Koji Tsuruta

Predictors of malignancy and natural history of main-duct intraductal papillary mucinous neoplasms of the pancreas.

Objectives: Because the prevalence of carcinoma is high in main-duct intraductal papillary mucinous neoplasms (IPMNs) of the pancreas, surgical resection is recommended for all main-duct type IPMNs. This study aimed to investigate the clinical predictors of malignancy and natural history of main-duct IPMNs. Methods: Preoperative clinical characteristics reliably correlated with malignancy in 26 surgically resected patients with main-duct IPMN, and long-term outcome in 20 conservatively followed patients with main-duct IPMN was examined. Results: Age at diagnosis was significantly older in conservatively followed IPMN patients than in surgically resected IPMN patients. Main pancreatic duct (MPD) dilatation 10 mm or greater and mural nodules were significantly more frequent in malignant IPMNs. Obvious progression of dilatation of the MPD was detected in all 4 conservatively followed patients who developed invasive pancreatic carcinoma. The histology of IPMN at autopsy of 4 conservatively followed patients who died of other causes 21 to 120 months later was adenoma. Seven conservatively followed without malignant findings did not show obvious progression of MPD dilatation. Conclusions: Although surgical resection is indicated for many main-duct IPMNs, conservative follow-up may be an option for elderly asymptomatic patients with main-duct IPMNs with the MPD less than 10 mm, no obvious mural nodule, and negative cytology.

Papillary carcinoma of the extrahepatic bile duct: characteristic features and implications in surgical treatment☆

BACKGROUND Papillary carcinoma of the extrahepatic bile duct presents clinically and histologically distinct features relevant to surgical decision-making. STUDY DESIGN Serial sections of 15 specimens of resected papillary carcinoma of the bile duct were histologically examined to determine mode of spread, possibility of multicentric tumor origins, and coincidence with other neoplastic lesions. The presence of anomalous pancreaticobiliary ductal union was also investigated. These characteristics were considered with regard to surgical treatment. RESULTS Three patients displaying pancreaticobiliary maljunction and one of three patients with a long common channel (> or = 8 mm) exhibited multicentric tumors. Eight patients (53%) demonstrated superficial spread along a mean length of 37.8 mm (range, 5 to 67 mm) of bile duct mucosa. Multicentric tumors developed synchronously in 4 patients, while metachronous tumors were identified in three patients displaying tumor histology similar to the primary lesions. Two of these three underwent successful repeated resection. Concomitant neoplastic lesions in the biliary tract were identified as mucosal dysplasia in four patients and cholangiocellular carcinoma of the liver in two. All tumors but one were removed via hepatic lobectomy or pancreatoduodenectomy, or both, resulting in a 5-year survival rate of 60%. CONCLUSIONS Aggressive resection offers clear survival benefits for patients presenting with tumors displaying extensive superficial spread or multicentric origins. Closer attention should be paid to long common channels in relation to carcinogenesis of the bile duct, in addition to pancreaticobiliary maljunction. The risk of secondary tumor development remains, particularly in patients with pancreaticobiliary maljunction even after excision of the tumor-bearing extrahepatic bile duct.

Nonmyeloablative allogeneic stem cell transplantation for patients with unresectable pancreatic cancer.

Objectives: To clarify whether nonmyeloablative allogeneic stem cell transplantation (NST) can produce the graft versus tumor (GVT) effect in patients with pancreatic cancer. Methods: A pilot trial of NST was conducted in 5 patients with unresectable pancreatic cancer. Preparative conditioning consisted of administration of 60 mg/kg cyclophosphamide on days 6 and 7 before transplantation, followed by 25 mg fludarabine per square meter of body surface on each of the last 5 days prior to transplantation. Cyclosporine was started 4 days before transplantation. Peripheral blood stem cells from the patients’ HLA-identical siblings were transfused into the patients. Results: Complete donor T-cell chimerism in peripheral blood was obtained in 4 patients on day 15 after transplantation. NST resulted in tumor reduction in 2 patients as determined by CT, decreasing levels of tumor markers in 2 patients, pain relief in 2 patients, and a decrease in pleural fluid in 1 patient. Two patients developed acute graft versus host disease (GVHD) of grade II or III and 2 had chronic GVHD involving skin and/or liver. Administration of immunosuppressive drugs for the treatment of GVHD resulted in the elevation of tumor marker levels. Conclusion: These findings are the first to suggest that NST induces a GVT effect on pancreatic cancer.

Pancreaticoduodenectomy in portal annular pancreas: report of a case

Portal annular pancreas (PAP) is a rare anatomical anomaly in which the pancreatic parenchyma surrounds the superior mesenteric vein and portal vein (PV) annularly. This anomaly requires careful consideration in pancreatic resection. A case is presented and the technical issues are discussed. A 61-year-old female was referred to the hospital for suspected papilla Vater adenocarcinoma. Preoperative computed tomography showed that the PV was annularly surrounded by pancreatic parenchyma. Surgery revealed the uncinate process extended extensively behind the PV and fused with the pancreatic body. The pancreas was first divided above the PV, and it was divided again in the body after liberating the PV from pancreatic annulation. The postoperative course was uneventful without pancreatic fistula. It is safer to divide the pancreatic body on the left of the fusion between the uncinate process and the pancreatic body to reduce the risk of pancreatic fistula in pancreaticoduodenectomy for PAP.

