Palliative treatment of obstructive jaundice in patients with carcinoma of the pancreatic head or distal biliary tree. Endoscopic stent placement vs. hepaticojejunostomy.

CONTEXT: Palliative procedures play an important role in the treatment of malignancies of the pancreatic head/distal biliary tree, as only 20-30% can be cured by surgical resection. OBJECTIVE: We sought to determine if surgical or non-surgical management was the most appropriate therapy for the treatment of obstructive jaundice in the palliative setting. SETTING: High volume center for pancreatic surgery. PATIENTS: Analysis of 342 palliatively-treated patients with adenocarcinoma of the pancreatic head or the distal biliary tree. MAIN OUTCOME MEASURES: We studied the outcomes with regard to treatment, complications and survival times. DESIGN: The patients were divided into three groups. Group 1: endoscopic bile duct endoprosthesis (no. 138, 56%); Group 2: preoperative stenting followed by laparotomy (if patients were found to be unresectable, palliative hepaticojejunostomy was performed) (no. 68, 28%); Group 3: hepaticojejunostomy without preoperative stenting (no. 41, 16%). We also determined the frequency of re-hospitalization for recurrent jaundice. RESULTS: Two hundred and sixty-one (76%) patients showed obstructive jaundice. Mortality in Groups 1, 2, and 3 was 2.2%, 0%, and 2.4%, respectively and morbidity was 5.1%, 17.6%, and 14.6%, respectively. The mean interval between stent exchanges was 70.8 days. Median survival for patients treated only with an endoscopic stent (Group 1) was significantly shorter than that of patients who were first stented and subsequently treated with hepaticojejunostomy (Group 2) (5.1 vs. 9.4 months; P<0.001). CONCLUSIONS: Hepaticojejunostomy can be performed with satisfactory operative results and acceptable morbidity. Considering that biliary stents can occlude, a hepaticojejunostomy may be superior to endoscopic stenting; hepaticojejunostomy should be especially favored in patients whose disease is first found to be unresectable intraoperatively.

Surgical therapy of intrapancreatic metastasis from renal cell carcinoma.

BACKGROUND: Pancreatic metastases from renal cell carcinoma (RCC) are clinically rare but highly resectable. The aim of this article is to identify patients who profit from pancreatic resection of RCC despite the invasiveness of the surgery. METHODS: Between January 1996 and December 2007, data from 744 patients were collected in a prospective pancreatic surgery database, and patients with metastasis into the pancreas from RCC were identified. RESULTS: Resective surgery was performed in 14 patients with metastasis to the pancreas from RCC. Most patients were clinically asymptomatic. The median interval between primary treatment of RCC and occurrence of pancreatic metastasis was 94 months (range 32-158). The morbidity rate was 42.8%. Patients with a metastasis size <2.5 cm had a much better survival after resection (100 months) than those with a metastasis size >2.5 cm (44 months). Moreover, the number of metastases predicts the survival after resection. CONCLUSIONS: In patients with pancreatic metastases from RCC who have only limited disease, complete resection of all lesions can be successfully performed with a low rate of complications. Thus, patients with a history of RCC should be monitored for more than 10 years after nephrectomy to detect recurrence.

Curative resection of a primarily unresectable acinar cell carcinoma of the pancreas after chemotherapy.

BACKGROUND: Acinar cell carcinoma (ACC) represents only 1-2% of pancreatic cancers and is a very rare malignancy. At the time of diagnosis only 50% of the tumors appear to be resectable. Reliable data for an effective adjuvant or neoadjuvant treatment are not available. CASE PRESENTATION: A 65-year old male presented with obstructive jaundice and non-specific upper abdominal pain. MRI-imaging showed a tumor within the head of the pancreas concomitant with Serum-Lipase and CA19-9. During ERCP, a stent was placed. Endosonographic fine needle biopsy confirmed an acinar cell carcinoma. Laparotomy presented an locally advanced tumor with venous infiltration that was consequently deemed unresectable. The patient was treated with five cycles of 5-FU monotherapy with palliative intention. Chemotherapy was well tolerated, and no severe complications were observed. Twelve months later, the patient was in stable condition, and CT-scanning showed an obvious reduction in the size of the tumor. During further operative exploration, a PPPD with resection of the portal vein was performed. Histopathological examination gave evidence of a diffuse necrotic ACC-tumor, all resection margins were found to be negative. Eighteen months later, the patient showed no signs of recurrent disease. CONCLUSION: ACC responded well to 5-FU monochemotherapy. Therefore, neoadjuvant chemotherapy could be an option to reduce a primarily unresectable ACC to a point where curative resection can be achieved.

