Small pancreatic carcinoma misdiagnosed as superficially spreading cholangiocarcinoma

We report a case of small pancreatic carcinoma misdiagnosed as superficially spreading cholangiocarcinoma using percutaneous transhepatic cholangioscopy (PTCS). The patient was a 72-year-old man admitted to a local hospital with obstructive jaundice. The patient underwent percutaneous transhepatic biliary drainage and PTCS. He was referred to our hospital with a diagnosis of superficially spreading cholangiocarcinoma. Cholangiography revealed a stenosis of the common bile duct, and also revealed some irregularities from the common hepatic duct to the left hepatic duct, suggesting a superficial spread of cancer. No pancreatic tumor was identified by endoscopic retrograde pancreatography or by enhanced computed tomography. Cholangioscopy disclosed an elevated tumor with torsional vessels and granular mucosal lesions, which were extended to the left hepatic duct. Repeated cholangioscopic biopsies of the bile duct mucosa revealed adenocarcinoma. The patient was diagnosed with superficially spreading cholangiocarcinoma extending to the left hepatic duct and the right anterior hepatic duct. Left trisectionectomy combined with pancreatoduodenectomy was performed. The cut surface of the resected specimen showed a pancreatic head tumor that was 8 mm in diameter. Histological findings of the resected specimen revealed adenocarcinoma arising from the pancreatic head with invasion in the common bile duct. Additionally, extensive inflammatory granulation tissue was observed along the surface of the bile duct, without any evidence of carcinoma. This case implies to us that the results of PTCS, even after repeated biopsies, should be interpreted with great caution.     

Recurrence of mucosal carcinoma of the bile duct, with superficial flat spread, 12 years after operation

We report herein a case of recurrent mucosal cancer of the extrahepatic bile duct, with superficial flat spread, 12 years after operation. A 67‐year‐old woman had undergone common bile duct (CBD) resection and Roux‐en‐Y reconstruction. Histologically, the tumor was papillary adenocarcinoma, with superficial flat spread, with no invasive component. The epithelium at the distal margin had been exfoliated, so the absence or presence of any remnant cancerous lesion was unclear. But the superficial flat spread had expanded to within at least 3 mm from the distal margin. About 12 years postoperatively, she was hospitalized with upper abdominal pain, and duodenoscopy demonstrated a tumor in the second portion of the duodenum. Biopsy identified adenocarcinoma. Computed tomography showed a low‐density mass between the duodenum and pancreatic head. Pancreatoduodenectomy was performed. Histologically, papillary adenocarcinoma was found within the whole of the intrapancreatic bile duct, and its histological appearance resembled that of the original tumor. Moderately differentiated tubular adenocarcinoma had invaded around the tissue of the intrapancreatic CBD. These findings suggest that remnant intramucosal flat carcinoma within the intrapancreatic bile duct had developed into invasive carcinoma over the course of 12 years. This case suggests that remnant intraepithelial flat carcinoma within the CBD may develop a late local recurrence.     

Differences in Fine Mucosal Structure between Superficial Spreading Carcinoma and Non-neoplastic Bile Duct Mucosa Detected by Percutaneous Transhepatic Cholangioscopy

Abstract: Papillogranular mucosa is reportedly characteristic of superficial spreading bile duct carcinoma, but may also be seen in non-neoplastic ductal tissue. This study was designed to clarify differences between these conditions by examining fine mucosal structure with percutaneous transhepatic cholangioscopy (PTCS) and methylene blue (MB) staining. Sixty-three patients with malignant bile duct stenoses and 11 with benign bile duct disorders were examined by PTCS and the relationship between fine mucosal structure and histology was defined using endoscopic photographs and biopsy samples. Papillogranular mucosal samples contained superficial spreading carcinoma significantly more often than smooth mucosal samples (p<0.0001). Papillogranular mucosa was classified by fine structure into four types : regular papillogranular, nodular, finely reticulogranular and highly papillary. The latter three types were associated with superficial spreading carcinoma significantly more often than with non-neoplastic mucosa (p<0.05). However, regular papillogranular mucosa was associated with both neoplastic and non-neoplastic tissue. All papillogranular mucosal samples not stained with MB contained superficial spreading carcinoma. In 19% of papillogranular mucosa samples fine mucosal structure was identified by routine observation, while in 84% fine structure was determined by a combination of routine observation and MB staining. In conclusion, nodular, finely reticulogranular and highly papillary forms of papillogranular mucosa, as well as papillogranular mucosa which does not stain with MB, are characteristic of superficial spreading carcinoma. The combination of routine observation and MB staining is useful for analyzing the fine mucosal structure of papillogranular mucosa. However, meticulous observation is needed to diagnose superficial spreading carcinoma in regular papillogranular mucosa.     