Resection versus palliation: Treatment of stage III and IVA carcinomas of the pancreas employing intraoperative radiation

Whether advanced pancreatic carcinomas should be surgically removed has been a basic issue because performing an extended resection is futile if it has only a minimum impact on survival. The purpose of this study was to compare the results of pancreatic resection with those of a bypass operation for patients with stage III or IVA pancreatic carcinomas while applying intraoperative radiation therapy (IORT). The therapeutic outcomes of 132 patients who had received IORT for stage III or IVA carcinoma were analyzed retrospectively. The patients were divided into two groups: Group 1 included 68 patients with locally unresectable tumors who underwent a bypass operation; group 2 included 64 patients with resectable tumors who underwent pancreatic resection. Postoperative external beam radiation therapy (EBRT) was also delivered to 90 patients. Multivariate analysis indicated that strong independent predictors of increased survival were EBRT for group 1 (p < 0.0001) and R0 resection for group 2 (p = 0.017). Twenty patients who had been subjected to R0 resection showed the best survival, with a 3-year survival rate of 45%. The survival of group 1 patients receiving EBRT (n = 47) nearly equaled that of group 2 patients undergoing R1 or R2 resection (n = 44) (p = 0.72); but group 1 patients with tumors ≤ 6 cm (n = 31) had a better survival rate than group 2 patients with tumors > 3 cm (n = 28) (p = 0.03). We concluded that postoperative EBRT is essential for improving the survival outcome, even after administering IORT. Patients with stage III lesions undergoing an R0 resection and receiving IORT demonstrated an excellent 3-year survival. A bypass operation plus IORT in combination with EBRT is preferred over IORT used as an adjuvant to R1 or R2 resection.

Differentiating Immunoglobulin G4-Related Sclerosing Cholangitis from Hilar Cholangiocarcinoma

Background/Aims Few studies have differentiated immunoglobulin G (IgG) 4-related sclerosing cholangitis (IgG4-SC) from hilar cholangiocarcinoma (CC). Thus, we sought to investigate useful features for differentiating IgG4-SC from hilar CC. Methods We retrospectively compared clinical, serological, imaging, and histological features of six patients with IgG4-SC and 42 patients with hilar CC. Results In patients with hilar CC, obstructive jaundice was more frequent (p<0.01), serum total bilirubin levels were significantly higher (p<0.05), serum CA19-9 levels were significantly higher (p<0.01), and serum duke pancreatic monoclonal antigen type 2 levels were frequently elevated (p<0.05). However, in patients with IgG4-SC, the serum IgG (p<0.05) and IgG4 (p<0.01) levels were significantly higher and frequently elevated. The pancreas was enlarged in all IgG4-SC patients but only in 17% of hilar CC patients (p<0.01). Salivary and/or lacrimal gland swelling was detected in only 50% of IgG4-SC patients (p<0.01). Endoscopic retrograde cholangiography revealed that the hilar or hepatic duct was completely obstructed in 83% of hilar CC patients (p<0.01). Lower bile duct stenosis, apart from hilar bile duct stenosis, was more frequent in IgG4-SC patients (p<0.01). Bile duct wall thickening in areas without stenosis was more frequent in IgG4-SC patients (p<0.01). Conclusions An integrated diagnostic approach based on clinical, serological, imaging, and histological findings is necessary to differentiate IgG4-SC from hilar CC.

Pancreatobiliary Disorders Associated with Pancreaticobiliary Maljunction

Aim: To clarify the features of biliary carcinomas and pancreatic disorders associated with pancreaticobiliary maljunction (PBM). Method: A total of 107 PBM patients with biliary dilatation were reviewed (52 with and 55 without PBM). Clinicopathological findings of biliary carcinomas, and acute or chronic pancreatitis were examined in association with PBM. We also investigated pancreatographic findings in PBM patients and the relationship to their clinical findings in view of pancreatic juice flow. Results:Gallbladder and bile duct carcinomas were seen in 11 (21%) and 8 (15%) of the 52 patients with PBM and biliary dilatation, respectively. In patients with PBM without biliary dilatation (n = 55), only gallbladder carcinoma was detected in 36 (65%) patients. At diagnosis, patients with gallbladder or bile duct carcinoma associated with PBM were younger than those without PBM (p < 0.01). Gallstones were detected only in 6% of the patients with PBM-associated gallbladder carcinoma. Multiple biliary carcinomas were detected in 3 patients (38%) with PBM-associated bile duct carcinoma. While 48 patients (60%) with biliary carcinoma and PBM had a normal pancreatic duct system, only 2 gallbladder carcinomas occurred in 11 dorsal pancreatic duct (DPD)-dominant patients (p < 0.05). Amylase concentration in the bile of DPD-dominant patients was significantly lower than that of patients with a normal pancreatic duct system (p < 0.05). Ten PBM patients had pancreatic disorders: acute pancreatitis (n = 3), chronic pancreatitis (n = 5), and pancreatic carcinoma (n = 2). Conclusions: In PBM patients, pancreatobiliary reflux frequently leads to biliary cancer, and biliopancreatic reflux often leads to acute or chronic pancreatitis. The biliary tract of PBM patients can be considered premalignant.

