Shishir K. Maithel

Clinical and Economic Validation of the International Study Group of Pancreatic Fistula (ISGPF) Classification Scheme

Objective:The authors sought to validate the ISGPF classification scheme in a large cohort of patients following pancreaticoduodenectomy (PD) in a pancreaticobiliary surgical specialty unit. Summary Background Data:Definitions of postoperative pancreatic fistula vary widely, precluding accurate comparisons of surgical techniques and experiences. The ISGPF has proposed a classification scheme for pancreatic fistula based on clinical parameters; yet it has not been rigorously tested or validated. Methods:Between October 2001 and 2005, 176 consecutive patients underwent PD with a single drain placed. Pancreatic fistula was defined by ISGPF criteria. Cases were divided into four categories: no fistula; biochemical fistula without clinical sequelae (grade A), fistula requiring any therapeutic intervention (grade B), and fistula with severe clinical sequelae (grade C). Clinical and economic outcomes were analyzed across all grades. Results:More than two thirds of all patients had no evidence of fistula. Grade A fistulas occurred 15% of the time, grade B 12%, and grade C 3%. All measurable outcomes were equivalent between the no fistula and grade A classes. Conversely, costs, duration of stay, ICU duration, and disposition acuity progressively increased from grade A to C. Resource utilization similarly escalated by grade. Conclusions:Biochemical evidence of pancreatic fistula alone has no clinical consequence and does not result in increased resource utilization. Increasing fistula grades have negative clinical and economic impacts on patients and their healthcare resources. These findings validate the ISGPF classification scheme for pancreatic fistula.

Factors influencing readmission after pancreaticoduodenectomy: a multi-institutional study of 1302 patients.

Objective and Background:Morbidity, mortality, and length of hospital stay after pancreaticoduodenectomy (PD) have significantly decreased over recent decades. Despite this progress, early readmission rates after PD have been reported as high as 50%. Few reports have delineated factors associated with readmission after PD. Methods:The medical records of 6 high-volume institutions were reviewed for patients who underwent PD between 2005 and 2010. Data collection included patient characteristics, medical comorbidities, and perioperative factors. Analysis included readmissions up to 90 days after PD. Results:A total of 1302 patients underwent PD across all institutions. The 30-day and 90-day readmission rates were 15% and 19%, respectively. The most common reasons for 30-day readmission included infectious complications (n = 65) and delayed gastric emptying (n = 29). The most common reasons for readmission after 90 days included wound infections and intra-abdominal abscess (n = 75) and failure to thrive (n = 38). On multivariate analysis, factors associated with higher readmission rates included a preoperative diagnosis of chronic pancreatitis, higher transfusion requirements, and postoperative complications including intra-abdominal abscess and pancreatic fistula (all P < 0.02). Factors not associated with higher readmission rates included advanced age, body mass index, cardiovascular/pulmonary comorbidities, diabetes, steroid use, Whipple type (standard vs pylorus preserving PD), preoperative endobiliary stenting, and vascular reconstruction. Conclusions:These multi-institutional data represent a large experience of PD without the biases typically of single center studies. Factors related to infection, nutritional status, and delayed gastric emptying were the most common reasons for readmission after PD. Postoperative complications including pancreatic fistula predicted higher rates of readmission.

A prospective randomized trial of acute normovolemic hemodilution compared to standard intraoperative management in patients undergoing major hepatic resection.

