Can Surgeons Reliably Identify Non-cirrhotic Liver Disease During Laparoscopic Bariatric Surgery?

INTRODUCTION: Identification of liver disease during bariatric operations is an important task given the patients risk for occult fatty liver disease. Surgeon's accuracy of assessing for liver disease during an operation is poorly understood. The objective was to measure surgeons' performance on intra-operative visual assessment of the liver in a simulated environment. METHODS: Liver images from 100 patients who underwent laparoscopic bariatric surgery and pre-operative ultrasound elastography between July 2020 and July 2021 were retrospectively evaluated. The perception of 15 surgeons regarding the degree of hepatic steatosis and fibrosis was collected in a simulated clinical environment by survey and compared to results determined by ultrasonographic exam. RESULTS: The surgeons' ability to correctly identify the class of steatosis and fibrosis was poor (accuracy 61% and 59%, respectively) with a very weak correlation between the surgeon's predicted class and its true class (r = 0.17 and r = 0.12, respectively). When liver disease was present, surgeons completely missed its presence in 26% and 51% of steatosis and fibrosis, respectively. Digital image processing demonstrated that surgeons subjectively classified steatosis based on the "yellowness" of the liver and fibrosis based on texture of the liver, despite neither correlating with the true degree of liver disease. CONCLUSION: Laparoscopic visual assessment of the liver surface for identification of non-cirrhotic liver disease was found to be an inaccurate method during laparoscopic bariatric surgery. While validation studies are needed, the results suggest the clinical need for alternative approaches.

Association between Preoperative Steroids and Outcomes in Patients Undergoing Pancreaticoduodenectomy using the National Surgical Quality Improvement Program.

BACKGROUND: A national study analyzing the association between preoperative steroid use and outcomes after pancreatic resections is lacking. The purpose of this study is to evaluate the association between preoperative steroids and outcomes after pancreaticoduodenectomy using a national database. MATERIALS AND METHODS: A retrospective analysis of patients undergoing pancreaticoduodenectomy was performed using the National Surgical Quality Improvement Program (NSQIP) database (2014-2019). In addition, we utilized propensity score matching to compare patients on preoperative steroids to those who were not. Outcomes measured included 30-day complications and mortality, need for readmission, a prolonged hospital length of stay, delayed gastric emptying, and pancreatic fistula. RESULTS: After propensity score matching, there were 438 patients in the steroid group and 876 patients in the no steroid group. There was no difference in pancreatic fistula (23.8% vs. 21.7%; p-0.3), delayed gastric emptying (21.1% vs.20.1%; p-0.06), major complications (31.8% vs. 30.1%; p-0.1), and mortality (3.5% vs. 3.2%; p-0.6) between the two groups. CONCLUSION: Glucocorticoids did not reduce the incidence of overall complications, postoperative fistula, and delayed gastric emptying following pancreaticoduodenectomy.

Assessing the perioperative complications and outcomes of robotic pancreaticoduodenectomy using the National Cancer Database: is it ready for prime time?

Robotic pancreaticoduodenectomy has generated significant interest in recent years. Our study aimed to evaluate the difference in surgical, oncological, and survival outcomes after pancreaticoduodenectomy (PD) by either a robotic (RPD) or open approach (OPD). Using the National Cancer Database, we identified patients from 2010 and 2017 diagnosed with pancreatic adenocarcinoma and underwent pancreaticoduodenectomy by either robotic PD or open approach. Patients who underwent robotic PD during 2010 were compared to patients receiving the same procedure in 2017. In addition, a secondary analysis was performed to assess outcomes of robotic PD to open PD for the 2017 patient cohorts. Our primary outcomes included 30-day and 90-day mortality, length of stay, as well as 30-day readmission. Secondary outcome measures were surgical margins, lymph node yield, and adjuvant chemotherapy initiation within 12 weeks of surgery. When we compared the 2017 data to 2010 data, we found that robotic pancreaticoduodenectomy had lower 30- and 90-day mortality rates in 2017 compared to 2010. Additionally, we found that the lymph node yield in robotic PD increased during the study period. When we compared robotic PD to open PD for 2017, we found no statistically significant differences in readmission rates (10.1% vs. 9.7%: p-0.4), lymph node yield, or negative margin between the groups. Outcomes of robotic PD have improved over the years. In 2017, outcomes of robotic PD were similar to open PD.

