Superior mesenteric artery syndrome with vascular calcification in a maintenance hemodialysis patient.

INTRODUCTION: Superior mesenteric artery (SMA) syndrome is defined as trapping of the third portion of the duodenum between the SMA and the aorta. In this case, vascular calcification associated with dialysis might have contributed to the onset of SMA syndrome. CASE: The patient was a 74-year-old woman who had been receiving maintenance hemodialysis. She developed sudden onset of severe recurrent vomiting during admission for pseudo-gout. CT of the abdomen revealed duodenal obstruction with an abrupt cutoff in the third portion of the duodenum, and dilatation of the first and second portions of the duodenum. The aortomesenteric angle was significantly sharp. In addition, severe vascular calcification was revealed in the SMA and aorta. The initial treatment was decompression of the obstruction by a nasogastric tube and parenteral nutrition for the management of fluid and electrolyte imbalance. She recovered with only conservative treatment. CONCLUSION: Vascular calcification of the SMA and aorta might have contributed to compression of the third portion of the duodenum. Vascular calcification associated with dialysis could be a factor in SMA syndrome.

Multidetector-row CT analysis of time-dependent changes in lung fields after chest irradiation: usefulness of precision scans.

Time-dependent changes in lung fields after chest irradiation were analyzed using multidetector-row CT. Routine scans at 3-mm raw thickness and 8-mm recon thickness and precision scans at 0.5-mm raw thickness and 0.5-mm recon thickness were compared with respect to the number of each finding and the time-dependent changes in the rate of each finding. Among the findings visualized by these scans, ground-glass opacity (GGO) showed the highest overall appearance rate. Precision scans exceeded routine scans in the rates of all findings except GGO and confluent shadows, and the two types of scans showed the greatest difference in the rate of GGO. Since we found that GGO tended to be overestimated on routine scans, we confirmed it by a phantom experiment. Precision scans were similar or superior to routine scans in the rates of findings except 3 months after irradiation. We consider that the concomitant use of precision scans is useful in that it allows more accurate evaluation of various post-irradiation changes in lung fields including GGO, in which the lesion is in a reversible stage.

A randomized clinical trial of radiation therapy versus thermoradiotherapy in stage IIIB cervical carcinoma.

To clarify the role of thermoradiotherapy for FIGO Stage IIIB cervical carcinomas, both the clinical response and survival of patients treated with radio- or thermoradiotherapy were investigated. Forty patients with Stage IIIB uterine cervix carcinoma were treated with external beam irradiation to the pelvis, combined with iridium 192 high-dose-rate intracavitary brachytherapy. All patients were divided randomly into the following two groups: the radiotherapy (RT) group of 20 patients, who underwent radiotherapy alone; and the thermoradiotherapy (TRT) group of 20 patients, who underwent three sessions of hyperthermia in addition to radiotherapy. The primary endpoint of this study was local complete response and survival. A complete response was achieved in 50% (10 of 20) in the RT group versus 80% (16 of 20) in the TRT group (p = 0.048). The 3-year overall survival and disease-free survival of the patients who were treated with TRT (58.2 and 63.6%) were better than those of the patients treated with RT (48.1 and 45%), but these differences were not significant. The 3-year local relapse-free survival of the patients who were treated with TRT (79.7%) was significantly better than that of the patients treated with RT (48.5%) (p = 0.048). TRT, as delivered in this trial, was well tolerated and did not significantly add to either the relevant clinical acute or long-term toxicity over radiation alone. TRT resulted in a better treatment response and 3-year local relapse-free survival rate than RT for patients with FIGO Stage IIIB cervical carcinoma.

Determination of p53-mediated transactivational ability in radiation-treated cervical cancer.

To establish a new predictor of human cervical cancer radioresponse, we investigated the transactivational ability of p53 gene in tumor tissue for use as a marker of both pretreatment and postirradiation levels of mRNA of its downstream gene, WAF1. A total of 38 wild-type p53-bearing patients with histologically proved uterine cervical cancer were treated with definitive radiotherapy. Their p53 status was investigated using a single-strand conformation polymorphism analysis, and human papilloma virus 16, 18, 33, and 58 E6 was determined by polymerase chain reaction in pretreatment biopsy specimens. WAF1 mRNA was estimated by reverse transcriptase-polymerase chain reaction in both pretreatment specimens and those obtained after the administration of 10.8 Gy. Undetectable or low pretreatment levels of WAF1 mRNA were associated with complete response in the majority of cases, whereas only a few patients with a high pretreatment WAF1 level responded to treatment (P = .03). The increase in the postirradiation level of WAF1 mRNA positively correlated with better treatment response and long survival (P = .02). Although the human papilloma virus infection did not change the radiation response directly, it decreased the inducibility of WAF1. Consequently, the lower inducibility of WAF1 resulted in a poor treatment response. This is the first clinical report showing that the transactivational ability of p53 may be a determinant of the efficacy of cervical cancer radiotherapy.

