Sherri Yong

Unfavourable prognosis associated with K-ras gene mutation in pancreatic cancer surgical margins

Background: Despite intent to cure surgery with negative resection margins, locoregional recurrence is common in pancreatic cancer. Aims: To determine whether detection of K-ras gene mutation in the histologically negative surgical margins of pancreatic cancer reflects unrecognised disease. Patients: Seventy patients who underwent curative resection for pancreatic ductal adenocarcinoma were evaluated. Methods: All patients had surgical resection margins (pancreatic transection and retroperitoneal) that were histologically free of invasive cancer. DNA was extracted from these paraffin embedded surgical margins and assessed by quantitative real time polymerase chain reaction to detect the K-ras gene mutation at codon 12. Detection of K-ras mutation was correlated with standard clinicopathological factors. Results: K-ras mutation was detected in histologically negative surgical margins of 37 of 70 (53%) patients. A significant difference in overall survival was demonstrated between patients with margins that were K-ras mutation positive compared with negative (median 15 v 55 months, respectively; p = 0.0008). By univariate and multivariate analyses, detection of K-ras mutation in the margins was a significant prognostic factor for poor survival (hazard ratio (HR) 2.8 (95% confidence interval (CI) 1.5–5.3), p = 0.0009; and HR 2.8 (95% CI 1.4–5.5), p = 0.004, respectively). Conclusions: Detection of cells harbouring K-ras mutation in histologically negative surgical margins of pancreatic cancer may represent unrecognised disease and correlates with poor disease outcome. The study demonstrates that molecular-genetic evaluation of surgical resection margins can improve pathological staging and prognostic evaluation of patients with pancreatic ductal adenocarcinoma.

The development of de novo hepatocellular carcinoma in patients on a liver transplant list: Frequency, size, and assessment of current screening methods

Chronic end stage liver disease is the most frequent indication for liver transplantation. Individuals with end stage cirrhosis, and therefore individuals on liver transplant lists, are at increased risk of developing a hepatic cancer. Those individuals on liver transplant lists also may represent the best group available for evaluating the current methods for screening and surveillance for the development of hepatic cancer as an examination of the explant liver provides a gold standard for tumor assessment. Assuming that only tumor free individuals were screened at the onset of this study, the data obtained enables one to determine the frequency of new hepatic cancers since listing and evaluate the positive and negative predictive values of each assessment method over the surveillance interval. All patients listed for liver transplantation with end stage chronic liver disease, who did not have a hepatoma at the time of transplant listing, were followed and assessed for the development of a hepatic cancer while on the waiting list. The screening techniques utilized included quarterly α fetoprotein (αFP) determinations and ultrasound (US) studies as well as semi‐annual triple phase computed tomography (CT) scans of the liver. αFP failed to identify any cases of de novo hepatic cancer in patients waiting for a liver transplant. In contrast, US and especially CT scanning with intravenous contrast identified new hepatic masses. The later method, which identified early enhancing mass lesions, was the more valuable method at identifying masses that subsequently were shown by pathologic examination of the explant liver to be hepatic cancers. However, only 14 of 20 individuals found to have a de novo tumor were identified by this method. Once identified however, the treatments utilized for hepatic tumor ablation while waiting for a transplant appear to be effective with a mean of 57.8±8.3% necrosis of the treated masses being identified at the time of explant examination. In conclusion these data suggest that: 1 The development of a hepatocellular carcinoma (HCC) in an individual on a transplant list is not rare and occurs in as many as 20% of cases; 2 The most effective method for the detection of de novo HCC appears to be semi‐annual triphasic CT scan with the identification of a new early enhancing lesion; and 3 Once recognized, the presence of the tumor enables the individual to move up on the waiting list as result of the additional model endstage liver disease (MELD) points allowed for individuals with HCCs. (Liver Transpl 2004;10:631–637.)