Background:Hepatic resection is the most effective treatment for many malignant and benign conditions affecting the liver and biliary tree. Despite improvements, major partial hepatectomy can be associated with considerable blood loss and transfusion requirements. Transfusion of allogeneic blood products, although potentially life-saving, is associated with many potential complications. The primary aim of this study was to determine if acute normovolemic hemodilution (ANH), an established blood conservation technique, reduces the requirement for allogeneic red cell transfusions in patients undergoing major hepatic resection. Methods:One hundred thirty patients undergoing major hepatic resection (≥3 segments) were prospectively randomized to undergo either ANH or standard anesthetic management (STD). In the ANH group, intraoperative blood collection was performed to a target hemoglobin of 8.0 g/dL. Low central venous pressure anesthetic technique was used intraoperatively for both groups. A standardized transfusion protocol was applied to all patients intraoperatively and throughout the hospital stay. Results:From April 2004 to March 2007, 63 patients were randomized to ANH and 67 to STD. Demographics, diagnoses, liver function, extent of resection, intraoperative blood loss, operative time, incidence and grade of complications, and length of hospital stay were similar between the 2 groups. ANH reduced the overall allogeneic red cell transfusion rate by 50% compared with STD [12.7% (n = 8) vs. 25.4% (n = 17), respectively; P = 0.067. ANH patients were less often transfused intraoperatively (n = 1, 1.6%) compared with the STD group (n = 7, 10.4%) (P = 0.036), had higher postoperative hemoglobin levels (P = 0.01), and tended to require fewer red cell units overall (28 vs. 47 units). In patients with intraoperative blood loss ≥800 mL, ANH reduced not only the allogeneic red cell transfusion rate (18.2% vs. 42.4%, P = 0.045) but also the proportion of patients requiring fresh frozen plasma (21.1% vs. 48.3%, P = 0.025). Conclusion:For patients undergoing major liver resection, ANH is safe, effectively reduces the need for allogeneic transfusions, and should be considered for routine use. Given the modest transfusion rate in the STD arm, future efforts should attempt to target ANH use to patients most likely to benefit.

Modified FOLFIRINOX regimen with improved safety and maintained efficacy in pancreatic adenocarcinoma.

Objectives FOLFIRINOX (5-fluorouracil [5-FU], oxaliplatin, and irinotecan) as compared with gemcitabine in pancreatic cancer (PC) has superior activity and increased toxicity. The bolus 5-FU contributes to the toxicity. We hypothesized that the elimination of bolus 5-FU and use of hematopoietic growth factor will improve the safety profile without compromising the activity of FOLFIRINOX. Methods Sixty patients with PC treated with modified FOLFIRINOX (no bolus 5-FU) were reviewed. Patients were divided into metastatic or nonmetastatic (locally advanced or borderline resectable) disease. Toxicity, response rate, progression-free survival, and overall survival were evaluated. Results Nonmetastatic and metastatic disease were present in 24 (40%) and 36 (60%) patients, respectively. The incidence of grade 4 neutropenia, grade 3/4 diarrhea, and fatigue were 3%, 13%, and 13%, respectively. Response rate was 30%. The median progression-free survival for nonmetastatic disease was 13.7 months (95% confidence interval [CI], 9.6–24.6 months), and that for metastatic disease was 8.5 months (95% CI, 3.7–11.0 months), respectively. The median overall survival for nonmetastatic disease was 17.8 months (95% CI, 9.9 months to not estimable), and that for metastatic disease was and 9.0 months (95% CI, 7.1 months to not estimable), respectively. Conclusions Modified FOLFIRINOX has an improved safety profile with maintained efficacy in metastatic PC. Modified FOLFIRINOX has promising activity in nonmetastatic disease.

Ampullary Region Carcinomas: Definition and Site Specific Classification With Delineation of Four Clinicopathologically and Prognostically Distinct Subsets in an Analysis of 249 Cases

