A Multicenter, 10-Year Experience With Hepatocellular Adenoma: Risk Factors and Disease Course.

BACKGROUND: Management of hepatocellular adenoma (HA) is marked by a paucity of recent studies. Long-term follow-up data from an equal access health care system may facilitate our understanding of the natural disease course of HA and identify modifiable risk factors. METHODS: A multi-institutional, retrospective review of patients with HA from 2008-2017 was performed. Patient demographics, disease characteristics, and clinical outcomes were analyzed. RESULTS: Of 124 patients identified, 94% were women with a mean age at diagnosis of 39.5 years (range 20-82). Median follow-up was 22.5 months (range 0-114) with thirty-four (27.4%) patients eventually undergoing hepatectomy. Mean BMI of the study population was 30.5 kg/m2 (range 16-72). Stratified by size, average BMI for adenomas ≥5 cm was 34 kg/m2 compared to 28 kg/m2 for those <5 cm (P < .05). The predominant symptom at presentation was abdominal pain (41.1%), while just 4% presented with acute rupture. Overall incidence of the malignancy was 2.5%. Among all patients, oral contraceptive use was documented in 74 (59.7%) patients, of whom 36 (29.0%) discontinued OC for at least six months. Regression after OC cessation occurred in seven patients (19.4%) while the majority (77.8%) remained stable. DISCUSSION: This decade-long review analyzing the impact of modifiable risk factors identifies a direct correlation between BMI and hepatocellular adenoma size. Rupture and malignant transformation are rare entities. Cessation of OC appears to be an effective strategy in the management of hepatic adenoma. Further investigations are warranted to determine if addressing modifiable risk factors such as BMI might induce further HA regression.

Outcomes of neoadjuvant therapy for cholangiocarcinoma: A review of existing evidence assessing treatment response and R0 resection rate.

Adjuvant chemotherapy for cholangiocarcinoma (CCA) has not been shown to gain significant improvements in survival. Factors contributing to suboptimal treatment response include aggressive disease biology and late clinical presentation. When feasible, surgical resection is the first line of treatment. Yet, recurrence remains high and long-term survival is rare. Neoadjuvant therapy is an appealing approach, with oncologic advantages in allowing the treatment of occult systemic disease and selection of patients most likely to benefit from radical surgery. However, given the surgery-first treatment paradigm for CCA, there is a paucity of data supporting neoadjuvant therapy. This review summarizes the current evidence on treatment response and margin-negative (R0) resection rate associated with neoadjuvant therapy for CCA.

Long-Term Nononcologic Outcomes for Laparoscopic Liver Resection: Improvement over Open Hepatectomy?

Prior studies of laparoscopic liver resection (LLR) have evaluated long-term outcomes in terms of cancer survival, but few have evaluated nononcologic outcomes. This study analyzes long-term nondisease-specific complications associated with LLR and open liver resection (OLR). We performed a retrospective single-institution review of patients undergoing liver resection for any reason from January 2005 to December 2014. Long-term complication was defined as any complication not related to the primary disease process, and occurring more than 90 days after surgery, emphasizing incisional hernia (IH) and small bowel obstruction (SBO). A total of 208 patients were included in the OLR group and 79 patients in the LLR group. Forty-one patients (19.6%) developed IH after OLR, whereas only six patients (7.5%) developed IH after LLR (P = 0.01). About 3.8 per cent of patients developed IH requiring surgical repair in both groups. Seven patients developed SBO (3.4%) after OLR; no patient developed SBO after LLR. Median time to development of complications was 13.8 months (range 3-54 months) after OLR compared with 8.5 months after LLR (range 6-36 months). Male gender, body mass index, prior abdominal surgery, and OLR were independent risk factors for development of long-term complications. There is a higher incidence of nondisease-specific complications after OLR than LLR.

Porcelain Gallbladder: No Longer an Indication for Prophylactic Cholecystectomy.

Porcelain gallbladder (PG) was historically associated with gallbladder cancer (GBC), (range 12-62%, largest series n = 26). Presently, cholecystectomy is still performed in many patients with PG. The objective of this study was to determine the incidence of GBC in patients with radiographic diagnosis of PG. We conducted a retrospective chart review of the Kaiser Permanente southern California electronic medical record database and identified patients with radiographic diagnosis of PG between 2008 and 2013. Extracted were patient demographics, imaging modality, symptoms, surgical and observational outcomes, and pathology results. Out of 192 PG patients, 102 underwent cholecystectomy, and 90 were observed. None of the patients in the surgery group had GBC on pathology review, and none of the observed patients developed GBC during follow-up (mean 3.5 years). In the surgery group, 82 per cent of the patients were asymptomatic with a perioperative complication rate of 10.7 per cent. Among symptomatic patients, the complication rate was 16.7 per cent. Rate of conversion to open surgery was 5 per cent. Complications led to eight endoscopic or percutaneous interventions and five additional operations. PG is not associated with increased risk of GBC but is associated with high risk of postoperative complications. Cholecystectomy should not be recommended in asymptomatic patients with PG.

Impact of statin use on survival in patients undergoing resection for early-stage pancreatic cancer.

