Impact of a national nutritional support programme on loss to follow-up after tuberculosis diagnosis in Kenya.

SETTING: Undernourishment is prevalent among tuberculosis (TB) patients. Nutritional support is given to TB patients to prevent and treat undernourishment; it is also used to improve treatment outcomes and as an incentive to keep patients on treatment. OBJECTIVE: To determine whether nutritional support is associated with a reduction in the risk of loss to follow-up (LTFU) among TB patients in Kenya. DESIGN: This was a retrospective cohort study using national programmatic data. Records of 362 685 drug-susceptible TB patients from 2012 to 2015 were obtained from Treatment Information from Basic Unit (TIBU), a national case-based electronic data recording system. Patients who were LTFU were compared with those who completed treatment. RESULTS: Nutrition counselling was associated with an 8% reduction in the risk of LTFU (RR 0.92, 95%CI 0.89-0.95), vitamins were associated with a 7% reduction (adjusted RR [aRR] 0.93, 95%CI 0.90-0.96) and food support was associated with a 10% reduction (aRR 0.90, 95%CI 0.87-0.94). Among patients who received food support, the addition of nutrition counselling was associated with a 23% reduction in the risk of LTFU (aRR 0.77, 95%CI 0.67-0.88). CONCLUSION: Nutritional support was associated with a reduction in the risk of LTFU. Providing nutrition counselling is important for patients receiving food support.

First Report of Powdery Mildew Caused by Golovinomyces sonchicola on Ixeris chinensis in Korea.

Ixeris chinensis (Thunb.) Nakai, known as Chinese ixeris, is distributed from Siberia to Japan, including Korea, Taiwan, and China. The whole plant has been used in folk medicine in Asia (4). In Korea, the plants of Chinese ixeris have been gathered and used as a wild root vegetable. During summer to autumn of 2011, Chinese ixeris leaves were found to be heavily infected with a powdery mildew in several locations of Korea. Symptoms first appeared as thin white colonies, which subsequently developed into abundant hyphal growth on both sides of the leaves, leading to drying of the leaves. The same symptoms on Chinese ixeris leaves were continuously observed in 2012 and 2013. Voucher specimens (n = 10) were deposited at Korea University Herbarium (KUS). Hyphal appressoria were moderately lobed or nipple-shaped. Conidiophores arose from the lateral part of the hyphae, measured 100 to 270 × 10 to 12.5 µm, and produced 2 to 6 immature conidia in chains with a sinuate outline. Basal parts of foot-cells in conidiophores were curved. Conidia were barrel-shaped to ellipsoid, measured 26 to 36 × 13 to 19 µm (length/width ratio = 1.7 to 2.4), lacked fibrosin bodies, and showed reticulate wrinkling of the outer walls. Primary conidia were ovate with conical-obtuse apex and subtruncate base. Germ tubes were produced on the perihilar position of conidia. Chasmothecia were not observed. The morphological characteristics were typical of the Euoidium type anamorph of the genus Golovinomyces, and the fungus measurements and structures were consistent with those of G. sonchicola U. Braun & R.T.A. Cook (1). To confirm the identification, internal transcribed spacer (ITS) region of rDNA sequences from a representative material (KUS-F26212) was amplified using primers ITS5/P3 and sequenced (3). The resulting 416-bp sequence was deposited in GenBank (Accession No. KF819857). A GenBank BLAST search revealed that the isolate showed >99% sequence similarity with those of G. cichoracearum from Sonchus spp. (e.g., AB453762, AF011296, JQ010848, etc.). G. sonchicola is currently confined to G. cichoracearum s. lat. on Sonchus spp., based on molecular sequence analyses (1). Pathogenicity was confirmed through inoculation by gently pressing a diseased leaf onto leaves of five healthy potted Chinese ixeris. Five non-inoculated plants served as controls. Inoculated plants developed symptoms after 6 days, whereas the controls remained symptomless. The fungus present on the inoculated plants was identical morphologically to that originally observed on diseased plants. Powdery mildew infections of I. chinensis associated with Golovinomyces have been known in China (2). To our knowledge, this is the first report of powdery mildew disease caused by G. sonchicola on I. chinensis in Korea. Farming of Chinese ixeris has recently started on a commercial scale in Korea. Though no statistical data are available, we postulate the cultivation area in Korea to be approximately 200 ha, mostly growing without chemical controls. Occurrence of powdery mildews poses a potential threat to safe production of this vegetable, especially in organic farming. References: (1) U. Braun and R. T. A. Cook. Taxonomic Manual of the Erysiphales (Powdery Mildews), CBS Biodiversity Series No.11. CBS, Utrecht, 2012. (2) F. L. Tai. Bull. Chinese Bot. Sci. 2:16, 1936. (3) S. Takamatsu et al. Mycol. Res. 113:117, 2009. (4) S. J. Zhang et al. J. Nat. Prod. 69:1425, 2006.

