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Verrucous carcinoma of the esophagus is a very rare esophageal cancer. We present a case of verrucous carcinoma of the esophagus, the 14th such case reported. In contrast to the previous cases, our patient had no symptoms and did not have a history of severe or repeated injury of the esophagus. The patient was completely resected by endoscopy and was well after 3 yr of follow-up, without recurrence of the disease.
Many reports have demonstrated that thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) are biomarkers for the response and prognosis of patients treated with 5-fluorouracil (5-FU)-based chemotherapy. A newly developed orally administered drug, fluoropyrimidine (S-1), has been developed with clinical efficacy when combined with an inhibitor of DPD. In this study, the relationship between immunoreactivity to TS and DPD in biopsy specimens and the effects of chemotherapy was investigated in 41 patients treated with S-1 therapy for advanced gastric cancer. Response rates were 54% (13/24) in TS(+) and 53% (9/17) in TS(-) patients (p=0.938), and those of DPD(+) and (-) patients were 61% (11/18) and 48% (11/23) (p=0.397), respectively. The median survival time of all the subjects was 253 days. There was no significant difference in median survival time between TS(+) patients (284 days) and (-) patients (189 days: p=0.670). The 18 DPD(+) patients had median survival times slightly longer (338 days) than the 23 patients with DPD(-) (207 days: p=0.206). This study indicates that S-1 may be effective in the treatment of gastric cancer patients, regardless of intratumoral TS and DPD immunoreactivity status. Further studies are needed to confirm these results with larger numbers of patients.
The true endpoints of cancer chemotherapy have to be prolongation of survival, palliation of symptoms, or improvement of quality of life in cancer patients, while the response rate is considered to be a surrogate endpoint. When conducting a phase III trial, not only the response rate but also data on survivals in the phase II study should be taken into consideration. New response evaluation criteria and various objective markers in analyzing survival have been developed recently. Our data on chemotherapy for gastrointestinal malignancies reveal correlations between CR cases and survival prolongation among esophageal cancer patients treated with chemoradiotherapy, and between responder and survival prolongation in gastric cancer patients treated with chemotherapy. A review of the literature might reveal a correlation between response and survival prolongation in colorectal chemotherapy patients, though our data did not support such a correlation. At present, it is necessary to recognize that "evidence" should be based on the results of randomized phase III trials with large sample sizes and good quality assurance other than the response rates in phase II trials.
BACKGROUND AND PURPOSE: Gamma knife radiosurgery has become an important treatment option for vestibular schwannoma. The effect of treatment can be assessed only by neuroimaging. We analyzed the evolution of follow-up MR imaging findings after gamma knife radiosurgery to provide information for the clinical management of these tumors. METHODS: Changes in tumor volume and enhancement were assessed visually on 341 follow-up MR studies obtained in 78 of 86 consecutive patients with unilateral vestibular schwannoma who underwent gamma knife radiosurgery. RESULTS: Follow-up MR studies were obtained between 10 and 63 months (mean, 34 months) after treatment. Tumor control rate was 81%. Changes in tumor volume were classified as temporary enlargement (41%), no change or sustained regression (34%), alternating enlargement and regression (13%), or continuous enlargement (12%). Temporary enlargement occurred within 2 years after radiosurgery. Changes in tumor enhancement were classified as transient loss of enhancement (84%), continuous increase in enhancement (5%), or no change in enhancement (11%). There was no significant correlation between changes in tumor volume and tumor enhancement. Areas of T2 hyperintensity in adjacent brain tissue appeared in 31% of patients. CONCLUSION: Dynamic changes in vestibular schwannoma are seen on serial follow-up MR studies obtained after gamma knife radiosurgery. An increase in tumor size up to 2 years after radiosurgery is likely to be followed by regression. Changes in contrast enhancement are not predictive of clinical outcome. Neuroimaging follow-up is recommended.