Loss of heterozygosity on chromosome 6p21.2 as a potential marker for recurrence after radiotherapy of human cervical cancer.

Cervical carcinomas develop as a result of multiple genetic alterations, and specific alterations lead to specific clinical behavior. However, the effect of such alterations on the recurrence of cervical cancer after radiotherapy remains unknown. Chromosome arm 6p is one of those most frequently involved in a loss of heterozygosity (LOH) in patients with cervical carcinoma. The aim of this study was to identify the correlation between the LOH on chromosome 6p21.2 and the recurrence of cervical cancer after radiotherapy. A total of 62 patients with cervical cancer (stage I, 4 patients; stage II, 9 patients; stage III, 37 patients; and stage IV, 12 patients) were included in this study. All patients were treated with definitive radiotherapy. We analyzed specimens from the tumors and venous blood of all patients. Tumors and normal DNA were analyzed by PCR for genetic losses at three polymorphic microsatellite loci (D6S276, D6S1624, and D6S1583). Chromosome 6p21.2 is involved in the LOH in 46.8% (29 of 62) of the informative carcinomas. Ten patients had a local recurrence, 4 had distant metastases, and 13 had both local recurrence and distant metastases after radiotherapy. To evaluate the relationship between the recurrence after radiotherapy and LOH on chromosome 6p21.2, we divided the patients into those with cancer recurrence (n = 27) and those without recurrence (n = 35). LOH on chromosome 6p21.2 was correlated with recurrence after radiotherapy (P = 0.006). The tumors in patients with recurrence were significantly larger than those in patients without recurrence (P = 0.003). However, there was no correlation between the sizes and stages of tumors and the LOH on chromosome 6p21.2. In addition, both overall survival and relapse-free survival were significantly worse for the patients with LOH as compared with those without LOH (P = 0.02 and P = 0.002, respectively). The results of this study suggest that LOH on 6p21.2 is correlated with recurrence of cervical carcinoma after radiotherapy.

Bax and Bcl-2 protein expression following radiation therapy versus radiation plus thermoradiotherapy in stage IIIB cervical carcinoma.

BACKGROUND: The relative amounts of Bcl-2 and Bax proteins determine cell survival or death following an apoptotic stimulus. To clarify the molecular mechanism of cell death after radiotherapy or thermoradiotherapy and its relation to the response of AJCC/UICC Stage IIIB cervical carcinomas, the expression of Bax and Bcl-2 proteins was investigated both before and in the course of treatment given during this study. METHODS: Thirty-seven patients with Stage IIIB carcinoma of the uterine cervix were treated with external beam irradiation to the pelvis combined with iridium-192 high-dose-rate intracavitary brachytherapy. All patients were randomized to one of the following two groups: the radiotherapy (RT) group of 19 patients who were given radiotherapy alone, and the thermoradiotherapy (TRT) group of 18 patients who were given 3 sessions of hyperthermia in addition to RT. Specimens of the cervical tumors were obtained by punch biopsy both before and in the course of the treatment (after a total dose of 10.8 grays ¿Gy for the RT group or after 10.8 Gy plus 1 session of hyperthermia for the TRT group). The tumor sections were stained with anti-Bax and anti-Bcl-2 monoclonal antibody. On the basis of the percentage of immunopositive cells, both pretreatment and posttreatment samples were scored. Furthermore, relative changes in protein expression were determined by comparing the pretreatment scores with those in the course of treatment. In addition, treatment response was evaluated. RESULTS: A complete response was achieved in 52.6% (10 of 19) of the RT group versus 83. 3% (15 of 18) of the TRT group (P = 0.049). Better tumor control was accompanied by increased Bax expression, i.e., 10.5% (2 of 19) of the RT group versus 44.4% (8 of 18) of the TRT group (P = 0.02). The respective number of patients who partially responded (PR) or did not respond to treatment (NC) was 26.3% (5 of 19) and 21.1% (4 of 19) of the RT group versus 11.1% (2 of 18) and 5.6% (1 of 18) of the TRT group (P = 0.2 for both the PR and NC subgroups). CONCLUSIONS: TRT was found to result in better treatment responses than RT for patients with Stage IIIB cervical carcinoma. An additive or synergistic antitumor effect of TRT is likely to occur through induction of apoptosis involving one of the bax pathways.