Ampullary (AMP) carcinomas comprise a heterogenous group of cancers lacking adequate subcategorization. In the present study, 249 strictly defined primary AMP carcinomas (ACs) identified in 1469 malignant pancreatoduodenectomy specimens were analyzed for defining features. Gross and microscopic findings were used to determine tumor epicenter and extent of preinvasive component. ACs were classified into 4 distinct subtypes based on location: (1) Intra-AMP (25%): Invasive carcinomas arising in intra-ampullary papillary-tubular neoplasms with zero to minimal, duodenal surface involvement (<25% of the tumor). These tumors were more commonly found in men, they had a relatively large overall size (mean, 2.9 cm) but had smaller invasive component (mean, 1.5 cm), and were predominantly of a lower TNM stage (85%, T1/2; and 72% N0). They carried the best prognosis among the 4 groups (3-y survival, 73%). (2) AMP-ductal (15%): These were tumors forming constrictive, sclerotic, plaque-like thickening of the walls of the common bile duct and/or pancreatic duct resulting in mucosa-covered, button-like elevations of the papilla into the duodenal lumen. There was no significant exophytic (preinvasive) growth. These were the smallest tumors (mean overall size, 1.9 cm; mean invasion size 1.7 cm), but carried the worst prognosis (3-y survival, 41%), presumably due to the pancreatobiliary histology/origin (in 86%); however, even this group had significantly better prognosis when compared with 113 ordinary pancreatic ductal adenocarcinomas (3 y, 11%; P<0.0001). (3) Peri-AMP-duodenal (5%): Massive exophytic, ulcero-fungating tumors growing into the duodenal lumen and eccentrically encasing the ampullary orifice with only minimal intra-ampullary luminal involvement. These were mostly of intestinal phenotype (75%) and some had mucinous features. Although these tumors were the largest (mean overall size 4.7 cm; and mean invasion size 3.4 cm), and had the highest incidence of lymph node metastasis (50%), they carried an intermediate prognosis (3-y survival, 69%) to that seen among a group of 55 nonampullary duodenal carcinoma controls. (4) AC—not otherwise specified (“papilla of Vater”; 55%): Ulcero-nodular tumors located at the papilla of Vater, which do not show the specific characteristics identified among the other 3 subtypes. In conclusion, ACs comprise 4 clinicopathologic subtypes that are prognostically distinct.

Is It Time to Abandon Routine Operative Drain Use? A Single Institution Assessment of 709 Consecutive Pancreaticoduodenectomies

BACKGROUND Routine use of operative (primary) drains after pancreaticoduodenctomy (PD) remains controversial. We reviewed our experience with PD for postoperative (secondary) drainage and postoperative pancreatic fistula (POPF) rates based on use of primary drains. STUDY DESIGN We identified consecutive patients who underwent PD between 2005 and 2012 from our pancreatectomy database. Primary closed suction drains were placed at the surgeons discretion. Patient and operative factors were assessed, along with POPF, complications, and secondary drain placement rates. RESULTS There were 709 PDs performed, and 251 (35%) patients had primary drains placed. Age, sex, body mass index, and comorbidities were similar among groups; however, drained patients had slightly larger pancreatic ducts (mean diameter 3.8 mm vs 2.2 mm; p < 0.01). The overall secondary drainage rate was 7.1%. Primary drain placement did not affect the need for secondary drainage (with primary drain, 8.4% vs without primary drain 6.3%, p = 0.36), reoperation (5.6% vs 5.7%, p = 1.00), readmission (17.5% vs 16.8%, p = 0.89), or 30-day mortality (2.0% vs 2.5%, p = 0.80). When compared with the no drain group, patients with primary drains experienced higher rates of overall morbidity (68.1% vs 54.1%, p < 0.01) and significant POPF (16.3% vs 7.6%; p < 0.01), as well as longer hospital stays (13.8 days vs 11.3 days; p < 0.01). On multivariate analysis, primary drain placement remained an independent risk factor for pancreatic fistula formation (hazard ratio 3.3, p < 0.01), but did not have an impact on secondary drainage rates (p = 0.85). CONCLUSIONS Placement of closed suction drains during pancreaticoduodenectomy does not appear to decrease the rate of secondary drainage procedures or reoperation, and may be associated with increased pancreatic fistula formation and overall morbidity. These data support foregoing routine primary operative drainage at time of pancreaticoduodenectomy.

