[Usefulness of S-1/gemcitabine combination therapy for advanced pancreatic cancer].

Combination chemotherapy with S-1 and gemcitabine(GEM)was given to patients with advanced pancreatic cancer and favorable results were obtained. These patients were 77-(Stage IVa), 68-(Stage IVb), and 64-year-old males (Stage IVb). They were administered S-1 at a dose of 80-100 mg/day for 2 weeks and GEM at a dose of 1,000-1,200 mg/body on days 8 and 15 followed by a 2-week recovery period. One course consisted of a 2-week treatment period and a recovery period; this course was repeated in all of these patients. The 3 types of patients have survived for a year and five months, a year and three months, and nine months, respectively, after diagnosis. In the first patient, who was in Stage IVa, the primary cancer has been maintained in a reduced state without metastasis. In the other two patients, who were in Stage IVb, the primary cancer and hepatic metastatic lesions have been reduced remarkably. Quality of life is good in all the patients. Combination therapy with S-1 and GEM can be provided for a long-term treatment with few adverse reactions on an outpatient basis. Based on the changes in tumor markers, we observed that the inhibitory effects of this combination chemotherapy are immediate and persistent with long-term treatment. Therefore, we expect S-1/GEM combination therapy to be the chemotherapy of choice for advanced pancreatic cancer.

Late toxicity in complete response cases after definitive chemoradiotherapy for esophageal squamous cell carcinoma.

BACKGROUND: We retrospectively investigated long-term toxicity after concurrent chemoradiotherapy (CRT) for patients with esophageal squamous cell carcinoma (ESCC). METHODS: Concurrent chemoradiotherapy was performed in 110 patients with T1 to T4 disease containing M1 lymph node (LYM) disease. Chemotherapy consisted of protracted infusion of 5-fluorouracil 400 mg/m(2) per 24 h on days 1 to 5 and 8 to 12, combined with 2-h infusion of cisplatin 40 mg/m(2) on days 1 and 8. Radiation treatment of the mediastinum at a dose of 30 Gy in 15 fractions was administered concomitantly with chemotherapy. A course schedule with a 3-week treatment and a 2-week break was applied twice, with a total radiation dose of 60 Gy. For the assessment of toxicity, the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer late radiation morbidity scoring schema was adopted. RESULTS: A total of 81 patients were recruited in patients with stage I to IVA. Of 34 patients with complete response, 1 patient died as a result of acute myocardial infarction. Grade 2, 3, and 4 late toxicities occurred with the following incidences: pericarditis in 3 patients, 1 patient, and 2 patients, respectively; heart failure in 0, 0, and 3 patients; pleural effusion in 2, 3, and 0 patients; and radiation pneumonitis in 0, 0, and 1 patient, respectively. CONCLUSIONS: Definitive chemoradiotherapy for ESCC is effective with substantial toxicities. Further investigation is warranted to minimize the normal tissue toxicities.

Interobserver and intra-observer consistency in the endoscopic assessment of colonic pit patterns.

BACKGROUND: The colonic pit pattern is recognized as an aid to the differential diagnosis between hyperplastic lesions, adenoma, and carcinoma, and is a focus for observation by magnification chromoendoscopy, especially in Japan. This study evaluated intra- and interobserver agreement of experienced endoscopists in the assessment of colonic pit patterns when using the Kudo classification. METHODS: A total of 220 magnification chromoendoscopic pictures of colonic lesions were selected, of which 215 were collected from a consecutive series of patients. The pictures were randomly displayed twice to 6 experienced endoscopists at an interval of 1 week. Each picture was assessed for predominant pit pattern by using the classification of Kudo. Histopathologic diagnosis also was predicted based on the pit pattern diagnosis. Kappa statistics were used to estimate intra- and interobserver variation. RESULTS: The mean (standard deviation) inter- and intra-observer kappa values for experienced endoscopists were 0.716 (0.031) and 0.810 (0.084), respectively. For prediction of histopathology according to the pit pattern diagnosis, the mean (standard deviation) inter- and intra-observer kappa values were 0.776 (0.032) (p = 0.001) and 0.862 (0.069) (p = 0.028), respectively. CONCLUSIONS: For experienced endoscopists, the inter- and intra-observer reproducibility of the classification of colonic pit pattern is good.

Clinical significance in molecular detection of p53 mutation in serum of patients with colorectal carcinoma.