Cystic glucagonoma: a rare variant of an uncommon neuroendocrine pancreas tumor

Glucagon-producing neuroendocrine tumors typically present with a characteristic constellation of symptoms including necrolytic migratory erythema, non-insulin-dependent diabetes, weight loss, anemia, glossifis, and an increased thrombotic tendency. Most ghicagonomas are solid and arise in the body or tail of the pancreas. We report two cases of cystic glucagonoma, one found incidentally in an asymptomatic patient and one in a patient with weight loss and diabetes but no rash. In the first patient, distal pancreatectomy and splenectomy were curative, whereas the second patient continued to exhibit elevated serum glucagon levels and symptoms of glucose intolerance in the absence of demonstrable metastases. Cystic glucagonoma is a unique variant of classic glucagonoma and should be considered in the differential diagnosis of cystic pancreatic neoplasms.

Adenosquamous carcinoma of the pancreas

SummaryBackgroundAdenosquamous carcinoma of the pancreas most probably represents squamous metaplasia of an adenocarcinoma. Metastases are typically an admixture of both elements, but more frequently, adnocarcinoma.MethodsA review of 102 pancreaticoduodenectomies for masses of the head of the pancreas done between 1994 and 1998 revealed two patients with adenosquamous carcinoma of the pancreas.ResultsBoth patients underwent successful pancreaticoduodenctomy, but were found to have nodal metastasis. One patient lived 13 mo and the other lived 14 mo with both dying from metastatic disease.ConclusionAdenosquamous carcinoma of the pancreas is a rare tumor, and because its presentation, clinical features, and course are identical to adenocarcinoma of the pancreas, it should be considered in the differential diagnosis for any mass of the head of the pancreas. Survival is poor for these patients. In this series, it was 13 and 14 mo, respectively.

Primary Malignant Melanoma of the Common Bile Duct A Case Report and Review of the Literature

Primary malignant melanoma of the common bile duct is rare. To our knowledge, only 6 cases have been reported previously. The pathologic diagnosis of primary malignant melanoma in extracutaneous sites often requires the use of confirmatory immunohistochemical stains and electron microscopy studies, as well as tests to rule out other possible remote or concurrent primary sites. The presence of junctional activity adjacent to the tumor is another important requisite for the diagnosis of this entity. Nevertheless, absolute exclusion of a metastatic melanoma from an unknown occult site or regressed site is not entirely possible. We describe our observations in a case of primary malignant melanoma of the common bile duct in a 48-year-old man and discuss the criteria for diagnosis of primary melanoma.

Pancreaticoduodenectomies in patients without periampullary neoplasms: lesions that masquerade as cancer

BACKGROUND Most pancreaticoduodenectomies (PDs) are performed to treat periampullary malignancies (PMs). Final pathologic analysis on these specimens does not always contain PMs. Our aim was to classify diseases that preoperatively mimic PMs. METHODS A prospective database of PDs performed at a single institution was reviewed. Clinicopathologic data on patients without PM on pathologic review with preoperative suspicion of PM were studied. RESULTS Of the 461 PDs performed at our institution, 45 (10%) had no PM; of these cases, 35 (78%) were performed for a clinical suspicion of malignancy. The final pathologic review showed chronic pancreatitis (CP) in 23 (66%) patients, biliary tract disease in 10 (28%) patients, duodenal ulcer in 1 (3%) patient, and distal common bile duct stricture with localized pancreatic fibrosis in 1 (3%) patient. CONCLUSION Most patients undergoing PD have evidence of a PM. A subset of patients may have lesions that mimic a PM. In these patients, when PM cannot be ruled out, if possible, they should be offered PD.

Should all branch-duct intraductal papillary mucinous neoplasms be resected?

BACKGROUND The relationship between branch-duct intraductal papillary mucinous neoplasms (IPMNs) and malignancy remains controversial and difficult to assess. METHODS Between January 1, 1999 and January 1, 2013, we identified 84 patients with IPMN who underwent resection. RESULTS Preoperatively, 55 patients underwent endoscopic ultrasounds and 58 underwent biopsy. Only 7 lesions were specified preoperatively as branch-duct, which inconsistently correlated with the surgical specimen. Of the 82 patients where the duct was specified, there were 33 malignant lesions. There was no correlation between branch-duct origin and invasive carcinoma. Malignant tumor size did not significantly differ by the duct of origin. Of the 28 patients with invasive carcinoma, branch-duct lesions were significantly associated with the presence of positive lymph nodes, perineural invasion, and lymphovascular invasion. CONCLUSIONS Our study supports the resection criteria for branch-duct IPMN based on size and symptoms. However, it also questions the reliability of our preoperative testing to rule out malignant branch-duct IPMN lesions.

