[Gemcitabine treatment in patients with stage IV pancreatic cancer and prognostic factors for survival of patients with stage IVb(a retrospective survey at 15 hospitals in Niigata Prefecture)].

We performed a retrospective survey at 15 hospitals in Niigata Prefecture to assess the effectiveness of gemcitabine in patients with stage IV pancreatic cancer and to analyze prognostic factors impacting survival in patients with stage IVb. The subjects were 244 unresectable or metastatic pancreatic cancer patients(IVa 68, IVb 176)who were treated with gemcitabine as first-line therapy. The overall response rate was 6.1% and the median survival time(MST)was 194 days. The MST of stage IVa(312 days)was double that of stage IVb(167 days). Prognostic factors for survival of patients with stage IVb were analyzed(performance status, response rate, liver metastasis, peritonitis carcinomatosa, paraaortic lymph node metastasis)with the Cox proportional hazards model. Performance status, response rate, and liver metastasis were significant factors influencing survival. When we compare an effect of other chemotherapy with GEM, we should treat stage IVa and stage IVb separately, and subdivision is necessary for stage IVb.

[Gemcitabine versus combined chemotherapy with 5-fluorouracil and cisplatin in advanced pancreatic cancer].

Gemcitabine hydrochloride (GEM) is a first-line therapeutic agent for advanced pancreatic cancer, but there is no established second-line treatment after GEM failure. We assessed the clinical benefit of systemic combined chemotherapy with 5-fluorouracil and cisplatin (FP therapy) in 19 patients compared with GEM in 32 patients, respectively. Tumor response rates were 10.5% and 15.6% for FP therapy and GEM, respectively. The median survival time in the FP therapy and GEM was 137 days and 241 days, respectively. Although clinical benefit was similar in both types of therapy, median survival time was more favorable for GEM, especially for Stage IVb. Nausea and vomiting were the most commonly observed toxicity in the FP therapy group. Our data indicate that FP therapy is not considered to be a useful second-line agent in patients with GEM pretreated pancreatic cancer.

Balloon-occluded retrograde transvenous obliteration of gastric varix draining to the IVC via the circumaortic renal vein.

The authors encountered a patient with gastric varices draining to the IVC not only via the usual route of the left renal vein but also via a circumaortic renal vein. Balloon-occluded retrograde transvenous obliteration (B-RTO) of the gastric varix was performed with balloon occlusion of the circumaortic renal vein and retrograde injection of sclerosing agent (5% of ethanolamine oleate) into the varix. Eradication of the gastric varix was confirmed on endoscopic examination 2 months later. We document the first case of B-RTO performed for gastric varix via the circumaortic renal vein. Details of this rare occurrence and implications for treatment are presented herein.

[A case of successful management of nonresectable pancreas cancer with liver metastasis by intra-arterial infusion chemotherapy with gemcitabine hydrochloride, 5-FU, CDDP and administration of tegafur/uracil].

We report a case of a 43-year-old man with liver metastasis of advanced pancreatic cancer successfully treated with intra-arterial regional chemotherapy. The patient was admitted to our hospital suffering from anorexia and back pain. Abdominal CT showed pancreatic tail cancer with liver and Schnitzler metastasis. We decided a curative operation was impossible. Then, enteric-coated tegafur/uracil (400 mg) was administered. Simultaneously, intraarterial infusion with CDDP, 5-fluorouracil (500 mg) and infusion of gemcitabine (1,000 mg) with 50 microg of AT-II was given once a week. After 3 courses, the pancreatic tumor was reduced and the tumor markers decreased. Multiple metastatic liver tumors remarkably decreased. As a result, the maximum diameter of the pancreatic tumor decreased from 7 cm to 5 cm on the CT-scan. Serum carbohydrate antigen 19-9 (CA19-9) decreased from 122,000 U/ml to 10,200 U/ml. Moreover, the performance status of patient also improved. He was able to receive outpatient treatment despite his terminal cancer. Furthermore, the patient can take sufficient meals without any adverse effects. His quality of life has been preserved. This regimen could well be effective for advanced pancreatic cancer.

[A case of advanced gastric cancer with liver and intra-abdominal lymph node metastasis treated by hypertensive selective chemotherapy with pharmacokinetic modulating chemotherapy].

There have been few effective chemotherapeutic regimens for advanced gastric cancer with liver and intra-abdominal lymph node metastasis. A 78-year-old male patient was admitted to our hospital because of anorexia and abdominal discomfort. Gastroendoscopy showed a type 4 advanced gastric cancer in the antrum of the stomach. Histological study of biopsy specimens from the tumor revealed poorly differentiated adenocarcinoma. Examination by computed tomography and ultrasonography showed swollen paraaortic lymph nodes and liver metastasis. He was diagnosed as having advanced gastric cancer with liver and lymph node metastasis. This patient was treated weekly with an intraarterial 5-FU (500 mg) and MTX (100 mg) including AT-II by subcutaneously implanted port system placed into the celiac artery. Furthermore, he was administered tegafur/uracil (400 mg/day) 5 days weekly as pharmacokinetic modulating chemotherapy (PMC). After ten courses of treatment with PMC, the liver and lymph node metastases were reduced in size. This therapy was considered to be an effective treatment for advanced gastric cancer with liver and lymph node metastasis. The theoretical purpose of hypertensive chemotherapy used together with injection of angiotensin-II is to increase the delivery of anticancer drug to the target tumor tissue by increasing the blood flow in the tumor. We conclude that this chemotherapy is effective in cases of advanced gastric cancer with liver and lymph node metastasis from the viewpoints of toxicities, antitumor effect and QOL of the patient.