Peroral cholangioscopy for non-invasive papillary cholangiocarcinoma with extensive superficial ductal spread

Papillary carcinoma arising from the extrahepatic bile duct often shows superficial ductal spread. We report herein the case of a patient with extensive superficial spread of non-invasive papillary cholangiocarcinoma, which was depicted with peroral cholangioscopy. A 65-year-old woman presented with the sudden-onset of severe epigastric pain. Ultrasonography revealed acute acalculous cholecystitis. Endoscopic retrograde cholangiography found small protruding lesions around the confluence of the cystic duct, suggestive of a cholangiocarcinoma. As the contour of the middle and upper bile ducts it was slightly irregular on the cholangiogram, the presence of superficial ductal spread was suspected. Peroral cholangioscopy revealed small papillary lesions around the confluence of the cystic duct and fine granular mucosal lesions in the middle and upper bile ducts and the right hepatic duct, suggesting a superficially spreading tumor. A right hepatectomy with bile duct resection was performed and no residual tumor was found. Histological examination revealed a non-invasive papillary carcinoma arising from the cystic duct with extensive superficial spread. Our experience of this case and a review of the literature suggest that a fine granular or fine papillary appearance of the ductal mucosae on cholangioscopy indicates superficial spread of papillary cholangiocarcinoma, for which peroral cholangioscopy is an efficient diagnostic option.     

Adenoendocrine cell carcinoma of the extrahepatic bile duct: a case report and review of the literature

Extrahepatic bile duct cancer with an endocrine cell component has rarely been reported. We report here on a case of adenoendocrine cell carcinoma in the middle bile duct. An 82-year-old man was admitted to hospital for jaundice and anorexia. Computed tomography and magnetic resonance imaging examination showed a papillary low-density mass in the middle bile duct. Endoscopic retrograde cholangiography showed obstruction of the bile duct, and blushing cytology of the bile duct revealed an adenocarcinoma. We resected the extrahepatic bile duct with regional lymph node dissection. A pathological examination revealed a neuroendocrine component showing small cytoplasmic cells with hyperchromatic nuclei and a rosette-like structure in the middle of the tumor. In the peripheral mucosal region, there was a well-differentiated adenocarcinoma composed of columnar and cuboidal epithelial cells with clear and slightly granular eosinophilic cytoplasm. Immunohistochemical analysis showed positive staining for CD56, following the diagnosis of adenoendocrine cell carcinoma. The Ki-67 rate was >30% suggesting a small-cell endocrine carcinoma. The adenocarcinoma component infiltrated into the endocrine component, and some of the endocrine component was positive for cytokeratin, suggesting transdifferentiation of the adenocarcinoma into the endocrine component rather than originating from the common precursor cell. The patient experienced liver metastasis 3 months after the operation and died 6 months after the operation. Adenoendocrine tumor of the bile duct is extremely rare and adjuvant chemotherapy is necessary according to the malignant potential of the neuroendocrine tumor rather than the adenocarcinoma.     