National Trends in Cholecystectomy and Endoscopic Retrograde Cholangiopancreatography During Index Hospitalization for Mild Gallstone Pancreatitis.

BACKGROUND: Guidelines call for cholecystectomy during the index hospitalization for patients with gallstone pancreatitis. Therefore, the study sought to determine the trends for cholecystectomy and Endoscopic Retrograde Cholangiopancreatography (ERCP) for mild gallstone pancreatitis. METHODS: A retrospective analysis of the 2010-2018 Nationwide Readmission Database (NRD) was performed to identify patients with mild gallstone pancreatitis. The primary aim was to identify the trends in the use of cholecystectomy in these patients, and the secondary aim was to assess if ERCP alone was protective against readmission. RESULTS: A total of 510,470 patients with mild gallstone pancreatitis were identified. There has been an increasing trend in ERCP use (25% in 2018 vs. 22% in 2010; p-0.001) and a decline in cholecystectomy (37% in 2018 vs. 46% in 2010; p-0.001) prior to discharge. Multivariate analysis revealed higher 30-day readmission for patients who underwent ERCP without cholecystectomy (odds ratio1.3; 95% confidence interval, 1.1-3.5) during the index admission. CONCLUSIONS: There has been a decline in the use of cholecystectomy during index hospitalization for mild gallstone pancreatitis. In addition, ERCP was not protective against 30-day readmission from mild gallstone pancreatitis.

The First Study Evaluating the Safety of Pre-Surgery Administration of Metformin in Patients with Colorectal and other Gastrointestinal Cancers and Effect on Cancer Stem Cells.

BACKGROUND: The cancer stem cell (CSC) hypothesis of tumor genesis suggests that unlike most cancer cells within tumor CSC resist chemotherapy and can regenerate various cell types in tumor thereby causing relapse. Hence drugs that selectively target CSC may offer great promise for cancer therapy especially when combined with chemotherapy. Current treatment options for colorectal cancer (CRC) and other gastrointestinal (GI) tumors rely on combination of surgical resection, cytotoxic and targeted drugs. Recent findings showed that metformin, an ant diabetic drug was associated with a significantly lower risk of CRC (0.63 [0.47 - 0.84]; P = 0.002) in patients with type 2 diabetes. We therefore hypothesize that administration of metformin will reduce CSC. METHODS: Patients with CRC and other GI cancers undergoing resection were enrolled. Metformin was administered at 500 mg orally twice daily for up to 14 days and terminated 24 hours, prior to planned surgery. Both tumor and normal tissue was procured. Adverse events (AEs) were graded according to NCI CTCAE Version 3.0. Primary objective was to establish the safety of administering metformin prior to resection. Secondary objective was to evaluate the effects of metformin on the expression of CSC markers by measuring relative mRNA levels of CD133, OCT4 and NANOG by RT-PCR and immunohistochemistry. RESULTS: A total of 10 patients (4 Male; 6 Female) received metformin. Grade 3 AEs included anemia, hypoalbuminemia, alanine aminotransferase elevation, abdominal pain and nausea but none of these were related to metformin. No hypoglycemia and lactic acidosis were observed. No unexpected post-operative complications were witnessed. Comparison of markers of CCSC results showed that expression of CD133, OCT4 and NANOG expression were decreased following metformin. CONCLUSIONS: Our pilot study showed feasibility of metformin before surgery in GI cancers and indicated impact on CSC. This preliminary data warrants further investigation in a larger randomized placebo-control study to assess these markers and their correlation with survival.

