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Background: There is no consensus on the postoperative outcomes of tongue reconstruction. Therefore, the authors developed a novel risk model for predicting dysphagia after tongue reconstruction., Methods: This retrospective study was conducted by the Oral Pharyngeal Esophageal Operation and Reconstruction Analytical, or OPERA, group across 31 cancer centers and university hospitals in Japan. A total of 532 patients [390 (73.3%) men and 142 (26.7%) women; median age at surgery, 60 years (range, 15 to 88 years)] who were diagnosed with oral tongue squamous cell carcinoma and underwent tongue reconstruction following glossectomy between 2009 and 2013 were included. Independent risk factors were identified using univariate regression analysis and converted to a binary format for multivariate analysis. An integer value was assigned to each risk factor to calculate a total score capable of quantifying the risk of feeding tube dependence., Results: Overall, 54 patients (10.2%) required a feeding tube at the time of evaluation. Predictive factors for feeding tube dependence were advanced age, lower American Society of Anesthesiologists physical status, low body mass index, lower serum albumin, comorbid hypertension and diabetes, extended tongue defect, resection beyond the tongue, laryngeal suspension, postoperative radiation therapy, and no functional teeth. In multivariate logistic regression analysis, age greater than or equal to 58.5 years, postoperative radiation therapy, wider tongue defect, and body mass index less than 21.27 kg/m 2 earned 6, 4, 3, and 2 points, respectively, for a maximum total score of 15., Conclusion: The authors' risk model provides a mathematical tool for estimating the individual risk of postoperative feeding tube dependence before tongue reconstruction., Clinical Question/level of Evidence: Risk, III., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Plastic Surgeons.)

Purpose: Activated Notch receptor signaling has been implicated in tumor growth and progression in colorectal cancer (CRC). However, the pathogenic relevance of NOTCH gene alterations remains unclear. The aim of this study was to clarify mutational landscapes and assess their clinical significance in patients with metastatic CRC., Methods: Pre-chemotherapy tumor tissues obtained from 1154 metastatic CRC patients in the Nationwide Cancer Genome Screening Project in Japan between April 2017 and March 2019 were studied using the Oncomine Comprehensive Assay., Results: The frequencies of NOTCH1, NOTCH2, and NOTCH3 nonsynonymous sequence variants were 11.5%, 4.4%, and 10.4%, respectively. The majority of variants were missense of unknown significance that were distributed across all domains of all three NOTCH genes. The gain-of-function mutations in NOTCH reported in multiple malignancies were not identified. The NOTCH amplification rate was less than 1%. No NOTCH fusions were detected. In patients who were registered before, or within 1 year of, first-line chemotherapy, overall survival for 51 patients with only NOTCH3 variants was significantly longer than for 540 patients with no NOTCH variants (median, 40.2 months vs 27.7 months; P = 0.04). Multivariate analysis revealed that variant NOTCH3 was an independent prognostic factor for increased survival (hazard ratio 0.61, 95% confidence interval, 0.39-0.94; P = 0.03) besides poor prognostic factors associated with mutant TP53, KRAS, and BRAF, as well as amplified MYC., Conclusion: NOTCH genes are unlikely to harbor driver mutations and amplifications in patients with metastatic CRC. NOTCH3 variant should be further investigated as a favorable prognostic marker., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The efficacy of adjuvant chemotherapy for high-risk stage II colon cancer (CC) has not been well established. We compared the effects of surgery with and without oral uracil and tegafur plus leucovorin (UFT/LV) in patients with high-risk stage II CC, adjusting for potential risk factors., Methods: We enrolled patients with histologically confirmed stage II colon adenocarcinoma with at least one of the following conditions: T4 disease, perforation/penetration, poorly differentiated adenocarcinoma/mucinous carcinoma, or < 12 dissected lymph nodes. Patients chose to be non-randomized or randomized to undergo surgery alone (NR-Group S or R-Group S) or surgery followed by 6 months of UFT/LV (NR-Group U or R-Group U). The primary endpoint was disease-free survival (DFS) after adjusting for previously reported risk factors using propensity score matching (1:2) and inverse probability of treatment weighting (IPTW) in the non-randomized arm., Results: Overall, 1,902 (98%) and 36 (2%) patients were enrolled in the non-randomized and randomized arms, respectively. There were too few patients in the randomized arm and these were therefore excluded from the analysis. Of the 1,902 patients, 402 in NR-Group S and 804 in NR-Group U were propensity score-matched. The 3-year DFS rate (95% confidence interval) was significantly higher in NR-Group U (80.9% [77.9%-83.4%]) than in NR-Group S (74.0% [69.3%-78.0%]) (hazard ratio, 0.64 [0.50-0.83]; P = 0.0006). The 3-year overall survival rate was not significantly different between NR-Group S and NR-Group U. Significantly higher 3-year DFS (P = 0.0013) and overall survival (P = 0.0315) rates were observed in NR-Group U compared with NR-Group S using IPTW., Conclusions: Adjuvant chemotherapy with UFT/LV showed a significant survival benefit over surgery alone in patients with high-risk stage II CC characterized by at least one of the following conditions: T4 disease, perforation/penetration, poorly differentiated adenocarcinoma/mucinous carcinoma, or < 12 dissected lymph nodes., Trial Registration: Japan Registry of Clinical Trials: jRCTs031180155 (date of registration: 25/02/2019) (UMIN Clinical Trials Registry: UMIN000007783 , date of registration: 18/04/2012)., (© 2022. The Author(s).)