Comparative analysis of the use of complementary and alternative medicine by Korean patients with androgenetic alopecia, atopic dermatitis and psoriasis.

BACKGROUND: Complementary and alternative medicine (CAM) is being increasingly used among Koreans with chronic dermatologic diseases, such as androgenetic alopecia (AGA), atopic dermatitis (AD) and psoriasis. OBJECTIVE: To quantify the usage of CAM in Korean patients with AGA, AD or psoriasis, and to offer valid information for the physicians frequently encountering such disorders. METHODS: Outpatients (n = 678) from three tertiary hospitals were investigated independently by constructed and self-directed questionnaire. RESULTS: Of the respondents, 62.1% (421/678) of the subjects reported current or previous use of CAM for their dermatologic conditions (AGA, 67.2%; AD, 68.9%; psoriasis, 46.6%). In AGA, topical applicants (50.2%) were most often used, followed by dietary therapy and health supplements. In AD, bath therapy (39.4%) was most often used, followed by oriental medicine and topical applicants. In psoriasis, oriental medicine (33.9%) was most frequently used, followed by bath therapy and health supplements. The proportion of patients who believed that CAM helped to improve their skin condition was relatively low (AGA, 16.1%; AD, 31.7%; psoriasis, 15.0%). LIMITATIONS: The results may not be applicable to other countries and generalized to general populations. CONCLUSION: These results indicate that CAM is widely used in Korean patients with chronic dermatological diseases despite their dissatisfactions. Thus, the advantages and disadvantages of CAM must be considered before its clinical practice.

Effects of honeybee venom supplementation in drinking water on growth performance of broiler chickens.

The effects of water supplementation of bee venom (BV) on performance, antioxidant activity, and liver function in Arbor Acres broiler chickens were investigated. Hence, 3 experimental treatment groups (control, 0.5 mg/L of BV, and 1 mg/L of BV) were allocated to 3 replicates of 5,000 one-day-old chicks each. The control group was kept on tap water, whereas the other 2 groups were supplied water supplemented with 0.5 and 1 mg of BV, respectively, per liter of drinking water. Broilers were provided ad libitum access to feed for the experimental period of 1 to 28 d of age. Supplementing drinking water with BV significantly increased BW gain at 28 d of age (P < 0.05). The average daily weight gain from d 1 to 28 was increased for birds supplemented with BV compared with control birds. The increase in BW gain was more pronounced with supplementation of 1 mg/L of BV compared with 0.5 mg/L of BV. An improved feed intake was noted in groups supplemented with BV as compared with control chicks. Liver function enzymes, aspartate aminotransferase, and alanine aminotransferase activities including total cholesterol, total protein, albumin, and globulin were not changed by BV supplementation. Tap water supplementation of BV did not alter the number of leukocytes, erythrocytes, heterophils, and lymphocytes. However, the antioxidative activities estimated as a superoxide dismutase-like activity of broiler chicks supplemented with BV was significantly increased (P < 0.05) in comparison with those without BV supplementation. These data indicate a possibility of better broiler performance through BV supplementation under conditions of severe stressful challenges the newly born chicks encounter.

The implication of nigrostriatal dopaminergic degeneration in the pathogenesis of REM sleep behavior disorder.

