Leveraging real-world data to predict cancer cachexia stage, quality of life, and survival in a racially and ethnically diverse multi-institutional cohort of treatment-naïve patients with pancreatic ductal adenocarcinoma.

Introduction: Cancer-associated cachexia (CC) is a progressive syndrome characterized by unintentional weight loss, muscle atrophy, fatigue, and poor outcomes that affects most patients with pancreatic ductal adenocarcinoma (PDAC). The ability to identify and classify CC stage along its continuum early in the disease process is challenging but critical for management. Objectives: The main objective of this study was to determine the prevalence of CC stage overall and by sex and race and ethnicity among treatment-naïve PDAC cases using clinical, nutritional, and functional criteria. Secondary objectives included identifying the prevalence and predictors of higher symptom burden, supportive care needs, and quality of life (QoL), and examining their influence on overall survival (OS). Materials and methods: A population-based multi-institutional prospective cohort study of patients with PDAC was conducted between 2018 and 2021 by the Florida Pancreas Collaborative. Leveraging patient-reported data and laboratory values, participants were classified at baseline into four stages [non-cachexia (NCa), pre-cachexia (PCa), cachexia (Ca), and refractory cachexia (RCa)]. Multivariate regression, Kaplan Meier analyses, and Cox regression were conducted to evaluate associations. Results: CC stage was estimated for 309 PDAC cases (156 females, 153 males). The overall prevalence of NCa, PCa, Ca, and RCa was 12.9%, 24.6%, 54.1%, and 8.4%, respectively. CC prevalence across all CC stages was highest for males and racial and ethnic minorities. Criteria differentiated NCa cases from other groups, but did not distinguish PCa from Ca. The most frequently reported symptoms included weight loss, fatigue, pain, anxiety, and depression, with pain significantly worsening over time. The greatest supportive care needs included emotional and physical domains. Males, Black people, and those with RCa had the worst OS. Conclusions: Using clinical, nutritional, and functional criteria, nearly one-quarter of the PDAC cases in our diverse, multi-institutional cohort had PCa and 62.5% had Ca or RCa at the time of diagnosis. The PCa estimate is higher than that reported in prior studies. We recommend these criteria be used to aid in CC classification, monitoring, and management of all incident PDAC cases. Findings also highlight the recommendation for continued emotional support, assistance in alleviating pain, and supportive care needs throughout the PDAC treatment journey.

Management of SHDB positive patient with metastatic bilateral giant retroperitoneal paragangliomas.

Paragangliomas are rare neuroendocrine tumors that can vary in size and metabolic activity. We report a case of giant bilateral malignant retroperitoneal paragangliomas (PGL) in a patient with germline succinate dehydrogenase B (SDHB) mutation. This patient, who presented in an emaciated and debilitated state, was managed with adrenergic blockade followed by radical primary surgery. After being metabolically and radiographically disease free for 4 years, he underwent salvage resection for recurrent retroperitoneal disease and palliative radiation to a site of solidary vertebral metastasis. We review incidence and prognosis of metastatic PGL.

The Florida Pancreas Collaborative Next-Generation Biobank: Infrastructure to Reduce Disparities and Improve Survival for a Diverse Cohort of Patients with Pancreatic Cancer.

Background: Well-annotated, high-quality biorepositories provide a valuable platform to support translational research. However, most biorepositories have poor representation of minority groups, limiting the ability to address health disparities. Methods: We describe the establishment of the Florida Pancreas Collaborative (FPC), the first state-wide prospective cohort study and biorepository designed to address the higher burden of pancreatic cancer (PaCa) in African Americans (AA) compared to Non-Hispanic Whites (NHW) and Hispanic/Latinx (H/L). We provide an overview of stakeholders; study eligibility and design; recruitment strategies; standard operating procedures to collect, process, store, and transfer biospecimens, medical images, and data; our cloud-based data management platform; and progress regarding recruitment and biobanking. Results: The FPC consists of multidisciplinary teams from fifteen Florida medical institutions. From March 2019 through August 2020, 350 patients were assessed for eligibility, 323 met inclusion/exclusion criteria, and 305 (94%) enrolled, including 228 NHW, 30 AA, and 47 H/L, with 94%, 100%, and 94% participation rates, respectively. A high percentage of participants have donated blood (87%), pancreatic tumor tissue (41%), computed tomography scans (76%), and questionnaires (62%). Conclusions: This biorepository addresses a critical gap in PaCa research and has potential to advance translational studies intended to minimize disparities and reduce PaCa-related morbidity and mortality.