OBJECTIVES: It has been suggested that statins exert potential anti-tumor effects. The relationship between statin use and outcomes in pancreatic cancer is controversial. We hypothesized that statin use at baseline would impact survival among patients with early-stage pancreatic cancer and that the effect might vary by individual statin agent. METHODS: We conducted a retrospective cohort study on data from an integrated healthcare system. We included patients with pancreatic cancer stage I-IIb who underwent resection for curative intent between January 2005 and January 2011. Baseline statin use was characterized as any prior use as well as active use of either simvastatin or lovastatin. Intensity of exposure was calculated as average daily dose prior to surgery. Overall and disease-free survival was assessed from surgery until the end of study (April 2014). We used the Kaplan-Meier method and Cox proportional hazards regression to evaluate the impact of baseline statin use on survival, adjusting for age, sex, Charlson comorbidity score, resection margin, disease stage, and receipt of adjuvant chemotherapy. RESULTS: Among 226 patients, 71 (31.4%) had prior simvastatin use and 27 (11.9%) had prior lovastatin use at baseline. Prior simvastatin but not lovastatin use was associated with improved survival (median 28.5 months (95% confidence limit (CL) 20.8, 38.4) for simvastatin vs. 12.9 months (9.6, 15.5) for lovastatin vs. 16.5 months (14.1, 18.9) for non-statin users; log-rank P=0.0035). In Cox regression, active simvastatin use was independently associated with reduced risk for mortality (adjusted hazard ratio (HR) 0.56 (95% CL 0.38, 0.83), P=0.004) and risk for recurrence (adjusted HR 0.61 (0.41, 0.89), P=0.01). Survival improved significantly among patients who received moderate-high-intensity (median 42.1 months (24.0,52.7)) doses compared with those who received low-intensity doses of simvastatin (median 14.1 months (8.6, 23.8), log-rank P=0.03). CONCLUSIONS: The effects of statins varied by agent and dose. Active use of moderate-high-dose simvastatin at baseline was associated with improved overall and disease-free survival among patients undergoing resection for pancreatic cancer.

Prediction of malignancy in cystic neoplasms of the pancreas: a population-based cohort study.

OBJECTIVES: Pancreatic cystic neoplasms (PCNs) are being detected with increased frequency. The aims of this study were to determine the incidence of malignancy and develop an imaging-based system for prediction of malignancy in PCN. METHODS: We conducted a retrospective cohort study of patients ≥18 years of age with confirmed PCN from January 2005 to December 2010 in a community-based integrated care setting in Southern California. Patients with history of acute or chronic pancreatitis were excluded. Malignancy diagnosed within 3 months of cyst diagnosis was considered as pre-existing. Subsequent incidence of malignancy during surveillance was calculated based on person-time at risk. Age- and gender-adjusted standardized incidence ratio (SIR) was calculated with the non-cyst reference population. Recursive partitioning was used to develop a risk prediction model based on cyst imaging features. RESULTS: We identified 1,815 patients with confirmed PCN. A total of 53 (2.9%) of patients were diagnosed with cyst-related malignancy during the study period. The surveillance cohort consisted of 1,735 patients with median follow-up of 23.4 months. Incidence of malignancy was 0.4% per year during surveillance. The overall age- and gender-adjusted SIR for pancreatic malignancy was 35.0 (95% confidence level 26.6, 46.0). Using recursive partitioning, we stratified patients into low (<1%), intermediate (1-5%), and high (9-14%) risk of harboring malignant PCN based on four cross-sectional imaging features: size, pancreatic duct dilatation, septations with calcification as well as growth. Area under the receiver operator characteristic curve for the prediction model was 0.822 (training) and 0.808 (testing). CONCLUSIONS: Risk of pancreatic malignancy was lower than previous reports from surgical series but was still significantly higher than the reference population. A risk stratification system based on established imaging criteria may help guide future management decisions for patients with PCN.

Staging of regional lymph nodes in melanoma: a case for including nonsentinel lymph node positivity in the American Joint Committee on Cancer staging system.

IMPORTANCE: Survival varies widely in patients with stage III melanoma. The existence of clinical significance for positive nonsentinel lymph node (NSLN) status would warrant consideration for incorporation into the American Joint Committee on Cancer staging system and better prediction of survival. OBJECTIVE: To evaluate whether disease limited to sentinel lymph nodes (SLNs) represents different clinical significance than disease spread into NSLNs. DESIGN, SETTING, AND PARTICIPANTS: The database of the John Wayne Cancer Institute at Saint John's Health Center, Santa Monica, California, was queried for all patients with SLNs positive for cutaneous melanoma who subsequently underwent completion lymph node dissection. MAIN OUTCOMES AND MEASURES: Disease-free survival, melanoma-specific survival (MSS), and overall survival. RESULTS: A total of 4223 patients underwent SLN biopsy from 1986 to 2012. Of these patients, 329 had a tumor-positive SLN. Of the 329, 250 patients (76.0%) had no additional positive nodes and 79 (24.0%) had a tumor-positive NSLN. Factors predictive of NSLN positivity included older age (P = .04), greater Breslow thickness (P < .001), and ulceration (P < .02). Median overall survival was 178 months for the SLN-only positive group and 42.2 months for the NSLN positive group (5-year overall survival, 72.3% and 46.4%, respectively). Median MSS was not reached for the SLN-only positive group and was 60 months for the NSLN positive group (5-year MSS, 77.8% and 49.5%, respectively). On multivariate analysis, NSLN positivity had a strong association with recurrence (hazard ratio [HR], 1.75; 95% CI, 1.23-2.50; P = .002), shorter overall survival (HR, 2.24; 95% CI, 1.48-3.40; P < .001), and shorter MSS (HR, 2.23; 95% CI, 1.46-3.07; P < .001). To further control for the effects of total positive lymph nodes, comparison was done for patients with only N2 disease (2-3 total positive lymph nodes); the results of this comparison confirmed the independent effect of NSLN status (MSS; P = .04). CONCLUSIONS AND RELEVANCE: Nonsentinel lymph node positivity is one of the most significant prognostic factors in patients with stage III melanoma. Subclassification of melanoma by NSLN tumor status should be considered for the American Joint Committee on Cancer staging system.