of therapeutic IgG-based molecules. It is a competition-based assay, wherein the IgG-Fc containing test molecule competes with a fixed concentration of fluorescently-labeled IgG-Fc moiety in solution for binding to the cell-expressed FcRn. The cell-bound fluorescence is read on a flow cytometer. Response of the test sample is analyzed relative to the standard sample and the results are reported as % relative binding. The assay is robust and meets the qualification criteria for specificity, method linearity, accuracy and precision over the relative binding range of 60%-160%. This assay was shown to effectively characterize altered Fc-FcRn interactions for photo-stressed, heat-stressed, oxidized, and Fc mutant samples. It was observed that the relative binding of the IgG-Fc to the cell-surface-expressed FcRn in the assay varies across different molecules, even within the same IgG subclass. This indicates that the Fc-FcRn binding can be influenced by the antigen-binding region of the molecules in addition to the IgG subclass. Overall, this assay is reflective of the in vivo mechanism of immunoglobulin binding to membrane-bound FcRn, and can be used as an analytical tool for assessing lot-to-lot consistency and stability testing across different batches of the same molecule. Additionally, the assay can be used as an effective tool for elucidating the amino acids in the IgG-Fc domain that are critical for FcRn binding and also for comparing the binding of different IgG-Fc containing molecules to FcRn.

Dysregulated Alternative Splicing Pattern of PKCδ during Differentiation of Human Preadipocytes Represents Distinct Differences between Lean and Obese Adipocytes.

Obesity and its comorbidities affect millions of people. Here, we demonstrate that human preadipocytes are susceptible to programmed cell death (apoptosis) while mature adipocytes are resistant to apoptosis. The molecular mechanisms underlying the phenotype of apoptosis-resistant adipocytes are lesser known. To study the role of apoptosis and define molecular differences in the developmental process of adipogenesis, human preadipocytes were differentiated in vitro to mature adipocytes. Many genes in the apoptosis pathway are alternatively spliced. Our data demonstrates that during differentiation PKC δ , Bclx, and Caspase9 switch to their prosurvival splice variants along with an increase in Bcl2 expression when the cells terminally differentiate into mature adipocytes. Next we determined the expression pattern of these genes in obesity. Our data indicated high expression of PKC δ VIII in adipose tissue of obese patient in different depots. We demonstrate a shift in the in vitro expression of these splice variants in differentiating preadipocytes derived from obese patients along with a decrease in adipogenesis markers. Hence, the programmed splicing of antiapoptotic proteins is a pivotal switch in differentiation that commits adipocytes to a prosurvival pathway. The expression pattern of these genes is dysregulated in obesity and may contribute to adipose tissue dysfunction.

The perforated appendiceal carcinoid in children: a surgical dilemma.

The decision for aggressive reoperation after discovery of an appendiceal carcinoid is generally based upon criteria such as size, grade, degree of involvement of the mesoappendix or the appendiceal base, lymphovascular invasion, and the presence of goblet cell or adenocarcinoid features. No guidelines currently exist for the management of perforated appendiceal carcinoids. We present a case of perforated appendiceal carcinoid that was subsequently treated with right hemicolectomy, and we review the pertinent literature.