BACKGROUND: It remains controversial whether chemotherapy and/or radiotherapy are/is contraindicated for esophageal carcinoma patients with malignant fistulae. In some case reports, closure of fistulae by chemotherapy or radiotherapy has been reported. The current study investigated chemoradiotherapy for these patients using various primary treatments to manage the pulmonary complications. The aim of this study was to evaluate the efficacy and feasibility of chemoradiotherapy for patients with locally advanced esophageal carcinoma with malignant fistulae. METHODS: Patients with endoscopically or radiologically confirmed fistulae were treated with concomitant chemoradiotherapy. Closure of fistulae was assessed by esophagography or endoscopy. Oral food intake also was assessed before and after treatment. RESULTS: Of 202 esophageal carcinoma patients treated at National Cancer Center Hospital East between July 1992 and May 1998, 24 patients (11.9%) developed malignant fistulae. Twelve patients developed fistulae before treatment and the remaining patients developed fistulae during treatment. Closure of the fistulae after chemoradiotherapy was observed in 17 of these patients (70.8%), and 16 of these 17 patients (94.1%) had oral alimentation restored after successful treatment. The median survival time from the diagnosis of the fistula for all patients with fistulae was 198 days; in the patients whose fistulae were present before chemoradiotherapy, the median survival time was 238 days. CONCLUSIONS: These results suggest that the presence of malignant fistulae does not contraindicate chemoradiotherapy. Once the inflammation due to the fistula has been controlled, chemoradiotherapy should be utilized because it may provide the best chance for survival and palliation of severe dysphagia.
BACKGROUND: Central catecholamines, particularly dopaminergic and noradrenergic systems, have affected the appetitive behavior in patients with anorexia nervosa (AN). The purpose of this study is to distinguish the characteristics of contingent negative variation (CNV) and postimperative negative variation (PINV), which may reflect the level of catecholamine in children with AN. METHODS: Eight children with AN aged 10 to 15 years and 23 age-matched healthy children were recruited. Contingent negative variation was recorded from the frontal midline (Fz), central midline (Cz) and parietal midline (Pz) referenced to linked earlobes during 30 trials consisting of a warning stimulus and an imperative stimulus with an interstimulus interval of 2 s and an intertrial interval of 10 s. The imperative stimulus of each trial required a button press. RESULTS: Children with AN had a diminished amplitude of the CNV. They had a significantly more attenuated early CNV and late CNV amplitude at Cz than normal children. No significant differences were observed between AN children and normal children in the amplitude of PINV at all three electrode sites. No difference could be found between the two groups in the frequencies of normal and abnormal duration of PINV. CONCLUSION: These findings suggest that early CNV may be diminished by norepinephrine deficiency and late CNV may be attenuated by dopaminergic deficiency in children with AN. Reduced CNV may represent impaired cognitive processes which reflect impaired appetitive behavior in AN children.
BACKGROUND: Abnormal sympathetic skin response (SSR) has been reported in adult patients with diabetic neuropathy. In addition, other studies have revealed abnormal SSR in diabetic patients not having autonomic symptoms and autonomic dysfunctions. These findings have been only obtained from adult patients. There have been few reports on the autonomic functions in diabetic children. Accordingly, it is not clear whether the autonomic neuropathy occurs in diabetic children. The aim of the present study is to clear autonomic function in children with insulin-dependent diabetes mellitus by SSR. METHODS: The SSR was measured in 28 normal healthy children and in eight patients with IDDM not having symptoms of dysautonomia. The SSR was elicited using 10 stimuli on programmed Nihonkoden Neuropack Sigma model machine. Following a single electrical stimulation, four SSR were recorded in both the palms and the soles simultaneously. RESULTS: The SSR were simultaneously obtained in 100% of the two groups. The amplitudes in the palms and soles were not significantly different between the two groups. The mean and shortest latency in the soles were significantly longer in the IDDM group than in the control group (P < 0.01). None of the measurements of SSR revealed correlation with duration of diabetes and onset of illness. CONCLUSIONS: Diabetic neuropathy may not have occurred in young patients having shorter duration of illness. Conversely, assuming that prolonged latency is abnormal, it may even have occurred in them. Follow up on these patients with prolonged latencies would be required.
BACKGROUND AND STUDY AIMS: The reason for the difference in fluorescence between normal and diseased tissues (carcinoma and adenoma) in the colon observed on autofluorescence endoscopy is unclear, flavins, NADPH and collagen being regarded as possible major sources of fluorescence. The purpose of this study was to identify the reason for this difference in fluorescence. PATIENTS AND METHODS: Samples of human colonic tissues (adenoma: n = 6, cancer: n = 11, normal: n = 11) were obtained from resected specimens. The flavin content of human colonic tissue was measured by high performance liquid chromatography. Fluorescence microscopy under blue light excitation (400-440 nm) was performed using frozen sections of normal, adenomatous and cancerous tissues, and examining them for the presence and characteristics of fluorescence. RESULTS: The flavin content of normal and diseased tissue was not significantly different. Fluorescence microscopy of normal colonic tissue revealed strong fluorescence in the submucosal layer, which corresponded to collagen. Tissue fluorescence did not decrease in reducing agent or acid solution. No difference in fluorescence was detected in normal mucosa, adenoma or cancerous tissue on fluorescence microscopy. These findings indicate that flavins and NADPH do not affect tissue fluorescence, and that submucosal collagen is the main source of tissue fluorescence in the colon. CONCLUSION: The reason for the decreased fluorescence in diseased tissues appears to be a decrease in collagen fluorescence due to the screening effect of mucosal thickening or replacement of submucosa by cancer cells.
