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.

Peritoneal Lavage Cytology Following Neoadjuvant Chemotherapy for Gastric Adenocarcinoma: Low Yield in Detecting Peritoneal Metastases.

BACKGROUND: Peritoneal lavage cytology (PLC) can detect advanced disease in gastric adenocarcinoma (GC); however, routine practice remains controversial. Furthermore, the effect of neoadjuvant chemotherapy (NAC) on cytological detection of carcinomatosis is unknown. METHODS: Using a 2012-2020 prospective database, we retrospectively reviewed patients with GC who underwent NAC followed by a staging laparoscopic peritoneal lavage with or without biopsy of suspicious peritoneal nodules. PLC results were considered discordant if they did not align with the peritoneal biopsy results. Patients with benign peritoneal cytology (Cyt-) or biopsy results who had postoperative time to carcinomatosis of <6 months were considered to have diagnostic failure of peritoneal lavage. RESULTS: Fifty-five patients with GC who underwent NAC followed by staging diagnostic laparoscopy with peritoneal lavage were identified. The majority of the patients in the cohort had Cyt- lavage (89.1%). Of the patients who underwent resection, 76.1% had T3 or greater disease on final pathology and 66% had nodal metastases. In 23 patients (41.8%) who had both peritoneal lavage and biopsy, four cases (17.4%) had discordant results. Diagnostic failure rate was 20% at 6 months and 42.2% at 12 months. The median time to carcinomatosis in patients who were Cyt- or biopsy negative was 7.9 months. CONCLUSION: PLC after NAC has a high diagnostic failure rate and inaccurately predicts carcinomatosis in 20% of patients with GC. Novel methods for identifying cytology positive GC after NAC should also be developed and evaluated, since the risk of peritoneal dissemination is high.

Examining Perioperative Risk Associated with Simultaneous Resection of Primary Neuroendocrine Tumors and Synchronous Hepatic Metastases.

BACKGROUND: Surgical debulking of primary neuroendocrine tumors (NETs) and hepatic resection of metastatic NET disease may each independently improve overall survival. However, evidence for combined primary site debulking and metastasectomy on survival and impact on short-term perioperative outcomes is limited. METHODS: The 2014-2016 ACS-NSQIP targeted hepatectomy database was queried for all patients undergoing liver resection for metastatic NET. Secondary procedure codes were evaluated for major concurrent operations. Multivariable analysis was performed to determine risk factors for 30-day morbidity and mortality. RESULTS: A total of 472 patients were identified, of whom 153 (32.4%) underwent ≥1 additional concurrent major operation. The most common concurrent procedures were small bowel resection (14.6%), partial colectomy (8.9%), and radical lymphadenectomy (7.4%). Among all patients, overall 30-day mortality and morbidity were 1.5% and 25.6%, respectively. Modifiable and treatment-related factors associated with increased major postoperative morbidity risk included >10% weight loss within six months of surgery (p = 0.05), increasing number of hepatic lesions treated (p = 0.05), and biliary reconstruction (p = 0.001). No major concurrent procedure was associated with increased 30-day morbidity (all p > 0.05). CONCLUSIONS: Approximately one-third of patients with stage IV NET underwent combined hepatic and multi-organ resection. Although modifiable and treatment-related factors predictive of perioperative morbidity were identified, performance of concurrent major procedures did not increase perioperative morbidity. These results support consideration of multi-organ resection in carefully selected patients with metastatic NET.

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.

Pancreatectomy in Stage I pancreas cancer: national underutilization of surgery persists.

BACKGROUND: Pancreatectomy in early pancreas adenocarcinoma has been historically underutilized. This retrospective study examines recent trends in the use of pancreatectomy in clinical Stage I (T1-2N0M0) pancreas cancer. METHODS: Using the 2004-2014 National Cancer Database, patients with clinical Stage I pancreas cancer were identified. Patients who underwent surgery or failed to undergo surgery with no identifiable reason were included in analysis. Chi-square, binary logistic regression, and Kaplan Meier estimate were used to identify risk factors for failure to undergo surgery. RESULTS: 23,365 patients were identified. Pancreatectomy increased from 38.4% in 2004 to 52.3% in 2014 (p < 0.001). 50% (n = 11,922) of patients underwent surgery and 48.0% (n = 11,433) did not, of whom 6.8% had a prohibitive co-morbidity, and 36.1% (n = 8594) had no identifiable reason for the lack of operation. Failure to operate was associated with older age, African American race, residence in lower income and less educated areas, lack of insurance, and treatment at community hospitals (all p < 0.001). 5-year survival was maximized in patients who underwent surgery and chemotherapy at 28.1%. CONCLUSION: While utilization of surgery increased overtime, 36% of patients fail to undergo surgery without an identifiable reason. Future investigation is warranted to explain continuing underuse of surgery in early pancreas cancer.