Obesity affects outcomes of pancreatoduodenectomy.

BACKGROUND: Obesity is a major global health problem, and it has reached epidemic proportions worldwide. Therefore, surgeons will confront an increasingly larger proportion of obese candidates for pancreatoduodenectomy (PD) in the future. Several small retrospective studies have been conducted to evaluate the role of Body Mass Index (BMI) in postoperative surgical complications after PD, with conflicting results. The aim of this study was to use a large multi-institutional database to clarify the impact of different levels of obesity after PD. METHODS: The American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database was queried for patients who underwent PD from 2014 to 2016. Patients were categorized in the following six BMI groups: <18.5 (Underweight), 18.5-24.9 (Normal Weight), 25-29.9 (Overweight), 30-34.9 (Class I obesity), 35-39.9 (Class II Obesity) and >40 (Class III Obesity). The primary outcomes of interest were 30-day mortality and morbidity after PD among the six BMI groups. RESULTS: The final population consists of 10,316 patients. Class III is associated with higher risk of 30-day mortality (OR 2.56, 95% CI 1.25-5.25, p = 0.011), major complications (OR 2.23, 95% CI 1.54-3.22, p < 0.001), clinically relevant postoperative pancreatic fistula (OR 2.48, 95% CI 1.89-3.24, p < 0.001), surgical site infections (OR 2.06, 95% CI 1.61-2.65, p < 0.001) and wound dehiscence (OR 3.47, 95% CI 1.7-7.1, p < 0.001) in multivariable analysis. CONCLUSIONS: In conclusion, our study shows that obesity is significantly associated with higher risk of postoperative complications in patients undergoing PD and patients with BMI≥40 have increased risk of mortality after PD.

Modified frailty index predicts complications and death after non-bariatric gastrectomies.

BACKGROUND: The modified frailty index (mFI) has been shown to predict mortality and morbidity after major operations. The aim of the present study was to assess the mFI as a preoperative predictor of short-term postoperative complications and 30-day mortality in patients undergoing gastrectomy for non-bariatric diseases. METHODS: The American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database was queried for patients who underwent total or partial gastrectomy from 2005 to 2011. A mFI was calculated based on 11 variables as previously described. The population divided into the following four categories based on the mFI score: the non-frail (mFI 0), the low frail (mFI 1), the intermediate frail (mFI 2) and frail (mFI ≥3). Thirty-day mortality and postoperative complications were evaluated. RESULTS: Overall, 5,711 patients underwent a gastrectomy for non-bariatric diseases. Higher mFI score was associated with higher rates of mortality (from 1.2% in the non-frail group to 10.7% in frail group, P<0.001), overall morbidity (26.7% vs. 51.1%, P<0.001), postoperative Clavien IV complication (6% vs. 24.6%, P<0.001), serious complications (19.3% vs. 42.6%, P<0.001), sepsis-related complications (8.4% vs. 16.4%, P<0.001), cardiopulmonary complications (5% vs. 20.7%, P<0.001) and failure to rescue (5.7% vs. 21.8%, P<0.001). CONCLUSIONS: Higher mFI score in patients undergoing non-bariatric gastrectomy, is associated with a stepwise greater risk of postoperative morbidity and mortality. MFI Score can be easily calculated preoperatively, from the patient's history, and it can be used as an exceptionally useful criterion for treatment planning.

Perioperative Outcomes Following Combined Versus Isolated Colorectal and Liver Resections: Insights From a Contemporary, National, Propensity Score-Based Analysis.