Sedation and plasma concentration of clonidine hydrochloride for pre-anesthetic medication in pediatric surgery.

Clonidine hydrochloride has been used for pre-anesthetic medication to provide a pre-operative sedation in pediatric surgery. The purpose of this study is to determine the plasma clonidine concentration, which gives satisfactory sedation in pediatric surgery. Sixteen pediatric patients (age: 1-11 years, weight: 9-33 kg) received either 2 or 4 microg/kg of clonidine lollipop before entering the operating room. Plasma clonidine concentrations were determined 120 min after administration of clonidine lollipop. Pre-operative sedation was evaluated by 5-point scoring systems at entering the operating room. The changes in systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR) were also assessed before and after administration of clonidine lollipop. The patients with satisfactory sedation had higher plasma clonidine concentration than that of the patients with unsatisfactory sedation (0.45+/-0.16 ng/ml vs. 0.26+/-0.16 ng/ml, p<0.05). The clonidine concentrations in the satisfactory group ranged from 0.28 to 0.81 ng/ml. There was no significant difference in hemodynamic parameters (SBP, DBP and HR) before and after administration of clonidine lollipop in both satisfactory and unsatisfactory sedation groups. Plasma clonidine concentration of 0.3-0.8 ng/ml would be sufficient to produce satisfactory sedation without changes in hemodynamic parameters in pediatric surgery.

The hypnotic and analgesic effects of oral clonidine during sevoflurane anesthesia in children: a dose-response study.

UNLABELLED: Although clonidine has both hypnotic and analgesic actions, the dose relationship for each actions is still unknown in a clinical setting when clonidine is used as a premedication in children. We studied 80 ASA physical status I children (age range, 3-8 yr). Subjects were randomly divided into two groups (minimum alveolar anesthetic concentration [MAC]-Awake group, n = 40; MAC-Tetanus group, n = 40). Each patient received one dose of clonidine from 1 to 5 microg/kg orally, 100 min before arrival at the operating room. Anesthesia was induced and maintained with sevoflurane in oxygen and air. Before tracheal intubation, end-tidal sevoflurane was decreased stepwise by 0.2% at the start of 1.2%, a verbal command was given to the patients, and MAC-awake was determined in each patient. We also investigated MAC-tetanus, determined with transcutaneous electric tetanic stimulations, after tracheal intubation in each patient by observing the motor response to a transcutaneous electric tetanic stimulus to the ulnar nerve at a sevoflurane concentration decreased stepwise by 0.25% at the start of 2.75%. The initial reduction in MAC-tetanus was not as steep as that in MAC-awake. Clonidine reduced MAC-tetanus by 40% at the maximal dose of 5 microg/kg, whereas MAC-awake was already reduced by 50% at 2 microg/kg. We conclude that separate dose-response relationships for oral clonidine are present regarding the hypnotic and analgesic effects in children undergoing sevoflurane anesthesia. IMPLICATIONS: Separate dose-response relationships for oral clonidine were found regarding the hypnotic and analgesic effects in children undergoing sevoflurane anesthesia.

The reduction in minimum alveolar concentration for tracheal extubation after clonidine premedication in children.

UNLABELLED: The effects of clonidine on minimum alveolar concentration for tracheal extubation (MAC-ex) have not been elucidated. Clonidine may lead to prolonged emergence from anesthesia. We investigated the effects of oral clonidine premedication on MAC-ex and examined the emergence properties of sevoflurane in children. Sixty ASA physical status I pediatric patients, aged from 2 to 9 yr, were randomly divided into one of three groups and received placebo, clonidine 2 microg/kg, or clonidine 4 microg/kg (n = 20 each) orally, 100 min before the induction of anesthesia. The induction of anesthesia, tracheal intubation, and maintenance of anesthesia were performed with sevoflurane in air and oxygen. MAC-ex was defined according to the modification of Dixon's up-and-down method, with 0.25% as a step size. In addition, in the Control and 4 microg/kg groups, the time from tracheal extubation to spontaneous eye opening (eye-opening time) and the time from tracheal extubation to leaving the operating room (awakening time) were recorded. MAC-ex for sevoflurane (mean +/- SD) was 1.63% +/- 0.13%, 1.04% +/- 0.26%, and 0.66% +/- 0.09% respectively in the Control group, 2 microg/kg group, and 4 microg/kg group. Significant differences were observed among the three groups. The eye-opening times were 5.7 +/- 3.5 min in the Control group and 5.1 +/- 1.0 min in the 4 microg/kg group. The awakening times were 9.7 +/- 3.7 min in the Control group and 9.2 +/- 3.8 min in the 4 microg/kg group. No significant differences were observed among the groups. IMPLICATIONS: Oral clonidine premedication decreased MAC for tracheal extubation for sevoflurane dose dependency and did not prolong emergence from anesthesia.