Color Doppler imaging predicts portal invasion by pancreatic adenocarcinoma.

BACKGROUND: Tumor infiltration of the intima of the portal vein (PV) and superior mesenteric vein (SMV) by pancreatic adenocarcinoma is classically considered a criterion for unsuitability for resection and poor prognosis. This study was performed to evaluate modern color duplex imaging (CDI) for the assessment of PV/SMV infiltration by pancreatic adenocarcinomas. METHOD: From 1994 to 2005, Whipple's procedure or pylorus-preserving pancreato-duodenectomy (PPPD) was performed in 303 patients with pancreatic adenocarcinoma; 35 of these underwent partial PV/SMV resection. Applying a previously reported CDI score, we evaluated the integrity of the echogenic border layer between the vein and tumor (mural demarcation) and maximum blood flow velocity (V (max)) in the PV segment in contact with the tumor. The results were compared to the final histological findings in the resected venous walls. RESULTS: CDI findings correlated well with the histological invasion grades. By measuring V (max )and evaluating mural demarcation, we observed a sensitivity of 66.7% and 100% and a specificity of 98.3% and 93.9%, respectively, in predicting full thickness vein invasion, including the intima. V (max) above 80 cm/s and lack of mural demarcation were predictors of PV/SMV invasion. The postoperative survival rates depended on the depth of tumor infiltration into the PV/SMV. CONCLUSIONS: Modern CDI is a reliable and valid technique for evaluation of morphological and hemodynamic parameters in the portal vein segment adjacent to pancreatic adenocarcinoma. Maximal blood-flow velocity in the portal segment in contact with the tumor and absence of the echogenic vessel-parenchymal sonographic interface are parameters predictive of tumor infiltration of the portal intima.

A randomized multi-center phase II trial of the angiogenesis inhibitor Cilengitide (EMD 121974) and gemcitabine compared with gemcitabine alone in advanced unresectable pancreatic cancer.

BACKGROUND: Anti-angiogenic treatment is believed to have at least cystostatic effects in highly vascularized tumours like pancreatic cancer. In this study, the treatment effects of the angiogenesis inhibitor Cilengitide and gemcitabine were compared with gemcitabine alone in patients with advanced unresectable pancreatic cancer. METHODS: A multi-national, open-label, controlled, randomized, parallel-group, phase II pilot study was conducted in 20 centers in 7 countries. Cilengitide was administered at 600 mg/m2 twice weekly for 4 weeks per cycle and gemcitabine at 1000 mg/m2 for 3 weeks followed by a week of rest per cycle. The planned treatment period was 6 four-week cycles. The primary endpoint of the study was overall survival and the secondary endpoints were progression-free survival (PFS), response rate, quality of life (QoL), effects on biological markers of disease (CA 19.9) and angiogenesis (vascular endothelial growth factor and basic fibroblast growth factor), and safety. An ancillary study investigated the pharmacokinetics of both drugs in a subset of patients. RESULTS: Eighty-nine patients were randomized. The median overall survival was 6.7 months for Cilengitide and gemcitabine and 7.7 months for gemcitabine alone. The median PFS times were 3.6 months and 3.8 months, respectively. The overall response rates were 17% and 14%, and the tumor growth control rates were 54% and 56%, respectively. Changes in the levels of CA 19.9 went in line with the clinical course of the disease, but no apparent relationships were seen with the biological markers of angiogenesis. QoL and safety evaluations were comparable between treatment groups. Pharmacokinetic studies showed no influence of gemcitabine on the pharmacokinetic parameters of Cilengitide and vice versa. CONCLUSION: There were no clinically important differences observed regarding efficacy, safety and QoL between the groups. The observations lay in the range of other clinical studies in this setting. The combination regimen was well tolerated with no adverse effects on the safety, tolerability and pharmacokinetics of either agent.