A Study of Malignant Bile Duct Stenosis Using Percutaneous Transhepatic Cholangioscopy

Abstract: From June, 1987 to November, 1989, 11 patients with malignant bile duct stenosis, which was later confirmed by surgery or autopsy, were examined by percutaneous transhepatic cholangioscopy (PTCS) and by an endoscopic biopsy. The endoscopic findings obtained with the usual observation methods and methylene blue staining and the histological findings of the biopsy specimens were compared. A fine vascular proliferation was seen in all of the patients and a granular appearance was noted in patients with carcinoma of the major papilla. The papillary appearance was noted in one case each of pancreatic carcinoma, bile duct carcinoma and carcinoma of the major papilla. Marginal protrusion was not noted in patients with pancreatic carcinoma. A distorted narrow segment was seen only in cases of pancreatic carcinoma. The presence of a granular appearance indicated that the carcinoma was exposed on the surface. A high degree of fine vascular proliferation and a papillary appearance tended to indicate a carcinoma which invaded mainly into the fibromuscular layer without invasion of the mucosa. The methylene blue staining method was simple and effective for better visualization of the surface structure of the abnormal area, normal mucosa and the border zone.     

OPTIMUM NUMBER OF PERCUTANEOUS TRANSHEPATIC CHOLANGIOSCOPY‐GUIDED BIOPSIES FOR HISTOLOGIC DIAGNOSIS OF BILE DUCT CARCINOMA

Background: Percutaneous transhepatic cholangioscopy (PTCS)‐guided biopsy is used for the diagnosis of bile duct carcinoma, but the number of biopsy specimens required for diagnosis is unclear. The aim of this study was to clarify whether multiple PTCS‐guided biopsies are needed for accurate histologic diagnosis. Methods: We examined the relationships between size of the first biopsy specimen, endoscopic, cholangiographic, and pathologic features, and the presence of carcinoma in the first biopsy specimen of the primary lesion in 27 bile duct carcinomas. Results: Twenty‐six of 27 carcinomas (96%) were histologically diagnosed by PTCS‐guided biopsy; 20 (74%) were detected in the first biopsy specimen, six in the second or third biopsy specimen, and one was not detected in four biopsy specimens. Carcinomas with papillogranular mucosa by endoscopy, convex margins by cholangiography, or macroscopic types (except for sclerosing type) were detected on the first biopsy specimen more frequently than were others (15/15 vs 5/12, P <0.001; 13/13 vs 7/14, P <0.01; and 15/16 vs 5/11, P <0.01, respectively). There was no relationship between positivity for carcinoma and size of the first biopsy specimen, vascular dilatation by endoscopy, or histologic type. With the combination of preoperative endoscopy and cholangiography, main lesions with papillogranular mucosa and/or convex margins were proven to be carcinoma on the first biopsy specimen significantly more frequently than were others (17/17 vs 3/10, P <0.0001). Conclusion: If the main lesion contains neither papillogranular mucosa nor a convex margin, multiple PTCS‐guided biopsies should be performed in order to increase the sensitivity for diagnosing bile duct carcinoma.     

Concomitant adenosquamous carcinoma of the common bile duct and early adenocarcinoma of the gall-bladder

We report a 59 year old male with obstructive jaundice and a clinical diagnosis of carcinoma of the midportion of the common bile duct. Examination of the surgical specimen revealed a small tumour in the neck of the gall-bladder. Histologic examination revealed the tumour in the common bile duct was an adenosquamous carcinoma whereas that in the gall-bladder was an early papillary adenocarcinoma. Thus, this is a rare case of the simultaneous development of adenosquamous carcinoma and early papillary adenocarcinoma in the biliary tree.     

A case of adenocarcinoma in situ of the distal common bile duct diagnosed by percutaneous transhepatic cholangioscopy

Extrahepatic cholangiocarcinoma is often clinically challenging to diagnose. Even multidisciplinary approaches which include computed tomography, magnetic resonance imaging, and endoscopic retrograde cholangiography are unsatisfactory in some cases, especially with biliary stricture. Percutaneous transhepatic cholangioscopy (PTCS) with its direct visualization for biopsy appears to be a promising technique for detecting cholangiocarcinoma at an early stage. We report a case of adenocarcinoma in situ of the distal common bile duct (CBD) that was confirmed by PTCS. This case suggests the useful role of PTCS in the differential diagnosis of a distal CBD obstruction, particularly when other diagnostic modalities do not provide definitive information.     