BACKGROUND AND PURPOSE: The pathogenesis of rapid eye movement (REM) sleep behavior disorder (RBD) is not clear despite its frequent association with Parkinson's disease (PD). We investigated whether the nigrostriatal dopaminergic system is involved in the development of idiopathic RBD. METHODS: Fourteen patients with RBD, 14 patients with PD and 12 normal controls were included in the study. The diagnosis of RBD was confirmed on polysomnography. All the participants performed single-photon emission computed tomography imaging 3 h after injection of [(123)I]FP-CIT. During REM sleep of the RBD patients, each 30-s epoch was rated as 'tonic' when there was at least 50% of tonically maintained chin electromyography (EMG) activity in the epoch. Phasic EMG activities were calculated as the percentage of 3-s mini-epoch containing phasic EMG events (leg and chin, separately). RESULTS: The RBD patients showed a trend of lower binding in the striatum than the normal controls (P = 0.07), and the significance was revealed in the putamen (P = 0.02). However, in 11 individual cases of the 14 RBD patients, the dopamine transporter (DAT) densities in the putamen still remained within the normal range. In the RBD patients, there was no correlation between EMG activities and DAT densities. CONCLUSIONS: Nigrostriatal dopaminergic degeneration could be a part of the pathogenesis of RBD, but not essential for the development of RBD. The lack of correlation between RBD severity and DAT densities suggests that another pathogenic process not related to nigrostriatal dopaminergic transmission may be implicated in RBD.

Phase III trial of adjuvant 5-fluorouracil and adriamycin versus 5-fluorouracil, adriamycin, and polyadenylic-polyuridylic acid (poly A:U) for locally advanced gastric cancer after curative surgery: final results of 15-year follow-up.

BACKGROUND: This phase III trial was to compare 5-fluorouracil (5-FU), adriamycin, and polyadenylic-polyuridylic acid (poly A:U) against 5-fluorouracil plus adriamycin (FA) for operable gastric cancer. PATIENTS AND METHODS: From 1984 to 1989, patients who had D(2-3) curative resection were randomly assigned to receive chemotherapy or chemoimmunotherapy. Chemotherapy consisted of 12 mg/kg 5-FU every week for 18 months and 40 mg/m2 adriamycin every 3 weeks for 12 cycles. Chemoimmunotherapy consisted of FA plus 100 mg of poly A:U weekly for six cycles and was followed 6 months later by six weekly 50-mg booster injections. RESULTS: A total of 292 patients were enrolled. After excluding 12 ineligible patients, 142 and 138 patients were allocated to each treatment. Patients were balanced with prognostic variables: age, sex, tumor location, differentiation, degree of tumor invasion (T2-T4a), and lymph node status (N0-N2). During the 15-year follow-up, chemoimmunotherapy significantly prolonged overall (P = 0.013) and recurrence-free (P = 0.005) survivals compared with chemotherapy alone. The survival benefits were prominent in the subset of patients with T3/T4a, N2, or stage III. Treatments were generally well tolerated in both arms. CONCLUSIONS: These results indicate a survival advantage of chemoimmunotherapy with a regimen of FA and poly A:U in curatively resected gastric adenocarcinoma.

Adjuvant chemotherapy with 5-fluorouracil, doxorubicin and mitomycin-C (FAM) for 6 months after curative resection of gastric carcinoma.

AIM: This study aimed to evaluate the efficacy and safety of 5-fluorouracil (5-FU), doxorubicin and mitomycin-C (FAM) adjuvant chemotherapy in patients who had undergone curative resection of gastric carcinoma. METHODS: From Nov 1999 to Jan 2002, 291 consecutive patients with stage IB-IIIB gastric adenocarcinoma were given FAM adjuvant chemotherapy. Chemotherapy comprised intravenous 5-FU 600 mg/m(2) (days 1, 8, 29 and 36), doxorubicin 30 mg/m(2) (days 1 and 29) and mitomycin-C 10 mg/m(2) (day 1), every 8 weeks for 6 months. RESULTS: The median follow-up time was 60.6 months, 92 patients died, and 93 patients had recurrent disease. The 5-year overall survival (OS) rates were 85.9% for stage IB, 72.1% for stage II, 58.0% for stage IIIA, and 48.2% for stage IIIB (p=0.002). The 5-year relapse-free survival (RFS) rates were 85.2% for stage IB, 71.2% for stage II, 53.3% for stage IIIA, and 39.2% for stage IIIB (p<0.001). A total of 769 cycles of chemotherapy were delivered, and 15 patients experienced grade 3 or higher leukopenia. The most common grade 3 or higher non-hematologic toxicity was nausea/vomiting (11 patients), followed by stomatitis (3 patients). CONCLUSIONS: Adjuvant chemotherapy with FAM for 6 months for gastric carcinoma indicated comparable RFS and OS with an acceptable toxicity profile.

Phase II study of capecitabine and cisplatin as first-line combination therapy in patients with gastric cancer recurrent after fluoropyrimidine-based adjuvant chemotherapy.

