Outcomes of hepatic artery infusion therapy for hepatic metastases from colorectal carcinoma after radiological placement of infusion catheters.

AIM: The aim of this study is to evaluate the safety and efficacy of hepatic artery infusion (HAI) of 5-fluorouracil (5FU) for patients with liver metastases from colorectal carcinoma after radiological placement of infusion catheters. METHODS: Forty-two patients with liver metastases from colorectal carcinoma received radiological placement of infusion catheters using the distal fixation method. They received continuous HAI of 5FU 1,000-1,500mg for 5h weekly or biweekly. Tumor status was assessed by chest-abdominal computed tomography (CT) scan after every 10 infusions. Hepatic perfusion was checked by CT arteriography via the infusion port after every 10 infusions. RESULTS: Radiological placements of catheters were performed successfully in all cases. Each patient received an average of 36 treatments (range: 10-98). Catheter failure was found in 3 patients (7.1%). Nine incidents of grade 1 toxicity were observed in 8 patients (19.0%). There was a complete response in 6 patients, partial remission in 18, stable disease in 9, and progression of disease in 9 (response rate: 57.1%). Overall median survival time was 29.1 months. Using Cox's proportional hazard model, lymph node metastases in primary colorectal carcinoma and pre-treatment serum CEA affected overall survival (P=0.011, P=0.005). CONCLUSIONS: HAI after radiological placement of infusion catheters is a safe and effective treatment particularly for patients with no lymph node metastasis in primary carcinoma or with a low pre-treatment serum CEA level.

Intraoperative location of small gastrointestinal cancers with a handheld gamma probe.

The location of a small lesion must be precisely identified during laparoscopic surgery. A gamma probe that is usually used for navigating sentinel lymph nodes was evaluated for its usefulness in locating small gastrointestinal lesions (14 gastric and 10 colonic). A total of 2 mCi of a Tc(99m)-labeled rhenium colloid was injected endoscopically around a tumor 16 h prior to surgery. During operation, the abdominal cavity was scanned using a handheld gamma probe (Navigator GPS, Tyco HealthCare, Norwalk, CT, USA). In all cases, the injection site was identified as the highest spot in the abdominal cavity, with 2585 counts per second on average (range, 910-8800 counts per second). The highest count in a lymph node was 637 per second on average. The gamma probe is a useful tool for identifying small gastrointestinal lesions during open and laparoscopic operations.

Spasmolytic effect of peppermint oil in barium during double-contrast barium enema compared with Buscopan.

AIM: To evaluate the efficacy of peppermint oil in barium as a spasmolytic agent during a double-contrast barium enema (DCBE). MATERIALS AND METHODS: A total of 383 DCBEs with positive results from occult blood tests were assessed. Patients were assigned to one of four groups: peppermint in barium (n=91), peppermint in tube (n=90), Buscopan (n=105), or no treatment (n=97). After a screening sigmoidoscopy, the DCBEs were performed using air as a distending gas. In the Buscopan group, the DCBE was performed with an intramuscular injection of 20mg Buscopan at the start of the examination. Patients in the no-treatment group underwent DCBE without any spasmolytic agent. A peppermint oil preparation (30ml) was mixed in the barium solution for patients in the peppermint-in-barium group, and the same dose of peppermint oil was included in the enema tube in the peppermint-in-tube group. The presence of spasm on a series of spot films was evaluated without information about the type of spasmolytic agent used. RESULTS: The percentage of patients in the four groups (no treatment, Buscopan, peppermint in tube, and peppermint in barium) with absence of spasm in the entire colon on the series of spot films was 13.4, 38.1, 41.8, and 37.8%, respectively. In the group using peppermint oil or Buscopan, the rate of patients with non-spasm examination was higher than that in no-treatment group (p<0.0005). Peppermint oil had the same spasmolytic effect as the systemic administration of Buscopan in the transverse and descending colon. Peppermint oil had a stronger effect in the caecum and the ascending colon than a Buscopan injection (p<0.005). There was no advantage to placing peppermint oil in the enema tube over mixing it in the barium solution. A total of 157 polyps were found during the DCBE procedures, and no differences were observed in the number of lesions among the four groups. Peppermint oil did not impair image quality. CONCLUSION: Barium solution mixed with peppermint oil was safe and effective for the elimination of colonic spasm during the DCBE procedure, and it could be used instead of Buscopan.

An easy method for the intraluminal administration of peppermint oil before colonoscopy and its effectiveness in reducing colonic spasm.

BACKGROUND: Systemic administration of a cholinergic blocking agent or glucagon is used to reduce spasms, but it is inconvenient and sometimes causes side effects. This study is an evaluation of the intracolonic administration of peppermint oil during colonoscopy for the control of colonic spasm. METHODS: Each patient in the treated group (n = 409) was given approximately 200 mL of the solution (a mixture of 8 mL of peppermint oil and 0.2 mL of Tween 80 per 1 L of water with 0.04% indigo carmine) by using a hand pump attached to the accessory channel of the colonoscope. Changes in patient posture were made to distribute the solution. The patients in the control group (n = 36) were given the solution without peppermint oil. RESULTS: A satisfactory spasmolytic effect was seen in 88.5% of the treated patients and in 33.3% of those in the control group (p<0.0001). No adverse effect was observed. The mean time to onset was 21.6 +/- 15.0 seconds, and the effect continued for at least 20 minutes. In patients with irritable bowel syndrome, efficacy was significantly lower (p < 0.0001). CONCLUSIONS: The intraluminal administration of peppermint oil by using a hand pump is a simple, safe, and convenient alternative to the systemic injection of a cholinergic blocking agent or glucagon during colonoscopy.

