Stefan Buettner

Defining Post Hepatectomy Liver Insufficiency: Where do We stand?

BackgroundPost-hepatectomy liver failure (PHLF) is a major source of morbidity and mortality in patients undergoing liver resection. The aim of this review is to summarize the recent literature available on PHLF including its definition, predictive factors, preoperative risk assessment, severity grading, preventative measures, and management strategies.MethodsA systematic literature search was carried out with the search engines PubMed, Medline, and Cochrane Database using the keywords related to “liver failure”, “posthepatectomy”, and “hepatic resection”.ResultsLiver resection is a curative treatment of liver tumors. However, it leads to concurrent death and regeneration of the remaining hepatocytes. Factors related to the patient, liver parenchyma and the extent of surgery can inhibit regeneration leading to PHLF.ConclusionGiven its resistance to treatment and the high postoperative mortality associated with PHLF, great effort has been put in to both accurately identify patients at high risk and to develop strategies that can help prevent its occurrence.

The relative effect of hospital and surgeon volume on failure to rescue among patients undergoing liver resection for cancer

BACKGROUND Although previous reports have focused on factors at the hospital level to explain variations in postoperative outcomes, less is known regarding the effect of provider-specific factors on postoperative outcomes such as failure-to-rescue (FTR) and postoperative mortality. The current study aimed to quantify the relative contributions of surgeon and hospital volume on the volume-outcomes relationship among a cohort of patients undergoing liver resection. METHODS Patients undergoing liver surgery for cancer were identified using the Nationwide Inpatient Sample from 2001 and 2009. Multivariable logistic regression analysis was performed to identify factors associated with mortality and FTR. Point estimates were used to calculate the relative effects of hospital and surgeon volume on mortality and FTR. RESULTS A total of 5,075 patients underwent liver surgery and met inclusion criteria. Median patient age was 62 years (interquartile range, 52-70) and 55.2% of patients were male. Mortality was lowest among patients treated at high-volume hospitals and among patients treated by high-volume surgeons (both P < .001). Similar patterns in FTR were noted relative to hospital and surgeon volume (hospital volume: low vs intermediate vs high; 10.3 vs 9.0 vs 5.2%; surgeon volume: low vs intermediate vs high, 11.1 vs 9.1 vs 4.1%; both P < .05). On multivariable analysis, compared with high-volume surgeons, lower volume surgeons demonstrated greater odds for mortality (intermediate: odds ratio [OR], 2.27 [95% CI, 1.27-4.06; P = .006]; low, OR, 2.83 [95% CI, 1.52-5.27; P = .001]), and FTR (intermediate: OR, 2.86 [95% CI, 1.53-5.34, P = .001]; low, OR, 3.40 [95% CI, 1.75-6.63; P < .001]). While hospital volume accounted for 0.5% of the surgeon volume effect on increased FTR for low-volume surgeons, surgeon volume accounted for nearly all of the hospital volume effect on increased FTR in low-volume hospitals. CONCLUSION The risk of complications, mortality, and FTR were less among both high-volume hospitals and high-volume surgeons, but the beneficial effect of volume on outcomes was attributable largely to surgeon volume.

Patient perceptions regarding the likelihood of cure after surgical resection of lung and colorectal cancer: Perception of Cure After Surgery

The objective of the current study was to characterize the prevalence of the expectation that surgical resection of lung or colorectal cancer might be curative. The authors sought to assess patient‐level, tumor‐level, and communication‐level factors associated with the perception of cure.

Quality of life after treatment of neuroendocrine liver metastasis

BACKGROUND A large subset of patients with neuroendocrine liver metastasis (NELM) is symptomatic at the time of presentation. In addition to improving survival, treatment of NELM seeks to provide palliation of symptoms. However, data on health-related quality of life (QoL) are uncommon. We sought to define patient-reported QoL after treatment of NELM. METHODS Patients who underwent treatment of NELM at Johns Hopkins Hospital between 1998 and 2013 and who were alive as of March 2014 were identified (n = 125). These patients were invited to complete a QoL survey designed using validated assessment tools, to assess their physical, mental, and general health before treatment, after the most recent treatment and at the time of the study. Clinicopathologic data were collected and correlated with QoL data. RESULTS The response rate was 68.0% (n = 85). Median patient age was 55 y and most were male (59.2%). Most patients had a pancreatic (24.7%) or a small bowel (37.7%) primary tumor; the overwhelming majority had multiple NELM (83.5%). Patient-reported symptoms before any treatment included diarrhea (41.1%), flushing (34.1%), fatigue (36.5%), and osteoarticular pain (18.8%). Initial treatment of NELM consisted of surgery in 55 patients (64.7%) and nonsurgical treatment in 30 patients (35.3%). Many patients reported an overall improvement in physical health and mental health. Specifically, the proportion of patients reporting diarrhea (before any treatment, 41.1% versus currently, 25.9%; P = 0.019) and flushing (before any treatment, 34.1% versus currently, 10.5%; P < 0.001) tended to decrease over time and a lower proportion of patients reported to be currently sad about being ill (before any treatment, 31.8% versus currently, 23.2%; P = 0.009). Patients with a very poor QoL at the time of the diagnosis were more likely to experience an improvement in QoL after treatment. Interestingly, there was no difference in the improvement in overall QoL whether the initial treatment for NELM was surgical or nonsurgical; however, a lower proportion of patients were dissatisfied with surgery versus nonsurgical therapy (5.4% versus 9.4%; P = 0.001). CONCLUSIONS Less than one-fourth of patients experienced a significant improvement in QoL after treatment of NELM. The patients who benefit the most of treatment were those who were more symptomatic before any treatment.