Is There any Survival Benefit of Maintenance Chemotherapy Following Adjuvant Chemotherapy in Patients with Resected Pancreatic Cancer Patients with Post-Surgery Elevated CA 19-9?

BACKGROUND: Pancreatectomy offers only potential for cure but is only possible in a minority of patients. Even in those patients who receive adjuvant chemotherapy, majority of them succumb to death due to metastases. Radiation Therapy Oncology Group 9704 showed that post-surgery CA 19-9 levels are an important predictor of survival. European study group for pancreatic cancer-3 showed that completion of all 6 cycles of adjuvant chemotherapy was an independent prognostic factor. Any survival benefit of an intensified chemotherapy strategy has not been demonstrated in patients with persistently elevated CA 19-9 following surgery. The object of this study was to investigate any benefit of maintenance chemotherapy following adjuvant in these patients. METHODS: Twenty patients with R0 surgery of pancreatic cancer who received adjuvant chemotherapy with post-surgery elevated CA 19-9 but no radiographic evidence of cancer was identified from 2005-2017. Either biopsy or positron emission tomography scan determined recurrence of cancer. Efficacy endpoints including overall survival and disease-free survival were assessed. RESULTS: Maintenance and additional chemotherapeutic agents included 5-FU, capecitabine, platinum agents, irinotecan and nab-paclitaxel. CA 19-9 normalized in 3 patients while 22 persisted to be elevated or had further increase in the marker. Two patients underwent metastatectomy. Median disease-free survival was 14.5m (9-18), OS 29m (19-96) and OS rates were 80%, 50% at 1 and 2 years respectively. CONCLUSIONS: We believe that the longer overall survival of our patients with elevated CA 19-9 post-surgery was due to maintenance and additional chemotherapy following planned 6-months of adjuvant therapy, close monitoring with monthly CA 19-9 and 3-monthly computed tomography scans. Our study also underlines importance of collecting pre-surgery CA 19-9 and complete staging including chest. Prospective study aiming to evaluate role of maintenance or intensified chemotherapy or targeted agents are indicated.

Simplified/Same Day(s)-GOLF as First-line Treatment of Metastatic Carcinoma of Unknown Primary (CUP), Suggestive of Pancreatobiliary Tumors.

BACKGROUND: Carcinoma of unknown primary represents a therapeutic challenge in oncological practice. Evidence lacks to support particular chemotherapy selection and empirical therapies are commonly extrapolated from data on patients where primary tumor site is known. Gemcitabine, Oxaliplatin, Leucovorin and 5-Fluorouracil was previously developed to treat pancreatic cancer. These agents have also demonstrated activities in other gastrointestinal malignancies. Considering promising anti-tumor effects of GOLF, we performed a retrospective study to investigate anti-tumor activity and safety of a simplified Gemcitabine, Oxaliplatin, Leucovorin and 5-Fluorouracil in patients with Carcinoma of unknown primary in whom immunohistostaining was suggestive of either upper gastrointestinal cancers or pancreatobiliary cancers. METHODS: This retrospective study included 18 patients recorded to have a diagnosis of Carcinoma of unknown primary between Aug 2010-Dec 2015, who received biweekly G 1000 mg/m2, O 85 mg/m2, L 200 mg/m2 and F 2400 mg/m2 over 46-h on day 1 with pegfilgrastim on day 3 every 14 days. IHC staining pattern favored upper GI origin, including stomach, bile duct or pancreas. Tumor assessments were repeated every 8 weeks. RESULTS: Median age was 67 years (range: 46-76), with ECOG PS<2, and 50% were women. Median number of cycles was 4 (range: 3-14). 7 partial responses were obtained (RR: 39%) and 7 achieved stable disease with overall disease control of 78%. Median time to tumor progression was 4 months (range: 2-9). 8 (44%) patients received liver-directed therapy and 1 underwent HIPEC (5%). Median survival time was 10.5 months (range: 6.7-14.5) and 1-year overall survival rate was 35%. Grade 3-4 toxicities included neutropenia, febrile neutropenia, thrombocytopenia, nausea, diarrhea, mucositis and oxaliplatin-induced neuropathy. CONCLUSION: Simplified Gemcitabine, Oxaliplatin, Leucovorin and 5-Fluorouracil regimen appears to be feasible with promising activity for Carcinoma of unknown primary and deserves to be evaluated in future trials.