To evaluate the efficacy and safety of capecitabine and cisplatin in patients with recurrent gastric cancer after fluoropyrimidine-based adjuvant therapy. Patients with histologically confirmed and measurable advanced gastric cancer that had relapsed after fluoropyrimidine-based adjuvant chemotherapy received oral capecitabine (1250 mg m(-2) twice daily, days 1-14) and intravenous cisplatin (60 mg m(-2) over 1 h, day 1) every 3 weeks. In total, 32 patients were enrolled, of whom 30 were evaluable for efficacy and 32 for safety. A median of 5 cycles (range 1-10) was administered. One patient achieved a complete response and eight had partial responses, giving an overall response rate of 28% (95% CI, 13-44%). The median time to progression and median overall survival were 5.8 months (95% CI, 4.1-7.5 months) and 11.2 months (95% CI, 5.5-16.9 months), respectively. Grade 3 neutropenia and thrombocytopenia were observed in 38 and 6% of patients, respectively. Grade 2/3 nonhaematological toxicities included diarrhoea (19%), stomatitis (19%) and hand-foot syndrome (31%). No grade 4 toxicity, neutropenic fever or treatment-related deaths occurred. Capecitabine in combination with cisplatin was effective and well tolerated as first-line treatment in patients with recurrent gastric cancer after fluoropyrimidine-based adjuvant chemotherapy.

Evidence of thalamic disinhibition in patients with hemichorea: semiquantitative analysis using SPECT.

OBJECTIVES: Hemichorea sometimes occurs after lesions that selectively involve the caudate nucleus, putamen, and globus pallidus. Some reports have hypothesised that the loss of subthalamic nucleus control on the internal segment of the globus pallidus, followed by the disinhibition of the thalamus may contribute to chorea. However, the pathophysiology is poorly understood. Therefore, clinicoradiological localisation was evaluated and a comparison of the haemodynamic status of the basal ganglia and thalamus was made. METHODS: Six patients presenting with acute onset of hemichorea were assessed. Neuroimaging studies, including MRI and SPECT examinations in addition to detailed biochemical tests, were performed. A semiquantitative analysis was performed by comparing the ratio of blood flow between patients and normal controls. In addition, the ratio of perfusion asymmetry was calculated as the ratio between each area contralateral to the chorea and that homolateral to the chorea. The comparison was made with a two sample t test. RESULTS: The causes of hemichorea found consisted of four cases of acute stroke, one non-ketotic hyperglycaemia, and one systemic lupus erythematosus. Brain MRI indicated lesion sites in the contralateral putamen, globus pallidus, caudate nucleus, and subthalamic nucleus. A significant decrease in the ratio of blood flow in the basal ganglia contralateral to the chorea and a significant increase in the thalamus was found when comparing the perfusion asymmetries, which were calculated as the ratio of cerebral blood flow (CBF) for each region to that in the homolateral occipital area (p<0.05). CONCLUSION: An alteration in CBF in both the contralateral thalamus and basal ganglia reflect the loss of pallidal inhibitory input from the pallidum to the thalamus. This change in CBF may be one of epiphenomena, which implicates an occurrence of hemichorea in humans.

Isolation and in vivo and in vitro antifungal activity of phenylacetic acid and sodium phenylacetate from Streptomyces humidus.

The antifungal substances SH-1 and SH-2 were isolated from Streptomyces humidus strain S5-55 cultures by various purification procedures and identified as phenylacetic acid and sodium phenylacetate, respectively, based on the nuclear magnetic resonance, electron ionization mass spectral, and inductively coupled plasma mass spectral data. SH-1 and SH-2 completely inhibited the growth of Pythium ultimum, Phytophthora capsici, Rhizoctonia solani, Saccharomyces cerevisiae, and Pseudomonas syringae pv. syringae at concentrations from 10 to 50 microg/ml. The two compounds were as effective as the commercial fungicide metalaxyl in inhibiting spore germination and hyphal growth of P. capsici. However, the in vivo control efficacies of the two antifungal compounds against P. capsici infection on pepper plants were similar to those of H(3)PO(3) and fosetyl-AI but less than that of metalaxyl.

Adjuvant 5-fluorouracil plus doxorubicin in D2-3 resected gastric carcinoma: 15-year experience at a single institute.

