Risk of Infectious Complications After Simultaneous Gastrointestinal and Liver Resections for Neuroendocrine Tumor Metastases.

BACKGROUND: Neuroendocrine tumors (NETs) are a relatively rare category of cancers that arise in the gastrointestinal (GI) tract and other organs. Extended hepatectomies including resection of multiple organs are often necessary to achieve negative margins. METHODS: We performed a review of patients undergoing liver resection for NET liver metastases from 2005 to 2015 using National Surgical Quality Improvement Program. We compared patients undergoing hepatectomy alone (HA) versus hepatectomy and a concomitant GI surgery procedure (colorectal, small bowel, and pancreatic) to evaluate postoperative infectious complications. RESULTS: During the study period, 354 patients underwent liver resection for metastatic NET. Hepatectomy alone was performed in 98 patients, and concomitant GI surgery was performed in 256 patients, including 83 colorectal resections (HCCR), 68 small bowel resections, 75 distal pancreatectomies, and 35 pancreaticoduodenectomies (HCPD). Infectious complications were more likely to occur in those undergoing HCPD (60%, P < 0.001), and HCCR (32.5%, P < 0.05) than in those undergoing HA (16.3%). Patients undergoing HCPD and HCCR had a 7.69-fold and 2.52-fold increased risk of infectious complication, respectively, compared with HA after adjustment for other infection risk factors. CONCLUSIONS: Neuroendocrine liver metastases requiring liver resection with concomitant colorectal resection or pancreaticoduodenectomy are at significantly increased risk of developing infectious complications.

Effect of operative duration on infectious complications and mortality following hepatectomy.

BACKGROUND: To study mortality and infectious complications (IC) risk relative to operative duration in a large and contemporary cohort of patients undergoing hepatectomy. METHODS: A retrospective cohort study of 21,443 patients from the National Surgical Quality Improvement Program dataset of patients who underwent liver resection from 2012 to 2016. RESULTS: Patients undergoing hepatectomy during the study period (N = 21,443) had a mean operative duration of 243.5 min of which 16.6% (3533) developed at least one IC. The overall 30-day mortality was 1.6%. A significant increase in mortality and IC was demonstrated from 3 h of operating time (OR: 1.99 and OR: 1.94, respectively), peaking at 8 h (OR: 7.15 and OR: 6.37, respectively). Pneumonia, sepsis/septic shock, and SSI presented high prevalence and were linked to significant mortality. After case-matching, elective hepatectomy was associated with a 4-fold increased risk of infectious complications. CONCLUSIONS: Operative duration was associated with a linear increased risk of mortality and IC after hepatectomy. The most critical determinants of IC were ASA class, COPD, CHF, and type of hepatectomy.

Long term outcomes of patients transplanted for hepatocellular carcinoma with human immunodeficiency virus infection.

BACKGROUND: We aimed to study outcomes in HIV + patients with HCC in the US following Liver Transplantation (LT) using the UNOS dataset. METHODS: The database was queried from 2003 to 2016 for patients undergoing LT with HCC, HIV+, and HCC/HIV+. RESULTS: Out of 17,397 LT performed for HCC during the study period, 113 were transplanted for HCC with HIV infection (91 isolated livers). Patients transplanted for HCC/HIV+ were younger (55.54 ± 5.89 vs 58.80 ± 7.37, p < 0.001), had lower total bilirubin (1.20 vs 1.60, p = 0.042) significantly lower BMI (25.35 ± 4.43 vs 28.39 ± 5.17, p < 0.001) and were more likely to be co-infected with HBV (25.3% vs 8.2% p < 0.001) than those transplanted for HCC alone. HCC/HIV + patients were found to have a 3.8 fold increased risk of peri-operative mortality at 90 days after matching. HCC/HIV + recipients had 54% decreased long-term survival within the HCC cohort. Our initial analysis of overall graft and patient survival found significant differences between HCC/HIV and HCC/HIV + recipients. However, these variances were lost after case-matching. Recurrence and disease free survival were similar in HCC alone vs HCC/HIV + recipients. CONCLUSIONS: Our analysis suggests that excellent outcomes can be achieved in selected patients with HCC/HIV+.

Effect of critical care complications on perioperative mortality and hospital length of stay after hepatectomy: A multicenter analysis of 21,443 patients.

OBJECTIVE: To determine predictors of critical care complications (CCC) in patients undergoing hepatectomy. METHODS: All hepatectomy patients in NSQIP from 2012 to 2016 were analyzed. CCC included prolonged ventilation (>48 h), sepsis/septic shock, renal failure/insufficiency, cardiac arrest/AMI and pulmonary embolism. RESULTS: A total of 21,443 patients underwent hepatectomy during the study period. Overall rate of CCC was 11%, with the most common being sepsis/septic shock (6.1%) and respiratory failure (4.9%). On multivariate analysis the preoperative risk factors associated with CCC included ASA Class IV-V (OR:2.04, p < 0.0001), diabetes (OR = 1.28, p = 0.0001), pre-operative ventilator use (OR: 17.75, p = 0.0003); COPD (OR: 1.65, p < 0.0001); pre-operative weight loss >10% (OR: 1.35, p = 0.0026); pre-operative sepsis (OR: 2.14, p < 0.0001). Propensity score matched analysis demonstrated a significant increased risk of mortality in patients with CCC (OR: 26.75, p < 0.0001) and a prolonged LOS of 10.5 days above the mean (ß Estimate: 10.51, p < 0.0001). CONCLUSIONS: ASA class, diabetes, COPD, pre-operative weight loss >10% and pre-operative sepsis are the strongest predictors of CCC after hepatectomy. The presence of CCC significantly increased the risk of peri-operative mortality 26-fold.

Autophagic flux modulation by Wnt/ß-catenin pathway inhibition in hepatocellular carcinoma.

Autophagy targets cellular components for lysosomal-dependent degradation in which the products of degradation may be recycled for protein synthesis and utilized for energy production. Autophagy also plays a critical role in cell homeostasis and the regulation of many physiological and pathological processes and prompts this investigation of new agents to effect abnormal autophagy in hepatocellular carcinoma (HCC). 2,5-Dichloro-N-(2-methyl-4-nitrophenyl) benzenesulfonamide (FH535) is a synthetic inhibitor of the Wnt/ß-catenin pathway that exhibits anti-proliferative and anti-angiogenic effects on different types of cancer cells. The combination of FH535 with sorafenib promotes a synergistic inhibition of HCC and liver cancer stem cell proliferation, mediated in part by the simultaneous disruption of mitochondrial respiration and glycolysis. We demonstrated that FH535 decreased HCC tumor progression in a mouse xenograft model. For the first time, we showed the inhibitory effect of an FH535 derivative, FH535-N, alone and in combination with sorafenib on HCC cell proliferation. Our study revealed the contributing effect of Wnt/ß-catenin pathway inhibition by FH535 and its derivative (FH535-N) through disruption of the autophagic flux in HCC cells.