BACKGROUND: There is a difference in the location of colorectal mucosal lesions and invasive cancers. AIMS: To ascertain whether the location of colorectal neoplasms reflects the carcinogenesis pathway. METHODS: The subject material consisted of 4147 neoplastic lesions that had been resected endoscopically or surgically from 5025 patients. Mucosal lesions and submucosal cancers were classified into depressed and non-depressed types endoscopically or histologically. The relations between macroscopic type, size, histology, and location were investigated. RESULTS: (a) Non-depressed type. A total of 1774 of 3454 (51%) mucosal lesions were located in the right colon, 1212 (35%) in the left colon, and 468 (14%) in the rectum. The incidence of mucosal lesions larger than 10 mm was 10% (185/1774) in the right colon, 21% (254/1212) in the left colon, and 27% (127/468) in the rectum. The incidence of mucosal lesions with villous components was 2% (32/1774) in the right colon, 5% (63/1212) in the left colon, and 13% (62/468) in the rectum. The ratio of submucosal cancers to mucosal lesions was significantly higher in the rectum (0.064, 30/469) than in the left (0.034, 43/1279) or right (0.010, 18/1857) colon. (b) Depressed type. The incidences of depressed type mucosal lesions and submucosal cancers were 5% (83/1857) and 17% (3/18) in the right colon, 5% (67/1279) and 5% (2/43) in the left colon, and 0.2% (1/469) and 0% (0/30) in the rectum, respectively. CONCLUSION: There may be some mechanisms that promote the progression of mucosal lesions to invasive cancers in the left colon and rectum, whereas a de novo pathway from depressed type lesions may be implicated in some cancers of the right colon.
PURPOSE: A phase II study of a combination chemotherapy regimen of cisplatin (CDDP) and irinotecan (CPT-11) was conducted to assess its efficacy and feasibility in patients with metastatic gastric cancer. PATIENTS AND METHODS: Eligibility criteria included the following: (1) histologically proven gastric cancer with measurable metastatic lesions, (2) performance status of 2 or less, (3) age of 75 years or younger, (4) one or no prior chemotherapy regimens, (5) adequate bone marrow, liver, renal, and cardiac functions, and (6) written informed consent. The treatment consisted of CPT-11 (70 mg/m2) on day 1 and day 15 and CDDP (80 mg/m2) on day 1, repeated every 4 weeks. RESULTS: Forty-four patients were entered onto the study. The overall response rate was 48% (21 of 44 patients, 95% confidence interval [CI], 33% to 63%) and included one complete remission (2%). The response rate of the patients who had not received prior chemotherapy was 59% (17 of 29 patients, 95% CI, 39% to 77%). The median survival time was 272 days for all patients and 322 days for the 29 patients who had not received prior chemotherapy. Grade 4 neutropenia was observed in 25 patients (57%), and grade 3 or 4 diarrhea was observed in nine patients (20%). Other adverse reactions were mild. No treatment-related deaths occurred. CONCLUSION: This combination chemotherapy regimen is active and well tolerated. It may be an appropriate regimen for future phase III trials.
PURPOSE: To investigate the efficacy and feasibility of concurrent chemoradiotherapy for locally advanced carcinoma of the esophagus. PATIENTS AND METHODS: Fifty-four patients with clinically T4 and/or M1 lymph node (LYM) squamous cell carcinoma of the esophagus were enrolled. Patients received protracted infusion of fluorouracil 400 mg/m(2)/24 hours on days 1 to 5 and 8 to 12, 2-hour infusion of cisplatin 40 mg/m(2) on days 1 and 8, and concurrent radiation therapy at a dose of 30 Gy in 15 fractions over 3 weeks. Filgrastim was prophylactically administered to 35 patients. This schedule was repeated twice every 5 weeks, for a total radiation dose of 60 Gy, followed by two courses of fluorouracil (800 mg/m(2)/24 hours for 5 days) and cisplatin (80 mg/m(2) on day 1). RESULTS: There were 21 patients with T4M0 disease, one with T2M1 LYM, 17 with T3M1 LYM, and 15 withT4M1 LYM. Forty-nine patients (91%) completed at least the chemoradiotherapy segment. The 18 patients (33%) who achieved a complete response included nine (25%) of the 36 with T4 disease and nine (50%) of the 18 with non-T4 disease. Major toxicities were leukocytopenia and esophagitis; there were four (7%) treatment-related deaths. Prophylactic filgrastim reduced the incidence of grade 3 or worse leukopenia without improving dose-intensity or response. With a median follow-up duration of 43 months, median survival time was 9 months. The 3-year survival rate was 23%. CONCLUSION: Despite its significant toxicity, this combined modality seemed to have curative potential even in cases of locally advanced carcinoma of the esophagus.