BACKGROUND: The authors evaluated the efficacy of adjuvant chemotherapy with 5-fluorouracil (5-FU) plus doxorubicin in gastric carcinoma after D2-3 curative resection. They also evaluated the effect of dose-related factors (delivered total dose/m(2), actual dose intensity [ADI], relative dose intensity [RDI]) of this regimen on patient survival. METHODS: A total of 301 patients with Stage II to IV (en bloc resected T4b; 1984 American Joint Committee on Cancer staging) were accrued between 1984 and 1996. Chemotherapy was started within 4 weeks of surgery according to the following schedule: intravenous bolus injection of doxorubicin 40 mg/m2 every 3 weeks for 12 cycles and 5-FU 400 mg/m2 weekly for 60 weeks. The toxicity and survival were evaluated. RESULTS: The median follow-up duration was 58 months. Sixty-four percent of the total patients and 71.7% of the patients who did not experience recurrence during the chemotherapy finished the protocol completely with acceptable toxicities. The 5- and 10-year disease free survival rates of total 301 patients were 58.4% and 46.5%, and the overall survival rates were 62.1% and 50.5%, respectively. Treatment completion group showed survival benefit over the early termination group in 5-year survival (75.2% vs. 52.9%; P = 0.0005). The median ADI of 5-FU and doxorubicin were 349 and 11 mg/m2/week, and the median RDIs of 5-FU and doxorubicin were 0.87 and 0.83, respectively. Multivariate analysis demonstrated that completion of chemotherapy is an independent prognostic factor of both disease free and overall survival. However, ADI and RDI did now show any effect on survival. CONCLUSIONS: Adjuvant chemotherapy with 5-FU plus doxorubicin for 60 weeks after D2-3 dissection induced promising survival duration with acceptable toxicities. Full administration of the planned dosage of the combined drugs is recommendable as opposed to early termination of the chemotherapy in gastric carcinoma.

Monthly 5-days 5-fluorouracil and low-dose leucovorin for adjuvant chemotherapy in colon cancer.

We investigated the dose-related effect of the 5-fluorouracil (5-FU)/leucovorin regimen on survival in 139 colon cancer patients with Dukes' B2 and C2 stage disease. Chemotherapy consisted of 400 mg/m(2) of 5-FU and 20 mg/m(2) of leucovorin injected daily for 5 days in every 4 weeks for a maximum of 12 cycles. The total dose of 5-FU administered per body surface area had a significant effect on the 5-year disease-free survival and 5-year overall survival in stage B2 and C2 colon cancer patients (P=0.0018, P=0.0011). Analysis with reference to the median DSDI demonstrated that there was a significant difference in 5-year survival in Dukes' C2 (P=0.0016), but survival was not affected by the dose intensity. Multivariate analysis demonstrated that only the total dose of 5-FU administered per surface area affected the 5-year disease-free survival and 5-year overall survival (P=0.0016, P=0.0007, respectively). It can be concluded that the total dose of 5-FU administered is important in planned dosage schedule of adjuvant chemotherapy in colon cancer.

Cloning and expression of a ferritin subunit for Galleria mellonella.

Ferritin was purified from iron-fed Galleria mellonella hemolymph by ultra centrifugation and FPLC (Superose 6). SDS-PAGE revealed three bands of 26, 30, and 32 kDa. The ferritin 26 kDa subunit cDNA was obtained from RT-PCR using primer designed from N-terminal sequence analysis. 5'-RACE was used to obtain the complete protein coding sequence. The sequence encodes a 211 amino acid polypeptide including a 20 amino acid leader peptide. An IRE (iron-responsive element) sequence with a predicted stem-loop structure was present in the 5'-UTR of ferritin mRNA. Sequence alignment has a sequence identity with Calpodes ethlius (S)(74%), Drosophila melanogaster (50%), and Aedes aegypti (39%). Northern blot analysis indicated that there were 1.5- and 1.75-fold increases in the expression of ferritin mRNA after iron-fed fat body and midgut, respectively. Also, we confirmed that the ferritin mRNA is not expressed in adult ovary and testis. Arch.

Adjuvant (cisplatin, etoposide, and 5-fluorouracil) chemotherapy after curative resection of gastric adenocarcinomas involving the esophagogastric junction.