Resectable Distal Pancreas Cancer: Time to Reconsider the Role of Upfront Surgery.

BACKGROUND: Neoadjuvant chemotherapy (NAC) is increasingly utilized to optimize survival in proximal pancreatic adenocarcinoma. However, few studies have explored the impact of NAC in distal pancreas cancer. METHODS: Patients with resectable pancreatic adenocarcinoma of the body or tail treated with either upfront pancreatectomy or NAC followed by surgery were identified in the 2006-2014 National Cancer Database. Trends in utilization, predictors of use, and impact of NAC on overall survival were determined. RESULTS: Of 1485 patients, 176 (11.9%) received NAC. Use of NAC increased from 9.3% in 2006 to 16.9% in 2013 [odds ratio 1.14; 95% confidence interval (CI) 1.05-1.24; p = 0.001]. NAC patients were younger, had higher clinical stage, and preoperative CA 19-9 levels (all p < 0.05). After adjustment for patient-, tumor-, and treatment-related factors, increased clinical stage was the greatest independent predictor of neoadjuvant approach (p < 0.001). On multivariable analysis, survival benefit from NAC did not reach threshold of significance (95% CI 0.66-1.04; p = 0.10) for the entire cohort. However, NAC was associated with a significant survival advantage in clinical stage III with a 51% decreased yearly risk of death (adjusted hazard ratio 0.49; 95% CI 0.25-0.98; p = 0.04). A trend towards improved survival with NAC was observed among stage IIA (p = 0.09) and IIB (p = 0.07) patients. CONCLUSIONS: Neoadjuvant chemotherapy is associated with improved overall survival in Stage III distal pancreatic adenocarcinoma and shows promise in earlier stage disease. However, only a small percentage of patients receive NAC. Prospective evaluation of NAC in distal pancreatic adenocarcinoma is warranted based on these findings.

Pasireotide is not effective in reducing the development of postoperative pancreatic fistula.

BACKGROUND: In a single trial, perioperative pasireotide demonstrated reduction in postoperative pancreatic fistula (POPF) following pancreatectomy, yet recent studies question the efficacy of this drug. METHODS: All patients who underwent pancreatic resection between January 2014 and August 2017 at a single institution were prospectively followed. Starting in February 2016, pasireotide was administered to all pancreatectomies. Pancreaticoduodenectomy (PD) patients were additionally risk-stratified using a validated clinical risk score. The primary endpoint was the development of clinically relevant POPF (CR-POPF), and was compared between patients who received pasireotide and controls. RESULTS: Of 116 patients, 87 patients (75%) underwent PD, and 43 patients (37.1%) received pasireotide. CR-POPF occurred in 28.4% patients. The use of pasireotide was not associated with reduced CR-POPF among the total cohort (25.6% vs. 30.1%, P = 0.599), distal pancreatectomy patients (P = 0.339), PD (P = 0.274), or PD patients with elevated risk scores (P = 0.073). Pasireotide did not decrease hospital length of stay, use of parenteral nutrition, delayed gastric emptying, surgical site wound infection, or readmission rate. CONCLUSION: Use of pasireotide after pancreatic resection does not decrease CR-POPF, nor is it associated with reduced length of stay or postoperative complications. A multi-center randomized trial is warranted to study its true effect on outcomes after pancreatectomy.

Robotic Minor Hepatectomy Offers a Favorable Learning Curve and May Result in Superior Perioperative Outcomes Compared with Laparoscopic Approach.

Minorhepatectomy (MH) is a common type of robotic-assisted liver resection, but few studies compared it with laparoscopic. We compared the perioperative outcomes of patients who underwent robotic (RH) or laparoscopic (LH) minor hepatectomy and evaluated the effect of surgeon's experience on outcomes. A prospective database was used to identify patients from 2009 through 2016 who underwent RH or LH. Two surgeons performed RH starting in 2014, whereas LH had been established before that. Of the 93 patients, 42 were in RH and 51 in LH group. The mean patient age, gender, race, American Society of Anesthesiologists score, proportion of patients with cirrhosis and hepatocellular carcinoma were similar. Operative time, estimated blood loss (EBL), conversion to open, 30-day complication rate, Clavien-Dindo grade ≥ 3 complications, and length of hospital stay (LOS) were similar. There was no difference in average tumor size, specimen volume, or achievement of R0 margin. In RH group, after completing 15 cases, there were no conversions to open. After 25 cases, EBL, LOS, and 30-day complication rate were improved as compared with LH. Perioperative outcomes of robotic MH are equivalent to laparoscopic. After approximately 25 cases, robotic-assisted MH may result in superior outcomes compared with laparoscopic.