Variations in surgical treatment and outcomes of patients with pancreatic cancer: a population-based study.

BACKGROUND: There is ongoing debate on how variations in surgical technique affect outcomes in pancreatic cancer. This population-based study examines current surgical practice and outcomes for cancer of the pancreatic head. METHODS: All patients 18 to 85 years old diagnosed with nonmetastatic adenocarcinoma of the pancreatic head from 1998 through 2003 were identified from the Surveillance, Epidemiology and End Results (SEER) Program registry. Multivariable regression was used to elucidate factors associated with the type of pancreaticoduodenectomy performed, extent of lymph node (LN) assessment, early mortality, and late survival. RESULTS: Overall, 2111 patients were included in the study, with 83.7% treated with a standard Whipple pancreaticoduodenectomy (PD). However, there was marked regional variation in the use of pylorus-preserving pancreaticoduodenectomy (PPPD; range, .03%-32.0%; P < .0001) and total pancreatectomy (TP; range, .04%-19.5%; P < .0001). TP was associated with significantly higher early mortality (odds ratio, 2.6; 95% confidence interval, 1.6 to 4.1; P < .0001), but late survival did not differ significantly between TP, PPPD, and PD (P = .69). Significant variation was also seen in the number of LN assessed (range across SEER regions, 7.3-13.5; P < .0001). Decreased LN assessment reduced the odds of diagnosing a patient as node positive and was associated with worse late survival. CONCLUSIONS: In this population-based study, we found marked clinically important variability in the surgical treatment of adenocarcinoma of the pancreatic head, with respect to the use of TP, PPPD, or PD, and the extent of LN assessment. Further research is warranted to elucidate the underlying reasons, and to clarify the role of adequate lymphadenectomy.

Surgical management of intrahepatic cholangiocarcinoma--a population-based study.

BACKGROUND: Cholangiocarcinoma (CCA) is associated with poor survival and therapeutic nihilism. To date, there has not been an examination of the surgical management of CCA at a population level. METHODS: Using the Surveillance, Epidemiology and End Results (SEER) database, we identified all patients with intrahepatic CCA diagnosed between 1988 and 2003. Tumors categorized as a single, unilobar lesion with no evidence of vascular invasion were defined as localized. It was then determined whether patients received cancer directed surgery (CDS). Multivariable logistic regression was used to evaluate factors associated with CDS in patients with localized disease. The influence of CDS on overall survival (OS) was evaluated using Kaplan-Meier curves and Cox proportional hazards modeling. RESULTS: Only 446 (12%) of 3,756 patients with intrahepatic CCA underwent CDS. On multivariable analysis, non-Klatskin tumor (p < 0.01) and younger age (p = 0.02) was associated with CDS. Localized disease was strongly associated with CDS (p < 0.01); however, only 91 (37%) of these 248 patients underwent CDS. Of patients with localized disease, those who had CDS had significantly better survival than those who did not (p < 0.01), with median overall survival (OS) of 44 months versus 8 months, and five-year OS of 42% versus 4%, respectively. CONCLUSIONS: Patients with localized CCA who are selected for CDS are strongly associated with improved survival, with rates approaching that found in single institution studies. However, many patients with localized tumors do not receive potentially curative cancer-directed surgery. Further study is warranted to address the barriers to the delivery of appropriate care to these patients.

Does microvascular invasion affect outcomes after liver transplantation for HCC? A histopathological analysis of 155 consecutive explants.

Macroscopic vascular invasion (macroVI) is associated with poor outcomes after liver transplantation (LT) for hepatocellular carcinoma (HCC). Whether microvascular invasion (microVI) is associated with the same adverse prognosis is unclear. One hundred and fifty-five consecutive patients with confirmed HCC after LT from March 1991 to 2004 at our institution were reviewed. Patients had to satisfy Milan criteria to be accepted for LT. They were followed with surveillance images every 3 months while on the waiting list. Disease-free survival (DFS) and overall survival (OS) were evaluated by Kaplan-Meier analysis. Demographic, tumor, and histopathologic characteristics were tested for their prognostic significance. Median follow-up after LT was 30 months. Overall graft survival rates were 87, 74, and 65% at 1, 3, and 5 years, respectively. All recurrences (22/155, 14%) developed within 4 years after LT with an overall 5-year DFS of 79%. Vascular invasion, either microVI or macroVI, was more likely in patients with multicentric HCC (n>or=3, p<0.001) and larger tumor size>4 cm (p=0.04). Tumor size>5 cm (p=0.04), advanced pathological TMN stage (p=0.007), microVI (p=0.001), and macroVI (p<0.001) predicted poor tumor-free survival on univariate analysis, but only macroVI was significant in multivariate analysis (hazard ratio 54.2, 95% confidence interval 11, 266). Furthermore, only macroVI was a significant predictor of mortality after LT (p=0.01). Macrovascular invasion is strongly associated with high rates of recurrence and diminished survival after LT whereas microVI is not an independent risk factor.

Accuracy of staging as a predictor for recurrence after liver transplantation for hepatocellular carcinoma.