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BACKGROUND: Recent Japanese studies have shown that histogenesis of small colorectal carcinomas can be divided into two groups: polypoid growth arising from polypoid neoplasia, and nonpolypoid growth arising from flat or depressed neoplasia. This classification should be verified with genetic as well as morphologic characteristics. SUBJECTS AND METHODS: In order to classify our subject into polypoid growth and nonpolypoid growth types both histologically and endoscopically, we selected 42 colorectal carcinomas < 2 cm in size (35 submucosal and seven more advanced). Clinicopathological findings, presence or absence of Ki-ras gene mutation and overexpression of p53 protein were compared between the two types. RESULTS: Histologically, the cases were divided into 27 of the polypoid growth type and 15 of the nonpolypoid growth type. None of the nonpolypoid growth cases contained adenomatous remnant, wheras this was found in 75% of the polypoid growth cases. No Ki-ras mutation was observed in any of the nonpolypoid growth cases, although it appeared in 44% of the polypoid growth cases. Regarding the overexpression of p53 protein, no significant difference was observed between the two types. The histological and the colonoscopic polypoid growth-nonpolypoid growth classifications correlated well with each other (agreement rate 98%), except for one lesion, which was classified as polypoid growth type endoscopically but as nonpolypoid growth type histologically. CONCLUSIONS: The histologically defined polypoid growth-nonpolypoid growth classification may indicate a difference in pathway of colorectal carcinogenesis. Also, colonoscopic polypoid growth-nonpolypoid growth classification is available for preoperative estimation of the genetic characteristics of small carcinomas.
Hereditary nonpolyposis colorectal cancer is an autosomal, dominantly inherited disease, characterized by an early age of onset, right colon predominance and an association with various extracolorectal malignancies. We present a case of a 47-year-old woman who met the clinical criteria for the diagnosis of hereditary nonpolyposis colorectal cancer from her past and family histories. She had undergone operations for uterine cancer (histology not confirmed) at age 35 and for advanced cancer of the ascending colon at age 45. Gastroendoscopy revealed a flat elevated lesion, 20 mm in size, with a protrusion (type IIa + Is) in the second portion of the duodenum in March 1996. Additionally, colonoscopy showed a flat elevated lesion, 30 mm in size, with an irregular and nodular surface (type IIa, laterally spreading tumor) in the descending colon. After the operation, the resected specimen of the duodenum histologically showed a well-differentiated adenocarcinoma associated with a tubulo-villous adenoma which had invaded the submucosal layer. The tumor of the colon was histologically confirmed to be a moderately-differentiated adenocarcinoma with submucosal invasion. A high frequency of replication error positivity (4/5 loci) was detected in both of the tumors. Reports of early cancer of the duodenum, associated with extracolorectal malignancies in hereditary nonpolyposis colorectal cancer, are very rare in the literature. Although it is difficult to determine which extracolorectal tumor sites should be taken into consideration by screening programs, we believe that careful observation by upper gastrointestinal endoscopy, which includes the duodenum, is necessary for patients with hereditary nonpolyposis colorectal cancer.
The purpose of this study was to evaluate the feasibility and efficacy of 3-hour infusional paclitaxel for the treatment of advanced gastric cancer with measurable metastatic diseases. Eligibility criteria included no more than one regimen of prior chemotherapy. Paclitaxel was administered as an intravenous infusion over 3 hours at a dose of 210 mg/m2 every 3 weeks. Premedication of dexamethazone, ranitidine, and diphenhydramine were given to all patients. Sixteen patients were registered in the study. One patient did not receive paclitaxel because of gastrointestinal bleeding before the initiation of drug's administration. Thirteen of the 15 patients had a prior history of chemotherapy. Although 10 patients (67%) developed grade 4 neutropenia, no serious infections occurred during the study. Nonhematologic toxicities were generally mild. Three (20%) patients who showed evidences of resistance to the previous intensive regimen achieved a partial response. In conclusion, a 3-hour infusion of paclitaxel is a safe and promising treatment for advanced gastric cancer. Paclitaxel appears to be non-cross resistant to other agents that are commonly used for gastric cancer. A large-scale phase II study is now underway.