Squamous cell carcinoma arising in a mature teratoma with metastasis to the urinary bladder.

We describe a patient with squamous cell carcinoma arising in a mature teratoma. Magnetic resonance (MR) images revealed a solid lobulated mass attached to the ovarian cyst containing a fat-fluid level. The solid component with extension into pelvic fat showed as hypointensity on T2-weighted MR images with good enhancement. A metastatic tumor to the urinary bladder was also demonstrated.

Genetic alterations on chromosome 17p associated with response to radiotherapy in bulky cervical cancer.

Chromosome 17 alterations are found in more cancers than those of any other chromosome, and frequently involve the p53 gene on 17p13. The aim of this study was to identify the correlations between the presence of loss of heterozygosity (LOH) and microsatellite instability (MI) on chromosome 17p13 in patients with cervical cancer and the patients' response to radiotherapy. A total of 50 patients were treated with definitive radiotherapy. We performed biopsies and took specimens from the tumour and venous blood of all patients. Tumour and normal DNAs were analysed by polymerase chain reaction for genetic losses and instability at three polymorphic microsatellite loci mapped to 17p13. Nineteen of the 50 tumours (38%) displayed a genetic alteration (GA) on 17p13, 16 (32%) were found to have LOH, and three (6%) showed MI. The sizes of the tumours of the GA-positive patients were significantly greater than those of the GA-negative patients (P = 0.009). The mean tumour diameter of all patients was 6 +/- 2.4 cm. We divided the patients into those with tumours smaller than 6 cm in diameter (n = 26) and those with tumours equal to or greater than 6 cm in diameter (n = 24). The former group survived significantly longer compared to the latter group (P = 0.0002). Among the patients with < 6 cm tumours, all six GA-positive patients are alive with no evidence of disease (NED), whereas of the 20 GA-negative patients, 18 have NED and two are alive with disease (AWD) or suffered cancer-caused death (CD). Thus, there was no correlation between GA and radiotherapy response in the tumours smaller than 6 cm. However, among the patients with > or = 6 cm tumours, two of the GA-positive patients have NED and 11 are AWD/CD, whereas seven of the GA-negative patients have NED and four are AWD/CD. Among the patients with > or = 6 cm tumours, the response to radiotherapy of the GA-positive patients were significantly poorer than those of the GA-negative patients (P = 0.02). In addition, the GA-negative patients survived significantly longer compared to the GA-positive patients (P = 0.026). The results of this study suggest that GA increases with tumour growth. Improved success in the management of bulky cervical cancer requires a better understanding of its biological behaviour.

Bax and Bcl-2 expressions predict response to radiotherapy in human cervical cancer.

PURPOSE: The ratio of Bcl-2 to Bax expression determines survival or death following an apoptotic stimulus. In order to establish a new predictor of the outcome of treatment for human cervical carcinoma, we investigated the relationship between the expressions of the Bax and Bcl-2 proteins and the response to radiotherapy after the administration of 10.8 Gy. METHODS: A total of 44 patients with histologically proven carcinoma of the uterine cervix, including three with recurrent cervical stump carcinomas, were treated with definitive radiotherapy. The presence of mutations in exons 5-8 of the p53 gene was analyzed by a single-strand conformation polymorphism analysis and DNA sequencing. RESULTS: Forty patients were found to have wild-type p53, and the remaining four had mutant p53. The Bax and Bcl-2 protein expressions prior to radiotherapy did not correlate with response and survival. However, the Bax and Bcl-2 protein expressions after radiotherapy correlated with both response and survival. Bax-positive tumors showed significantly better responses than the Bax-negative tumors after 10.8 Gy radiation (P = 0.0002). In contrast, the Bcl-2-positive tumors showed significantly poorer responses than the Bcl-2-negative tumors after radiation (P = 0.002). Increased Bax expression after the 10.8 Gy radiotherapy was found to be correlated with good survival (P = 0.04). In contrast, increased Bcl-2 expression after such radiotherapy was correlated with poor survival (P = 0.002). CONCLUSION: The levels of Bax and Bcl-2 expression after 10.8 Gy radiotherapy are useful prognostic markers in patients with human cervical carcinoma.

[Bax and Bcl-2 expression predict response to radiotherapy in human cervical cancer].

