Laparoscopic cholecystectomy, Calot's triangle, and variations in cystic arterial supply.

BACKGROUND: The extrahepatic biliary tree with the exact anatomic features of the arterial supply observed by laparoscopic means has not been described heretofore. Iatrogenic injuries of the extrahepatic biliary tree and neighboring blood vessels are not rare. Accidents involving vessels or the common bile duct during laparoscopic cholecystectomy, with or without choledocotomy, can be avoided by careful dissection of Calot's triangle and the hepatoduodenal ligament. METHODS: We performed 244 laparoscopic cholecystectomies over a 2-year period between January 1, 1995 and January 1, 1997. RESULTS: In 187 of 244 consecutive cases (76.6%), we found a typical arterial supply anteromedial to the cystic duct, near the sentinel cystic lymph node. In the other cases, there was an atypical arterial supply, and 27 of these cases (11.1%) had no cystic artery in Calot's triangle. A typical blood supply and accessory arteries were observed in 18 cases (7.4%). CONCLUSION: Young surgeons who are not yet familiar with the handling of an anatomically abnormal cystic blood supply need to be more aware of the precise anatomy of the extrahepatic biliary tree.

Possible role of hepatic bile mucus glycoprotein in development of intrahepatic gallstones.

To study the role played by hepatic bile mucus glycoprotein in the development of hepatolithiasis, mucus glycoprotein, isolated from the bile of patients with intrahepatic gallstones by gel filtration and ultracentrifugation, was examined for precipitability in control hepatic bile obtained postoperatively from patients successfully treated for cholecysto- and/or choledocho-lithiasis. When the mucus glycoprotein was incubated at 38 degrees C for 48 h in the control hepatic bile in the presence of calcium ions, massive precipitation was produced. The precipitation was inhibited by treating the mucus glycoprotein with acid, alkali, a reducing reagent, or protease, the inhibition being most effective with acid, which splits up carbohydrate chains. This suggests that the precipitability of the mucus glycoprotein resides mainly in its carbohydrate chains. These observations imply that the development of intrahepatic gallstones, calcium bilirubinate stones in particular, could be prevented by degrading mucus glycoprotein in hepatic bile.

[Transfer of carmofur (HCFU) to the serum, bile, pancreatic juice and pancreatic tumor tissue in the cases of peri-pancreatic head cancer].

The concentrations of carmofur, 1-hexyl-carbamoyl-5-fluorouracil (HCFU), in the serum, bile, pancreatic juice and pancreatic tumor tissue were studied in 18 cases of peri-pancreatic head cancer with drainages of the pancreatic and biliary ducts after pancreatico-duodenectomy. As a result, high concentrations of HCFU and 5-FU were detected in the serum, bile and pancreatic juice after a per-oral administration of HCFU, 200 mg: HCFU was high in the order of serum > bile and pancreatic juice, and 5-FU in the order of bile, serum and pancreatic juice. Two hours after administration, 5-FU concentration in the bile and serum attained to the maximum levels of 0.45 and 0.19 micrograms/ml, respectively, which demonstrated a lasting transfer of 5-FU to the bile at high concentration. HCFU and 5-FU levels in the tumor tissue were 0.079 and 0.024 micrograms/g, respectively. In conclusion, antitumor effect against the malignant tumors of the pancreatobiliary system can be expected by peroral administration of carmofur.

Targeting chemotherapy using antibody-combined liposome against human pancreatic cancer cell-line.

Anti-tumor effect of Adriamycin (ADM)-encapsulated and CA19-9 antibody-conjugated artificial lipid membrane follicle liposomes against a human pancreatic cancer cell-line PK-1 was studied in vitro and in vivo. The liposome compound (lipo c ADM = Ab) showed a stronger cell damage than ADM-encapsulated liposome (lipo c ADM) and free ADM, especially when the contact time was short and the concentration was low. The intra-tumor concentration of ADM in the group of i.v. injection of lipo c ADM = Ab showed the highest value, over twice those of lipo c ADM and free ADM after 120 hr. Lipo c ADM = Ab showed a significant inhibitory effect on the tumor growth inhibition test in vivo, and the final tumor weight at the 19th day was 27% in the group of lipo c ADM = Ab and 52% in the group of free ADM as compared with the control. The targeting chemotherapy using liposomes was demonstrated to have a stronger anti-tumor effect than the administration of anti-cancer drug alone owing to enhanced tumor accessibility and good targeting.

A new range of instruments ensuring easy and effective surgery for laparoscopic cholecystectomy.

To work with ease and comfort in laparoscopic cholecystectomy, four instruments (Tohoku dissector, Tohoku forceps, short mantis device, and long mantis device) have been developed that can be used by any surgeon, even one not accustomed to this new procedure. These instruments have the advantage of offering a feel of open surgery and have been in use since February 1991 with significant comfort and safety.

Growth-inhibitory effect of combination chemotherapy for human pancreatic cancer cell lines.

Sensitivities to anti-tumor drugs, mitomycin C (MMC), aclarubicin hydrochloride (ACR), doxorubicin hydrochloride (ADR), cisplatin, and 5-fluorouracil (5FU), were examined using PK-1, -8, -9, -12, -14, and -16 cell lines derived from human pancreatic cancer. These cell lines showed different sensitivities to each of the above anti-tumor drugs. The concentrations required for 50% growth-inhibition (IC50) after 2 hours of exposure were 0.096 to 0.35 micrograms/ml for MMC, 0.0074 to 0.0076 micrograms/ml for ACR, 0.033 to 0.23 micrograms/ml for ADR, 0.35 to 1.9 micrograms/ml for cisplatin, and 21 to 42 micrograms/ml for 5FU, IC50 of each anti-tumor drug decreased significantly after 48 hours of exposure. The combination of any two out of MMC, ACR, and 5FU showed synergistic inhibition of the growth of PK-1 and PK-8 cell lines. These results show that MMC, ACR, ADR, cisplatin, and 5FU have sufficient anti-tumor effect against six human pancreatic cancer cell lines even at clinically achievable concentrations and exposure times, and chemotherapy for pancreatic cancers requires naturally effective drug delivery into cancer tissues.

