Bidhan C. Das

Analysis of the relationships between clinicopathologic factors and survival time in intrahepatic cholangiocarcinoma

BACKGROUND This study elucidated the relationships between various clinicopathologic factors and the outcome of patients with intrahepatic cholangiocarcinoma (ICC) treated by hepatic resection. METHODS A total of 37 ICC patients were treated by hepatic resection in our department between March 1979 and March 2001. Eleven clinicopathological variables (age, sex, preoperative jaundice, operative curability, number of tumors, UICC [Union Internationale Contre le Cancer] pT factor, UICC pN factor, UICC pM factor, histological tumor type, 10-year period during which they initially examined, and adjuvant therapy) were selected for univariate and multivariate analysis to evaluate their influence on the outcome. RESULTS The actuarial 1-, 3-, and 5-year survival rates in the 37 resected cases were 54.1%, 34.0%, and 23.9%, respectively. The stage of the ICC influenced their overall survival rate. The univariate analysis revealed that curative resection (P = 0.0018), UICC pT factor (P = 0.0445), pN factor (P = 0.0029), pM factor (P = 0.0022), and histological type (P = 0.0030) were significant risk factors for survival. Multivariate analysis revealed that noncurative resection, lymph node metastasis, and less differentiated histological type were significant risk factors for poor outcome. All 6 of the 37 patients who survived more than 5 years had undergone curative resection, all of their tumors were well differentiated, and none had lymph node metastasis. CONCLUSIONS Curative surgical resection remains the only effective approach to the treatment of ICC. Extensive resection is not indicated if lymph node metastasis can be identified preoperatively or intraoperatively. Current adjuvant therapy is ineffective, and it will be necessary to assess the efficacy of new adjuvant therapy strategies or the addition of new agents in terms of the outcome of ICC.

Prognostic significance of biologic factors in squamous cell carcinoma of the esophagus.

Esophageal carcinoma is one of the most lethal tumors. Therefore, it is important to identify prognostic factors for patients with this disease. The objective of this study was to clarify the relation between clinicopathologic and biologic factors in esophageal carcinoma and to determine the prognostic significance of different biologic factors.

Analysis of 100 Consecutive Hepatectomies: Risk Factors in Patients with Liver Cirrhosis or Obstructive Jaundice

Abstract. We analyzed various pre-, intra-, and postoperative variables in 100 consecutive patients treated by hepatectomy for various malignant and benign liver diseases to identify patients at risk of developing postoperative complications. Patients were divided into three groups: those with normal liver (NL, n= 53); those with liver cirrhosis (LC, n= 32); and those with obstructive jaundice (OJ, n= 15). The overall postoperative morbidity and mortality rates were 14% and 4% (due to liver failure), respectively. In the LC group the combined presence of abnormal levels of serum hyaluronic acid (HA, > 200 ng/ml), indocyanine green retention rate at 15 minutes (ICGR15, > 15%), and hepatic uptake ratio of 99mTc-galactosyl human serum albumin (GSA) at 15 minutes (LHL15, < 0.9) preoperatively was found to be a risk factor with a 100% morbidity rate. Operative blood loss of more than 1000 ml in LC patients was associated with high morbidity. In the OJ group preoperative parameters were almost normal after biliary drainage, but the extent of liver resection, blood loss > 2000 ml, and high serum interleukin-6 12 hours after hepatectomy correlated with high postoperative morbidity. No morbidity or mortality was reported in the NL group, except in a single patient who received long-term intraarterial chemotherapy preoperatively. Consequently, the extent of hepatectomy should be carefully determined according to the preoperative risk factors in LC patients; and in OJ patients hepatectomy, which tends to become extensive, should be carefully performed to minimize surgical stress because preoperative factors do not help predict outcome. Furthermore, the present study revealed that a serum HA level higher than 500 ng/ml on postoperative day 1 or day 7 (or both) was a useful marker for hepatic failure.

S4a + S5 with caudate lobe (S1) resection using the Taj Mahal liver parenchymal resection for carcinoma of the biliary tract.

