Faculty Bibliography

OBJECTIVES: Management of liver metastasis (LM) from a non-colorectal, non-neuroendocrine primary carcinoma remains controversial. Few data exist on the management of hepatic metastasis from primary renal cell carcinoma (RCC). This study sought to determine the safety and efficacy of surgery for RCC LM. METHODS: A total of 43 patients who underwent surgery for RCC hepatic metastasis between 1994 and 2011 were identified in a multi-institution hepatobiliary database. Clinicopathologic, operative and outcome data were collected and analysed. RESULTS: Mean patient age was 62.4 years and most patients (67.4%) were male. The mean tumour size of the primary RCC was 6.9 cm and most tumours (72.1%) were designated as clear cell carcinoma. Nine patients (20.9%) presented with synchronous LM. Among the patients with metachronous disease, the median time from diagnosis of the primary RCC to treatment of LM was 17.2 months (range: 2.1-189.3 months). The mean size of the RCC LM was 4.0 cm and most patients (55.8%) had a solitary metastasis. Most patients (86.0%) underwent a minor resection (up to three segments). Final pathology showed margin status to be negative (R0) in 95.3% of patients. Postoperative morbidity was 23.3% and there was one perioperative death. A total of 69.8% of patients received perioperative chemotherapy. Overall 3-year survival was 62.1%. Three-year recurrence-free survival was 27.3% and the median length of recurrence-free survival was 15.5 months. CONCLUSIONS: Resection of RCC hepatic metastasis is safe and is associated with low morbidity and near-zero mortality. Although recurrence occurs in up to 50% of patients, resection can be associated with long-term survival in a well-selected subset of patients.

BACKGROUND:Margin status is one of the strongest prognosticators after resection of pancreatic ductal adenocarcinoma (PDAC). The clinical significance of pancreatic intraepithelial neoplasia (PanIN) at a surgical margin has not been established. METHODS:A total of 208 patients who underwent R0 resection for PDAC between 2004 and 2008 were selected. Intraoperative frozen section slides containing the final pancreatic parenchymal transection margin were evaluated for presence or absence, number, and grade of PanINs. Data were compared to clinicopathologic factors, including patient survival. RESULTS:PanIN lesions were present in margins in 107 of 208 patients (51.4%). Median number of PanINs per pancreatic resection margin was 1 (range, 1-11). A total of 72 patients had PanIN-1 (34.6%), 44 had PanIN-2 (21.1%), and 16 had PanIN-3 (7.2%) at their margin. Overall median survival was 17.9 (95% confidence interval, 14-21.9) months. Neither the presence nor absence of PanIN nor histological grade had any significant correlation with important clinicopathologic characteristics. There were no significant survival differences between patients with or without PanIN lesions at the resection margin or among patients with PanIN-3 (carcinoma in situ) versus lower PanIN grades. However, patients with R1 resection had a significantly worse outcome compared with patients without invasive cancer at a margin irrespective of the presence of PanIN (P=0.02). CONCLUSIONS:The presence of PanINs at a resection margin does not affect survival in patients who undergo R0 resection for PDAC. These results have significant clinical implications for surgeons, because no additional resection seems to be indicated when intraoperative frozen sections reveal even high-grade PanIN lesions.

Only a minority of patients who undergo surgical resection for pancreatic ductal adenocarcinoma are cured. Since patient outcome is not reliably predicted using pathological factors (tumor stage, differentiation, and resection margin status) alone, markers of tumor behavior are needed. One candidate predictor of pancreatic cancer outcome is E-cadherin status. CDH1 is a tumor suppressor gene encoding an important cell adhesion molecule (E-cadherin). The aim of this study was to determine if, among patients undergoing pancreaticoduodenectomy for pancreatic adenocarcinoma, loss of E-cadherin expression was an independent predictor of poor outcome. We examined patterns of loss of E-cadherin by immunohistochemistry in tissue microarrays of 329 surgically resected pancreatic ductal adenocarcinomas. E-cadherin expression was then correlated with outcome. Kaplan-Meier analysis and Cox proportional hazards regression modeling were used to assess the mortality risk. One hundred forty-one pancreatic adenocarcinomas (43%) had partial or complete loss of E-cadherin expression within the analyzed tissue cores. In most instances (134 cases, 41%), this loss was partial. Patients whose pancreatic adenocarcinomas had either complete loss (n=7; median survival, 5.5 months) or partial loss (n=134; 12.7 months) of E-cadherin expression had significantly worse median survival than those with uniformly intact E-cadherin expression (n=188; 18.5 months) by univariate (P=0.002) and multivariate (P=0.006) analyses. In subgroup analysis, patients with poorly differentiated cancers had a worse prognosis if their cancers had partial loss of E-cadherin expression (P=0.02). Among patients undergoing pancreaticoduodenectomy for pancreatic ductal adenocarcinoma, partial loss of tumoral E-cadherin expression is an independent predictor of poor outcome.