Intraoperative radiation therapy for pancreatic adenocarcinoma: the Komagome hospital experience.

Abstract: We analyzed 144 patients with pancreatic adenocarcinoma who had received intraoperative radiation therapy (IORT) in combination with external beam radiation therapy (EBRT) within the past 20 years. The patients were divided into 2 groups: group 1 contained 65 patients with locally unresectable tumors who underwent bypass operations and group 2 contained 68 patients with resectable tumors who underwent pancreatic resection. As a pilot study, we performed additional arterial infusion chemotherapy after changing peripancreatic hemodynamics during EBRT in the remaining 11 patients. The 30 patients who received R0 resection had the best survival rates (3-year survival rate of 35.4%), while 3 patients with stage III disease survived more than 5 years. The survival of group 1 patients nearly equaled that of group 2 patients who underwent R1 or R2 resection (median survival, 10.9 vs. 11.1 months, respectively; P = 0.43). The 1-year survival rate for the 11 patients receiving arterial infusion chemotherapy was 45.4%, and 5 patients survived over 1 year without developing hepatic metastasis or regrowth of primary tumors. The survival benefits obtained using this form of radiotherapy are apparently limited. On the other hand, additional arterial infusion chemotherapy employing a new drug delivery system using hemodynamic change does appear promising.

Importance of early diagnosis of pancreaticobiliary maljunction without biliary dilatation

AIM To clarify the strategy for early diagnosis of pancreaticobiliary maljunction (PBM) without biliary dilatation and to pathologically examine gallbladder before cancer develops. METHODS The anatomy of the union of the pancreatic and bile ducts was assessed by using endoscopic retrograde cholangiopancreatography (ERCP). Patients with a long common channel in which communication between the pancreatic and bile ducts was maintained even during sphincter contraction were diagnosed as having PBM. Of these, patients in which the maximal diameter of the bile duct was less than 10 mm were diagnosed with PBM without biliary dilatation. The process of diagnosing 54 patients with PBM without biliary dilatation was retrospectively investigated. Histopathological analysis of resected gallbladder specimens from 8 patients with PBM without biliary dilatation or cancer was conducted. RESULTS Thirty-six PBM patients without biliary dilatation were diagnosed with gallbladder cancer after showing clinical symptoms such as abdominal or back pain (n = 16) or jaundice (n = 12). Radical surgery for gallbladder cancer was only possible in 11 patients (31%) and only 4 patients (11%) survived for 5 years. Eight patients were suspected as having PBM without biliary dilatation from the finding of gallbladder wall thickening on ultrasound and the diagnosis was confirmed by ERCP and/or magnetic resonance cholangiopancreatography (MRCP). The median age of these 8 patients was younger by a decade than PBM patients with gallbladder cancer. All 8 patients underwent prophylactic cholecystectomy and bile duct cancer has not occurred. Wall thickness and mucosal height of the 8 resected gallbladders were significantly greater than controls, and hyperplastic changes, hypertrophic muscular layer, subserosal fibrosis, and adenomyomatosis were detected in 7 (88%), 5 (63%), 7 (88%) and 5 (63%) patients, respectively. Ki-67 labeling index was high and K-ras mutation was detected in 3 of 6 patients. CONCLUSION To detect PBM without biliary dilatation before onset of gallbladder cancer, we should perform MRCP for individuals showing increased gallbladder wall thickness on ultrasound.

Tumor size significantly correlates with postoperative liver metastases and COX-2 expression in patients with resectable pancreatic cancer.

Background/Aim: Local treatment often fails in patients with resectable pancreatic cancer due to the postoperative development of distant metastases, especially liver metastases. We determined the prognostic factors for postoperative liver metastases in pancreatic cancer patients following surgical resection with combined radiotherapy. Methods: Sixty-four patients with nonmetastatic, resectable pancreatic cancer were entered into this study. All of these patients had pancreatic resection surgery combined with radiotherapy. The development of postoperative liver metastases was carefully followed, and the survival ratio was evaluated using the Kaplan-Meier method. The prognostic importance of clinicopathological factors and molecular characteristics was analyzed by the Cox proportional hazards model. The correlation study was performed using Fisher’s exact test. Results: Tumor size, curability, and histological type of differentiation were statistically significant independent prognostic factors. On multivariate analysis, curability and histological type of differentiation were statistically significant. Only tumor size (≧3 cm) was significantly correlated with postoperative liver metastases, as well as cyclooxygenase-2 expression. Conclusions: There were three significant prognostic factors in patients with resectable pancreatic cancer who had local therapy. Patients who have a large tumor require particularly careful follow-up for postoperative liver metastases.