Importance of Low Preoperative Platelet Count in Selecting Patients for Resection of Hepatocellular Carcinoma: A Multi-Institutional Analysis

BACKGROUND Low platelet count is a marker of portal hypertension but is not routinely included in the standard preoperative evaluation of patients with hepatocellular carcinoma (HCC) because it pertains to liver function (Child/model for end-stage liver disease [MELD] score) and tumor burden (Milan criteria). We hypothesized that low platelet count would be independently associated with increased perioperative morbidity and mortality after resection. STUDY DESIGN Patients treated with liver resection for HCC between January 2000 and January 2010 at 3 institutions were eligible. Preoperative platelet count, Child/MELD score, and tumor extent were recorded. Low preoperative platelet count (LPPC) was defined as <150 × 10(3)/μL. Postoperative liver insufficiency (PLI) was defined as peak bilirubin >7 mg/dL or development of ascites. Univariate and multivariate regression was performed for predictors of major complications, PLI, and 60-day mortality. RESULTS A total of 231 patients underwent resection, of whom 196 (85%) were classified as Child A and 35 (15%) as Child B; median MELD score was 8. Overall, 168 (71%) had tumors that exceeded Milan criteria and 134 (58%) had major hepatectomy (≥3 Couinaud segments). Overall and major complication rates were 55% and 17%, respectively. PLI occurred in 25 patients (11%), and 21 (9%) died within 60 days of surgery. Patients with LPPC (n = 50) had a significantly increased number of major complications (28% versus 14%, p = 0.031), PLI (30% versus 6%, p = 0.001), and 60-day mortality (22% versus 6%, p = 0.001). When adjusted for Child/MELD score and tumor burden, LPPC remained independently associated with increased number of major complications (odds ratio [OR] 2.8, 95% confidence intervals [CI] 1.1 to 6.8, p = 0.026), PLI (OR 4.0, 95% CI 1.4 to 11.1, p = 0.008), and 60-day mortality (OR 4.6, 95% CI 1.5 to 14.6, p = 0.009). CONCLUSIONS LPPC is independently associated with increased major complications, PLI, and mortality after resection of HCC, even when accounting for standard criteria, such as Child/MELD score and tumor extent, used to select patients for resection. Patients with LPPC may be better served with transplantation or liver-directed therapy.

Laparoscopic distal pancreatectomy: trends and lessons learned through an 11-year experience.

BACKGROUND As compared with open distal pancreatectomy, laparoscopic distal pancreatectomy (LDP) is associated with lower morbidity and shorter hospital stays. Existing reports do not elucidate trends in patient selection, technique, and outcomes over time. We aimed to determine outcomes after LDP at a specialized center, analyze trends of patient selection and operative technique, and validate a complication risk score (CRS). STUDY DESIGN Patients undergoing LDP between January 2000 and January 2011 were identified and divided into 2 equal groups to represent our early and recent experiences. Demographics, tumor characteristics, operative technique, and perioperative outcomes were examined and compared between groups. A CRS was calculated for the entire cohort and examined against observed outcomes. RESULTS A total of 132 LDPs were attempted, of which 8 (6.1%) were converted to open procedures. Thirty-day overall and major complication rates were 43.2% and 12.9%, respectively, with mortality < 1%. Pancreatic fistulas occurred in 28 (21%) patients, of which 14 (11%) were clinically significant. Recent LDPs (n = 66) included patients with increasingly severe comorbidities (Charlson scores > 2, 40.9% vs 16.7%, p = 0.003), more proximal tumors (74.2% vs 26.2%, p < 0.001), more extended resections (10.6 vs 8.3 cm, p < 0.001), shorter operative times (141 vs 172 minutes, p = 0.007), and less frequent use of a hand port (25.8% vs 66.6%, p < 0.001). No significant differences were found in perioperative outcomes between the groups. As compared with the hand access technique, the total laparoscopic approach was associated with shorter hospital stays (5.3 vs 6.8 days, p = 0.032). Increasing CRS was associated with longer operative time, significant fistulas, wound infections, blood transfusions, major complications, ICU readmissions, and rehospitalizations. CONCLUSIONS This large, single-institution series demonstrates that despite a shift in patient selection to sicker patients with more proximal tumors, similar perioperative outcomes can be achieved with laparoscopic distal pancreatectomy. The CRS appears to be a reliable preoperative assessment tool for assessing other adverse perioperative outcomes in addition to predicting overall complications and fistulas as originally published.