Circulating DNA can be isolated from serum of patients with various carcinomas and p53 mutation can be observed in colorectal carcinoma. The aim of this study was to investigate the correlation between p53 mutation in DNA extracted from colorectal carcinoma and that in DNA extracted from serum of patients with colorectal carcinoma. The clinical significance in molecular detection of p53 mutation in serum of patients with colorectal carcinomas was also investigated. DNA was extracted from tumors and non-tumorous colorectal tissues of 46 patients with single sporadic colorectal carcinomas of stage I (n=6), stage II (n=18), stage III (n=15), and stage IV (n=7) according to the TNM classification. Circulating DNA was also extracted from the serum of the 46 patients with colorectal carcinoma and from 7 healthy volunteers for normal control. Mutations of the p53 gene were analyzed using a fluorescence-based polymerase chain reaction (PCR)-single-strand conformation polymorphism (SSCP) method. DNA sequences were determined in DNA fragments with shifted peaks by SSCP methods. Mutations in tumors were found in 22 (48%) of 46 patients, and mutations in serum were found in 3 (14%) of these 22 patients. Of 4 patients with stage IV disease, 3 (75%) had serum p53 mutation and the mutation pattern of these 3 patients was the same in both tumor and serum. No correlation was seen between p53 mutation in serum and the level of serum DNA. There was no significant difference between the presence of p53 mutation in serum and tumor size, depth of invasion, vascular invasion, or lymph node metastasis. However, liver metastasis showed significant difference (p=0.0026). The presence of p53 mutation in serum was associated with a clinically advanced stage accompanied by liver metastasis.

Primary small cell carcinoma of the stomach.

We report on an 80-year-old man with primary gastric small cell carcinoma (SmCC). He was admitted to hospital with hematemesis. An upper gastrointestinal examination revealed an irregularly ulcerated tumor, 60 mm in diameter, on the lesser curvature of the stomach body extending to the cardia. An endoscopic biopsy revealed a solid proliferation of intermediate-sized tumor cells with hyperchromatic nuclei and scanty cytoplasm. Immunohistochemically, the neoplastic cells were positive for neuron-specific enolase and chromogranin A, but negative for carcinoembryonic antigen. No tumor was detected on examination of the chest. Therefore, primary gastric SmCC was diagnosed preoperatively. To date, only 38 cases of primary gastric SmCC, including our case, have been reported. By using endoscopic biopsy, approximately two-thirds of cases have been diagnosed incorrectly. In the reported cases of gastric SmCC, the endoscopic findings frequently indicated a submucosal tumor. Gastric SmCC is clinically aggressive and has an extremely poor prognosis, even when discovered at an early stage. Most patients with gastric SmCC die within 1 year of diagnosis. Although a standard treatment for gastric SmCC has not been established, intensive chemotherapy should be considered to promote long-term survival. We believe that careful examination, including immunohistochemical investigation, is necessary for determining the therapeutic strategy whenever gastric SmCC is suspected during endoscopy.

A comparison of magnifying and nonmagnifying colonoscopy for diagnosis of colorectal polyps: A prospective study.

BACKGROUND: Discrimination between neoplastic and non-neoplastic colorectal polyps is essential for determining appropriate treatment. The mucosal crypt pattern of polyps can be observed with a nonmagnifying colonoscope; however, mucosal crypt patterns are better seen by magnifying colonoscopy, which can also be a noninvasive means for predicting histopathology. This study prospectively compared the ability to distinguish between neoplastic and non-neoplastic lesions by magnifying and nonmagnifying colonoscopy. METHODS: Six hundred sixty patients were randomly assigned to undergo magnifying or nonmagnifying colonoscopy (2 groups each of 330 patients). The mucosal crypt pattern of colorectal lesions was classified into types I through V after spraying with 0.2% Indigo carmine dye. The histopathology of all lesions was confirmed by evaluation of endoscopic resection specimens or biopsy specimens. Only lesions 10 mm or less in diameter were included in the study. RESULTS: The accuracy of magnifying colonoscopy in distinguishing neoplastic from non-neoplastic lesions (92%, 372/405) was significantly higher than for nonmagnifying colonoscopy (68%, 278/407). Insertion of magnifying and nonmagnifying colonoscopes to the cecum was successful in, respectively, 321 patients (97%) and 317 patients (96%), with no significant differences in the average time to reach the cecum or average total procedure time. No serious complication was observed during or immediately after the examinations. CONCLUSIONS: Observation of mucosal crypt pattern with magnifying colonoscopy is superior to nonmagnifying colonoscopy for distinguishing between neoplastic and non-neoplastic colorectal lesions.

Evaluation of endoscopic ultrasonography in colorectal villous lesions.