Distinguishing between solid-pseudopapillary neoplasms (SPNs) and pancreatic neuroendocrine tumors (PanNETs) may pose a diagnostic dilemma. Both can demonstrate solid growth patterns, and both can be immunoreactive with neuroendocrine markers such as synaptophysin and CD56. One well-established feature of SPNs is the presence of hyaline globules, which in contrast has only rarely been reported in PanNETs. Clinicopathologic features of 361 cases originally classified as PanNETs were examined. Of these, 24 tumors (6.6%) had hyaline globules, raising the possibility of SPN. Immunohistochemistry for β-catenin was performed on these 24 neoplasms, and showed nuclear labeling in 6 cases. These 6 cases, which also demonstrated cytoplasmic CD10 staining, were reclassified as SPNs. The remaining 18 cases maintained their original diagnosis as PanNETs, and the hyaline globules in these cases were periodic acid-Schiff (PAS) positive, diastase resistant, and immunoreactive with α-1-antitrypsin. All 24 cases were histologically re-evaluated, and the pattern of invasion, presence of clear cells, and nuclear grooves were found to be helpful in distinguishing SPNs from PanNETs. We conclude that the presence of hyaline globules should raise SPNs in the differential diagnosis of a solid cellular neoplasm of the pancreas. However, this should not be used as the sole criterion in the diagnosis of SPNs, as hyaline globules may also be seen in 5% of PanNETs. Immunohistochemical and histologic features supporting the diagnosis of SPNs over PanNETs include CD10 and nuclear β-catenin labeling, an insidious pattern of invasion, clear cells, and nuclear grooves.

BACKGROUND:As indications for liver resection expand, objective measures to assess the risk of peri-operative morbidity are needed. The impact of sarcopenia on patients undergoing liver resection for colorectal liver metastasis (CRLM) was investigated. METHODS:Sarcopenia was assessed in 259 patients undergoing liver resection for CRLM by measuring total psoas area (TPA) on computed tomography (CT). The impact of sarcopenia was assessed after controlling for clinicopathological factors using multivariate modelling. RESULTS:Median patient age was 58 years and most patients (60%) were male. Forty-one (16%) patients had sarcopenia (TPA ≤ 500 mm(2) /m(2) ). Post-operatively, 60 patients had a complication for an overall morbidity of 23%; 26 patients (10%) had a major complication (Clavien grade ≥3). The presence of sarcopenia was strongly associated with an increased risk of major post-operative complications [odds ratio (OR) 3.33; P= 0.008]. Patients with sarcopenia had longer hospital stays (6.6 vs. 5.4 days; P= 0.03) and a higher chance of an extended intensive care unit (ICU) stay (>2 days; P= 0.004). On multivariate analysis, sarcopenia remained independently associated with an increased risk of post-operative complications (OR 3.12; P= 0.02). Sarcopenia was not significantly associated with recurrence-free [hazard ratio (HR) = 1.07] or overall (HR = 1.05) survival (both P > 0.05). CONCLUSIONS:Sarcopenia impacts short-, but not long-term outcomes after resection of CRLM. While patients with sarcopenia are at an increased risk of post-operative morbidity and longer hospital stay, long-term survival is not impacted by the presence of sarcopenia.

OBJECTIVES/OBJECTIVE:Defining perioperative mortality as death that occurs within 30 days of surgery may underestimate 'true' mortality among patients undergoing hepatic resection. To better define perioperative mortality, trends in the risk for death during the first 90 days after hepatectomy were assessed. METHODS:Surveillance, Epidemiology and End Results (SEER) Medicare data were used to identify 2597 patients who underwent hepatic resection during 1991-2006. Data on their clinicopathological characteristics, surgical management and perioperative mortality were collected and survival was assessed at 30, 60 and 90 days post-surgery. RESULTS:Overall, 5.7% of patients died within the first 30 days. Postoperative mortality at 60 and 90 days were 8.3% and 10.1%. In-hospital mortality after hepatic resection was greater among patients with hepatocellular carcinoma (HCC) than among those with colorectal liver metastases (CRLM) (8.9% and 3.8%, respectively; P < 0.001). In CRLM patients, mortality increased from 4.3% at 30 days to 8.4% at 90 days, whereas mortality in HCC patients increased from 9.7% at 30 days to 15.0% at 90 days (both P < 0.05). Patients with HCC were twice as likely as CRLM patients to die within 30 days [odds ratio (OR) 2.03], 60 days (OR = 1.74) and 90 days (OR = 1.71) (all P < 0.001). Differences in 30- and 90-day mortality were greatest among HCC patients undergoing major hepatic resection (P < 0.05). CONCLUSIONS:Reporting deaths that occur within a maximum of 30 days of surgery underestimates the mortality associated with hepatic resection. Traditional 30-day definitions of mortality are misleading and surgeons should report all perioperative outcomes that occur within 90 days of hepatic resection.

BACKGROUND:The American Joint Committee on Cancer staging system for hilar cholangiocarcinoma may be inaccurate because the bile duct lacks discrete tissue boundaries. OBJECTIVES/OBJECTIVE:To examine the accuracy of the American Joint Committee on Cancer staging schemes and to determine the prognostic implications of tumor depth. DESIGN, SETTING, AND PATIENTS/METHODS:From January 1, 1987, through December 31, 2009, there were 106 patients who underwent resection of hilar cholangiocarcinoma who had pathologic slides available for re-review. MAIN OUTCOME MEASURES/METHODS:Tumor depth and overall survival. RESULTS:Overall median survival was 19.9 months. The 6th and 7th editions of the T-classification criteria were unable to discriminate among T1, T2, and T3 lesions (P > .05 for all). Median survival was associated with the invasion depth of the tumor (≥5 mm vs <5 mm): 18 months vs 30 months (P = .01). On multivariate analysis, tumor depth remained predictive of disease-specific death (hazard ratio, 1.70; P = .03). CONCLUSIONS:The American Joint Committee on Cancer T-classification criteria did not stratify patients with regard to prognosis. Depth of tumor invasion is a better predictor of long-term outcome.