Safety and Efficacy of Doxorubicin Drug-eluting Bead Transarterial Chemoembolization in Patients with Advanced Hepatocellular Carcinoma

PURPOSE To investigate the safety and efficacy of transarterial chemoembolization using doxorubicin drug-eluting beads (DEBs) in patients with Barcelona Clinic Liver Cancer (BCLC) C stage hepatocellular carcinoma (HCC). METHODS Consecutive patients with initial staging of BCLC C HCC who received DEB transarterial chemoembolization over the last 5 years were studied. The study included 121 patients (mean age, 61.2 years old). Adverse events (AEs) after DEB transarterial chemoembolization were studied in detail and were recorded as per the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03 criteria. Survivals were analyzed according to parameters from the time of first DEB transarterial chemoembolization. Kaplan-Meier method by log-rank test and Cox proportional hazard model were used for survival analysis. RESULTS AEs occurred in 30.2% of patients. No AEs were greater than Common Terminology Criteria for Adverse Events grade III. Grade I and II AEs included nausea and vomiting in 7.8% of patients and abdominal pain in 23.8% of patients. Grade III AEs were noted in 1.06% of patients. There were no gastrointestinal or hepatic complications. There were no deaths within 30 days after DEB transarterial chemoembolization. The overall median survival was 13.5 months. Among the Child-Pugh class A patients, those without PVT and metastasis (28.9%) had better survival when treated with DEB transarterial chemoembolization than those with PVT and metastases (9.9%) (18.8 mo versus 4.4 mo, P = .001). Ascites, performance status, Okuda stage HCC, serum alpha fetoprotein levels, and etiologic factor for chronic liver disease predicted survival. CONCLUSIONS DEB transarterial chemoembolization appears to be a safe and effective treatment option for patients with BCLC C HCC. Patients with Child-Pugh class A without PVT and metastasis benefited most from DEB transarterial chemoembolization.

Rates and patterns of recurrence after curative intent resection for gastric cancer: a United States multi-institutional analysis.

BACKGROUND Reports on recurrence and outcomes of US patients with gastric cancer are scarce. The aim of this study was to determine incidence and pattern of recurrence after curative intent surgery for gastric cancer. STUDY DESIGN Using the multi-institutional US Gastric Cancer Collaborative database, we identified 817 patients undergoing curative intent resection for gastric cancer between 2000 and 2012. Patterns and rates of recurrence along with associated risk factors were identified using adjusted regression analysis. Recurrences were classified as locoregional, peritoneal, or hematogenous. RESULTS Median patient age was 65.8 years (interquartile range [IQR] 56.4, 74.7); the majority of patients were male (n = 462, 56.6%) and white (n = 511, 62.5%). At the time of surgery, the majority of patients underwent a partial gastrectomy (n = 481, 59.2%) with a complete R0 resection achieved in 91.6% (n = 748) of patients. At the time of last follow-up, 244 (29.9%) of 817 patients developed a recurrence; 163 (66.8%) patients had recurrence at only a single site; the remaining 81 (33.2%) had multiple sites of initial recurrence. Among patients who recurred at a single site, recurrence was most common at a distant location and included hematogenous (n = 57, 23.4%) or peritoneal (n = 47, 19.3%) only metastasis. Tumors at the gastroesophageal junction (odds ratio [OR] 3.18, 95% CI 1.08 to 9.40; p = 0.04) were associated with higher risk of locoregional recurrence, while the presence of multiple lesions (OR 10.82, 95% CI 3.56 to 32.85; p < 0.001) remained associated with an increased risk of distant hematogenous recurrence after adjusted analysis. Recurrence was associated with worse survival, with a median recurrence-free survival of 10.8 months (IQR 8.9, 12.8) among those who experienced a recurrence. CONCLUSIONS Nearly one-third of patients experienced recurrence after gastric cancer surgery. The most common site of recurrence was distant.