Background: In immediate one-stage implant-based breast reconstruction, acellular dermal matrix (ADM) is widely used around the world due to its ability to cover the outside part of the pectoralis major muscle. Unfortunately, ADM has not yet been approved in Japan. Consequently, in our institution, we have performed safe one-stage implant-based breast reconstruction without ADM by employing several unique techniques and have obtained excellent results., Methods: The data of 186 patients were reviewed. In each case, we performed three unique steps to determine which cases were suitable for one-stage implant-based breast reconstruction as follows. First, ICG fluorescence imaging was performed to confirm the blood flow of the skin after mastectomy. Next, a serratus anterior muscle/fascial and external oblique fascial flap was elevated to completely cover the implant together with the pectoralis major muscle. We used a sizer to confirm the skin tension and the form of the breast. After confirming correct size, shape and coverage, we selected cases in which implant could be safely performed. We evaluated the final cosmetic outcome based on three measurements: the inframammary fold position, and the bilateral balance of both breast size and form., Results: The rate of immediate one-stage implant-based reconstruction was 85.7%. An implant was removed in one case because of complications, and infection developed in five cases. Among all patients, the overall cosmetic evaluation of the final outcome was evaluated as good, fair and poor in 84.3%, 13.5% and 2.2% of cases, respectively., Conclusions: Immediate one-stage implant-based breast reconstruction without ADM can be a useful and safe procedure, based on our unique techniques in breast cancer patients who hope for immediate prosthetic breast reconstruction in Japan.

