胆管内乳头状肿瘤的研究进展

胆管内乳头状肿瘤（IPNB）是一类少见的胆道肿瘤,以肿瘤细胞在胆管内呈乳头状或绒毛状生长、胆管扩张,部分合并黏液分泌为特征。IPNB术前诊断困难,病史以腹痛、黄疸、胆管炎常见,如能够对其临床特点有深入的认识,有可能提高术前的诊断率。IPNB目前仍在病理学定义上仍存在争议,乳头状胆管癌是否归属于IPNB仍无定论。病理上可合并多发且性质不同的病变,应注意浸性型癌的比例。病理学分类上胰胆管亚型提示预后较差,黏液核心蛋白（mucin core protein）-1是最重要的免疫组化指标。IPNB影像学检查有其固有的特点,通过联合CT、MRCP检查有可能在术前判断是否存在浸润性癌,从而对手术方式及预后有一定的指导作用。手术切除是目前的首选治疗方式,IPNB患者术后的总体预后较胆管癌好。     

Multicentric recurrence of intraductal papillary neoplasms of bile duct in the remnant intrahepatic bile duct after curative resection

IntroductionThere have been few reports on the prognosis of patients with intraductal papillary neoplasms of the bile duct (IPNB). Here we report a case of IPNB in a patient with early-stage carcinoma who had multicentric recurrence in the remnant hepatic bile duct after curative resection.Case presentationA 78-year-old man with hepatic dysfunction and cholestasis was referred to our hospital. Preoperative imaging studies revealed the presence of papillary tumors in the left hepatic duct and common hepatic duct, while no tumor lesions were detected in the right hepatic duct. This patient underwent left hepatectomy, extra-hepatic bile duct resection with biliary reconstruction, and regional lymphnode dissection. On the basis of pathological examination, this patient was diagnosed with multiple IPNB with early-stage adenocarcinoma with negative surgical margin. Postoperative work-up was periodically performed, indicating no evidence of recurrence, while the patient had sustained hepatic dysfunction, cholestasis, and repetitive cholangitis since the early postoperative period. Finally, recurrence in the remnant intrahepatic bile duct of the posterior segment was revealed by double balloon enteroscopy at 29 months after surgery. At 34 months after surgery, internal drainage stents were replaced in both endoscopic and percutaneous manners within the relapsed intrahepatic bile ducts to address repetitive cholangitis. These procedures enabled the patient to remain asymptomatic until death at 41 months after surgery.DiscussionMulticentric recurrence in the remnant intrahepatic bile duct after surgery may occur in IPNB patients with multiple lesions. An endoscopic approach may be useful in such cases, not only in the diagnosis of remnant intrahepatic bile duct recurrence but also for palliation of symptoms.     

Invasive carcinoma of the pancreas derived from intraductal papillary adenocarcinoma without mucin hypersecretion but with changes in the pancreatic duct on pancreatography

We present a case of invasive carcinoma of the pancreas derived from intraductal papillary adenocarcinoma without mucin hypersecretion in a 65-year-old man with a 45-year history of alcohol abuse and a 2-year follow-up of chronic pancreatitis. Two years previously, in May 1998, he was admitted for investigation of abdominal pain. Computed tomography (CT) showed diffuse dilation of the main pancreatic duct with atrophy of the pancreatic parenchyma. Endoscopic retrograde pancreatography (ERP) showed a diffusely dilated main pancreatic duct with irregular side branches in the head of the pancreas. Chronic alcoholic pancreatitis was diagnosed on the basis of the pancreatography findings. The patient was readmitted for investigation of progressive weight loss in August 2000. Serum CA19-9 levels were markedly elevated (750 U/ml) and CT showed enlargement of the head and body of the pancreas. ERP showed irregularity of the main pancreatic duct in the head of the pancreas, and the distal main pancreatic duct (which was dilated on initial ERP examination) was interrupted in the body of the pancreas. Suspected pancreatic carcinoma was diagnosed, and pylorus-preserving pancreatoduodenectomy was performed. Frozen section examination of the cut end of the pancreas revealed ductal carcinoma, and total pancreatoduodenectomy with portal vein resection was performed. Histologically, the resected tumor was diagnosed as an invasive carcinoma derived from intraductal papillary adenocarcinoma without mucin hypersecretion. We recommend observing changes in the pancreatic duct on pancreatography to diagnose invasive carcinoma of the pancreas derived from intraductal papillary adenocarcinoma in a resectable state. Received: February 6, 2002 / Accepted: June 10, 2002 Offprint requests to: S. Ariizumi     

Mucin-secreting bile duct adenoma--clinicopathological resemblance to intraductal papillary mucinous tumor of the pancreas