A clinicopathological study on the proximal border of bile duct carcinoma]

We studied the clinicopathological characteristics of the proximal border of bile duct cancer among 46 cases. In both the superficial and the superficially spreading type, cancer was located within the mucosa and the mucous membrane at its verge was more hypertrophic than the proximal noncancerous mucosa, but they didn't differ from each other in thickness at the fibromuscular and Glisson's fibrous layer. In bile duct cancer without superficial spread, on the other hand, the tumor involve the fibromuscular or Glisson's fibrous layer and fibromuscular or Glisson's fibrous layer at their verge was more hypertrophic than the proximal noncancerous bile duct, which resulted in the narrowing bile duct at the lesion. Percutaneous transhepatic cholangioscopy (PTCS) facilitates the preoperative diagnosis of the extent of the bile duct cancer, which shows a granular change of the mucosa and tumor vessels. The wall irregularity and narrowing of the bile duct demonstrated by the selective cholangiography are also referred to its extent.     

Advanced gallbladder carcinoma with biliobiliary fistula, resected by hepatopancreatoduodenectomy, in an aged patient

We report a 78-year-old man with a gallbladder carcinoma and biliobiliary fistula, diagnosed by percutaneous transhepatic cholangioscopic biopsy through the fistula. The impacted stones in the common hepatic duct were crushed, and then selective cholangiography under percutaneous transhepatic cholangioscopy (PTCS) revealed a biliobiliary fistula. Cholangioscopic biopsy tissues taken from the gallbladder revealed adenocarcinoma, but biopsies taken from the fistula revealed no evidence of malignancy. Further investigations indicated that the gallbladder carcinoma involved the duodenum and the distal common bile duct. A hepatopancreatoduodenectomy, including both an extended right hepatic lobectomy with resection of the caudate lobe and a pancreatoduodenectomy, was performed. Despite the patient's advanced age, he made an unremarkable postoperative recovery and was able to enjoy an active social life for 8 months after the surgery. We discuss biliobiliary fistula associated with gallbladder carcinomas and the use of hepatopancreatoduodenectomy for advanced biliary cancer in aged patients.     

A case report of anaplastic carcinoma of the pancreas with remarkable intraductal tumor growth into the main pancreatic duct

We herein report a case of anaplastic carcinoma of the pancreas with remarkable intraductal tumor growth into the main pancreatic duct.A 76-year-old male was referred to our hospital for treatment of a pancreatic tumor.Preoperative examinations revealed a poorly defined tumor in the main pancreatic duct in the body of the pancreas,accompanied with severe dilatation of the main pancreatic duct,which was diagnosed as an intraductal papillary-mucinous neoplasm.We performed distal pancreatectomy and splenectomy.The pathological examination revealed that the tumor consisted of a mixture of anaplastic carcinoma(giant cell type)and adenocarcinoma in the pancreas.There was a papillary projecting tumor composed of anaplastic carcinoma in the dilated main pancreatic duct.The patient is now receiving chemotherapy because liver metastasis was detected 12 mo after surgery.In this case,we could observe a remarkable intraductal tumor growth into the main pancreatic duct.We also discuss the pathogenesis and characteristics of this rare tumor with specific tumor growth.     

Living-donor liver transplantation for Caroli's disease with intrahepatic adenocarcinoma

A 36-year-old woman who had Caroli's disease with refractory cholangitis and complicated intrahepatic cholangiocarcinoma was successfully treated with living-donor liver transplantation. Preoperative computed tomography and ultrasonography showed a small nodule in the dilated intrahepatic bile duct. In the resected liver specimen, a small papillary tumor was located in the dilated intrahepatic bile duct of the right lobe. The pathological finding revealed a well differentiated papillary adenocarcinoma without invasion to the parenchyma. The patient is currently doing well 2.5 years after transplantation, with no signs of recurrence of the disease. For Caroli's disease, we believe we can achieve good results with liver transplantation, not only for cholangitis but also for the carcinoma when it is localized in the liver and the patient is carefully followed up.     

