Yoshiharu Tokoro

Intraductal papillary mucinous tumors of the pancreas

BACKGROUND An increasing number of intraductal papillary mucinous tumors of the pancreas have been reported in recent years. The indolent character and favorable prognosis of this neoplasm have been described. METHODS Intraductal papillary mucinous tumors were classified into main duct type (n = 8) and branch type (n = 28) according to the dominant location of the tumor. This single-institute study examined the clinicopathological features and outcome after surgical resection in patients with intraductal papillary mucinous tumors. RESULTS The gender, age, tumor size, and prognosis were quite similar for the main duct type and branch type groups. Branch type tumors were more frequently located in the head of the pancreas than were main duct type tumors. Histological examination revealed that 88% of main duct type tumors were adenocarcinomas; however, only 46% of branch type tumors were adenocarcinomas. Five-year survival rates for the patients with all main duct type tumors (n = 8), main duct type adenocarcinoma (n = 7), all branch type tumors (n = 28), and branch duct adenocarcinoma (n = 13) were 100%, 100%, 90.6%, and 90.9%, respectively. CONCLUSIONS Intraductal papillary mucinous tumors had a favorable prognosis after surgical treatment. A curative pancreatectomy should be indicated for this localized malignant tumor.

Inhibition of growth and invasive activity of human pancreatic cancer cells by a farnesyltransferase inhibitor, manumycin.

The effects of manumycin, a competitive farnesyltransferase (FTase) inhibitor, on pancreatic cancer cell lines with or without K-ras mutation were studied. Manumycin inhibited the growth of human pancreatic cancer cells (SUIT-2, MIA PaCa-2, AsPC-1, BxPC-3) in a dose-dependent manner. The 50% inhibitory concentration (IC50) in cell lines with a mutant K-ras gene (SUIT-2, MIA PaCa-2, AsPC-1) was lower than that in BxPC-3 with a wild-type ras. Both mitogen-activated protein kinase activity after growth stimuli and the ability for chemotactic invasion were markedly more inhibited by manumycin in SUIT-2 than in BxPC-3. These results suggest that mutated Ras is more sensitive to manumycin than the wild type. Furthermore, tumor growth and liver metastasis in nude mice inoculated with manumycin-treated SUIT-2 cells were inhibited dose dependently. Inhibition of Ras activity might be a new anticancer strategy in pancreatic cancer in which Ras plays a role.

Inferior head resection of the pancreas for intraductal papillary mucinous tumors

BACKGROUND Patients with intraductal papillary mucinous tumor have a favorable prognosis after surgical treatment. When this neoplasm is located in the head of the pancreas, resection has conventionally required pancreatoduodenectomy. Although pancreatoduodenectomy can now be performed with a low mortality rate, morbidity still occurs frequently. METHODS Between November 1982 and January 1999, 38 intraductal papillary mucinous tumors of the pancreas were resected at the Chiba University Hospital. Seven patients (18%) underwent inferior head resection of the pancreas. In this preliminary study, the operative technique is presented, and its efficacy in improvement of quality of life is evaluated. RESULTS Patients with intraductal papillary mucinous tumor underwent resection with no perioperative mortality. After discharge from hospital, 6 patients who underwent inferior head resection were still alive without recurrent disease after a median follow-up of 3 years. However, 1 patient developed peritoneal dissemination and died 18 months after inferior head resection. Patients had regained 98% of preoperative weight 1 year after inferior head resection. N-benzoyl-L-tyrosyl-p-amino-benzoic acid (BT-PABA) excretion test showed the same value before (73%) and after (73%) inferior head resection (n = 7). Pancreatic fistulas occurred more frequently after inferior head resection (38%), but the incidence of major complications was similar between inferior head resection and other types of pancreatic head resection. CONCLUSIONS Pancreatic function was well preserved, and patients regained 98% of preoperative weight after inferior head resection of the pancreas. The authors concluded that the limited involvement of intraductal papillary mucinous tumors enables the surgeons to perform inferior head resection of the pancreas.