We describe a case of mucin-secreting biliary adenoma associated with obstructive jaundice due to mucin production. Duodenal endoscopy revealed mucin secretion through an enlarged papilla of Vater. On the cholangiogram, large filling defects caused by mucin were observed in the dilated bile duct. Granular and/or papillary mucosa was noted from the hilar to the common bile duct by using percutaneous transhepatic cholangioscopy. Biopsy specimens taken from the papillary mucosa revealed slightly papillary projection without any evidence of malignancy. This lesion was diagnosed as mucin-secreting superficial adenoma and pancreatoduodenectomy was performed according to the malignant behavior. Using a histologic examination of the specimen, pure adenoma was documented. Since the surgical margin was positive, radiation was added for the residual adenoma in the intrahepatic bile ducts. The patient has been well without any evidence of recurrence for 21 months since her operation. It is only recently that the term 'intraductal papillary mucinous tumor (IPMT)', which is accepted as a distinct disease entity of pancreas, has begun to be used for mucin-secreting bile duct tumor. This case also seemed to clinicopathologically resemble an IPMT of the pancreas.     

Mixed ductal-endocrine carcinoma of the pancreas with synchronous papillary carcinoma-in-situ of the common bile duct: a case report and literature review--synchronous pancreatic and bile duct tumors

This report is a case of a 58-year-old woman with a mixed ductal-endocrine carcinoma of the pancreas and a synchronous carcinoma-in-situ of the common bile duct. She presented with intractable itching from obstructive jaundice. Magnetic resonance imaging scan showed dilated intrahepatic biliary and common bile ducts. Endoscopic retrograde cholangiopancreatography revealed an ulcerated lesion of the ampulla. Biopsies from this lesion showed adenocarcinoma. Subsequently, pancreatoduodenectomy was performed for the diagnosis of peri-ampullary carcinoma. Gross examination revealed a 2-cm irregular, ulcerated lesion obstructing the distal 0.5 cm of the common bile duct within the head of the pancreas. On histopathological examination, it was discovered that this lesion contained two separate neoplasms: papillary carcinoma-in-situ of the intraparenchymal portion of the common bile duct and a mixed ductal-endocrine carcinoma of the pancreas. Mixed ductal-endocrine carcinoma of the pancreas is very rare. Finding it in conjunction with a synchronous, overlying papillary carcinoma carcinoma-in-situ of the common bile duct has not been previously described.     

Cholangiographic spectrum of intraductal papillary mucinous neoplasm of the bile ducts

OBJECTIVE: To propose a cholangiographic classification for intraductal growth type intrahepatic cholangiocarcinoma (IG-ICC) and its precursor, collectively termed intraductal papillary mucinous neoplasm of the bile ducts (IPMN-B). SUMMARY BACKGROUND DATA: For the extensive clinicopathologic variations of IPMN-B, a detailed characterization of cholangiography for IPMN-B is beneficial for determining the optimal therapeutic strategy. METHODS: A total of 124 patients with cholangiography-available and pathologically proven IPMN-B were retrospectively studied. Numbers of IPMN-B type 1, type 2, type 3, and type 4 were 33, 17, 15, and 59, respectively. A cholangiographic classification was proposed based on the presence of hepatolithiasis, mucobilia, neoplasia localization, and concomitant malignancies. The demographics, histologic grading, management, and survival were also analyzed. RESULTS: All 33 IPMN-B type 1 and 12 of 17 IPMN-B type 2 displayed cholangiographic pattern IA demonstrating hepatolithiasis-related biliary stricture. The remaining 5 IPMN-B type 2 displayed cholangiographic pattern IB or IC, which demonstrated mucobilia without discernible neoplasia. Seven of 15 IPMN-B type 3 and 52 of the 59 IPMN-B type 4 displayed cholangiographic pattern IIA or IIB, which demonstrated overt intraductal neoplasia. Seven IPMN-B type 3 or 4 displayed cholangiographic pattern IIIA or IIIB, which demonstrated IPMN-B and concomitant malignancies. For those presenting with cholangiographic pattern IA, IC, IIA, IIB, and IIIA, straightforward hepatectomies for the diseased lobes were performed. For those with pattern IB, surgical resections were performed only when there was emergence of mucin-producing neoplasia. For those with IIIB, the concomitant malignancies were considered inoperable. No disease-related death occurred in IPMN-B type 1and 2. The mean survival rates of IPMN-B type 3 and type 4 were 55.5 +/- 17.1 months and 36.9 +/- 6.3 months, respectively. CONCLUSION: The presented cholangiographic classification facilitates the management for IPMN-B. Significant survival discrepancy at the various stages warrants a more aggressive surgical strategy.     