Intraductal oncocytic papillary neoplasm of the bile duct: the first case of peribiliary gland origin

We report herein the first case of intraductal oncocytic papillary neoplasm of the bile duct arising from a peribiliary gland of the left hepatic duct. The patient was a 63-year-old Japanese man. Radiological and cholangioscopic examinations revealed intraductal tumor of the left hepatic duct. After pathological diagnosis of adenocarcinoma by cholangioscopic biopsy, a surgical hepatobiliary resection was performed. Pathological examination revealed papillary tumor in the left hepatic duct. Histologically, the tumor was identified as papillary neoplasm comprising oncocytic cells and delicate fibrovascular cores. Interestingly, this tumor originated from the cystic space in the bile duct wall. This cystic space was histologically identified as a cystically dilated peribiliary gland. Carcinoma in situ was observed in this cystic peribiliary gland at the bottom of the tumor, but not on any areas of biliary epithelium. This case suggests that intraductal papillary neoplasm can arise from both biliary epithelium and peribiliary glands.     

A long-term surviving patient with cancer of papilla of Vater after local resection

We report successful local resection for cancer of papilla of Vater in an 86-year-old woman. She was referred to our hospital because of right hypochondralgia. Abdominal ultrasonography and computed tomography showed marked dilatation of the common bile duct (CBD). Endoscopic retrograde cholangiography disclosed a small shadow defect in the terminal of the dilated CBD. Biopsy of the papilla revealed well-to-moderately differentiated adenocarcinoma. Considering her extreme old age and keeping in mind her quality of life after the operation, and the finding that the tumor was localized within the papilla and highly differentiated, we performed local resection. In addition, the intrapancreatic portion of the CBD and part of the main pancreatic duct (MPD) were further resected to secure a negative margin, confirmed by frozen section. The MPD was reapproximated to the duodenal mucosa and a choledocho-duodenostomy was performed for CBD reconstruction. Histopathological examination showed the tumor was papillary adenocarcinoma, 10 × 15 mm in size; there was no invasion beyond the sphincter of Oddi, it had partly infiltrated the CBD, but had not invaded to the pancreas or duodenum. The patient's postoperative course was not eventful and she has had good quality of life for the past 6 years since the operation, without any evidence of recurrence. Although radical pancreaticoduodenectomy is now the standard procedure in patients with malignant tumor of the papilla of Vater, local resection is a reasonable alternative for high-risk patients with highly differentiated, apparently localized carcinomas.     

Biliary cystadenocarcinoma with superficial spread to the extrahepatic bile duct.

We report a case of biliary cystadenocarcinoma of the liver with superficial spread to the extrahepatic bile duct. Preoperative endoscopic retrograde cholangiography revealed communication between a 4.5-cm cyst in segment 4 of the liver and the bile duct. From the findings obtained by peroral cholangioscopy and intraoperative cholangioscopy, the granular mucosa in the bile duct was diagnosed as superficially spreading cancer. The right posterior segmental bile duct and the right anterior segmental bile duct were resected at the point where the spread of cancer was no longer traceable and left lobectomy plus caudate lobectomy was carried out. This achieved radical resection, leaving the resected margin of the bile duct free from cancer. Histopathologically, well-differentiated papillary adenocarcinoma was found on the inner surface of the cyst, and the cancer had superficially spread from the cyst to the extrahepatic bile duct via the 2.5-mm diameter communication between the cyst and bile duct. The cancer was limited only to the mucosal layer all over the lesion. When performing radical surgery for biliary cystadenocarcinoma, it is recommended that cholangioscopy be performed to examine whether the cancer has superficial spread to the extrahepatic bile duct or not. Bile duct resection should be carried out, depending on the extent of the superficial spread, so that the resected margin of the bile duct is free from cancer.     