Chemotherapy for intraperitoneal use: a review of hyperthermic intraperitoneal chemotherapy and early post-operative intraperitoneal chemotherapy.

Peritoneal spread of tumors is a major problem in cancer management. Patients develop a marked deterioration in quality of life and shortened survival. This is in part due to bowel obstructions, marked ascites, and overall increase debilitation. Standard medical management has shown to be inadequate for the treatment of these problems. Surgery can palliate symptoms, however, it is unable to be complete at the microscopic level by a significant spillage of tumor cells throughout the abdomen. Chemotherapy can have some improvement in symptoms however it is short lived due to poor penetration into the peritoneal cavity. The role of intraperitoneal chemotherapy is to maximize tumor penetration and optimize cell death while minimizing systemic toxicity. Hyperthermic intraperitoneal chemotherapy (HIPEC) and early post-operative intraperitoneal chemotherapy (EPIC) are two treatment methods that serve this role and have been shown to improve survival. This review will discuss different chemotherapies used for both of these treatment options.

Adjuvant therapy for pancreatic cancer.

Survival for patients with pancreas cancer is correlated to stage. Only 20% of patients present with localized disease amenable to potentially curative resection but, despite resection, the 5-year survival rate for early stage patients remains less than 25%. Current accepted standard of care is adjuvant gemcitabine following curative resection but there have been no conclusions regarding the role or timing of adjuvant chemoradiation. Although systemic disease represents the major risk for failure following resection, there are patients who would benefit from adjuvant local therapy that remain difficult to identify at present. This year at 2014 ASCO Gastrointestinal Cancers Symposium, Cho at al. (Abstract #325) presented the results of adjuvant gemcitabine with the addition of docetaxel followed by 5-FU chemoradiation for patients with resected pancreatic cancer. Kumar et al. (Abstract #330) compared adjuvant chemoradiation to adjuvant chemotherapy. Lastly Heestand et al. (Abstract #176) used a novel way to look at different biomarkers in serum of patients in the RTOG 9407 study and evaluated the survival depending on the type of chemotherapy used. A lower serum CEA and CA 19-9 gave a better overall survival in all patients which has already been established. Low levels of matrix metalloproteinase-7 (MMP-7) predicted an overall survival benefit from adjuvant gemcitabine, but not from 5-FU.

The effect of elevated body mass index on outcomes following cytoreductive surgery with hyperthermic intraperitoneal chemotherapy.

BACKGROUND: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) can prolong survival in peritoneal-based malignancies. These malignancies harbor in visceral and omental adipose tissue, and as a result, obesity may contribute to greater tumor burden. Obesity also is an independent risk factor for perioperative complications following major surgery. No studies to date have investigated the effect of elevated body mass index (BMI) on disease burden and perioperative outcomes in CRS-HIPEC patients. METHODS: Observational study of consecutive patients taken to the operating suite from 2007 to 2012 for CRS-HIPEC. Data were reviewed retrospectively, and patients for whom complete cytoreduction was not achieved and those with BMI <18.5 were excluded. Various operative data points, including peritoneal cancer index, surgery length, and estimated blood loss, were measured prospectively. Perioperative complications were identified and recorded. RESULTS: Complete data for review was available for 114 patients. Patients were subdivided based on BMI (group A 18.5-24.9, n = 43; group B 25-29.9, n = 49; group C ≥ 30, n = 22). There was no statistically significant difference in tumor burden, operative length, probability of unresectable disease, operative blood loss, or length of stay between groups. Rates of respiratory, gastrointestinal, infectious, renal, and hematologic complications were not statistically different, with the exception of deep vein thrombosis (A = 0, B = 13.5 %, C = 0; p = 0.026). CONCLUSIONS: CRS-HIPEC can be safely performed in overweight and obese patients without significant increase in perioperative morbidity. Despite the limitations in physical examination and increase in visceral fat, they do not appear to present later than patients with normal BMI, nor do they have higher tumor burden.