Our objective was to compare outcomes following combined versus isolated resections for metastatic colorectal cancer and/or liver metastases using a large, contemporary national database. Background: Controversy persists regarding optimal timing of resections in patients with synchronous colorectal liver metastases. Methods: We analyzed 11,814 patients with disseminated colorectal cancer and/or liver metastases who underwent isolated colon, rectal, or liver resections (CRs, RRs, or LRs) or combined colon/liver or rectal/liver resections (CCLRs or CRLRs) in the National Surgical Quality Improvement Program Participant Use File (2011-2015). We examined associations between resection type and outcomes using univariate/multivariate analyses and used propensity adjustment to account for nonrandom receipt of isolated versus combined resections. Results: Two thousand four hundred thirty-seven (20.6%); 2108 (17.8%); and 6243 (52.8%) patients underwent isolated CR, RR, or LR; 557 (4.7%) and 469 (4.0%) underwent CCLR or CRLR. Three thousand three hundred ninety-five patients (28.7%) had serious complications (SCs). One hundred forty patients (1.2%) died, of which 113 (80.7%) were failure to rescue (FTR). One thousand three hundred eighty-six (11.7%) patients experienced unplanned readmission. After propensity adjustment and controlling for procedural complexity, wound class, and operation year, CCLR/CRLR was independently associated with increased risk of SC, as well as readmission (compared with LR). CCLR was also independently associated with increased risk of FTR and death (compared with LR). Conclusions: Combined resection uniformly confers increased risk of SC and increased risk of mortality after CCLR; addition of colorectal to LR increases risk of readmission. Combined resections are less safe, and potentially more costly, than isolated resections. Effective strategies to prevent SC after combined resections are warranted.

Frailty Predicts Morbidity and Mortality After Laparoscopic Cholecystectomy for Acute Cholecystitis: An ACS-NSQIP Cohort Analysis.

BACKGROUND: Current guidelines recommend laparoscopic cholecystectomy be offered for patients with acute cholecystitis except those deemed as high risk. Few studies have examined the impact of frailty on outcomes for patients undergoing laparoscopic cholecystectomy. Therefore, the aim of this study was to determine the association of frailty with postoperative morbidity and mortality in patients undergoing laparoscopic cholecystectomy for acute cholecystitis. METHODS: Patients undergoing laparoscopic cholecystectomy for acute cholecystectomy were identified from 2005 to 2010 in the American College of Surgeons National Surgical Quality Improvement Project (NSQIP). The Modified Frailty Index (mFI) was used a surrogate for frailty, and patients were stratified as non-frail (mFI 0), low frailty (mFI 1-2), intermediate frailty (mFI 3-4) and high frailty (mFI ≥ 5). Univariable and multivariable analyses were performed. Receiver operator curves (ROC) and an area under the curve (AUC) were generated to determine accuracy of mFI in predicting postoperative morbidity and mortality. RESULTS: Of the 6898 patients undergoing laparoscopic cholecystectomy, 3245 (47%) patients were non-frail. There were 2913 (42%) patients with low-frailty, 649 (9%) patients with intermediate frailty, and 91 (2%) with high frailty. Clavien IV complications were higher for intermediate frail patients (OR 1.81, 95% CI 1.00-3.28, p = 0.050) and high-frail patients (OR 4.59, 95% CI 1.98-10.7, p < 0.001). Additionally, mortality was higher for patients with intermediate frailty (OR 4.69, 95% CI 1.37-16.0, p = 0.014) and high frailty (OR 12.2, 95% CI 2.67-55.5, p = 0.001). The mFI had excellent accuracy for mortality (AUC = 0.83) and Clavien IV complications (AUC = 0.73). CONCLUSION: Frailty is associated with postoperative morbidity and mortality in patients undergoing laparoscopic cholecystectomy for acute cholecystitis.

Early drain removal after hepatectomy: an underutilized management strategy.