Recently we have been performing S4a + S5 with total resection of the caudate lobe (SI) by using a dome-like dissection along the root of the middle hepatic vein at the pinnacle, which we refer to as the Taj Mahal liver parenchymal resection, for carcinoma of the biliary tract. This procedure offers the following advantages: (1) It allows total resection of the caudate lobe, including the paracaval portion (S9), and (2) because the cut surface of the liver is large, it allows intrahepatic jejunostomy to be performed more easily with a good field of view. The indications for this procedure include hilar bile duct carcinoma, gallbladder carcinoma, and choledochal cyst (type IVA). Because of the high rate of hilar liver parenchyma and caudate lobe invasion associated with hilar bile duct carcinoma, the liver must be resected. The Taj Mahal procedure is indicated in cases where extended liver resection is impossible. The dissection limits of this procedure are, on the left side, the B2 + 3 bifurcation at the right margin of the umbilical portion of the portal vein and, on the right side, the B8 of the anterior branch and the B6+7 bifurcation of the right posterior branch. This procedure could also be described as a reduced form of extended right hepatectomy and extended left hepatectomy. For gallbladder carcinoma, this procedure is indicated to ensure an adequate surgical margin and eradicate transvenous liver metastasis, particularly in cases of pT2 lesions. Hilar and caudate lobe invasion also occurs in liver bed-type gallbladder carcinoma, and bile duct resection and caudate lobe resection are required for the surgery to be curative. We performed this procedure in four cases of hilar bile duct carcinoma, five cases of gallbladder carcinoma, and one case each of choledochal cyst (type IVA) with carcinoma of the bile duct and gallbladder adenomyomatosis. Curative resection was possible in all except the patient with adenomyomatosis, and all of the patients are alive and recurrence free 10 to 37 months postoperatively. This procedure, in addition to preserving liver function, provides a wide field of view and facilitates reconstruction of multiple intrahepatic bile ducts. Thus it can be said to be a curative operation not only in patients considered high risk but also in those whose hilar bile duct carcinoma is limited to the bifurcation area (Bismuth type IIIa and IIIb) and in gallbladder carcinoma up to pT2 with slight extension on the hepatic side.

Surgical Treatment of Hilar Bile Duct Carcinoma: Experience With 25 Consecutive Hepatectomies

To evaluate our recent surgical policy regarding hilar bile duct carcinoma, we evaluated 62 cases treated between 1976 and 1993, and 25 cases treated between 1994 and 2000. In the late period we used percutaneous transhepatic portal vein embolization (PTPE) before extended right hepatectomy; S4a + S5 + S1 hepatectomy for elderly patients and those with poor liver function; and routine total caudate lobectomy including the paracaval portion and resection of the inferior portion of the medial segment (S4a). Sixtyfive (74.7%) of the 87 patients underwent hepatectomy: 40 in the early period and 25 in the late period. Bile duct resection alone was performed in 22 patients, all in the early period. Resection was curative in 54.8% in the early period and 88.0% in the late period. The 3- and 5-year survival rates in the early period were 27.1% and 20.2%, respectively, as compared to 59.9% and 49.9% in the late period. Analysis of the 25 hepatectomies in the late period revealed improved survival times compared to patients treated by PTPE with extended right hepatectomy. No complications occurred after extended left hepatectomy or S4a + S5 + S1 hepatectomy, but four patients (16%) who underwent extended right hepatectomy plus PTPE died postoperatively. Our policy has resulted in improved outcome in patients with hilar bile duct carcinoma.

Surgical treatment of type IV choledochal cysts

The benefit of total resection of the dilated bile duct has remained unclear. We describe here our surgical management of 13 patients with type IV choledochal cysts. All six younger patients (25-35 years old) underwent resection of the extrahepatic bile duct (EHBD) and hepaticojejunostomy (HJ), whereas three of the seven older patients (50-68 years old) underwent resection of the EHBD resection and HJ, with the remaining four older patients undergoing total resection of the dilated bile duct and removal of a pancreatobiliary maljunction (PBMJ) in the form of a S4a+S5 hepatectomy (so-called Taj Mahal) and/or pancreas head resection with second portion pancreaticoduodenectomy. No malignancies were detected in the dilated bile duct after resection in the younger patients, but cancer of the gallbladder and/or the dilated bile duct was found in two (27.5%) of the older patients. No cancers were detected during the long-term follow up (1974-2008) in those patients who underwent EHBD resection plus partial hepatectomy, but cancer developed in the remnant duct in one of the older patients who underwent EHBD resection alone. Based on our findings, we recommend that type IV choledochal cysts should be treated by total excision of the dilated bile duct, including the PBMJ, due to its frequent association with malignancy, and to prevent the development of cancer in the remnant duct and improve the long-term survival rate.

Liver retransplantation with external biliary diversion for progressive familial intrahepatic cholestasis type 1: a case report.