Objectives: Outcomes and prognostic factors remain obscure in patients with colorectal cancer after pulmonary metastasectomy who had previously received a curative hepatic metastasectomy., Methods: We collected data of 757 patients with pulmonary metastasis from colorectal cancer who underwent curative metastasectomy between 2004 and 2008 from 46 Japanese institutions, from which we extracted data on patients who previously received curative hepatic metastasectomy. Disease-free survival, overall survival, and prognostic factors were analyzed., Results: The subjects of this study were 160 patients, of whom 44% had primary rectal tumor, 73% had a single pulmonary metastasis, 11% had a bilateral pulmonary metastasis, and 39% had high (>5 ng/mL) serum carcinoembryonic antigen. Patients' median age was 66 years, and 58% were male. The median follow-up was 64 months. Five-year overall survival and disease-free survival were 65.2% (95% confidence interval, 56.8-72.5) and 33.5% (95% confidence interval, 26.1-41.0), respectively. In multivariable analyses, high prethoracotomy carcinoembryonic antigen level was an independent prognostic factor for overall survival (hazard ratio, 2.01; 95% confidence interval, 1.16-3.47) and disease-free survival (hazard ratio, 2.10; 95% confidence interval, 1.41-3.12). Five-year overall survival and disease-free survival of patients with normal prethoracotomy carcinoembryonic antigen level were 76.4% (95% confidence interval, 66.1-83.9) and 40.7% (95% confidence interval, 30.5-50.5), respectively., Conclusions: After pulmonary metastasectomy, approximately two thirds of patients with colorectal cancer with a history of curative hepatic metastasectomy survived for 5 years-half of them disease-free. Our results indicate that patients with colorectal cancer with pulmonary metastasis and a history of curative hepatic metastasectomy may benefit from sequential pulmonary metastasectomy, especially if prethoracotomy serum carcinoembryonic antigen levels are within normal range., (Copyright © 2019 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: In our previous randomised phase 2 study for patients with gemcitabine-refractory advanced pancreatic cancer, S-1 plus leucovorin improved progression-free survival compared with S-1 alone. Here, we evaluated the efficacy of TAS-118 (S-1 plus leucovorin) versus S-1 in overall survival (OS)., Patients and Methods: This randomised, open-label, phase 3 study was conducted at 58 centres in Japan and Korea. Patients with metastatic pancreatic cancer that progressed during first-line gemcitabine-based chemotherapy or recurred during or after post-operative gemcitabine-based adjuvant treatment were randomly assigned (1:1) to receive either S-1 (40-60 mg, twice daily for 4 weeks in a 6-week cycle) or TAS-118 (S-1 40-60 mg plus leucovorin 25 mg, twice daily for 1 week in a 2-week cycle). The primary end-point was OS., Results: A total of 603 patients were randomised, and 300 and 301 patients received TAS-118 and S-1, respectively. There was no difference in OS between groups (median OS for TAS-118 versus S-1, 7.6 months versus 7.9 months; hazard ratio [HR], 0.98 [95% confidence interval (CI), 0.82-1.16]; P = 0.756). Progression-free survival was significantly longer with TAS-118 than S-1 (median, 3.9 months versus 2.8 months; HR, 0.80 [95% CI, 0.67-0.95]; P = 0.009). There were interactions between Japan and Korea (P = 0.004) and between unresectable and recurrent disease (P = 0.025) in OS. Incidence, profile and severity of adverse events were similar between groups., Conclusion: TAS-118 did not improve OS in patients with gemcitabine-refractory advanced pancreatic cancer compared to S-1. Further studies are needed to find patients who have benefit from adding leucovorin to S-1., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Pulmonary metastases from colorectal cancer are resected due to the favourable 5-year overall survival rates of 30-60% reported in many studies. However, the efficacy of subsequent adjuvant chemotherapy remains unclear., Patient and Methods: We retrospectively collected clinical data of 1237 patients who underwent surgical resection of pulmonary metastasis from colorectal cancer at 46 Japanese institutions between 2004 and 2008. Patients with non-curative resection, pre-operative chemotherapy, extra-thoracic metastasis, complications after surgery, and inadequate data were excluded. Then, a 1:1 propensity score nearest-neighbour matching between patients with and without adjuvant chemotherapy was performed, considering relevant co-variables, and survival of patients between groups was compared., Results: Data of 524 patients (surgery alone, 269 patients; surgery with adjuvant chemotherapy, 255 patients) were used for matching. From each group, 192 patients with similar background characteristics between groups were selected. Adjuvant chemotherapies included fluoropyrimidine alone (71%), an oxaliplatin-containing regimen (23%), or an irinotecan-containing regimen (6%). In the surgery alone and adjuvant chemotherapy groups, 5-year overall survival rates were 68% and 69%, and 5-year disease-free survival rates were 40% and 34%, respectively. There were no significant differences between the two groups in terms of overall survival (hazard ratio [HR]: 1.00, 95% confidence interval [CI]: 0.69-1.45, P = 1.00) and disease-free survival (HR: 1.07, 95% CI: 0.82-1.39, P = 0.62)., Conclusions: Adjuvant chemotherapy after curative resection of lung-limited metastasis from colorectal cancer did not show a survival benefit in the propensity score-matched analysis and should not be recommended without further clinical trials., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: In a phase III study for advanced gastric cancer (AGC), the Japan Clinical Oncology Group (JCOG) 9912 trial, we previously identified the following four prognostic factors-performance status ≥1, number of metastatic sites ≥2, no prior gastrectomy, and abnormal serum alkaline phosphatase levels-and proposed a prognostic index (good risk with 0 or 1 factor, moderate risk with 2 or 3 factors, and poor risk with all 4 factors). To assess the generalizability of this index, we attempted an external validation study using an independent data set., Methods: Individual patient data from the SPIRITS and G-SOX trials were applied to the JCOG prognostic index. The accuracy of the index for predicting survival was assessed by the Cox proportional hazards model., Results: The available data were obtained from 936 (94.5%) of the 990 patients in these trials. The three risk groups categorized by the JCOG prognostic index demonstrated highly significant survival differences; the hazard ratios (95% confidence interval) were 1.71 (1.46-2.01) between the good (n = 338) and moderate (n = 537) risk groups and 3.32 (2.47-4.46) between good and poor (n = 61) risk groups. The median overall survival times of the good, moderate, and poor risk groups were 17.2, 12.0, and 7.8 months, respectively., Conclusions: The JCOG prognostic index was externally validated and can be widely utilized for clinical trials. Further studies are needed to apply this index to the Western population.

