Prediction of chemotherapeutic response by collagen gel droplet embedded culture-drug sensitivity test in human breast cancers

Collagen gel droplet embedded culture-drug sensitivity test (CD-DST) is the newly developed in vitro chemosensitivity test that has several advantages over the conventional ones. The aim of the present study is to examine the clinical usefulness of this test in the prediction of response to chemotherapy in breast cancer patients. Seventy patients with primary (n = 45) or locally recurrent (n = 25) breast cancers were recruited, and each patient underwent tumor biopsy before chemotherapy. The biopsy specimens were used for CD-DST and immunohistological examination of 6 biological markers (P-gp, erbB2, p53, BCL2, MIB1 and ER-alpha). As chemotherapy, cyclophosphamide 600 mg/m(2) plus epirubicin 60 mg/m(2) q3w (CE, n = 28) or docetaxel 60 mg/m(2) q3w (DOC, n = 42) was given. Interpretable results using the CD-DST assay were obtained from 84.3% (59/70) of tumor specimens studied. Of the 18 tumors diagnosed as CE sensitive by CD-DST, 15 (83.3%) exhibited a response to CE therapy and none of the 5 tumors diagnosed as CE resistant by CD-DST exhibited a response to CE therapy. Of the 14 tumors diagnosed as DOC sensitive by CD-DST, 13 (92.9%) exhibited a response to DOC therapy and only one of the 22 tumors diagnosed as DOC resistant by CD-DST exhibited a response to DOC therapy. P-gp expression was found to exhibit a significant (p < 0.05) association with the resistance to CE therapy but not to DOC therapy. Diagnostic accuracy (72.7%) achieved by P-gp was lower than that (87.0%) achieved by CD-DST in CE therapy. Expressions of other biological markers (erbB2, p53, BCL2, MIB1 and ER-alpha) were not significantly associated with response to CE or DOC therapy. These results demonstrate that CD-DST can predict the response to CE and DOC therapy with a high accuracy in breast cancer patients and seems to be superior to the conventional predictors.     

A trial of continuous and biweekly low-dose cisplatin and 5-FU with UFT chemotherapy for esophageal cancer

A 77-year-old man with advanced esophageal cancer with tracheal and esophageal obstruction underwent continuous low-dose FP chemotherapy for a total of seven weeks, resulting in a complete response (CR) and disappearance of the esophago-tracheal fistula. Since discharge from the hospital, he has maintained a stable good condition for about two years while receiving biweekly low dose FP chemotherapy and oral UFT. Eight patients who had post-operative recurrence and underwent noncurative operation for esophageal cancer were given low-dose FP chemotherapy. The results of this chemotherapy for those 8 patients and the present patient, for a total of 9 patients were 2 CR, 2 PR, 3 NC and 2 PD, with an overall response rate of 44%, and overall one-year and two-year survival rates of 44% and 22%, respectively.     

Gastric cancer with multiple liver metastases,which responded significantly to oral administration of TS-1 following intravenous FMP therapy under hospitalization

TS-1, a novel oral formation of 5-fluorouracil that consists of 1 M tegafur (FT), 0.4 M gimeracil and 1 M otacil potassium, was reported to achieve a relatively high response rate of 49% in patients with advanced gastric cancer in a late phase II study. We report a case of inoperable gastric cancer with multiple liver metastases, which responded significantly to the short-term administration of TS-1 following intravenous FMP therapy. A 79-year-old man, who had nothing of note in his past or family history, presented with multiple liver tumors and type 3 gastric tumor. His diagnosis was inoperable gastric cancer with liver metastases, and he underwent outpatient treatment of oral administration of TS-1, following FMP therapy under hospitalization. The main and metastatic lesions shrunk dramatically with the two courses of the chemotherapy. There were no noticeable adverse effects. QOL has been maintained and the patient remains in good condition. TS-1 can be considered well-tolerable and quite effective for inoperable gastric cancer, especially if preceding therapy with 5-FU shows significant efficacy. TS-1 may therefore be a new candidate as a first line drug in outpatient cancer treatment.     

Multishot echo-planar imaging with gadopentetate dimeglumine. Preliminary study of efficacy for detection of hypovascular metastatic liver tumors

OBJECTIVE: To evaluate the usefulness of sequential T2-weighted spin-echo type multishot echo-planar (T2-EP) imaging with gadopentetate dimeglumine for the detection of hypovascular metastatic liver tumors. MATERIAL AND METHODS: Fifteen consecutive patients with 56 proven hypovascular metastatic liver tumors were included in the study. Three observers blindly and independently read the whole-liver images obtained with T2-weighted spin-echo, T2-weighted single-shot fast spin-echo, T1-weighted fast multiplanar spoiled GRASS and T2-EP images obtained before and 25, 60, 90 and 120 s after injection of 0.2 mmol/kg b.w. of gadopentetate dimeglumine. The diagnostic accuracy was estimated by calculating the area under the observer-specific binomial receiver operating characteristics curves (Az). RESULTS: T2-EP images obtained 60 s after contrast injection showed significantly higher contrast-to-noise (C/N) ratios than the other imaging techniques. A combination of all phases of the T2-EP images produced the highest sensitivity and specificity. In terms of the Az value, the diagnostic accuracy for tumor detection achieved with a combination of all phases of the T2-EP images was significantly higher than that with T1-SPGR and T2-SSFSE images (p<0.01). The Az values of the T2-EP images (Az=0.975) were higher than those of T2-CSE images (Az=0.948), but the difference was not significant. CONCLUSION: Our preliminary study revealed that sequential imaging with enhanced T2-EP images was useful for the detection of hypovascular metastatic liver tumors because of its superior C/N ratio and sensitivity.     

