Recent investigations indicated that hyperthermia has antitumor effects. Several interstitial hyperthermic techniques were developed, and their clinical usefulness and safety were evaluated. However, few authors have attempted to study the use of interstitial hyperthermia for the treatment of pancreatic carcinomas. Therefore the efficacy of local selective thermocoagulation by radiofrequency was evaluated in 20 patients with unresectable carcinomas of the pancreas. A laparotomy and radiofrequency heating were performed in 20 patients with unresectable pancreatic carcinomas after informed consent. Local heat coagulation was induced by a 13.56-MHz radiofrequency pulse, produced by the heating apparatus. Four 2-cm needle electrodes were placed in the tumor, in a square array, at intervals of 2 cm. The heat was then administered for 15 min at a controlled temperature of 50 degrees C in the radiofrequency field (2x2x2 cc). All the patients were evaluated by computed tomographic scanning. Tumor markers in the blood also were assayed before and after the heating. Follow-up computed tomographic scans demonstrated that the tumor mass was enhanced heterogeneously, and after selective thermocoagulation, images revealed a change to a homogeneous low-density area. The blood levels of tumor markers decreased to below pretreatment values in 15 patients. Of the 20 cases treated with thermocoagulation, two had critical complications. One patient had septic shock, and another had gastrointestinal bleeding. The other 18 patients had no significant complications. These observations suggest that the selective thermocoagulation of tumor tissues using this equipment was relatively safe. These results justify further clinical trials for the treatment of patients with unresectable tumors without metastasis, or patients with benign pancreatic tumors such as insulinomas.

We have studied the antitumor activity and the novel DNA‐self‐strand‐breaking mechanism of CNDAC (1‐(2‐C‐cyano‐2‐deoxy‐β‐d‐arabino‐pentofuranosyl)cytosine) and its N4‐palmitoyl derivative (CS‐682). In vitro, CS‐682 showed strong cytotoxicity against human tumor cells comparable with that of CNDAC; both compounds displayed a similar broad spectrum. In vivo, however, orally administered CS‐682 showed a more potent activity against human tumor xenografts than CNDAC, 5′‐deoxy‐5‐fluorouridine, 5‐fluorouracil and 2′,2′‐difluorodeoxycytidine. Moreover, CS‐682 was effective against various human organ tumor xenografts at a wide dose range and with low toxicity, and was effective against P388 leukemic cells resistant to mitomycin‐C, vincristine, 5‐fluorouracil or cisplatin in syngeneic mice. CNDAC, an active metabolite of CS‐682, had a prolonged plasma half‐life after repeated oral administrations of CS‐682 but not after oral administrations of CNDAC itself. This difference may partially explain the higher antitumor activity of CS‐682 relative to CNDAC. In both CNDAC‐ and CS‐682‐treated carcinoma cells, CNDAC 5′‐triphosphate (CNDACTP) was generated and incorporated into a DNA strand. High performance liquid chromatography (HPLC) and mass spectrometric analysis of the nucleosides prepared by digestion of the DNA from the CNDAC‐treated cells detected ddCNC (2′‐C‐cyano‐2′,3′‐didehydro‐2′,3′‐dideoxycytidine), which was shown to be generated only when the self‐strand‐breakage of CNDACTP‐incorporated DNA occurred. The cytotoxicity of CNDAC was completely abrogated by the addition of 2′‐deoxycytidine and was low against cells with decreased deoxycytidine kinase. Our results suggest that CNDAC is converted to CNDACMP by deoxycytidine kinase and that the resulting CNDACTP incorporated into a DNA strand as CNDACMP may induce DNA‐self‐strand‐breakage. This novel DNA‐self‐strand‐breaking mechanism may contribute to the potent antitumor activity of CS‐682. Int. J. Cancer 82:226–236, 1999. © 1999 Wiley‐Liss, Inc.

BACKGROUND The examination of pancreatic juice cytology could hypothetically contribute to the establishment of a definite diagnosis of malignant intraductal papillary mucinous neoplasm of the pancreas (IPMN), but to the authors' knowledge, its significance has not been confirmed to date. The current study was conducted to assess the diagnostic value of pancreatic juice cytology in IPMN and to examine the usefulness of peroral pancreatoscopy (POPS) in sampling pancreatic juice. METHODS The study subjects were comprised of 103 patients with IPMN who underwent surgical resection of pancreatic tumors (adenoma in29 patients, borderline in17 patients, carcinoma in situ in 25 patients, and invasive carcinoma in 32 patients). Pancreatic juice was collected with a catheter in 71 patients and by POPS in 32 patients. Patients with pancreatic carcinoma (n = 81) and chronic pancreatitis (n = 76) also were investigated. RESULTS The cytologic diagnosis was found to be of nondiagnostic value in only one patient with an IPMN, whereas it was of no diagnostic value in 14 of the patients with pancreatic carcinoma (17.3%), a difference that was statically significant (P < 0.001). The location of the IPMN (either in the pancreas or the pancreatic ducts) was not found to significantly affect the diagnostic value of the test. The sensitivity for IPMN was 62.2% when pancreatic juice was collected by POPS, and was 38.2% when it was collected using a catheter. In the case of pancreatic carcinoma, the sensitivity of pancreatic juice cytology was found to be 25.4%, which was significantly lower than that for IPMN when the pancreatic juice was collected by POPS (P < 0.001). CONCLUSIONS Pancreatic juice cytology was found to have better diagnostic value in the patients with IPMNs compared with those with pancreatic carcinoma. POPS was found to be useful for the collection of pancreatic juice. Cancer 2005. © 2005 American Cancer Society.

Natural differences in 13C/12C ratios of various metabolic fuels can produce systematic changes in the 13C/12C ratio of breath CO2, and therefore introduce errors into 13CO2 breath tests. To gain insight into the potential problem, we compared 13C/12C ratios of plasma macronutrients to those of breath CO2 under conditions that should alter the percentages of carbohydrate and lipid being oxidized. In rats, 48 h of starvation decreased the 13C/12C ratio of breath CO2 by 3.5%. At this time the 13C/12C ratio of breath CO2 was very similar to that of plasma lipids. In humans, 30 min of heavy exercise increased the breath 13CO2/12CO2 ratio by 1.3%. These changes in breath 13C/12C ratios could be predicted from 13C/12C ratios of plasma macronutrients and the percentage of carbon dioxide derived from each macronutrient, but only when compared within the same populations. For example, the 13C/12C ratios of plasma macronutrients of residents of Chicago, Illinois (USA) and Tokyo (Japan) differed by 1-3%. An empirical correction of 13CO2 breath test data is recommended when breath tests are run under conditions that will change metabolic fuel utilization.