Background: To develop a triplet regimen containing gemcitabine, cisplatin, and S-1 (GPS), we assessed the recommended dose for patients with untreated advanced biliary tract cancer in this phase I study., Methods: Dose-limiting toxicities (DLTs) were evaluated for the following two dose levels: gemcitabine (1000 mg/m(2) for level 1 and 1200 mg/m(2) for level 2 on day 1), cisplatin (30 mg/m(2) fixed dose on day 1), and S-1 (40-60 mg/day fixed dose twice a day for 7 days), every 2 weeks until progression. DLTs for each level were evaluated in six or more patients during the first two cycles., Results: A total of 18 patients were enrolled and 16 patients were evaluated. DLTs at level 1 were observed in two of 10 patients. At level 2, a DLT was observed in one of six patients. The main grade 3 or 4 treatment-related adverse events were neutropenia and leukopenia, and a few non-hematological toxicities were observed. Among 14 patients with measurable lesions, the best response rate was 50%., Conclusions: GPS with a relative dose intensity corresponding to 90% of the standard gemcitabine plus cisplatin regimen could be administered safely, and showed preliminary antitumor activity. Survival benefits will be studied subsequently., (© 2015 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Colorectal cancer is a major cause of death in Japan, where it accounts for the largest number of deaths from malignant neoplasms among women and the third largest number among men. Many new methods of treatment have been developed during recent decades. The Japanese Society for Cancer of the Colon and Rectum Guidelines 2014 for treatment of colorectal cancer (JSCCR Guidelines 2014) have been prepared as standard treatment strategies for colorectal cancer, to eliminate treatment disparities among institutions, to eliminate unnecessary treatment and insufficient treatment, and to deepen mutual understanding among health-care professionals and patients by making these guidelines available to the general public. These guidelines have been prepared as a result of consensuses reached by the JSCCR Guideline Committee on the basis of careful review of evidence retrieved by literature searches and taking into consideration the medical health insurance system and actual clinical practice in Japan. They can, therefore, be used as a guide for treating colorectal cancer in clinical practice. More specifically, they can be used as a guide to obtaining informed consent from patients and choosing the method of treatment for each patient. As a result of the discussions of the Guideline Committee, controversial issues were selected as clinical questions, and recommendations were made. Each recommendation is accompanied by a classification of the evidence and a classification of recommendation categories, on the basis of consensus reached by Guideline Committee members. Here we present the English version of the JSCCR Guidelines 2014.