[Experimental study of the intra-operative radiation therapy in pancreatic cancer].

The radiosensitivity of pancreatic cancer, optimum dose of irradiation and the effect of 1-[(4'-Hydroxy-2'-Butenoxy) Methyl]-2-Nitrosoimidazole (RK-28) on irradiation were investigated using an experimental pancreatic cancer of hamster and the following results were obtained: i) The mean lethal dose (Do) and the 50% tumor control dose (TCD50) against the pancreatic cancer were 3.5 Gy and 73.7 +/- 6.9 Gy, respectively. These results indicate that the pancreatic cancer is resistant to irradiation, which could be explained by the existence of hypoxic cells consisting of 35% of the tumor. ii) The dose of intraoperative irradiation (10-40 Gy) seemed to be insufficient to bring long-term anti-tumor effect and long-term survival since that dose resulted in only temporary regression of the tumor. iii) The hypoxic cell sensitizer (RK28), which is known to specifically enhance the sensitivity of hypoxic cells to irradiation, lowered TCD50 of the pancreatic cancer to 53.8 +/- 1.57Gy. Therefore, RK-28 was effective in the treatment of the experimental pancreatic cancer (the enhancement ratio: 1.37). When combined with 30 or 40 Gy of irradiation, which is applicable to intraoperative irradiation, RK-28 induced a longer period of tumor suppression and a higher tumor regression ratio than irradiation alone. These results indicate that RK-28 significantly increases the effect of intraoperative irradiation and this combination therapy could possibly induce remarkable effect on tumor regression and long-term survival.

[Effects of urokinase on the transfer of 1-hexylcarbamoyl-5-fluorouracil (HCFU) into the blood, bile and pancreatic juice].

We studied effects of urokinase (Uronase) on the transfer of an oral anticancer agent, 1-hexylcarbamoyl-5-fluorouracil (HCFU) into blood, bile and pancreatic juice in 5 patients in whom pancreaticoduodenectomy has been performed for cancer of the periampullary region, and who had been simultaneously provided with drainage of the bile duct and pancreatic duct. Following oral administration of 500 mg of HCFU, HCFU and 5-FU concentrations in blood reached a peak at 2 hours, those in bile at 4 hours, and those in pancreatic juice at 4 to 6 hours. The administration of 24,000 IU of urokinase in combination with HCFU resulted in increased HCFU and 5-FU concentrations in blood, bile and pancreatic juice--the HCFU concentration in bile increased to 3 times and that in pancreatic juice, to about 5 times the level in the some counterparts in urokinase--untreated patients. These changes seemed to have resulted from the acceleration by urokinase of distribution of the anticancer agent into the organs.

Transferrin (Tf) polymorphism: an analysis by isoelectric focusing.

The polymorphism of the transferrin (Tf) system was studied in a total of 300 unrelated Japanese individuals from Miyagi prefecture, the northern part of Japan using isoelectric focusing in thin-layer polyacrylamide gel. In our population samples three common phenotypes and nine variants were observed. The calculated allele frequencies were TfC1 = 0.773, TfC2 = 0.212, TfDchi (Chinese) = 0.008, and the combined frequencies for the TfBvar (variants) = 0.007. Family data (n = 44) were in accordance with an autosomal codominant fashion of inheritance. The use of isoelectric focusing procedure among Japanese will raise the probability of excluding a man falsely accused of paternity to 15.8% as compared with 1.5% when the conventional electrophoretic methods are used.

Isoelectric focusing studies on the PGM1 subtypes in the northern Japanese population.

The distribution of the human red cell phosphoglucomutase (PGM1) subtypes in samples from Japanese population (n = 277) living in the Miyagi Prefecture, the northern part of Japan, was investigated by applying the thinlayer polyacrylamide gel isoelectric focusing. In our population sample all the ten common phenotypes were demonstrated, and the estimated allele frequencies for the genes PGM1+1, PGM1-1, PGM2+1, and PGM2-1 were 0.671, 0.107, 0.161, and 0.061, respectively. Family studies (n = 40) indicated an autosomal codominant inheritance and confirmed the four alleles. The new system will increase the probability of exclusion in paternity cases among Japanese to 29.4% compared with 14.3% if the two allele system is used.

Homicidal and camouflaged carbon monoxide poisoning in Japan.

There were 1,985 fatal cases of CO poisoning in the Tohoku district of Japan in the period from 1969 to 1980. Among them, 1,322 cases were suicidal, 662 accidental, and one homicidal, in which a man killed his wife with the self-made CO gas to obtain by fraud a large amount of life insurance. Our nationwide survey revealed four other cases of homicidal CO poisoning and two cases of camouflaged CO poisoning. The police and police surgeons should be cautious enough in cases of CO poisoning.

Alpha-1-antitrypsin (PiM) subtypes in Japanese.

Using isoelectric focusing (IEF) in thin-layer polyacrylamide gel, the polymorphism of the serum alpha-1-antitrypsin (Pi system) was investigated in 335 healthy unrelated Japanese individuals living in Miyagi prefecture, the northern part of Japan. Six common and five rare variant phenotypes were identified in our population samples, and the estimated allele frequencies for the genes PiM1, PiM2 and PiM3 were 0.718, 0.238 and 0.044, respectively. Family studies (n = 46) showed an autosomal codominant inheritance, and no exclusion was found in 23 mother-child pairs.