Microwave coagulation therapy with interruption of hepatic blood in- or outflow: an experimental study

PURPOSE: To determine how interruption of hepatic blood in- or outflow affects the coagulation diameter of microwave coagulation therapy (MCT) in the liver. MATERIALS AND METHODS: Laparotomic MCT at 60 W for 1 minute was performed in 11 Landrace pigs. MCT was performed under six different conditions: without occlusion (Group N; in seven lobes of seven pigs); with occlusion of the hepatic artery (Group A; in five lobes of five pigs); with occlusion of the portal vein (Group P; in five lobes of five pigs); with occlusion of the hepatic artery and portal vein (Group AP; in six lobes of six pigs); with occlusion of the hepatic vein (Group V; in five lobes of four pigs); and with occlusion of the hepatic artery and vein (Group AV; in seven lobes of seven pigs). The maximum diameters for each group were compared. RESULTS: The coagulation diameters (mean +/- SD) were 8.5 mm +/- 2.0, 10.0 mm +/- 1.6, 14.3 mm +/- 2.5, 14.4 mm +/- 2.4, 13.0 mm +/- 0.8, and 14.4 mm +/- 1.5 for Groups N, A, P, AP, V, and AV, respectively. The coagulation diameters for groups P, AP, V, and AV were statistically larger than those for groups N and A (P < .05). There was no significant difference between the coagulation diameters of Groups P, AP, V, and AV. CONCLUSION: The coagulation diameter depends mainly on the portal venous flow. In addition of direct interruption of the portal vein, interruption of the hepatic vein can also result in a substantial increase in the coagulation diameter.     

Development of behavioral function of cerebellar hypoplasia rats as induced by cytosine arabinoside (ara-C) (author's transl)

Cytosine arabinoside (ara-C), an antiproliferative agent, was given subcutaneously to Sprague-Dawley rats on the 2-4th postnatal day in doses of 12.5 and 25 mg/kg/day. Body weight and viability were found to be dose-dependently inhibited. The appearance of audio-startle response was delayed in the group on the high dose and up to 21 days of age, the ambulatory behavior resembled that seen in geriatric rats. The free-fall righting reflex failed to appear in the treated groups. The open field test revealed that only the treated females were hypoactive. The treated group showed a poor neuro-muscular ability in the rotarod performance and impairment of acquiring conditioned and unconditioned avoidance response in pole climbing. Histopathological and biochemical studies revealed a hypoplasia of the cerebellum. These findings are suggestive of behavioral dysfunction caused by ara-C-induced cerebellar disorders.     

Favorable Surgical Results in 433 Elderly Patients with Papillary Thyroid Cancer

Papillary thyroid cancer (PTC) has a good prognosis among patients younger than 45 years old, but the prognosis in elder is worse and treatment strategy is not well established. We retrospectively analyzed the clinical features and outcomes of 433 patients with PTC aged 70 years or older. The patients consisted of three groups: group A (n = 327); patients receiving surgical treatment, group B (n = 51); patients with microcancer (maximal diameter, ≤ 1.0 cm) who did not undergo surgical treatment, group C (n = 55); patients in whom surgery was contraindicated due to age, high surgical risk or complication by other illnesses. In group A, the mean tumor size was 2.6 ± 1.5 cm, and 218 patients (66.7%) had pathologically confirmed lymph node metastasis; 110 patients (33.6%) had extrathyroidal invasion. The 5- and 10-year overall survival rates (OSR) in group A were 97.2% and 85%, respectively, which was significantly higher than the 5-year OSR in group C (62.6%). The 5- and 10-year disease-specific survival rates (DSSR) in group A were 98.5% and 91.3%, respectively, which was also significantly higher than the 5-year DSSR in group C (81.8%). Although the patients in group B did not receive any treatment, none of them demonstrated cause-specific death or progression of disease. Papillary thyroid cancer in elderly patients, except for microcancers, may be biologically aggressive. Thus surgery is recommended for these patients, if their general status is judged able to tolerate the stress of anesthesia and surgery.     

Reevaluation of stringent low iodine diet in outpatient preparation for radioiodine examination and therapy

To decrease total body iodine is a key point in preparation for radioiodine study and therapy. We introduced a stringent self-managed low iodine diet (LID) and compared the outcome to that of the conventional restricted iodine diet (RID) for outpatients. We measured urine iodine to creatinine ratios (I/Cr) in patients prepared with RID for one week, LID for one week, or LID for two weeks. Mean urinary iodine excretion after RID for one week (n = 210) was 182.2 microg/gCr (range, 13-986 microg/gCr; standard deviation (SD) = 158.5) not reaching below the recommended level (I/Cr<100 microg/gCr). Urinary iodine excretion after LID for one week (n = 15) showed a lower mean urinary iodine level (I/Cr 119.4 microg/gCr; range, 23-218 microg/gCr; SD = 55.9) than RID for one-week, and two-week LID (n = 17) showed an even lower mean level (I/Cr 63.1 microg/gCr; range, 7-134 microg/gCr; SD = 38.7). The one-week LID period adequately (recommended level of I/Cr being less than 100 microg/gCr) prepared 26% of the patients, while two-weeks on the diet adequately prepared 70% of the patients. Furthermore, none of the two-week LID patients had I/Cr>150 microg/gCr, although a significantly greater number of one-week LID patients (19%) did. Our self-managed, outpatient LID successfully induced iodine deficiency, and two-week LID may be recommended for preparation in radioiodine study and therapy for thyroid cancer.