To define the current status of the multimodality treatment for large and critically located arteriovenous malformations (AVMs), we have made a retrospective review of 54 consecutive patients with Spetzler-Martin grade IV and V AVMs. The size of nidus is larger than 3 cm in diameter in all cases. Initially, all but one were treated by nidus embolization with the aim of size reduction. Only one patient had complete nidus occlusion by embolization alone. In 52 patients, the obliteration rate of nidus volume averaged 60% after embolization. Ten patients underwent complete surgical resection of AVMs following embolization with no postoperative neurological deterioration. Thirty-one patients underwent stereotactic radiosurgery following embolization. At the time of this analysis, 30 patients underwent follow-up angiography 2-3 years after radiosurgery. The results of radiosurgery correlated well with the preradiosurgical AVM volume. Of 16 patients with small residual AVMs (< 10 cm3, a mean volume of 4.7 cm3), nine (56%) had complete obliteration, and six (38%) had near-total or subtotal obliteration by 3 years after radiosurgery. In contrast, of 14 patients with large residual AVMs (> or = 10 cm3, a mean volume of 17.9 cm3), only two (14%) had complete obliteration, and eight (57%) had near-total or subtotal obliteration. Repeat radiosurgery was performed for the patients with remaining AVMs at 3-year follow-up review. This study indicates that a certain number of large and critically located AVMs can be safely treated by either microsurgery or radiosurgery following a significant volume reduction by nidus embolization. The present data also suggest the need and possible role of repeat radiosurgery in improving complete obliteration rate of large difficult AVMs, since many of those AVMs have significantly responded to initial radiosurgery.
A 24-year-old male patient with a history of gastric ulcer was referred to our hospital in September 1995. His chief complaints were epigastralgia and weight loss of 3 kg during a short period. The upper G.I endoscopy performed on 9/22/1995 revealed multiple ulcers with a histological diagnosis of atypical lymphoid cell proliferation. Follow-up endoscopy, one month later, showed an appearance of superficial gastric lymphoma, and histology of the biopsy specimen revealed MALT lymphoma associated with H. pylori. Despite an eradication therapy for H. pylori, which consisted of lansoprazole, teprenone and amoxicillin, the progression of the ulcerative lesions was observed on the endoscopy two weeks after initiation of the treatment. However, the subsequent endoscopy, one month later, disclosed a regression both macroscopically and histologically. The lymphoma disappeared completely on the follow-up endoscopy in April 1996 with no lymphoma cells in histology. No recurrences of the lymphoma have been observed up to now.
We investigated the utility of examining biological markers to predict chemoresponse and survival. The subjects consisted of 39 unresectable gastric cancer patients treated with a combination of 5-fluorouracil and cis-platinum. The expression of p53, bcl-2, thymidylate synthase (TS), glutathione S-transferase pi (GST-pi), and vascular endothelial growth factor (VEGF) in the formalin-fixed biopsy samples of primary tumors before chemotherapy was examined immunohistochemically. The positive rate for VEGF, bcl-2, TS, p53, and GST-pi was 51, 10, 46, 38, and 69%, respectively. VEGF-positive cases showed a higher response rate than did negative cases (11 of 20 versus 2 of 19 cases; P = 0.0057). The cases that were negative for p53, TS, bcl-2, and GST-pi were more likely to respond to chemotherapy than the cases that were positive for these markers. The 10 cases having 4 or 5 favorable phenotypes (VEGF positive, p53 negative, bcl-2 negative, TS negative, and GST-pi negative) survived longer than the remaining 29 cases (P = 0.0069). Multivariate analysis revealed that the number of favorable phenotypes (> or = 4 versus < or = 3) had a greater impact on survival than performance status (0 versus 1 or 2), age (> 60 years versus < or = 60 years), macroscopic type (scirrhous versus nonscirrhous), histological type (intestinal versus diffuse), or tumor extent (locally advanced versus metastatic). Immunohistochemical examination of biological markers in biopsy samples may be useful in predicting the clinical outcome of unresectable gastric cancer patients treated with 5-fluorouracil and cis-platinum.