Mucin-producing carcinoma of the gallbladder associated with primary sclerosing cholangitis and ulcerative colitis

Mucin-producing carcinoma of the gallbladder is very rare. We report here a case of mucin-producing carcinoma of the gallbladder associated with primary sclerosing cholangitis (PSC) and ulcerative colitis (UC). A 74-year-old female had been treated with salazosulfapyridine and ursodesoxycholic acid becase of UC and PSC. After 7 years of treatment, laboratory data showed that the liver function took a turn for the worse, and the patient was admitted to our hospital for further examination. Enhanced computed tomography and ultrasonography showed an enlarged gallbladder associated with wall thickening and diffuse papillary protrusion. Endoscopic retrograde cholangiography showed stenosis and dilatation of the bile duct, which were compatible with PSC. Under the diagnosis of an early carcinoma of the gallbladder, we performed simple cholecystectomy. The tumor showed a papillary growth pattern located diffusely in the gallbladder with a massive amount of mucin filling the gallbladder. Histologically, it was diagnosed as a papillary adenocarcinoma localized in the mucosal layer. To the best of our knowledge, this is the first case of mucin-producing carcinoma of the gallbladder associated with PSC and UC. PSC and UC patients should be regarded as a high-risk group not only for cholangiocarcinoma but also carcinoma of the gallbladder.     

DIRECT CHOLANGIOSCOPY USING A DOUBLE‐BALLOON ENTEROSCOPE: CHOLEDOCHOJEJUNOSTOMY WITH INTRADUCTAL BILIARY CARCINOMA

A 75‐year‐old man who underwent choledochojejunostomy for gallstones 30 years ago was hospitalized for general malaise. Abdominal computed tomography revealed marked dilation of the intrahepatic bile duct in the right lobe and an image of a hypervascular tumor. Endoscopic retrograde cholangiography using double‐balloon enteroscopy (DBE) showed a filling defect that was localized to the right hepatic bile duct. Furthermore, the scope was able to readily pass through the anastomosed site of the choledochojejunostomy and, therefore, we observed the interior of the bile duct using the same scope. We obtained an image showing a whitish, papillary‐like tumor, and a biopsy of the tumor rendered the pathology of intraductal papillary mucinous carcinoma. Direct cholangioscopy using DBE is a useful diagnostic tool, particularly in patients with a past history of choledochojejunostomy.     

Bile duct carcinoma arising in metaplastic biliary epithelium of the intestinal type: a case report

We report herein a case of distal bile duct carcinoma showing intestinal differentiation diagnosed 3 years after endoscopic sphincterotomy for choledocholithiasis. The diagnostic problem in this case was that the granular mucosa, which is a typical finding of superficial mucosal extension of bile duct carcinoma in general, was interpreted as hyperplasia accompanying metaplasia in cholangioscopic biopsy. Discrimination of superficial mucosal cancer extension from hyperplastic mucosa with metaplastic changes was impossible using cholangioscopic examination. In our case, reflux and stasis of the duodenal and pancreatic juice into the biliary tract might have occurred because of abnormal function of the papilla of Vater following endoscopic sphincterotomy. It might be suggested that endoscopic sphincterotomy contributed to the metaplastic changes in the bile duct mucosa in our case.     

Value of peroral cholangioscopy for mucin-producing bile duct tumor

Mucin-producing bile duct tumor is a rare biliary tract tumor. Despite the development of modern diagnostic technologies such as ultrasonography, and angiography, the precise determination of this tumor is difficult because of ambiguity caused by the abundant mucin secreted by the tumor and/or by the superficial mucosal spread of the tumor along the bile duct. Given these problems, selective percutaneous transhepatic biliary drainage (PTBD) and percutaneous transhepatic cholangioscopy (PTCS) are indispensable for the accuracy staging of this cancer. But, PTCS has a risk of a rare but serous complications, seeding metastasis at the sinus tract of PTBD, whereas the retrograde approach minimizes this risk. We report the case of a patient who underwent the successful resection of a mucin-producing bile duct tumor. The tumor was diagnosed preoperatively as originating in the left caudate lobe after ERC and peroral cholangioscopy (POCS).