Adjuvant therapy of pancreatic cancer.

There is no clear consensus on what type of adjuvant therapy should be used for patients with pancreatic cancer. Chemoradiation is the favored treatment modality by many in the United States while gemcitabine based chemotherapy is favored in Europe. Both of these approaches have been shown by large prospective, randomized trials to improve disease free intervals and in some studies overall survival. This year at the American Society of Clinical Oncology (ASCO) Gastrointestinal Cancer Symposium, the randomized phase III study presented by Uesaka et al. from Japan (Abstract #145) represents a newer paradigm of oral adjuvant S-1 chemotherapy in place of the traditional standard of care intravenous gemcitabine in terms of prolonging patients' survival. Another study by Fan et al. (Abstract #269) examined the value of targeted therapy using erlotinib with adjuvant chemoradiation and chemotherapy. We present the summary of these two studies and discuss the potential impact on our clinical practice on this highly lethal cancer.

New developments in the management of borderline resectable pancreatic cancer.

The optimal management of borderline resectable pancreatic cancer remains unclear. Neoadjuvant chemoradiation remains the most common approach in the United States, while neoadjuvant chemotherapy alone is also widely utilized and has demonstrated efficacy but there has been no clear consensus about a regimen that would be most beneficial in this setting. We will discuss three abstracts that were presented in the 2013 ASCO Gastrointestinal Cancers Symposium in which various regimens were evaluated in the neoadjuvant setting.

Hyperthermic intraperitoneal chemotherapy in ovarian cancer: first report of the HYPER-O registry.

INTRODUCTION: An analysis of experience of surgical and gynecologic oncologists in the United States with the use of hyperthermic intraperitoneal chemotherapy for women with invasive epithelial ovarian cancer (EOC). METHODS: An Internet-based registry (HYPER-O) collected data from collaborating institutions. Eligibility included women with EOC treated with hyperthermic intraperitoneal chemotherapy. Borderline and nonepithelial cancers were excluded. RESULTS: As of July 1, 2008, 141 women were eligible for analysis treated at the following time points: frontline (n = 26), interval debulking (n = 19), consolidation (n = 12), and recurrence (n = 83). The mean perfusion temperatures were 38.5 to 43.6 degrees C (median, 41.9 degrees C) for inflow and 36.9 to 42.9 degrees C (median, 41 degrees C) for outflow for 30 to 120 minutes. Treatment was with a platinum agent (n = 72), mitomycin (n = 53), or a combination (n = 14). Median follow-up was 18 months (range, 0.3-140.5 months) and median overall survival 30.3 months (95% confidence interval, 23.0-37.6) with 2-, 5-, and 10-year overall survival probabilities of 49.1%, 25.4%, and 14.3%, respectively. Of the 141 patients, 110 (78%) experienced recurrence of ovarian cancer and 87 died, 3 (0.5%) dying within 30 days of surgery. In the multivariable analysis, the factors significant for increased survival were sensitivity to platinum response (P = 0.048), completeness of cytoreduction scores of 1 or 0 (P = 0.025), carboplatin alone or a combination of 2 or more chemotherapy agents used (P = 0.011), and duration of hospital stays of 10 days or less (P = 0.021). CONCLUSIONS: Hyperthermic intraperitoneal chemotherapy is a viable additional treatment option for patients with invasive EOC and may extend life in selected groups. It warrants further study in randomized controlled trials.