BACKGROUND: Recent data suggest that routine drainage is unnecessary in patients undergoing hepatectomy, but many surgeons continue to utilize drains. We compared the outcomes of patients undergoing early versus routine drain removal after hepatectomy. METHODS: Patients having drains placed during major (≥3 segments) or partial hepatectomy (≤2 segments) were identified in the 2014-16 ACS-NSQIP database. Propensity matching between early (POD 0-3) and routine (POD 4-7) drain removal and multivariable regressions were performed. RESULTS: Early drain removal was performed in 661 (40%) of patients undergoing a partial hepatectomy and 211 (22%) of major hepatectomy patients. After matching, 719 early and 719 routine drain removal patients were compared. Early drain removal patients had lower overall (12 vs 19%, p < 0.001) and serious (9 vs 13%, p < 0.03) morbidity as well as fewer bile leaks (2.1% vs 5.0%, p < 0.003). Length of stay was two days shorter (4 vs 6 days, p < 0.01) and readmissions were less frequent (5.4 vs 8.1%, p = 0.02) for patients undergoing early drain removal. CONCLUSION: Early drain removal is associated with fewer overall and serious complications, shorter length of stay and fewer readmissions. Early drain removal after hepatectomy is an underutilized management strategy.

Hepatopancreatoduodenectomy in North America: are the outcomes acceptable?

BACKGROUND: Hepatopancreatoduodenectomies (HPD) are historically associated with high morbidity and mortality. Currently, no data with hepatopancreatobiliary-specific complications have been available for HPD in North America. The aim of this retrospective analysis was to compare the outcomes of HPD to those of major hepatectomy (MH) and pancreatoduodenectomy (PD) in North America. METHODS: The 2014-16 American College of Surgeons-National Surgical Quality Improvement Program database was queried for MH, PD, and HPD. Partial hepatectomies, wedge liver biopsies, distal pancreatectomies, pancreatic enucleations and total pancreatectomies were excluded. Propensity score matching was utilized to match 23 HPDs to 92 MHs and 138 PDs by 28 demographic, comorbidity, laboratory, operative and pathologic variables. Outcomes were compared among these three groups. RESULTS: The overall morbidity and mortality for HPD were 87% and 26%, respectively, and were significantly higher (p < 0.01) compared to both MH (51%, 7.6%) and PD (52%, 1.4%). Post-hepatectomy liver failure (PHLF) was more common (p < 0.01) in HPD patients, but pancreatic fistula rates were similar. CONCLUSION: The morbidity and mortality after HPD are significantly higher than after MH or PD alone and may explain why HPD is performed so infrequently in North America. Centralization of HPD to a very few centers may be a strategy to improve outcomes.

Guidelines Insights: Hepatobiliary Cancers, Version 2.2019.

The NCCN Guidelines for Hepatobiliary Cancers provide treatment recommendations for cancers of the liver, gallbladder, and bile ducts. The NCCN Hepatobiliary Cancers Panel meets at least annually to review comments from reviewers within their institutions, examine relevant new data from publications and abstracts, and reevaluate and update their recommendations. These NCCN Guidelines Insights summarize the panel's discussion and updated recommendations regarding systemic therapy for first-line and subsequent-line treatment of patients with hepatocellular carcinoma.

The Utility of Preoperative Vascular Grading in Patients Undergoing Surgery First for Pancreatic Cancer: Does Radiologic Arterial or Venous Involvement Predict Pathologic Margin Status?

Controversy exists on accurately grading vascular involvement on preoperative imaging for pancreatic ductal adenocarcinoma. We reviewed the association between preoperative imaging and margin status in 137 patients. Radiologists graded venous involvement based on the Ishikawa classification system and arterial involvement based on preoperative imaging. For patients with both classifications recorded, we categorized vascular involvement as "None," "Arterial only," "Venous only," or "Both" and examined the association of vascular involvement and pathologic margin status. Of 134 patients with Ishikawa classifications, 63%, 17%, 11%, and 9% were graded as I, II, III, and IV, respectively. Of 96 patients with arterial staging, 74%, 16%, and 10% were categorized as stages i, ii, and iii, respectively. Of 93 patients with both stagings, 61% had no vascular involvement, 7% had arterial only, 14% had venous only, and 17% had both involved. Ishikawa classification was strongly associated with a positive SMA and SMV margin (p<0.001). However, for arterial staging, there was no association with SMA or SMV margin. Overall, Ishikawa grading was more predicative of arterial involvement and remained significant on multivariate analysis. The use of diagnostic imaging in predicting positive margins is more accurate when using a venous grading system.