Intrahepatic cholangiocarcinoma: current perspectives

Intrahepatic cholangiocarcinoma (ICC) is the second most common malignancy arising from the liver. ICC makes up about 10% of all cholangiocarcinomas. It arises from the peripheral bile ducts within the liver parenchyma, proximal to the secondary biliary radicals. Histologically, the majority of ICCs are adenocarcinomas. Only a minority of patients (15%) present with resectable disease, with a median survival of less than 3 years. Multidisciplinary management of ICC is complicated by large differences in disease course for individual patients both across and within tumor stages. Risk models and nomograms have been developed to more accurately predict survival of individual patients based on clinical parameters. Predictive risk factors are necessary to improve patient selection for systemic treatments. Molecular differences between tumors, such as in the epidermal growth factor receptor status, are promising, but their clinical applicability should be validated. For patients with locally advanced disease, several treatment strategies are being evaluated. Both hepatic arterial infusion chemotherapy with floxuridine and yttrium-90 embolization aim to downstage locally advanced ICC. Selected patients have resectable disease after downstaging, and other patients might benefit because of postponing widespread dissemination and biliary obstruction.

Age of Transfused Blood Impacts Perioperative Outcomes Among Patients Who Undergo Major Gastrointestinal Surgery.

Objective: To evaluate the impact of transfused packed red blood cell (PRBC) age on perioperative morbidity among patients undergoing major gastrointestinal surgery. Background: Patients undergoing major surgery often receive PRBC transfusions. The effect of PRBC age (ie, storage duration before transfusion) on perioperative surgical outcomes remains poorly defined. Methods: In this study, 1365 patients were identified who underwent a hepato-pancreatic or colorectal resection and received ≥1 unit of PRBCs between 2009 and 2014 at the Johns Hopkins Hospital. Data regarding the storage duration of PRBCs, clinicopathologic characteristics, and perioperative outcomes were obtained and analyzed. Multivariable modified Poisson regression analyses were performed to assess the effect of PRBC age on perioperative morbidity. Results: A total of 5901 PRBC units were transfused for a median of 2 (interquartile range 2–4) units transfused per patient. In all, 936 (68.6%) patients received only units of blood that had been stored for less than 35 days (“fresh” blood), whereas 429 (31.4%) patients received at least 1 unit of PRBC that had been stored for ≥35 days (“older” blood). Overall postoperative morbidity was 32.8%. The incidence of postoperative complications (42.7% vs 28.3%) was higher among patients who received “older” vs “fresh” blood (P < 0.001). After adjusting for confounders on multivariable analysis, transfusion of “older” blood remained independently associated with an increased risk of perioperative morbidity (Relative Risk 1.20, P = 0.03). Conclusions: The use of “older” blood was an independent predictor of postoperative morbidity among patients undergoing hepato-pancreatic or colorectal procedures. Transfusion of “older” blood products may contribute to a higher risk of postoperative complications.

A model including sarcopenia surpasses the MELD score in predicting waiting list mortality in cirrhotic liver transplant candidates: A competing risk analysis in a national cohort

BACKGROUND & AIMS Frail patients with low model for end-stage liver disease (MELD) scores may be under-prioritised. Low skeletal muscle mass, namely sarcopenia, has been identified as a risk factor for waiting list mortality. A recent study proposed incorporating sarcopenia in the MELD score (MELD-Sarcopenia score). We aimed to investigate the association between sarcopenia and waiting list mortality, and to validate the MELD-Sarcopenia score (i.e. MELD + 10.35 * Sarcopenia). METHODS We identified consecutive patients with cirrhosis listed for liver transplantation in the Eurotransplant registry between 2007-2014 and measured skeletal muscle mass on computed tomography. A competing risk analysis was used to compare survival of patients with and without sarcopenia, and concordance (c) indices were calculated to assess performance of the MELD and MELD-Sarcopenia score. We created a nomogram of the best predictive model. RESULTS We included 585 patients with a median MELD score of 14 (interquartile range 9-19), of which 254 (43.4%) were identified as having sarcopenia. Median waiting list survival was shorter in patients with sarcopenia than those without (p <0.001). This effect was even more pronounced in patients with MELD ≤15. The discriminative performance of the MELD-Sarcopenia score (c-index 0.820) for three-month mortality was lower than MELD score alone (c-index 0.839). Apart from sarcopenia and MELD score, other predictive variables were occurrence of hepatic encephalopathy before listing and recipient age. A model including all these variables yielded a c-index of 0.851. CONCLUSIONS Sarcopenia was associated with waiting list mortality in liver transplant candidates with cirrhosis, particularly in patients with lower MELD scores. The MELD-Sarcopenia score was successfully validated in this cohort. However, incorporating sarcopenia in the MELD score had limited added value in predicting waiting list mortality. LAY SUMMARY In this study among patients with liver cirrhosis listed for liver transplantation, low skeletal muscle mass was associated with mortality on the waiting list, particularly in patients who were listed with low priority based on a low MELD score. However, adding these measurements to the currently used system for donor and organ allocation showed no added value.

