Kazufumi Kunitomo

Does the Type of Anomalous Arrangement of Pancreaticobiliary Ducts Influence the Surgery and Prognosis of Choledochal Cyst

A new classification of the anomalous arrangement of pancreaticobiliary ducts (APBD) has been proposed following amendments and modificiations of the previous one. Fifty-one cases of choledochal cyst complicated with APBD were extensively examined and analyzed for clear visualization of the APBD system to make a standard classification. APBD were classified broadly into three types: type I, type II, and type III with their subtypes. Type I of APBD was seen in 18 (35.3%), type II in 11 (21.6%) and type III in 22 (43.1%) cases, respectively. A radical operation, including complete excision of the dilated biliary duct followed by reconstruction of the biliary tract was the surgical treatment of choice, because the reflux of the pancreatic juice into the biliary tract is prevented. However, a dilated common channel or accessory pancreatic duct, according to the new Komi type Ib, IIb, and IIIc3 of APBD, could be the cause of relapsing pancreatitis leading to chronic pancreatitis, due to the formation of a protein plug or pancreatic calculus in the dilated duct, even after this radical operation. In two complicated cases of type IIIc3 of APBD in choledochal cyst, we performed a pylorus-preserving pancreatoduodenectomy as one of the operative methods of choice. Long-term follow-up, more than decades, is essential to evaluate the results of surgical procedure for choledochal cyst, especially in those complicated cases with type Ib, IIb, and IIIc3 of APBD according to the new Komis classification.

Choledochal cyst: Anomalous arrangement of the pancreaticobiliary ductal system and biliary malignancy

Congenital biliary dilatation (CBD) or choledochal cyst has previously been considered a rarity; however, the number of cases reported in the literature has been increasing. It is generally accepted that there is a predominance in Japanese, as more than one‐third of the cases are from Japanese literature.

Randomized controlled trial of the efficacy of adjuvant immunochemotherapy and adjuvant chemotherapy for colorectal cancer, using different combinations of the intracutaneous streptococcal preparation OK-432 and the oral pyrimidines 1-hexylcarbamoyl-5-fluorouracil and uracil/tegafur

BackgroundWe investigated the efficacy and safety of adjuvant immunochemotherapy and adjuvant chemotherapy for colorectal cancer, using different combinations of the intracutaneous streptococcal preparation OK-432 and the oral pyrimidines 1-hexylcarbamoyl-5-fluorouracil (carmofur, HCFU) and uracil/tegafur (UFT).MethodsPatients with stage II, III, or IV (Dukes’ B, C) colorectal cancer were enrolled and randomly assigned to one of three groups: an immunochemotherapy group (mitomycin C [MMC] + 5-fluorouracil [5-FU] + HCFU + OK-432), a chemotherapy group (MMC + 5-FU + HCFU), and a control group (surgery alone) for those with colon cancer (study 1); and an immunochemotherapy group (MMC + 5-FU + UFT + OK-432), a chemotherapy group (MMC + 5-FU + UFT), and a control group (surgery alone) for those with rectal cancer (study 2).ResultsA total of 760 patients with colon cancer and 669 patients with rectal cancer were entered into this randomized clinical trial (RCT). The incidence of side-effects was in the order of: immunochemotherapy group ≫ chemotherapy group ≫ control group in both the cohort of patients with colon cancer and the cohort with rectal cancer. In particular, the frequency of leucopenia and skin disorders was significantly higher than control groups. There were no severe adverse events such as death related to the adjuvant therapy. In both the colon cancer and rectal cancer cohorts, no significant difference in the 5-year survival rate and disease-free survival rate was noted among the three groups.ConclusionThe results of an RCT demonstrated that the combination of MMC + 5-FU + HCFU + OK-432 for colon cancer and that of MMC + 5-FU + UFT + OK-432 for rectal cancer could not prolong the survival of patients with surgically resected colorectal cancer, but that both combinations were well tolerated as adjuvant therapy.