The depth of post-treatment perirectal tissue invasion is a predictor of outcome in patients with clinical T3N1M0 rectal cancer treated with neoadjuvant chemoradiation followed by surgical resection

BACKGROUND To determine if patients with clinical stage III rectal cancer treated with neoadjuvant chemoradiotherapy (CRT) and surgery have an improved survival when the response to treatment results in a pathologic T3 tumor with a microscopic focus (≤5 mm) compared with a larger (>5 mm) invasion of the perirectal tissue. METHODS A retrospective review was conducted of 56 consecutive patients clinically diagnosed as T3N1M0 rectal cancer before treatment, who completed neoadjuvant CRT followed by surgical resection. Those with residual pathologic T3 disease (n = 28) were analyzed separately. Clinicopathologic data including T stage, lymph node status, k-ras status, and differentiation were reviewed. RESULTS Among all 56 patients, there was no identified predictor of survival following neoadjuvant CRT and surgery. Among those with residual T3 disease, tumors extending >5 mm invasion into the perirectal tissue were associated with a higher risk of recurrence (50% vs 17%) and worse overall survival (4.3 vs 6.8 years, P = .015) when compared to tumors with ≤5 mm invasion into the perirectal tissue. CONCLUSION The depth of residual T3 tumor invasion into the perirectal tissue correlates with recurrence and overall survival in patients who underwent neoadjuvant therapy followed by surgical resection for clinically staged T3N1M0 rectal cancer.

Support for a postresection prognostic score for pancreatic endocrine tumors

BACKGROUND Prognostic scores predicting long-term survival of patients with pancreatic neuroendocrine tumors (PNETs) have been created. The purpose of this study was to validate a prognostic scoring scheme at a single institution. METHODS We reviewed all resections for PNETs from 1996 to 2004. Prognostic scores based on patient age, tumor grade, and distant metastasis were calculated. Survival was compared with an established postresection prognostic score for PNETs. RESULTS A total of 34 PNETs were identified. Predicted 5-year survival for prognostic scores of 1, 2, and 3 were 76.7%, 50.9%, and 35.7%, respectively. Final prognostic scores of 1, 2, and 3 were observed in 13 (38%), 18 (53%), and 3 (9%) patients, with observed actual 5-year survivals of 92.3%, 72.2%, and 66.7%, respectively. CONCLUSIONS PNET prognostic scores were found to be inversely related to survival. PNET postresection prognostic score categories may be useful tools in predicting long-term survival.

The Association between Survival and the Pathologic Features of Periampullary Tumors Varies over Time

Introduction. Several histopathologic features of periampullary tumors have been shown to be correlated with prognosis. We evaluated their association with mortality at multiple time points. Methods. A retrospective chart review identified 207 patients with periampullary adenocarcinomas who underwent pancreaticoduodenectomy between January 1, 2001 and December 31, 2009. Clinicopathologic features were assessed, and the data were analyzed using univariate and multivariate methods. Results. In univariate analysis, perineural invasion had a strong association with 1-year mortality (OR 3.03, CI 1.42–6.47), and one lymph node (LN) increase in the LN ratio (LNR) equated with a 5-fold increase in mortality. In contrast, LN status (OR 6.42, CI 3.32–12.41) and perineural invasion (OR 5.44, CI 2.81–10.52) had the strongest associations with mortality at 3 years. Using Cox proportional hazards, perineural invasion (HR 2.61, CI 1.77–3.85) and LN status (HR 2.69, CI 1.84–3.95) had robust associations with overall mortality. Recursive partitioning analysis identified LNR as the most important risk factor for mortality at 1 and 3 years. Conclusions. Overall mortality was closely related to the LNR within the first year, while longer follow-up periods demonstrated a stronger association with perineural invasion and overall LN status. Therefore, the current staging for periampullary tumors may need to be updated to include the LNR.