To establish a new predictor of the outcome of treatment for human cervical carcinoma, we investigated the relationship between the expression of the Bax and Bcl-2 proteins and the response to radiotherapy after administration of 10.8 Gy. A total of 44 patients with uterine cervical carcinoma were treated with definitive radiotherapy. On univariate analysis, Bax and Bcl-2 protein expression prior to radiotherapy did not correlate with survival. Increased Bax expression after 10.8 Gy correlated with good survival (p = 0.003). In contrast, increased Bcl-2 expression after 10.8 Gy correlated with poor survival (p < 0.0001). On multivariate analysis, Bcl-2 expression after 10.8 Gy of radiation was the most important predictor of treatment outcome. The levels of Bax and Bcl-2 expression after 10.8 Gy of radiotherapy are useful prognostic markers in patients with human cervical carcinoma.

Therapeutic effect of secretin in patients with jaundice; double-blind placebo-controlled multicentric trial.

Secretin, a gastrointestinal hormone, has been shown to have a potent choleretic effect. Having already obtained some beneficial effects with secretin in patients with intrahepatic cholestasis, we sought to confirm its effects in a double-blind placebo-controlled study in patients with mild jaundice after acute or during chronic hepatitis, where total bilirubin level was in excess of 4.0 mg/dl for 3 days or more. Patients with primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), and familiar hyperbilirubinemia were excluded from the study. Ninety-three patients were included in this analysis, but the final evaluation covered 69 of them. No statistically significant differences were found in the reduction of serum bilirubin levels between secretin and placebo groups. As a number of patients with liver cirrhosis had been included, the subjects were subdivided into one group with cholestasis in hepatitis and one with liver cirrhosis. In the subgroup of cirrhotic patients who received secretin, serum levels of AST were significantly increased compared with the placebo group. However, since the choleretic effect of secretin is unique, further studies seem to be warranted.

[Highly effective preoperative intraarterial infusion chemotherapy with CDDP for progressive uterine corpus cancer with a Sister Mary Joseph's nodule].

A 57-year-old female patient complained of atypical genital bleeding and a noxious emanation from her navel. A histological examination of the uterine body and the navel area confirmed a diagnosis of adenocarcinoma. We diagnosed it as IVb stage of uterine corpus cancer with a Sister Mary Joseph's nodule. We selectively administered intraarterial injection chemotherapy (Cisplatin 120 mg, Pirarubicin 40 mg) in the uterus and navel area (three times, once every three weeks) prior to surgery. The isolated uterus showed that the cancerous tissue had been eradicated, and we judged the cancer to be grade 3 following histopathological effective grading standards. The metastasis exhibited extreme shrinkage, but affirmed changes in the tumor quality. Currently, the patient is receiving maintenance therapy of 600 mg of Hysron H, and 600 mg of UFT. There are no indications of recurrence, and the patient is progressing well.

Transcatheter arterial embolization with cisplatin: apoptosis in VX2 tumour uterus transplants.

Effects of chemoembolization with cisplatin on gynecological malignancies were investigated using rabbit uterine tumour. 4 weeks after inoculation, the 35 rabbits were divided into 3 groups. In the experimental groups, the tumour tissue specimens were stained with hematoxylin and eosin, ApopTag stain and proliferating cell nuclear antigen (PCNA) dye. In two days the Pt level of tumour tissue in the transcatheter arterial chemoembolization (TACE) group was 1.97 times more than that in the intra-arterial (IA) infusion group (p < 0.001). Apoptotic index was 1.03% in the IA group versus 5.9% in the TACE (p < 0.001). The PCNA index was 86.6% in the IA group, compared with 8.6% in the TACE group (p < 0.001). Experiments reported here have revealed enhanced effects of the simultaneous action of nutrient restriction and increase concentration of drug caused by the vascular occlusion on cell death.

Histopathological changes in rabbit uterus carcinoma after transcatheter arterial embolization using cisplatin.

The effects of chemoembolization with cisplatin on gynecological malignancy were investigated using rabbit uterine tumors. A group of 20 rabbits were subjected to inoculation of the uterus with 5 x 10(7) VX2 carcinoma cells and 4 weeks later were divided into four groups, each consisting of five rabbits: an untreated control group, a group given cisplatin intraarterially (IA), a group subjected to transcatheter arterial embolization (TAE) with Gelfoam particles and a group subjected to transcatheter chemoembolization (TACE) with Gelfoam particles plus 1 mg/kg cisplatin. All groups were examined histologically 2 days after treatment. The untreated control group was further investigated 4 weeks after inoculation. In the untreated control group, the tumor cell nuclei varied in size and were irregular in form, and multiple nuclei and nuclear division were also observed. No necrotic zones were found up to 4 weeks after inoculation. The IA group showed no necrosis, but a few apoptotic cells were scattered throughout the tumor. In the TACE group, necrosis was observed in the center of the tumors, but proliferating cells persisted at the periphery. In the TACE group, necrosis was observed in the central part with many apoptotic cells surrounding the necrotic region in layers. The proliferating cell nuclear antigen (PCNA) index was 95.88% in the untreated control group, 86.6% in the IA group, and 8.62% in the TACE group, indicating a significant reduction in cell proliferation in the TACE group. These findings suggest that TACE results in more effective cytotoxicity than the other two treatments in uterine cancer tumor transplants.