Gastric adenocarcinomas involving the esophagogastric junction represent a particular therapeutic problem because they lie in the border area between two body cavities: the thorax and the abdomen. The prognosis of gastric adenocarcinomas involving esophagogastric junction is poor because there is widespread lymphatic metastasis, making curative resection difficult. Even in patients with localized disease who are potentially curable, the 5-year survival rate is approximately 20% with curative resection only, somewhat lower than for those with cancer elsewhere in the stomach. The authors conducted a pilot study to evaluate the safety and possible efficacy of adjuvant chemotherapy with cisplatin, etoposide, and 5-fluorouracil (PEF) after curative resection of gastric adenocarcinoma involving esophagogastric junction. Three cycles of adjuvant PEF chemotherapy with cisplatin (20 mg/m2/day intravenously on days 1-5), etoposide (100 mg/m2/day intravenously on days 1, 3, and 5), and 5-fluorouracil (800 mg/m2/day continuous intravenous infusion on days 1-5) were given every 3 weeks after curative resection of gastric adenocarcinoma involving the esophagogastric junction. Between November 1989 and June 1995, a total of 50 patients with postoperative stage II, IIIA, or IIIB disease entered this trial. In 14 of 50 patients (28%), the disease recurred during the follow-up of 4-83 months (median 26 months). Disease-free survival was 4-83+ months (median 48 months), and the actuarial 5-year disease-free survival rate was 48% (95% CI: 41% to 55%). Overall survival was 4-83+ months (median 62 months), and the actuarial 5-year survival rate was 54% (95% CI: 40% to 68%). The prognostic factor analysis showed that the postoperative N stage and the interval between surgery and chemotherapy affected disease-free survival and overall survival. The toxicities of PEF adjuvant chemotherapy were leukopenia, nausea/vomiting, and alopecia, but they were mostly mild and reversible except in one patient who died because of treatment-related sepsis. Adjuvant chemotherapy with three cycles of PEF regimen was well tolerated and seems to be a promising treatment for gastric adenocarcinoma involving the esophagopstric junction, in comparison with previous treatments. To define the efficacy of adjuvant PEF chemotherapy for gastric adenocarcinoma involving esophagogastric junction, prospective randomized trials are warranted.

Highly porous polymer matrices as a three-dimensional culture system for hepatocytes.

Hepatocyte-based therapies (e.g., hepatocyte transplantation and extracorporeal support devices) may provide alternative therapies to treat patients with liver disease, but suitable approaches to localize these cells to a given location while maintaining liver-specific gene expression must be developed. The suitability of highly porous three-dimensional sponges fabricated from poly (L-lactic acid) [PLLA] as an hepatocyte culture system was evaluated in this study. Sponges were fabricated utilizing a particulate leaching technique, and were approximately 95% porous, with an average pore diameter of 180 microns. Hepatocytes seeded into these sponges adhered and remained viable for 14 days. However, the secretion rate of albumin from these cells, an indication of liver-specific gene expression, was low (approximately 6 pg/cell/day at day 1), and decreased steadily over the 14 days of the experiment. Coating sponges with collagen, and more preferably, immobilizing cells within the PLLA sponges with a collagen gel, led to enhanced cell survival and albumin secretion at all time points. These data suggest that porous PLLA sponges may provide a novel system for long-term culture of hepatocytes, and proper design of the system may allow the liver-specific gene expression of hepatocytes transplanted in these matrices to be enhanced.

P-glycoprotein: the intermediate end point of drug response to induction chemotherapy in locally advanced breast cancer.

Expression and clinical relevance of p-glycoprotein (p-gp) were evaluated in 31 cases of locally advanced breast cancer and 9 cases involving inflammatory breast cancer after induction chemotherapy. The de novo p-gp expression rate was 26% and increased up to 58% (p = 0.03) with the FAC (5-fluorouracil, adriamycin, cyclophosphamide) regimen. Although more clinically complete responders were found in the secondary p-gp negative group (p = 0.02), this difference was not found in pathological tumor response. Moreover, as the grade of the secondary p-gp expression increased, the chemotherapeutic effect decreased, suggesting an inverse relationship between p-gp expression and drug effect (p = 0.04). When we subgrouped the patients into 4 groups using these two parameters, p-gp negative patients presenting with a high drug effect showed a low recurrence rate (p = 0.05) and marginal survival benefits (p = 0.09) as opposed to patients with a low drug effect. But in p-gp positive groups, the recurrence rate was the same between the two groups regardless of the drug effect. Thus, in the p-gp negative patient with a high drug effect, adjuvant chemotherapy with the same regimen as induction chemotherapy may induce more prognostically favorable results. Therefore, clinical application of the secondary p-gp detection can be used as an intermediate endpoint in evaluating drug response for an induction regimen.