Abstract: PFIC1, originally described as “Byler disease,” is characterized by cholestatic feature and chronic diarrhea. Many patients require LT for the cure, but intractable diarrhea and prolonged growth retardation after LT are serious complications limiting the ultimate outcome of LT for this disease. EBD has recently been shown to be a promising and effective treatment. Recently, we successfully treated a five‐yr‐old boy with PFIC1 employing EBD after re‐transplantation. The patient received LDLT at the age of one yr. Six months after initial transplantation, he developed repeated attacks and diarrhea followed by the development of liver dysfunction and ascites. Liver biopsy at three yr after LDLT revealed the features of chronic graft rejection. With a diagnosis of chronic graft rejection with liver failure, we performed a repeat LDLT with EBD in which the jejunal loop used for hepaticojejunostomy was taken out of the body surface through the abdominal wall. Ten months after surgery, he is doing well, having no attack of diarrhea.

Primary carcinoma of the cystic duct associated with pancreaticobiliary maljunction

carcinoma, while CD is associated with both gallbladder carcinoma and bile duct carcinoma.6 The association between PBM and carcinogenesis is thought to be attributable to the reflux and stasis of a mixture of pancreatic juice and bile that occurs in the gallbladder of patients with NCD-PBM and in both the gallbladder and bile duct of patients with CD-PBM.5 The refluxed pancreatic juice irritates the biliary epithelium and promotes inflammation, which may ultimately lead to a sequence of hyperplasia, dysplasia, metaplasia, and, finally, carcinoma.9 However, the existence of an association between PBM and cystic duct carcinoma is unclear. In this issue of the Journal, Sato and coworkers10 report a case of cystic duct carcinoma with PBM, and they claim that it is first case ever reported. Actually, because of the continuous exposure to pancreatic juice in patients with PBM, the pathological process occurs throughout the entire biliary tract epithelium, and, thus, carcinoma can arise anywhere in the biliary tract. In 1978, Manabe and Sugie11 collected 21 cases of primary cystic duct carcinoma, including their own case, and reported that 3 of the patients presented with obstructive jaundice. In 1999, Morio et al.12 collected 51 cases of primary cystic duct carcinoma, and reported that the 13 patients in whom the disease had been diagnosed preoperatively had presented with manifestations of obstructive jaundice. We recently reported a case of cystic duct carcinoma (Tokai Surgical Congress, Nagoya, April 2000) associated with NCD-PBM that was diagnosed preoperatively, in which the patient presented with manifestations of obstructive jaundice and was treated surgically by combined liver and pancreatic head resection, as for hilar bile duct carcinoma. In their article in this issue of the Journal, Sato et al.10 retrieved 29 cases of cystic duct carcinoma that satisfied Farrar’s criteria in a search of the English-language and Japanese literature. Very recent statistics (1980 to 1998, collected by Tashiro and colleagues, of Tokushima University, Japan) reveal that 138 (39.8%) of 347 NCDPrimary carcinoma of the cystic duct is a rare condition. In 1951, when Farrar1 reported his case, he found very few cases in the literature, and none of them were indisputable instances of primary carcinoma of the cystic duct. He then proposed the following criteria for diagnosis of primary carcinoma of the cystic duct: (1) growth restricted to the cystic duct; (2) no neoplastic process present in the gallbladder, hepatic ducts, or common bile duct; and (3) histological confirmation of the presence of carcinoma cells in the mass.1 The cystic duct is a short structure, and, because carcinoma of the gallbladder, hepatic ducts, and the common bile duct can easily invade it, and because advanced primary carcinoma of the cystic duct can easily invade adjacent organs as well, Farrar’s criteria are not always helpful in making the diagnosis of primary cystic duct carcinoma, especially in advanced disease. Pancreaticobiliary maljunction (PBM) is also a rare condition, and, thus, the combination of PBM and cystic duct carcinoma is extremely rare. In 1959, Alonso-Lej et al.2 reported on congenital choledochal cyst and devised a classification system, based on anatomic descriptions, which was subsequently modified by Todani et al.3 in 1977. In 1969, Babbitt4 developed a new etiological concept regarding the association between choledochal cyst and PBM, and in 1985 Kimura et al.5 reported a few cases of PBM without biliary dilatation. As a result, PBM has been classified into two types: a choledochal dilatation (CD) type and a non-choledochal dilatation (NCD) type.6 Since 1980, many investigators have found an association between PBM and biliary tract carcinoma (20%–30%).7,8 It has also been found that NCD-PBM is associated with a higher incidence of gallbladder carcinoma and a lower incidence of bile duct