[A Japanese family with congenital abnormal plasminogen].

A Japanese family with congenital abnormal plasminogen is reported. The patient was a 44-year-old male with no past history of thrombosis. Since only the plasminogen (PLG) activity was reduced on laboratory tests before surgery for lumbar disc herniation, coagulation and fibrinolysis studies were performed in the patient and his family. The patient underwent resection of the nucleus pulposus and posteriorlateral fixation of the lumbar spine. The PLG activity was 8% in the patient and his sister, 55% in his father, and 53% and 48% in his nephew brothers. The PLG antigen level was normal in all members of his family examined. IEF of PLG antigen showed abnormal patterns in which all bands were shifted slightly to the cathode side in the patient and his sister, but his father and nephew brothers exhibited duplicated bands showing combinations of normal and abnormal patterns. From these results, the proband and his sister were considered to be homozygotes, and his father and nephew brothers to be heterozygotes for congenital abnormal plasminogen. Acute reactant substances (fibrinogen, CRP, CPK, C1IN, alpha 1AT, etc.) and PIC (plasmin, alpha 2-plasmin inhibitor complex) increased after the operation due to the surgical insult, but the surgery did not trigger thrombosis. This patient is considered not to have developed thrombosis although he was a homozygote for congenital abnormal plasminogen, because the anticoagulation process until thrombogenesis was normal.

Transcatheter arterial embolization as a method of cisplatin-retention enhancement on the VX2 tumor uterus transplants.

PURPOSE: Enhanced cisplatin (Pt) retention using transcatheter arterial chemoembolization (TAE) with Gelfoam particles was studied in rabbit uterine tumors. METHODS: Ten rabbit uteri were inoculated with 5 x 10(7) cells of VX2 carcinoma. Three to four weeks later cisplatin, 1 mg/kg, was injected, either with (TAE group) or without (IA group) being mixed with small Gelfoam particles, into the aortic bifurcation over 5 s. Blood and tissue concentration of cisplatin were determined. RESULTS: Slower arterial blood clearance of Pt was observed in the TAE group compared with the IA group, whereas the venous blood Pt clearance curves were similar for both groups. The uterine tumor Pt concentration at 80 min was found to be 2.52-fold higher after TAE compared with IA (p < 0.01). In the pelvic metastatic lymph nodes, the Pt concentration was 4.63 times higher after TAE than after IA (p < 0.01). CONCLUSION: These data indicate that TAE is an effective means of increasing tissue concentration in uterine tumors.

[Change in lobar uptake of 99mTc-galactosyl serum albumin after transarterial embolization therapy].

Liver function was studied by hepatic scintigraphy with 99mTc-galactosyl serum albumin (GSA) before and after transarterial embolization (TAE) therapy in 16 patients with hepatocellular carcinoma. The percent uptake of GSA in liver was measured separately in the treated and non-treated areas. GSA uptake increased in both areas. The change was more marked in the non-embolized lobe than the embolized lobe. We conclude that the increase in GSA uptake reflects the regeneration of liver cells after TAE.

[Clinical study of cyclic intra-arterial chemotherapy using mitoxantrone for advanced hepatocellular carcinoma].

Cyclic intra-arterial infusion chemotherapy using Mitoxantrone via reservoir system was prescribed for 8 patients with advanced hepatocellular carcinoma. According to the clinical staging system, two patients were in Stage III and the other six patients in Stage IV-A. Vp-3 portal invasion was observed in six out of the eight patients. Mitoxantrone (5-8 mg/body) was administered intra-arterially via port-a-cath device every 4 weeks. For tumor response, there were two PR cases, four NC cases, and two PD cases. Thus, the response rate was 25%. The mean survival period was 6.5 months, and 1-year survival rate was 13%. In one of two PR cases, the survival time has been more than two years so far. Gastrointestinal toxicities such as nausea and vomiting were not severe. Critical myelosuppression requiring medication was not observed. Although a temporary increase of serum bilirubin was found in two cases, no severe damage to hepatic function was observed. From our preliminary data, this arterial infusion chemotherapy using Mitoxantrone via reservoir system can be safely performed on non-hospitalized patients with advanced hepatocellular carcinoma, and may be a useful treatment modality.