Concurrent chemoradiation for resected gall bladder cancers and cholangiocarcinomas.

BACKGROUND: Gallbladder cancer (GBC) and cholangiocarcinoma (CCA) are rare entities with relatively poor prognoses. We compared treatment outcomes of definitive resection with or without neoadjuvant therapy in GBC and CCA patients. METHODS: All non-metastatic GBC and CCA patients at a single institution who underwent definitive resection from 1992-2016 were analyzed. We compared overall survival (OS), locoregional failure (LRF) and distant failure (DF) in patients who received neoadjuvant therapy (chemotherapy and/or radiation) versus those who did not receive neoadjuvant treatment. OS was analyzed using the Kaplan-Meier method and log rank tests. Cox proportional hazard models were used to analyze time to recurrence. RESULTS: Out of 128 patients, 90 had GBC and 38 had CCA, 25 patients (27%) among GBC and 8 patients (21%) with CCA were T3, T4 or node positive. Overall, 52 (40%) GBC and 25 (20%) CCA patients received neoadjuvant treatment, chemotherapy alone 60 patients (47%) or radiation with or without chemotherapy 17 patients (13%). Chemotherapy was single agent in 44 patients (34%) and multi-agent in 25 (20%). The median OS for GBC patients was 3.1 years with 2.6 years for no neoadjuvant group and 3.1 years for neoadjuvant group (P=0.6786). Median OS was 2.6 years for CCA patients, 3.6 years for no neoadjuvant therapy versus 2.0 years for neoadjuvant group (P=0.1613). There was a trend towards increased DF in patients with CCA and GBC receiving neoadjuvant therapy: HR 2.74, 95% CI, 0.73-10.3, P=0.14 and 0.92, 95% CI, 0.44-1.93, P=0.82 respectively. The hazard ratio for time to LRF in CCA patients receiving neoadjuvant treatment was 3.17, 95% CI, 0.62-16.31, P=0.16 whereas HR was 0.15, 95% CI, 0.10-1.76, P=0.23 for GBC patients. Among GBC patients, the pattern of first failure was locoregional in 8 (10%) having 3 LRF in neoadjuvant group (2 with chemotherapy, 1 with CRT, 0 with RT alone) as compared to 5 in adjuvant group. Among 28 (35%) patients with DF first, 15 patients received neoadjuvant therapy versus 13 patients in non-neoadjuvant group. In CCA patients, LRF occurred first in 6 patients receiving neoadjuvant treatment (3 with chemotherapy, 1 with CRT, 2 with RT alone) as compared to 2 patients who were treated with non-neoadjuvant CRT. DF was the first site of failure in 9 patients treated with neoadjuvant CRT (8 with chemotherapy, 0 with CRT and 1 with RT alone) as compared to 4 patients without neoadjuvant treatment. CONCLUSIONS: In this retrospective data set, a trend towards better survival was seen in adjuvantly treated CCA patients, but not in GBC patients. Recurrence patterns also appear different among the two, which might be attributed to treatment modality used, patient selection or unmeasured factors. KEYWORDS: Gallbladder cancer (GBC); cholangiocarcinoma (CCA); neoadjuvant; resection; chemoradiation; chemotherapy.

Evaluation and management of intrahepatic and extrahepatic cholangiocarcinoma.

Cholangiocarcinomas are rare biliary tract tumors that are often challenging to diagnose and treat. Cholangiocarcinomas are generally categorized as intrahepatic or extrahepatic depending on their anatomic location. The majority of patients with cholangiocarcinoma do not have any of the known or suspected risk factors and present with advanced disease. The optimal evaluation and management of patients with cholangiocarcinoma requires thoughtful integration of clinical information, imaging studies, cytology and/or histology, as well as prompt multidisciplinary evaluation. The current review focuses on recent advances in the diagnosis and treatment of patients with cholangiocarcinoma and, in particular, on the role of endoscopy, surgery, transplantation, radiotherapy, systemic therapy, and liver-directed therapies in the curative or palliative treatment of these individuals. Cancer 2016;122:1349-1369. © 2016 American Cancer Society.