胰腺导管内乳头状粘液性肿瘤的诊治

目的 总结胰腺导管内乳头状粘液性肿瘤（IPMT）的诊治经验,以提高对该疾病的认识和诊治水平。方法 自1993年5月至2000年8月共收治胰腺导管内乳头状粘液性肿瘤患者8例,男性6例,女性2例,年龄33-72岁,平均54岁,患者均行B超和CT检查,均提示有不同程度的胰管扩张,5例发现胰头囊实性占位,5例行ERCP检查,发现十二指肠乳头增大和粘液溢出者3例,血清CA19-9值6.5-108U/ml(平均66.88U/ml),CEA值有1例为32.2ng/L,其余均为小于15ng/L。结果 8例患者中只有3例在入院时诊断为IPMT,除1命名中层得拒绝手术外,7例均进行了手术治疗（胰十二指肠切除术）,术后病理诊断胰头导管内乳头状粘液性腺癌2例、胰头导管内乳头状粘液性腺瘤伴局部癌变2例、胰头导管内乳头状液性腺瘤伴不典型增生1例、胰头导内乳头状粘液性腺瘤2例,术后患者均健在,最长1例已6年,结论 胰腺有囊性占位伴胰管全程扩张的患者应考虑胰腺导管内乳头状粘液性肿瘤,ERCP发现十二指肠乳头有粘液溢出者可确诊该疾病,术前要鉴别良恶性较困难,手术切除是最有效的治疗,术后预后良好。     

胰腺导管内乳头状黏液性肿瘤的诊断与治疗

目的提高对胰腺导管内乳头状黏液性肿瘤(IPMTs)的认识,以改善其诊治水平。方法对1993年5月至2003年12月收治的15例IPMTs病人的临床、影像学表现及病理资料作回顾性分析。结果15例中男性12例,女性3例。年龄33～76岁,平均58岁。上腹痛为最常见症状。B超和CT检查,均提示有不同程度的胰管扩张和囊实性占位。11例行ERCP检查,发现十二指肠乳头肿大和黏液溢出者7例。14例行手术治疗(胰十二指肠切除术12例,胰体尾切除1例,全胰切除1例)。术后病理诊断胰头导管内乳头状黏液性腺癌3例、导管内乳头状黏液性腺瘤伴局部癌变6例、胰头导管内乳头状黏液性腺瘤伴不典型增生3例、胰头导管内乳头状黏液性腺瘤2例,术后除1例因肝广泛转移而死亡外,其余病人均健在,存活期最长1例已13年。结论胰腺有囊实性占位伴胰管全程扩张的病人应考虑IPMTs,ERCP发现十二指肠乳头增大有黏液溢出者可确诊该疾病。手术切除是最有效的治疗,术后预后良好。     

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.     

Pancreatic head resection with segmental duodenectomy for intraductal papillary mucinous tumors of the pancreas

Various modifications of organ-preserving pancreatic resections have been performed for intraductal papillary mucinous tumor (IPMT) of the pancreas. The aim of this study was to evaluate usefulness of pancreatic head resection with duodenal segmentectomy (PHRSD), which is one of the organpreserving pancreatic resections for IPMT. Pancreatic head resection with duodenal segmentectomy was indicated for the branch duct type of IPMT. Eight patients underwent PHRSD. The mean operative time was 390 minutes, and the mean blood loss was 1270 ml. Duodenal ischemia was prevented by preserving the duodenal branches of the gastroduodenal artery and the anterior inferior pancreaticoduodenal artery. Complications occurred in four patients: one with pancreatic leak, one with choledochoduodenal anastomotic stenosis, and two with delayed gastric emptying. However, no deaths occurred. The final pathologic diagnosis was adenoma in seven patients and carcinoma in situ in one patient. Six of eight patients had an adenoma with papillary growth in the main pancreatic duct. Postoperative pancreatic endocrine and exocrine functions were satisfactory. All patients were alive without recurrent disease at a median follow-up of 30 months. Pancreatic head resection with duodenal segmentectomy appears to be a useful procedure as an organ-preserving pancreatic resection for the branch duct type of IPMT, because this procedure allows a safe and complete resection of the pancreatic head without ischemia of the common bile duct and the duodenum.     

Laparoscopic-assisted spleen-preserving and pylorus-preserving total pancreatectomy for main duct type intraductal papillary mucinous tumors of the pancreas: a case report

Minimally invasive and function-preserving pancreatectomy would be the ideal approach for benign and borderline malignant tumors of the pancreas. Total pancreatectomy can be indicated for the main duct type of intraductal papillary mucin-producing tumor (IPMT) to achieve radical resection. Recently, several studies advocating total pancreatectomy in IPMT have been published, but they are all believed to be done by conventional laparotomy. Herein, we report a case of a 72-year-old female patient who successfully underwent laparoscopic-assisted total pancreatectomy with the spleen and pylorus preserved in borderline malignant main duct type IPMT. A marginal ulcer around the duodenojejunostomy was developed, but managed by a proton-pump inhibitor. She was discharged 20 days after surgery. She was followed for more than 2 years without evidence of tumor recurrence. Her blood sugar level was well controlled by insulin pump therapy and image study showed well-preserved spleen function.     