Colorectal cancer is a major cause of death in Japan, where it accounts for the largest number of deaths from malignant neoplasms in women and the third largest number in men. Many new treatment methods have been developed over the last few decades. The Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2010 for the treatment of colorectal cancer (JSCCR Guidelines 2010) have been prepared to show standard treatment strategies for colorectal cancer, to eliminate disparities among institutions in terms of treatment, to eliminate unnecessary treatment and insufficient treatment, and to deepen mutual understanding between health-care professionals and patients by making these Guidelines available to the general public. These Guidelines have been prepared by consensuses reached by the JSCCR Guideline Committee, based on a careful review of the evidence retrieved by literature searches and in view of the medical health insurance system and actual clinical practice settings in Japan. Therefore, these Guidelines can be used as a tool for treating colorectal cancer in actual clinical practice settings. More specifically, they can be used as a guide to obtaining informed consent from patients and choosing the method of treatment for each patient. As a result of the discussions held by the Guideline Committee, controversial issues were selected as Clinical Questions, and recommendations were made. Each recommendation is accompanied by a classification of the evidence and a classification of recommendation categories based on the consensus reached by the Guideline Committee members. Here we present the English version of the JSCCR Guidelines 2010.

Background: Even with a low energy setting, radiofrequency energy applications on the left atrial (LA) posterior wall may cause excessive transmural injury (ETI) during catheter ablation of atrial fibrillation (AF)., Objective: The purpose of this study was to clarify the prevalence and characteristics of ETI., Methods: This study included 104 patients with AF who underwent extensive encircling pulmonary vein isolation (EEPVI) followed by an endoscopic examination (≤48 hours after EEPVI). EEPVI was performed under conscious sedation, and the ablation settings at the LA posterior wall were a maximum energy of 20 to 25 W and duration of ≤30 seconds. The ETI was defined as any injury that resulted from EEPVI, including esophageal damage or periesophageal nerve injury., Results: ETIs were found in 10 (9.6%) patients and were all asymptomatic; esophageal damage in 4 patients and periesophageal nerve injury in the remaining 6. All patients with ETI were below normal weight (body mass index [BMI] < 24.9 kg/m(2)), and consisted of 17% of those below normal weight. The procedural parameters such as the type of energy source, total duration of energy applications to the LA posterior wall, additional LA linear ablation, and biochemical markers were not related to the ETI. In the logistic multiadjusted model, the BMI (per 1 kg/m(2)) was the only independent predictor of ETI (odds ratio = 0.76; 95% confidence interval = 0.59 to 0.97, P < .05)., Conclusion: Asymptomatic ETIs were not rare even with a low energy setting in patients below normal weight. Tailored energy settings based on the patient's BMI may be required when performing EEPVI., (Copyright © 2011 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Objective: To develop a predicting tool for survival of terminally ill cancer patients., Methods: This prospective, multicenter study was composed of two cohorts of samples: development and test. In the development sample of terminally ill cancer patients, 32 candidate predictors were studied to develop a new tool, Japan Palliative Oncology Study-Prognostic Index using the Cox proportional hazard model. Then the test sample was studied to validate Japan Palliative Oncology Study-Prognostic Index and compared it with the conventional predicting tools, such as palliative prognostic score and simplified palliative prognostic index., Results: Five significant predictors, physician's clinical prediction of survival, consciousness, pleural effusion, white blood cell count and lymphocyte % were derived from the analysis of 201 patients, and Japan Palliative Oncology Study-Prognostic Index was developed using these predictors. It could divide patients into three risk groups: low (A), intermediate (B) and high (C). Median survival times for Groups A, B and C were 51, 35 and 16 days, respectively. Survival probability for more than 30 days for Groups A, B and C in the development sample was 78%, 61% and 16%, respectively. Japan Palliative Oncology Study-Prognostic Index was studied in subsequent 208 patients for the test sample, and constant results (median survival times for Groups A, B and C; 67, 31 and 10 days, and survival probability for more than 30 days for Groups A, B and C; 81, 48 and 11%) were obtained. Palliative prognostic score can also predict three risk groups well, but simplified palliative prognostic index could not discriminate low risk from intermediate risk group., Conclusion: Japan Palliative Oncology Study-Prognostic Index, a tool to predict survival, has been developed. Its reliability should be confirmed further in the future study, comparing with palliative prognostic score.