Small hepatocellular carcinoma: high dose internal radiation therapy with superselective intra-arterial injection of I-131-labeled Lipiodol.

The aim of the present study was to deliver a high internal radiation dose to small hepatocellular carcinoma (HCC) lesions in an attempt to treat this disease. A total of 18 patients with HCC lesions measuring less than 4.5 cm in diameter (25 lesions) were treated with superselective intra-arterial injection of I-131-labeled Lipiodol (370-1,100 MBq in 3-5 ml) using a 5-F or coaxial catheter. All the lesions were nodular, multinodular, or hypervascular on pretreatment angiography. In all, 15 lesions that received over 180 Gy of cumulative radiation decreased in size in proportion to the Lipiodol retention on CT, and no pericapsular recurrence was found on angiography after 14-54 months of follow-up. In five patients who subsequently underwent surgery, 65% to 100% tumor necrosis was detected. No abnormal change in liver function tests or untoward clinical symptom of the lung, thyroid, or bone marrow was detected in patients who survived for more than 3 years after the treatment. Superselective high-dose internal radiation therapy of small HCC offers hope of treatment and long-term local control without complications.

Phase II trial for combined external radiotherapy and hyperthermia for unresectable hepatoma.

Hepatocellular carcinoma is a major malignant disease in parts of Africa and Asia, including Korea. Surgical resection, which represents the best hope for cure, is limited by the extent of the disease and the high incidence of concurrent liver cirrhosis in Korea. We designed a phase II trial of combined external radiotherapy and hyperthermia for hepatocellular carcinoma that was unresectable due to either locally advanced lesions or associated liver cirrhosis so as to evaluate the efficacy and the safety of this combination regimen. This trial was performed at Yonsei Cancer Center between April 1988 and July 1988. External radiotherapy was delivered to a total dose of 3060 cGy/3.5 weeks. Hyperthermia was applied twice a week for a total of six treatment sessions using an 8-MHz radio-frequency capacitive-type heating device, i.e., Thermotron RF-8 and Cancermia. In all cases, hyperthermia was carried out within 30 min of the radiotherapy for a period of 30-60 min. The temperature in the tumor was measured by inserting a thermocouple into the tumor mass under ultrasonographic guidance in patients who did not have a bleeding tendency. The tumor response was assessed by CT scan after completion of the designed treatment. No complete response was obtained. However, a symptomatic improvement in abdominal pain was observed in 78.6% of cases and a partial response was achieved in 40% of the patients. The most important factor affecting the tumor response was the type of tumor (single massive, 71.4%; diffuse infiltrative, 20%; multinodular, 0; P < 0.005). The 1-year survival values determined for all patients and for the partial responders were 34% and 50%, respectively. The overall median duration of survival was 6.5 months. The median duration of survival for the partial responders was longer than that for the nonresponders (11 vs 5 months; P < 0.05). A mild degree of heat sensation, fever, first-degree burns of the skin, and nausea were observed as treatment-related adverse reactions. In conclusion, although this study is being continued, the results obtained thus for indicate that combined radiotherapy and hyperthermia seem to be effective in providing local tumor control and pain palliation in unresectable hepatocellular carcinoma while producing an acceptable level of toxicity.

Nodular hepatocellular carcinoma. Treatment with subsegmental intraarterial injection of iodine 131-labeled iodized oil.

Internal radiation therapy with subsegmental arterial injection of iodine 131(131I)-labeled iodized oil (Lipiodol; Laboratorie, Guerbet, France) was evaluated in 24 patients with nodular hepatocellular carcinoma (HCC) ranging from 2.5 to 8.0 cm in size. 131I Lipiodol (555 to 2220 MBq in 3 to 8 ml) was injected depending on the tumor size. Tumor reduction was seen in 88.9% of tumors smaller than 4.0 cm in diameter, 65.5% of tumors between 4.1 to 6.0 cm, and 25.0% of tumors larger than 5.1 cm. The tumor size reduction corresponded to the gradual drop of serum alpha-fetoprotein (AFP) levels and devascularization on follow-up angiography. Adverse reactions from treatment included fever, mild abdominal pain, nausea, and elevation of transaminases. These were mild and well tolerated by patients. This method provided long-term local control without complications related to the thyroid, lung, gastrointestinal tract, and bone marrow.