BACKGROUND: Tumor number, size, and macrovascular invasion (MacroVI) are the most widely used predictors of survival after liver transplantation (LT) for hepatocellular carcinoma (HCC). We analyzed all patients undergoing LT for HCC at our center to establish the accuracy of preoperative clinical staging and to determine which patients have a higher probability of being understaged. METHODS: In all, 118 patients with confirmed HCC after LT from April 1991 to October 2004 at our institution were reviewed. All patients were monitored with serial imaging every 3 months to ensure their eligibility for LT within Milan criteria. Understaging in the 118 patients was defined as evidence on explant pathology that Milan criteria (TNM stage pT1 or pT2) had been exceeded. RESULTS: Five-year DFS was 78% with a recurrence rate of 15% after a median follow-up after LT of 30 months. On explant pathology, 43% (51/118) of patients exceeded Milan criteria and had a worse DFS (1 year, 95% vs. 87%; 3 year, 87% vs. 64%; P=0.03) compared to those who met LT criteria. Understaging was more likely in patients with imaging characteristics of > or = 2 tumor nodules (P=0.005) and tumor growth > 0.25 cm/month (P=0.02) and pathologic findings of vascular invasion (P=0.001) and bilobar tumors (P=0.002). CONCLUSIONS: Preoperative imaging every 3 months while on the waiting list frequently understages HCC as assessed by explant pathology. Recurrence after LT often occurred in patients that were understaged. Improving the accuracy of clinical staging and inclusion parameters will ensure proper organ allocation and acceptable outcomes after LT.

Surgery for gallbladder cancer: a population-based analysis.

BACKGROUND: Gallbladder cancer is an aggressive neoplasm, and resection is the only curative modality. Single institutional studies report an aggressive surgical approach improves survival. This analysis was performed to examine the components of surgical resection and resultant survival. STUDY DESIGN: From 1988 to 2003, patients aged 18 to 85 years, resected of T1-3 M0 gallbladder cancer, were identified from the Surveillance, Epidemiology, and End Results (SEER) registry. Resections were classified as en bloc (cholecystectomy + at least one adjacent organ) or simple (cholecystectomy only); lymphadenectomy was defined as three or more lymph nodes assessed. RESULTS: Of the 2,835 resected patients with T1-T3 M0 cancer, only 8.6% underwent an en bloc resection, and 5.3% had a lymphadenectomy. In multivariable analysis, age, year of resection, region, and advanced T-stage were associated with more aggressive resection. In univariate analysis, improved survival was associated with en bloc resection for T1/2 cancers, and lymphadenectomy for T2/3 cancers. In multivariable analysis, the following were associated with improved survival: for T1 cancers, en bloc resection, younger age, lower grade, and recent year of resection; for T2 cancers, Caucasian race (versus African-American), lower grade, and node negative disease, with trends for en bloc resection and lymphadenectomy; and for T3 cancers, female gender, Caucasian race (versus American Indian), lower grade, node negative disease, and recent year of resection, with a strong trend for lymphadenectomy. CONCLUSIONS: Very few patients underwent aggressive surgery. En bloc resection and lymphadenectomy may have stage-specific effects on survival. Additional studies should explore the underuse of aggressive operations, verify survival advantages, and define stage-specific resection strategies.

Role of sentinel lymph node biopsy in ductal carcinoma-in-situ treated by mastectomy.

BACKGROUND: Sentinel lymph node biopsy (SLNB) is a widely accepted alternative to axillary lymph node dissection in invasive breast cancer. Its role in ductal carcinoma-in-situ (DCIS) is unclear. The purpose of this study was to determine factors associated with the subsequent diagnosis of invasive disease and to determine the role of SLNB when performing a mastectomy for DCIS. METHODS: A retrospective study was conducted of all mastectomies performed on patients with a preoperative diagnosis of DCIS between 2000 and 2005 at a single tertiary-care institution. RESULTS: Ninety mastectomies for DCIS were included, 54 (60%) of which were performed with concurrent SLNB. Of 44 patients diagnosed preoperatively with DCIS by core biopsy only, 34 patients (63%) had a concurrent SLNB, while 10 patients (28%) were treated with mastectomy alone (P < .01). Overall, 30 patients (33%) had invasive disease, 22 of whom received concurrent SLNB. Seven SLNB patients (13%) had positive SLNs. On univariate analysis, multifocality (P = .03), multicentricity (P = .01), comedonecrosis (P = .01), and diagnosis by core biopsy (P < .001) were associated with invasive disease on pathology. On multivariate analysis, comedonecrosis (P = .04) and diagnosis by core biopsy (P < .01) were independent predictors for invasion. There was no statistically significant predictor for sentinel lymph node metastasis. CONCLUSIONS: Approximately one-third of patients with DCIS treated with mastectomy at our institution later had invasive disease, and factors associated with invasion have been identified. On the basis of our results, routine SLNB is recommended in this patient population.

An analysis of resection vs transplantation for early hepatocellular carcinoma: defining the optimal therapy at a single institution.

BACKGROUND: The reported survival after liver transplantation (OLT) for early hepatocellular carcinoma (HCC) is superior to the results of liver resection (LR), but few analyses have considered long waiting times and patient drop-offs due to tumor progression. METHODS: From 1995-2005, 347 patients with HCC were evaluated at our institution and underwent either LR (n = 174) or placed on the OLT waiting list (n = 173). Patients who only underwent ablation were not included. After eliminating patients with 1) incidental tumors after OLT, 2) tumors outside of Milan criteria, 3) preoperative vascular invasion prior to LR and 4) Child-Pugh Class C cirrhosis prior to OLT, 261 patients (LR = 121; OLT = 140) were included in this analysis. RESULTS: Median follow-up time was 35 months. Median waiting time for OLT was 7.7 months; during this time, 30 patients were taken off the waiting list. Overall survival (OS) from time of listing or LR was not different between the two groups; 1, 3, and 5 year OS after LR was 89%, 75%, and 56% compared with 90%, 70%, and 64% for OLT (P = .84). Only patients who waited <4 months for OLT (n = 67) had better survival than those who underwent LR (P = .05). Patients who waited longer that four months for OLT had a 2.5x higher risk of death in a Cox multivariate model [odds ratio (OR) 2.5; 95% confidence interval (CI): 1.3-5; P = .007]. CONCLUSION: Unless waiting time is short (< 4 months), the survival of patients with early HCC is similar between LR and LT.