Background and Aims: Kampo (Japanese herbal) medicines are often used in clinical practice in Japan. However, it is unclear how Kampo medicines are quoted and evaluated in current clinical practice guidelines (CPGs). Here, we systematically reviewed Japanese CPGs, and aimed to reveal how Kampo medicines are described in the CPGs., Materials and Methods: We reviewed the quasi-comprehensive list of Japanese CPGs available from the Toho University Medical Media Center (TUMMC) having the largest data base on Japanese CPGs, and also used a hand search. CPGs containing Kampo products were classified into three types based on how Kampo was handled. CPGs that provided recommendations based on evidence were classified as "type A". Those which cited references but did not provide any recommendations were classified as "type B". Those which described the Kampo practice or Kampo-related terms without providing any relevant references were classified as "type C"., Results: By the end of March of 2007, 35 (10.1%) of 346 CPGs listed by TUMMC contained descriptions of Kampo products. We discovered one Kampo-related CPGs in a hand search process. Of these 36 CPGs, 6 were "type A", 13 were "type B", and 17 were "type C". Although results from pertinent randomized controlled trials (RCTs) were available, we noticed that some well-known RCTs studying Kampo medicines are missing in corresponding CPGs., Conclusions: We revealed that the citation rate of Kampo medicines in CPGs was approximately 10% and that some pivotal trials for Kampo medicines were not quoted in CPGs. Kampo medicines in CPGs should be assessed more comprehensively and scientifically.

Gastric cancer is classified into intestinal and diffuse types, the latter including a highly malignant form, linitis plastica. A two-stage genome-wide association study (stage 1: 85,576 SNPs on 188 cases and 752 references; stage 2: 2,753 SNPs on 749 cases and 750 controls) in Japan identified a significant association between an intronic SNP (rs2976392) in PSCA (prostate stem cell antigen) and diffuse-type gastric cancer (allele-specific odds ratio (OR) = 1.62, 95% CI = 1.38-1.89, P = 1.11 x 10(-9)). The association was far less significant in intestinal-type gastric cancer. We found that PSCA is expressed in differentiating gastric epithelial cells, has a cell-proliferation inhibition activity in vitro and is frequently silenced in gastric cancer. Substitution of the C allele with the risk allele T at a SNP in the first exon (rs2294008, which has r(2) = 0.995, D' = 0.999 with rs2976392) reduces transcriptional activity of an upstream fragment of the gene. The same risk allele was also significantly associated with diffuse-type gastric cancer in 457 cases and 390 controls in Korea (allele-specific OR = 1.90, 95% CI = 1.56-2.33, P = 8.01 x 10(-11)). The polymorphism of the PSCA gene, which is possibly involved in regulating gastric epithelial-cell proliferation, influences susceptibility to diffuse-type gastric cancer.