Surgical management of pancreatic neoplasms: what's new?

Pancreatic cancer is the fourth leading cause of cancer deaths in the USA. Although some patients will present with premalignant pancreatic lesions (i.e., intraductal papillary mucinous neoplasms) or localized tumors amenable to curative resection, the majority of patients will unfortunately present with technically unresectable or metastatic disease. This review of the recent medical literature will discuss the optimal work-up and management of premalignant pancreatic lesions and the surgical management of localized, borderline resectable, and locally advanced (i.e., unresectable) pancreatic tumors. It will focus on new criteria used to define surgical "resectability," the significance and clinical impact of surgical margins, the role of multimodality therapy in the management of patients with borderline resectable or locally advanced tumors, the role of surgery for local or distant recurrence, and minimally invasive surgical approaches.

Do postliver transplant patients need thromboprophylactic anticoagulation?

Postoperative thromboprophylactic anticoagulation against Deep Vein Thrombosis (DVT) and Pulmonary Embolism (PE) is standard of care with current evidence-based guidelines. However, majority of liver transplant (LT) patients have thrombocytopenia and/or prolonged INR before surgery. Studies or guidelines regarding role of prophylactic anticoagulation after LT are lacking. There is a need to balance the risk of thrombosis with significant hemorrhage, implying those needing transfusion or return to OR due to bleeding. We conclude that after LT, anticoagulation is not required routinely for DVT/PE prophylaxis. Rather, it is indicated in specific circumstances, chiefly for prophylaxis of hepatic artery thrombosis or portal vein thrombosis in cases with use of grafts, pediatric cases, small size vessels, Budd Chiari syndrome, amongst others.

Impact of Donor Specific HLA Antibody Monitoring After Kidney Transplantation.

Kidney transplantation (KT) recipients with donor specific HLA antibodies (DSA) encounter higher rates of acute rejection and inferior allograft survival. We report our single center experience with prospective DSA monitoring and provide details of treatments utilized to overcome the potential impact of DSA in a cohort of predominantly African American adult KT recipients. Seventy-five flow crossmatch negative KT recipients underwent periodic screening for DSA utilizing the single antigen bead assay at 3, 6, 9, and 12 months post-transplant. Allograft biopsies were performed in the presence of DSA and/or evidence of graft dysfunction. The incidence of DSA was 23%, with a predominance of Class II antibodies. The rate of rejection was 6 times higher in DSA positive KT recipients compared to DSA negative patients (41% versus 7%, p = 0.004). In the DSA positive group, rejections occurred exclusively in the presence of de novo DSA and were predominantly antibody-mediated or mixed rejections. Despite a higher incidence of rejection in KT recipients with DSA, there were no significant differences in serum creatinine, graft survival, and patient survival between DSA positive and negative recipients at median follow-up of 18 months. DSA positive patients had significantly higher proteinuria compared to DSA negative recipients at 6 months, 1 year, and 3 years of follow-up. In conclusion, the detrimental effects of DSA on allograft function could be mitigated by serial DSA surveillance, protocol biopsies, and alterations in immunosuppression. With these measures, the improvement in graft survival in DSA positive KT recipients, at least at short-term, is encouraging.

Chronotropic incompetence on dobutamine stress echocardiography in candidates for a liver transplant.