BACKGROUND AND AIMS: The choice of therapeutic procedure for colorectal neoplasias depends largely on the depth of tumor invasion. This study examined the value of endoscopic ultrasonography (EUS) in determining whether local resection is applicable for colorectal villous lesions. MATERIALS AND METHODS: We performed EUS on 125 colorectal neoplasias classified into two categories, villous ( n=35) and nonvillous lesions ( n=90), according to their colonoscopic morphological features. We compared the EUS and clinicopathological findings for each lesion. RESULTS: The overall accuracy of EUS-based evaluation of tumor invasion depth was 60% in villous lesions and 91% in nonvillous lesions. In villous lesions 37% were overstaged and 3% understaged, and in of nonvillous lesions 6% were overstaged and 3% understaged. In differentiating mucosal neoplasias (M)/submucosal cancers with slight invasion (SM-s) from non-M/SM-s, the values in villous and nonvillous lesions were, respectively: sensitivity 60% and 86%, specificity 100% and 99%, and accuracy 66% and 96%. Large (>/=20 mm wide, >/=5 mm high) or rectal villous lesions were more likely than nonvillous lesions to be misjudged with regard to the differentiation between M/SM-s and non-M/SM-s. CONCLUSION: It is difficult to determine the depth of invasion in villous lesions, especially large or rectal lesions, using only EUS. EUS-based evaluation alone cannot determine the appropriate treatment for colorectal villous lesions.

Colorectal carcinoma with special reference to growth pattern classifications: clinicopathologic characteristics and genetic changes.

BACKGROUND: Many colorectal carcinomas are known to develop from preexisting polypoid adenomas; however, they can also develop from so-called "flat adenomas". To elucidate the growth patterns of flat- or depressed-derived colorectal carcinomas, we investigated the clinicopathologic characteristics and genetic changes of invasive carcinomas. METHODS: Seventy-five colorectal carcinomas were classified into three groups: 46 upward growth (UG) type, 22 downward growth (DG) type, and 7 lateral growth (LG) type. All of them had histologically infiltrated the submucosa (SM) and muscularis propria (MP). Ki-ras mutation was examined by polymerase chain reaction-single-strand conformation polymorphism analysis, and overexpression of p53 protein was analyzed by immunohistochemistry. RESULTS: No DG or LG carcinomas histologically demonstrated an adenomatous remnant, whereas UG carcinomas did (SM, 19 of 26; 73%; MP, 3 of 20; 15%). The percentage of tumors existing in the right colon was significantly higher in LG carcinomas (71%) than in the UG type (28%; P = 0.037). The frequency of Ki-ras mutation was significantly higher in the UG carcinomas than in the DG and LG carcinomas (52% vs 0%; P < 0.0001; and vs 0%; P = 0.014). However, the frequency of this mutation in SM-UG carcinomas with an adenomatous remnant (9 of 19; 47%) did not differ significantly from that in SM-UG carcinomas without an adenomatous remnant (3 of 7; 43%). The frequency of p53 overexpression did not differ among UG (57%), LG (57%), and DG (50%) carcinomas. CONCLUSIONS: These results suggest that UG carcinomas develop on the basis of the adenoma-carcinoma sequence, while the development of DG and LG carcinomas is different from that of UG carcinomas.

Implantation of self-expanding metallic stent for patients with malignant stricture after failure of definitive chemoradiotherapy for T3 or T4 esophageal squamous cell carcinomas.

BACKGROUND/AIMS: Definitive chemoradiotherapy can have curative potential in unresectable patients with malignant stricture due to locally advanced esophageal carcinoma, however, dysphagia is the principal problem in patients who had recurrence or who did not respond to chemoradiotherapy. In this prospective study, we investigated the efficacy and feasibility of metallic stent implantation for patients with dysphagia after chemoradiotherapy failed. METHODOLOGY: Concurrent chemoradiotherapy was performed in 40 patients with severe dysphagia due to esophageal squamous cell carcinomas accompanied by T3 or T4 disease containing M1 lymph node (LYM) disease. A self-expanding metallic stent was inserted for patients with malignant stricture of the thoracic esophagus after failure of chemoradiotherapy using identical protocols. RESULTS: Of 40 patients, 13 (33%) achieved a complete response. However, 12 patients complained of severe dysphagia again after chemoradiotherapy despite a good performance status. Esophageal stricture of these 12 patients was caused by stable disease (n = 4), local progression (n = 5), and compression of metastatic lymph node (n = 3). Metallic stents were successfully inserted for all 12 patients, and dysphagia improved in 10 (83%) of these 12 patients. Life-threatening complication (17%) of sepsis in two patients was found in an early phase after stent insertion, although approximately 200 days had passed in a dysphagia-free state after chemoradiotherapy. CONCLUSIONS: Implantation of self-expanding metallic stent for patients with malignant stricture after failure of chemoradiotherapy is effective, however, serious complication can occur in the early phase.