Pathologic features of mucin-producing bile duct tumors: two histopathologic categories as counterparts of pancreatic intraductal papillary-mucinous neoplasms

Tumors with clinically recognizable mucin production arising from bile duct, "mucin-producing bile duct tumors (MPBTs)," have not been studied yet for their pathologic features and classification in details. The clinical findings of MPBT have a lot of similarities to those of pancreatic intraductal papillary-mucinous neoplasm. In the present study, we examined 30 MPBTs and classified them into two distinct morphologic categories: 22 cases of "columnar type" composed of pseudostratified columnar cells with basophilic cytoplasm and columnar nuclei and 8 cases of "cuboidal type" composed of pancreaticobiliary and/or oncocytic pattern. Pancreaticobiliary pattern showed abundantly branched papillae lined by acidophilic cuboidal cells with round nuclei, whereas oncocytic pattern was characterized by intraepithelial lumina and cribriform pattern composed of abundant oxyphilic cells with round nuclei, and these patterns overlapped frequently. There were significant differences in the clinicopathologic findings including macroscopic findings, morphometric data, mucin expression profiles (MUC2 expression in columnar type and MUC6 expression in cuboidal type), and cell proliferative activities between columnar type and cuboidal type. Patients with columnar type showed significantly poorer survival than those with cuboidal type. We concluded that columnar type and cuboidal type of MBPTs belong to different lineage of neoplasm and that they are counterparts of "intestinal type" and "pancreaticobiliary type" of pancreatic intraductal papillary-mucinous neoplasm, respectively.     

Molecular factors promoting carcinogenesis and malignant behavior of intraductal papillary mucinous tumors

Many molecular factors related to the carcinogenesis and malignant behavior of pancreatic cancer were identified by investigation of intraductal papillary mucinous tumors (IPMTs). Molecules controlling the G1/S phase, such as p53, p21, p61, and cyclin D1, tumor suppressors including DPC-4, and many other factors such as MUC-1/2 contribute to the promotion of the malignant behavior of IPMTs. They will be important molecular targets for the radical treatment of pancreatic cancer.     

Intraductal papillary neoplasm of the bile duct: a case report

Intraductal papillary neoplasm of the bile duct (IPNB) is a rare variant of bile duct tumors, characterized by papillary growth within the bile duct lumen and is regarded as a biliary counterpart of intraductal papillary mucinous neoplasm (IPMN) of the pancreas. IPNBs are mainly found in patients from Far Eastern areas, where hepatolithiasis and clonorchiasis are endemic. The Western experience, however, remains limited. In this article, we report a 56-year-old man, referred to our hospital because of deranged liver function tests. Further imaging modalities showed a cystic lesion of 9?cm diameter, arising from the left hepatic duct. Inlying was a heterogeneous, lobulated mass. The patient underwent a left hemihepatectomy and adjuvant chemotherapy. Despite recent advanced technologies, diagnosis of IPNB is still challenging, especially in western countries due to its rarity. Early identification and resection of lesions, even in asymptomatic or minimally symptomatic patients, are however important prognostic factors.     

Undifferentiated carcinoma of the common bile duct with intraductal tumor thrombi: report of a case

We report a case of undifferentiated carcinoma of the common bile duct with intraductal tumor thrombi. A 73-year-old man presented with general malaise. Abdominal computed tomography and magnetic resonance imaging revealed a mass in the distal common bile duct, accompanied by dilatation of the intra- and extrahepatic bile ducts. The patient underwent pancreaticoduodenectomy with regional lymphadenectomy. Gross examination revealed that the distal common bile duct was obstructed by an elastic hard mass, 3.2 × 2.6 cm, accompanied by intraductal tumor thrombi. Microscopically, the nodule was well defined and composed of atypical large tumor cells with bizarre nuclei and little cytoplasm. Immunohistochemically, the tumor cells were diffusely positive for cytokeratin-7 and CAM5.2, but negative for CD56, chromogranin A, and synaptophysin. Thus, a histological diagnosis of undifferentiated carcinoma of the common bile duct was made. The patient recovered uneventfully and has remained free of any signs of recurrence for 18 months since the operation. Undifferentiated carcinomas of the extrahepatic bile duct can be detected early, with the chance of a good prognosis; however, because their biologic growth behavior is still considered aggressive, careful observation after surgery and the initiation of multidisciplinary treatment against recurrence are necessary.     

Clinical experience in tumors of the common bile duct

The authors, after a short review of the literature present 6 cases of cancer of the common bile duct. One was localized at the hepatic hilus, three in the middle of the c.b.d., two in the distal choledochus. In each case a c.b.d. resection was performed associated in one case to a minor hepatic resection, in two cases to a Whipple operation.