Elevated NLR in gallbladder cancer and cholangiocarcinoma – making bad cancers even worse: results from the US Extrahepatic Biliary Malignancy Consortium

BACKGROUND Gallbladder and extrahepatic biliary malignancies are aggressive tumors with high risk of recurrence and death. We hypothesize that elevated preoperative Neutrophil-Lymphocyte Ratios (NLR) are associated with poor prognosis among patients undergoing resection of gallbladder or extrahepatic biliary cancers. METHODS Patients who underwent complete surgical resection between 2000-2014 were identified from 10 academic centers (n=525). Overall (OS) and recurrence-free survival (RFS) were analyzed by stratifying patients with normal (<5) versus elevated (>5) NLR. RESULTS Overall, 375 patients had NLR <5 while 150 patients had NLR >5. Median OS was 24.5 months among patients with NLR<5 versus 17.0 months among patients with NLR>5 (p<0.001). NLR was also associated with OS in subgroup analysis of patients with gallbladder cancer. In fact, on multivariable analysis, NLR>5, dyspnea and preoperative peak bilirubin were independently associated with OS in patients with gallbladder cancer. Median RFS was 26.8 months in patients with NLR<5 versus 22.7 months among patients with NLR>5 (p=0.030). NLR>5 was independently associated with worse RFS for patients with gallbladder cancer. CONCLUSIONS Elevated NLR was associated with worse outcomes in patients with gallbladder and extrahepatic biliary cancers after curative-intent resection. NLR is easily measured and may provide important prognostic information.

Prognostic impact of complications after resection of early stage hepatocellular carcinoma

Resection is the most effective treatment for HCC. However, postoperative morbidity is common and its impact on long‐term oncological outcome remains unclear.

Association of Optimal Time Interval to Re-resection for Incidental Gallbladder Cancer With Overall Survival: A Multi-Institution Analysis From the US Extrahepatic Biliary Malignancy Consortium

Importance The current recommendation is to perform re-resection for select patients with incidentally discovered gallbladder cancer. The optimal time interval for re-resection for both patient selection and long-term survival is not known. Objective To assess the association of time interval from the initial cholecystectomy to reoperation with overall survival. Design, Setting, and Participants This cohort study was conducted from January 1, 2000, to December 31, 2014 at 10 US academic institutions. A total of 207 patients with incidentally discovered gallbladder cancer who underwent reoperation and had available data on the date of their initial cholecystectomy were included. Exposures Time interval from the initial cholecystectomy to reoperation: group A: less than 4 weeks; group B: 4 to 8 weeks; and group C: greater than 8 weeks. Main Outcomes and Measures Primary outcome was overall survival. Results Of 449 patients with gallbladder cancer, 207 cases (46%) were discovered incidentally and underwent reoperation at 3 different time intervals from the date of the original cholecystectomy: group A: less than 4 weeks (25 patients, 12%); B: 4 to 8 weeks (91 patients, 44%); C: more than 8 weeks (91 patients, 44%). The mean (SD) ages of patients in groups A, B, and C were 65 (9), 64 (11), and 66 (12) years, respectively. All groups were similar for baseline demographics, extent of resection, presence of residual disease, T stage, resection margin status, lymph node involvement, and postoperative complications. Patients who underwent reoperation between 4 and 8 weeks had the longest median overall survival (group B: 40.4 months) compared with those who underwent early (group A: 17.4 months) or late (group C: 22.4 months) reoperation (log-rank P = .03). Group A and C time intervals (vs group B), presence of residual disease, an R2 resection, advanced T stage, and lymph node involvement were associated with decreased overall survival on univariable Cox regression. Only group A (hazard ratio, 2.63; 95% CI, 1.25-5.54) and group C (hazard ratio, 2.07; 95% CI, 1.17-3.66) time intervals (vs group B), R2 resection (hazard ratio, 2.69; 95% CI, 1.27-5.69), and advanced Tstage (hazard ratio, 1.85; 95% CI, 1.11-3.08) persisted on multivariable Cox regression analysis. Conclusions and Relevance The optimal time interval for re-resection for incidentally discovered gallbladder cancer appears to be between 4 and 8 weeks after the initial cholecystectomy.