Randomized trial of the efficacy of adjuvant chemotherapy for colon cancer with combination therapy incorporating the oral pyrimidine 1-hexylcarbamoyl-5-fluorouracil

Background and aimsThe purpose of the present trial was to clarify the efficacy of postoperative adjuvant chemotherapy including an oral fluoropyrimidine anticancer drug, the 1-hexylcarbamoyl-5-fluorouracil (HCFU), for the treatment of colon cancer.MethodPatients with clinical stage Dukes’ B and C colon cancer, who had been treated surgically, were assigned to a chemotherapy group treated with mitomycin C, 5-fluorouracil (5-FU), and HCFU and to a control group that received no postoperative adjuvant chemotherapy.ResultsOf the 1,001 patients registered for the study, 17 (1.7%) were ineligible. The incidence of toxicity was significantly higher in the chemotherapy group than in the control group. However, there were few severe side effects and no deaths related to the treatment. Overall survival showed no significant difference between the groups. The disease-free survival or the recurrence-free intervals was significantly higher in the chemotherapy group than in the control group. The incidence of hepatic recurrence was significantly (P=0.003) lower in the chemotherapy group than in the control group.ConclusionThe results of this study demonstrated the efficacy of adjuvant chemotherapy for colon cancer, i.e., combined chemotherapy that included the 5-FU oral anticancer drug HCFU.

Relationship of P-glycoprotein and p53 protein to chemosensitivity in colorectal cancer

BackgroundResistance of tumors to chemotherapeutic agents is a major problem in cancer treatment. Recent advances in molecular biology have shown a role for oncogenes in this resistance.MethodsWe determined the positive or negative expression of P-glycoprotein and mutant p53 protein by immunohistochemistry on 101 human colorectal cancer and correlated the expression of these proteins with the chemosensitivity of the tumors to various anticancer agents using the succinate dehydrogenase inhibition (SDI) test.ResultsFifty-five (54.5%) of 101 tumors expressed P-glycoprotein and 53 (52.5%) expressed a mutant p53 protein. Thirty-seven of 55 tumors positive for P-glycoprotein also expressed a mutant p53 protein. The association between the coexpression of P-glycoprotein and p53 protein was statistically significant (P=0.001). Neither the expression of P-glycoprotein nor p53 protein affected the chemosensitivity of the tumor to doxorubicin hydrochloride, aclarubicin hydrochloride, pirarubicin, epirubicin hydrochloride, mitomycin C, 5-fluorouracil, cisplatin, carboplatin, or etoposide. However, a positive correlation was found between the control optical density and chemosensitivity in the P-glycoprotein or mutant p53 protein negative tumors. Oppositely, some P-glycoprotein or mutant p53 protein positive tumors showed low chemosensitivity in spite of their high control optical density.ConclusionsA highly statistically significant coexpression of P-glycoprotein and mutant p53 protein was found in colorectal cancer. Furthermore, differences in cell growth between the tumor samples indicate the possibility that the expression of P-glycoprotein and mutant p53 protein in colorectal cancer tumors could be associated with chemoresistance.

Case report of an anomalous arrangement of the pancreaticobiliary ducts and nuclear DNA ploidy analysis

Two cases with an anomalous arrangement of the pancreaticobiliary ducts (APBD) are reported in order to investigate the mechanism of carcinogenesis of the extrahepatic biliary tract from the aspect of DNA ploidy analysis. Highly elevated biliary enzymes were found in both cases. Although inflammatory changes without any metaplasia or neoplasia were observed histologically, a cytofluorometric nuclear DNA ploidy analysis showed an aneuploid low ploidy pattern in a histogram of the gall bladder, an aneuploid high ploidy pattern in a histogram of the common bile duct in one patient, and a diploidy pattern in the gall bladder, an aneuploid low pattern in the common bile duct in another case. These results may show that APBD may play a role in the development in DNA ploidy abnormality with refluxed pancreatic juice which may induce repeated irritation and inflammation. Radical surgery including a complete excision of the extrahepatic biliary tract followed by reconstruction may achieve better results with regard to undesirable consequences with an abnormal nuclear DNA ploidy pattern and decrease the likelihood of developing carcinoma.