Genetic analysis of obese diabetes in the TSOD mouse.

The molecular pathogenesis of diabetes remains poorly understood because of the genetic complexity of the disease. One possibly effective approach to elucidate the pathogenesis is to study an animal model with a similar phenotype. The TSOD (Tsumura, Suzuki, Obese Diabetes) mouse, a newly developed animal model, exhibits both diabetes and obesity with marked hyperinsulinemia and hypertrophy of the pancreatic islets and might represent a common form of obese type 2 diabetes in humans. Phenotypic characterization revealed that the TSOD mouse had both insulin resistance and impaired glucose-stimulated insulin secretion. A comprehensive genetic dissection of diabetes and obesity has been performed using F1 and F2 progeny between the TSOD and control BALB/cA strains. A genome-wide screen for loci linked to glucose homeostasis and body weight allowed us to map three quantitative trait loci (QTLs) involved in this disorder. The major genetic determinant of blood glucose levels was identified on chromosome 11. Furthermore, two independent QTLs involved in controlling body weight were found on chromosomes 1 and 2. The QTL on chromosome 2 also affected insulin levels significantly. Each QTL has distinct effects on different traits and a different mode of inheritance. Our study indicates that hyperglycemia and obesity are clearly controlled by distinct combinations of genetic loci in this mouse model and provides insights into the genetic basis of common forms of human type 2 diabetes with obesity.

Insulin receptor-related receptor is expressed in pancreatic beta-cells and stimulates tyrosine phosphorylation of insulin receptor substrate-1 and -2.

The receptor-type protein tyrosine kinases in murine pancreatic islets were screened to identify possible growth/differentiation factors in pancreatic beta-cells. The analysis revealed that insulin receptor-related receptor (IRR) is highly expressed in the islets as well as in several highly differentiated beta-cell lines derived from transgenic mice. Islets predominantly contain IRR as uncleaved proreceptors compared with IRR as processed forms in the beta-cell lines, suggesting that the activity of IRR is regulated on the level of processing proteases in vivo. To examine the IRR signaling pathway, a chimeric receptor consisting of the extracellular domain of insulin receptor and the intracellular domain of IRR was expressed in Chinese hamster ovary cells. The hybrid receptor is functional because insulin is capable of tyrosine-phosphorylating the catalytic domain in these cells. It also stimulates the tyrosine phosphorylation of insulin receptor substrate (IRS)-1 and IRS-2, indicating that both proteins serve as substrates of IRR-protein tyrosine kinase in intact cells. The phenotype of the IRS-2 knockout mouse recently reported suggests that an IRS-2-mediated signaling pathway controls the compensatory increase in pancreatic beta-cell mass in insulin-resistant states. From our findings of the specific expression of IRR and its ability of signaling to IRS-2, we speculate that this receptor might play a role in the regulation of beta-cell mass.

[The effect of serum free fatty acid on serum free thyroid hormone fractions in low T3 syndrome].

We studied the role of serum free fatty acid (FFA) in the elevation of serum dializable fraction of T4 (DFT4) and evaluated the serum free T4 (FT4) level in low T3 syndrome. Serum DFT4 and DFT3 were measured by equilibrium dialysis method with phosphate buffer, and serum FFA concentration was obtained by gas chromatography. In patients with nonthyroidal systemic illnesses who showed reduced serum total T3 (TT3) and normal total T4 (TT4) (low T3 group, TT3 48 +/- 14 ng/dl, n = 10), mean (+/- SD) DFT4 value (0.032 +/- 0.05%) was significantly higher than that of the group of systemic illnesses with normal TT3 and TT4 (normal T3 group, TT3 79 +/- 7 ng/dl, n = 10). Mean TT4 value of low T3 group (6.5 +/- 1.0 micrograms/dl) was lower than that of normal T3 group (8.6 +/- 2.4 microgram/dl, p less than 0.02). There was no difference in mean absolute FT4 (AFT4) value between the two groups (2.07 +/- 0.46 vs 2.19 +/- 0.53 ng/dl). On the other hand, there was no significant difference in DFT3 value between the groups (0.274 +/- 0.043 vs 0.247 +/- 0.035%), and mean AFT3 of low T3 group (1.29 +/- 0.39 pg/ml) was low than that of normal T3 group (1.92 +/- 0.26 pg/ml, p less than 0.01). In cases of low and normal T3 groups (n = 20), serum thyroxine binding globulin (TBG) concentration had a negative correlation with DFT3 (r = -0.707, p less than 0.001), but not with DFT4. Although there were no significant differences in serum albumin and TBG concentrations between the two groups, the mean serum total FFA concentration and molar ratio of FFA to albumin in low T3 group (579 +/- 249 microM and 1.31 +/- 0.61) were significantly higher than those in normal T3 group (345 +/- 170 microM and 0.75 +/- 0.32, p less than 0.05 and less than 0.025, respectively). All of FFA concentrations in low T3 group, especially oleate, were higher than those in normal T3 group. Moreover, the higher the total FFA concentration was, the greater was the percent fraction of oleate. DFT4 values were significantly increased by the addition of 1 mM oleate to the sera of low T3 group, and this effect was more marked in the sera of the patients with lower albumin concentration.(ABSTRACT TRUNCATED AT 400 WORDS)