Objective: As prognosis of advanced gastric cancer is still poor, a standard regimen after first-line fluorouracil (FU)-based chemotherapy has not yet been established. Therefore, we conducted a phase II study to evaluate the efficacy and toxicity of sequential treatment with methotrexate (MTX) and also 5-FU as second-line chemotherapy in patients with advanced gastric cancer., Methods: Treatment consisted of weekly doses of MTX (100 mg/m(2), i.v. bolus), followed by 5-FU (600 mg/m(2), i.v. bolus) 3 h after MTX administration. Leucovorin rescue therapy (six doses of 10 mg/m(2), given at 6-h intervals) was commenced 24 h after a treatment with MTX. The primary endpoint was the response rate., Results: Between December 1992 and June 1995, 56 patients were registered in this study and one was ineligible. All registered patients were included in all analyses. The median age of the patients was 60 years (20-75 years). Most patients (75%) had a performance status of 0 or 1, and 51 (90%) received 5-FU-based chemotherapy as first-line treatment. The major adverse events were myelosuppression and gastrointestinal toxicity. Grade 4 neutropenia occurred in 6.3% of the patients. The overall objective response rate was 9.0% [five partial responses among 56 patients, 95% confidence interval (CI): 3.0-20%]. The median overall survival time was 237 days, and the 1-year survival proportion was 21.4%., Conclusions: Sequential MTX/5-FU therapy provides good survival outcomes with tolerable toxicity despite a limited response in patients with previously treated advanced gastric cancer. This regimen is now being evaluated in a randomized study in patients with pretreated advanced gastric cancer, by the Japan Clinical Oncology Group.

To explore the association between hydration volume and laboratory findings, and between calculated fluid balance and changes in clinical signs of dehydration and fluid retention in terminally ill cancer patients, a secondary analysis of a large multicenter, prospective, observational study was performed. The study enrolled 125 abdominal cancer patients who received laboratory examinations in the last week before death. Patients were classified into two groups: the hydration group (n = 44), who received 1L or more of artificial hydration per day both 1 and 3 weeks before death, and the nonhydration group (n = 81). The mean albumin level 1 week before death was significantly lower in the hydration group than in the nonhydration group, and the interaction between hydration group and decrease in the albumin level was statistically significant after adjusting multiple covariates (from 2.8 +/- 0.68 mg/dL 3 weeks before death to 2.4 +/- 0.56 mg/dL 24 hours before death in the hydration group vs. a decrease of 2.8 +/- 0.53 to 2.6+ /- 0.45 mg/dL in the nonhydration group, P = 0.015). There was no significant difference between the groups in the mean blood urea nitrogen/creatinine, sodium, or potassium levels 1 week before death. Among 53 patients who had oral fluid intake of less than 500 mL/day throughout the last 3 weeks and completed a fluid balance study, the median of calculated fluid balance was -400 mL/day 3 weeks before death, -521 mL/day 1 week before death, and -421 mL/day 24 hours before death. Calculated fluid balances did not significantly differ between the patients with deterioration of dehydration signs, edema, ascites, and pleural effusion during the final 3 weeks and those without. These data suggest that active artificial hydration might result in hypoalbuminemia, with no clear beneficial effects on normalizing blood urea nitrogen/creatinine, sodium, or potassium levels. Fluid balance did not significantly correlate with changes in dehydration-and fluid retention-signs. Calculated fluid balance is not an appropriate alternative to direct monitoring of patient symptoms. More studies are needed to determine the clinical efficacy of artificial hydration for terminally ill cancer patients.

A 67-year-old man visited our hospital for the treatment of gastric carcinoma. Endoscopic mucosal resection was performed, however, histological examination of the resected specimen revealed tumor invasion to the submucosal layer with vessel invasion. Immunohistological studies were carried out on resected specimens and part of the cancerous lesion showed a positive reaction for alpha-fetoprotein (AFP), but the serum AFP level was normal. Additional distal gastrectomy with lymph node dissection revealed lymph node metastasis although there was no apparent finding of lymph node swelling by preoperative diagnostic imaging. This patient remains alive without disease for 3 years after surgery.