Chronic pancreatitis: early results of pancreatoduodenectomy and analysis of risk factors.

OBJECTIVES: Although mortality after pancreatoduodenectomy for chronic pancreatitis has declined, the complication rate remains high. Today, there is an increasing need to base clinical decisions on the available scientific evidence to provide the best available treatment for the patients. Therefore, we retrospectively analyzed comprehensive preoperative and postoperative characteristics of patients undergoing pancreatic head resection for chronic pancreatitis and performed an outcome analysis to provide prospective selection or managing criteria that could improve the early surgical results. METHODS: Data from 168 patients who underwent pancreatic head resection for chronic pancreatitis between October 1993 and November 2008 in our center were retrospectively analyzed. Risk factors for surgical complications were evaluated by multivariate analysis. RESULTS: Perioperative mortality was 0.6%, and surgical morbidity was 14.3%. Multivariate analysis identified hypertension as significant independent risk factor for surgical complications with an odds ratio (OR) of 3.24. We also found protective factors, namely, preoperative exocrine insufficiency (OR, 0.33) and preoperative diabetes (OR, 0.18). Both protective factors might indicate an advanced chronic pancreatitis. CONCLUSIONS: As patients undergoing pancreatic head resection are highly selected, the identified risk factors should only individually be considered in the decision to operate.

Quality of life in patients after pancreaticoduodenectomy for chronic pancreatitis.

PURPOSE: Pancreaticoduodenectomy (PD) is the most frequently performed resectional procedure in chronic pancreatitis. Only a few studies have evaluated quality of life (QOL) after PD for chronic pancreatitis. This retrospective study examined long-term quality of life and relief of symptoms in a homogenous consecutive cohort of 67 patients undergoing PD for chronic pancreatitis. METHODS: A standard QOL questionnaire was sent to 168 patients after PD who had undergone PD for chronic pancreatitis at the University Hospital Dresden between 1994 and 2008. QOL and long-term sequelae were evaluated by the EORTC quality of life questionnaire supplemented with complementary questions. Results were compared to general population data based on large random samples. RESULTS: Median follow-up was 69.1 months. Complete response was obtained from 67 (48.5%) patients. Long-term survival of our patients was lower than expected rates based on the Federal Republic of Germany life table analysis (p < 0.001). There was an improved pain control and an increase in weight gain. Overall, QOL scores were slightly inferior to those of the control group. A common problem after PD was onset of diabetes mellitus; however, exocrine function of the pancreas was stable. CONCLUSIONS: This is the largest single-institution experience assessing QOL after PD for chronic pancreatitis. Most patients have QOL scores comparable to those of the control patients and can function independently in daily activities.

Outcome of invasive and noninvasive intraductal papillary-mucinous neoplasms of the pancreas (IPMN): a 10-year experience.

BACKGROUND: Intraductal papillary-mucinous neoplasms (IPMN) were officially introduced into the TNM classification in 1996. Based on a two-center database, we reevaluated histopathological findings, clinicopathological pattern, predictive markers for malignancy, and outcome. METHODS: Between 1996 and 2006, a total of 1424 pancreatic resections were performed in the University Hospitals Dresden and Mannheim. Pathologists of both institutions reviewed the IPMN diagnoses and other with cystic or solid tumor diagnoses. All possible markers, such as diabetes, jaundice, etc., were analyzed for prediction of malignancy. We performed a survival analysis based on the morphologic classification to determine the prognosis of IPMN. RESULTS: There were 43 patients of primarily diagnosed IPMN along with 1174 patients with diagnoses, such as ductal adenocarcinoma. In 207 patients, the diagnoses revealed other cystic or small solid tumors. A histopathological review of the latter patients revealed 54 IPMNs, resulting in a total of 97 IPMN patients (29 noninvasive, 68 invasive). All IPMN patients had a median survival of 36 months. Recurrence occurred more frequently in invasive IPMN. Predictive markers of malignancy were pain, preoperative weight loss, jaundice, and elevated CA 19.9. The strongest independent prognostic factor was invasive growth. The survival analysis revealed excellent prognosis for noninvasive IPMN. CONCLUSIONS: Since the introduction of IPMN in 1996, even specialized centers have had to deal with a learning curve. By reevaluating all cystic or small solid tumors, centers can improve and their patients' treatment can be optimized. Because the preoperative diagnostic methods are not sensitive enough to differentiate between benign and malignant lesions, surgery is advocated for all main duct IPMN, because they have a high malignant potential. For branch duct IPMN, surgery is advocated if the lesion is symptomatic, >3 cm, or has enlarged nodules.