A case of gallbladder adenomyomatosis with pancreaticobiliary maljunction and an anomaly of the cystic duct joined the common channel

A 46-yr-old woman was admitted to our hospital with mild epigastric pain. Ultrasonography and computed tomography revealed an extremely thickened gallbladder wall. Endoscopic retrograde cholangiopancreatography demonstrated that the main pancreatic duct joined the nondilated common bile duct at the outer point of the duodenal wall (P-C type of pancreaticobiliary maljunction), and the cystic duct joined the common channel directly. The intraoperative amylase levels of the bile juices both in the common bile duct and the cystic duct were high. A cholecystectomy was performed. The wall of the gallbladder was markedly thick, yellowish, elastic, and soft. Histologically, Rokitansky-Aschoff sinus proliferation, hypertrophy of smooth muscles, and fibrosis were seen. The diagnosis was a generalized type of adenomyomatosis. The pathogenesis of the adenomyomatosis was believed to result from chronic stimulation as a result of pancreatic juice reflux. The etiology of this unusual type of junction was considered to be the result of the combination of pancreaticobiliary maljunction and an anomaly of lower junction of the cystic duct.

Virtual Pancreatoscopy of Mucin-Producing Pancreatic Tumors

We used computer-based virtual endoscopy techniques as a novel approach to clarify the three-dimensional (3D) surgical anatomy of the pancreas and of mucin-producing pancreatic tumors. Thirteen cases (18 lesions) of mucin-producing pancreatic tumors were investigated by virtual pancreatoscopy. Virtual endoscopic images were generated with virtual endoscopy software application on UNIX workstations. We created surface-rendered virtual endoscopic images derived from a computer reconstruction of the cross-sectional magnetic resonance imaging data. Virtual endoscopy could visualize the surfaces of the pancreatic duct and the bile duct, and also demonstrated all cystic tumors. The surfaces of malignant mucin-producing pancreatic tumors were illustrated as being more irregular than those of benign lesions. The virtual endoscopic technique could demonstrate not only a surface-rendered endoscopic image of the tumors but also a 3D reconstructed image of the pancreas. The relationship to anatomic structures located outside the surfaces is continuously maintained and displayed at the same time. Virtual pancreatoscopy was useful for surgical planning of minimally invasive resection of the pancreas.

Successful Gene Transfer Into Murine Pancreatic Islets Using Polyamine Transfection Reagents

SLET TRANSPLANTATION is considered to be the most theoretical option for insulin-dependent diabetes mellitus (IDDM). The islet graft survival is, however, still limited because of the difficulty of avoiding an acute rejection, despite of the use of immunosuppressant. To improve the results of clinical islet transplantation, a new approach to realize the complete inhibition of rejection should be developed. Gene transfection technique into the islets may become the new approach of immunosuppression and induction of the immunoacceptance. Retrovirus and adenovirus vector-mediated gene transfer technique, however, may not be suitable for clinical islet transplantation according to ethical view. Thus, in this study we examined the utility of the liposome-mediated gene transfer technique into murine pancreatic islets.

AN OPERATED CASE OF HEMORRHAGIC DUODENAL ULCER AT THE POSTERIOR BULB WITH DIFFICULTY IN DIFFERENTIATION FROM CANCER OF THE PANCREATIC HEAD

症例は55歳,女性.近医で胃潰瘍の加療中,症状が軽快しないため当科を受診.上部消化管内視鏡検査にて上十二指腸角から下行部にかけて,乳頭側3/4周を占める白苔を伴った潰瘍を認めたため入院.腹部超音波検査および造影CTでは膵鈎部に腫瘤を認め,肝外胆管および16番リンパ節の腫脹も認められた.閉塞性黄疸,肝機能異常も出現したため,膵癌あるいは十二指腸癌の可能性も考え,手術を行った.十二指腸下行部および膵頭部は一塊となっており根治切除不能と判断し,十二指腸を球部にて離断し十二指腸球部空腸吻合および胆道バイパスを行った.術後経過は良好で画像上腫瘤は縮小したが, 4カ月後黒色便および貧血が出現したため再手術を行った.十二指腸下行部を切開すると膵側に4cmの潰瘍を認め,中央には血管が露出していたため,膵頭十二指腸切除術を行った.術後経過は良好であった.