OBJECTIVES: We evaluated dobutamine stress echocardiography as an initial screening test for a cardiac evaluation before a liver transplant. MATERIALS AND METHODS: We retrospectively examined 111 liver transplant candidates who had undergone previous cardiac evaluation; 30 of whom had undergone a liver transplant. RESULTS: Eighty patients (72.1%) completed a dobutamine stress echocardiography (41 chronotropically competent, 39 incompetent), while 31 patients (27.9%) required us to terminate early. Overall, 68 patients (61%) were on ß-blockers (21 required early dobutamine stress echocardiography termination, 30 chronotropically incompetent, and 17 competent). Patient results were normal. Thirty patients underwent a liver transplant. Among candidates requiring termination of early dobutamine stress echocardiography, posttransplant cardiac events included 1 fatal acute myocardial infarction, 1 nonfatal acute myocardial infarction, and 1 idiopathic cardiomyopathy. Among chronotropically incompetent patients, 2 patients had transient bradycardia, and among those who were chronotropically competent, 1 had refractory atrial fibrillation, and 1 had transient bradycardia. CONCLUSIONS: Nearly 50% of patients with end-stage liver disease may not reach the target heart rate. Early termination of dobutamine stress echocardiography because of cardiac symptoms or significant echocardiographic changes have more effect in predicting postoperative cardiac events, but further evaluation is required even if their target heart rate is close to that desired. Lower target heart rate may be acceptable in chronotropically incompetent individuals provided they are asymptomatic, have no echocardiographic changes, or cardiovascular risk factors, especially if they are on ß-blockers.

Chylous ascites after liver transplant: case report and review of literature.

CASE: A 62-year-old man with cirrhosis, hepatitis C, and hepatocellular carcinoma, underwent a liver transplant. On day 11 after surgery, a chylous leak from a partial wound dehiscence was noted. The leak did not respond to 2 weeks of uninterrupted, fat-free clear liquid diet and 12-hour total parenteral nutrition at night. The same treatment was continued for another 6 weeks with fatty meal challenge every weekend, which he failed. He was then given a fat-free clear liquid diet, 24-hour total parenteral nutrition, and octreotide 100 µg subcutaneously every 8 hours for 14 days. A prompt response was noted. His recovery was excellent at the time of this writing (9 months' follow-up). DISCUSSION: Eleven major cases have been reported with 9 cases being managed conservatively. Four were given a diet plus total parenteral nutrition without octreotide producing a cure in 3 to 36 days. Two cases (including ours) were given the diet and total parenteral nutrition, which failed; octreotide was then added, and these cases were cured in 2 to 4 weeks. Therefore, diet with total parenteral nutrition failed in 33.3% of the cases (2/6). In 3 cases, octreotide was used from the outset. They were all cured in ≤ 2 weeks. One case was operated on for peritonitis; chylous ascites was found and a leak was ligated. One patient with congenital lymphatic disorder underwent peritoneovenous shunting. Octreotide was not used in any of the cases of chylous ascites that were treated surgically. CONCLUSIONS: If exploratory surgery is done for any other reason, it is best to identify a chylous leak and ligate it. Otherwise, we recommend octreotide combined with a fat-free, clear liquid diet, and supplementation with medium chain triglycerides and total parenteral nutrition from the outset.

Hypercoagulability in end-stage liver disease: prevalence and its correlation with severity of liver disease and portal vein thrombosis.

Contrary to well-recognized bleeding diathesis in chronic liver disease, thrombotic events can occur in these patients due to reduction or loss of synthesis of anticoagulant proteins. Forty-seven consecutive patients with end-stage liver disease (ESLD) were investigated for activity of protein C, protein S, antithrombin, and factor V Leiden mutation. Forty-two (89.4%) patients had low levels of at least 1 while 33 (70.2%) patients were deficient for all anticoagulant proteins studied. Forty-six (97.9%) patients were negative for factor V Leiden mutation. The deficiencies were more marked in hepatitis C virus-positive patients and patients with model for end-stage liver disease (MELD) score >15. Six (12.8%) patients had portal vein thrombosis (PVT), and all had diminished protein S activity. In conclusions, deficiency of anticoagulant proteins occur in early phase of chronic liver disease. The severity of deficiency is proportional to the severity of liver disease. Despite the high prevalence of hypercoagulability, the incidence of PVT is low. Further studies with larger cohort of patients are needed to support these conclusions and to study other associated factors.