Prognostic significance of immunohistochemical RhoA expression on survival in pancreatic ductal adenocarcinoma: a high-throughput analysis.

Among all human carcinomas, pancreatic cancer has one of the worst survival rates. Most patients will die of this cancer shortly after diagnosis, and currently, surgery is the only potential cure. Ductal adenocarcinoma is the most common histologic type. The search for prognostic parameters has progressed from mere physical or histomorphological tumor properties to molecular parameters. These, in turn, might point toward new therapeutic strategies. The K-ras oncogene is known to play a role in early stages of ductal adenocarcinoma carcinogenesis, and ras homologues are differentially expressed in cancerous versus normal ductal cells. RhoA belongs to a family of ras homologues comprising RhoA, RhoB, and RhoC. It is a guanosine triphosphatase associated with the cytoskeleton that seems to be involved in epithelial mesenchymal transition, a process of dedifferentiation. Immunohistologic RhoA expression was studied in a tissue microarray of 94 pancreatic ductal adenocarcinomas and correlated with clinicopathologic parameters and follow-up. RhoA protein expression, measured as labeling intensity or evaluated as percentage of reactive tumor cells, correlated with overall survival. A multivariate analysis demonstrated that RhoA protein expression is independent from other known prognostic parameters such as tumor size or grade. Moreover, a score combining RhoA expression with tumor size and grade resulted in a highly significant increase in the prognostic value for the overall survival of patients with pancreatic ductal adenocarcinoma.

Prospective evaluation of ultrasound and colour duplex imaging for the assessment of surgical resectability of pancreatic tumours.

BACKGROUND: This study was performed to evaluate colour duplex imaging (CDI) for the assessment of resectability of pancreatic tumours (PTs). METHOD: From October 1998 to December 2001, 182 patients consecutively having surgery for a PT were enrolled in this prospective study. Extension of the tumour to large blood vessels and retroperitoneum, the detection of liver metastases, enlarged lymph nodes and peritoneal carcinomatosis were defined as criteria for assessment. The patients were grouped into three classes of resectability: US-TU 1 = resectable/potentially curable, US-TU 2 = questionably resectable/curable, and US-TU 3 = non-resectable/not curable. CDI was performed by five different examiners. Results were compared with intra-operative findings. RESULTS: Using CDI, we classified 85 (46.7%) tumours as resectable, 64 (35.2%) as non-resectable, and 33 (18.1%) as questionably resectable. Overall, 46.2% ( n=84) were found to be resectable, and 53.8% ( n=98) to be non-resectable, intra-operatively. A correlation between CDI classification and intra-operative findings was found in 138 of 149 cases (92.6%) (sensitivity 88.4%, specificity 96.3%). With regard to the complete oncological status (local extension, metastases, lymph-node staging and peritoneal carcinomatosis), a sensitivity of 77.2% and specificity of 95.7% were found. Non-correlated findings were likely attributed to missing small liver metastases, peritoneal carcinomatosis without ascites, and on difficulties in the assessment of enlarged lymph nodes concerning tumour infiltration. CONCLUSION: The use of CDI in evaluation of PTs may provide valuable pre-operative assessment of surgical resectability and may be performed in the clinical setting.