Purpose: To compare the efficacy, toxicities, and pharmacokinetics of an oral regimen consisting of uracil/tegafur (UFT) and leucovorin (LV) between Japanese patients and patients in the United States with previously untreated metastatic colorectal cancer., Patients and Methods: Forty-four Japanese patients and 45 patients in the United States were enrolled in concurrent nonrandomized phase II trials. UFT 300 mg/m2/d and leucovorin 75 mg/d were administered orally for 28 days followed by a 7-day rest period. The total daily dose of each drug was divided into three equal doses. Treatment was repeated every 5 weeks until disease progression. Blood samples for the pharmacokinetic study were obtained after the initial dose on day 1 of the first course., Results: The response rate for the Japanese patients and the patients in the United States was 36.4% (95% CI, 22.4% to 52.2%) and 34.1% (95% CI, 20.5% to 49.9%), respectively. The only major toxicity was diarrhea, and other toxicities were mild in both populations. The incidence of grade 3 or higher diarrhea in the Japanese and Americans was 9% and 22%, respectively. Although the area under the curve and maximum concentration of fluorouracil were found to be slightly higher in the Japanese patients than the patients in the United States, and area under the curve-adjusted body surface area appeared to be comparable between the two groups., Conclusion: The efficacy and pharmacokinetic parameters of UFT and LV are comparable in Japanese and American patients; however, a difference in toxicity profile, specifically diarrhea, was noted. This oral regimen of UFT and LV is considered to have similar activity against metastatic colorectal cancer and to have acceptable toxicity in patients in both countries.

Although bronchial secretion is frequently observed in terminally ill cancer patients and can cause significant distress for both patients and family members, the pathophysiology is unclear. The primary aim of this study was to investigate the incidence and underlying etiologies of bronchial secretion. A multicenter, prospective, observational study was conducted on consecutive terminally ill patients with lung or abdominal malignancies. Primary physicians and nurses prospectively evaluated patients' symptoms. Of 310 patients enrolled, bronchial secretions were observed in 41% in the final 3 weeks, and oral/bronchial suctioning, with considerable distress, was required in 9%; bronchial secretions were severe in 4.5% of all patients. Multiple logistic regression analyses revealed that the determinants of the development of bronchial secretion were primary lung cancer, pneumonia, and dysphagia. There were no statistically significant effects of severity of peripheral edema and pleural effusion on development of bronchial secretions and requirement for oral/bronchial suctioning. Etiology-based classification of bronchial secretion is useful to identify the most suitable palliative treatments and to clarify treatment efficacy in each specific pathophysiology.

Background: The efficacy of systemic chemotherapy against peritoneal dissemination from advanced gastric cancer (AGC) remains unclear, because the peritoneal dissemination was not defined as a measurable lesion in conventional phase II studies. In this study, we evaluated the efficacy and toxicity of sequential MTX and 5FU therapy (MF) in chemotherapy-naive patients with AGC accompanied by malignant ascites in a phase II setting., Methods: The treatment schedule comprised weekly administration of MTX (100 mg/m2, i.v. bolus) followed by 5FU (600 mg/m2, i.v. bolus) with a 3 h interval. Leucovorin rescue (10 mg/m2 every 6 h, for a total of six times) was commenced 24 h after MTX administration., Results: Thirty-seven chemotherapy-naive patients with AGC presenting with malignant ascites were enrolled in this trial. The median age was 60 years (range, 25-74 years) and most patients (86%) had a performance status of 0-1. In total, 355 administrations of the sequential MTX/5FU therapy were performed. Major toxicity consisted of myelosuppression and gastrointestinal toxicity. Grade 4 neutropenia occurred in 10.8% of the patients. The overall objective response rate was 5.7% (two partial responses in 35 patients; 95% confidence interval: 0.7-19.2%). However, the response rate of ascites was 35.1% (complete disappearance in three patients and apparent decrease in 10 patients; 95% confidence interval: 20.2-52.5%)., Conclusions: Sequential MTX/5FU therapy is effective against AGC with malignant ascites with acceptable toxicity and warrants further investigations in a phase III setting.

Background: The prevalence of complementary and alternative medicine (CAM) is increasing worldwide because of the growing public interest in natural or holistic therapies and because of the flow of information through the Internet. However, there is a lack of communication between cancer patients and their physicians on topics relating to CAM. The authors performed a cross-sectional survey to evaluate the perceptions and attitudes of Japanese clinical oncologists toward cancer CAM., Methods: The CAM questionnaires were sent to 2118 clinical oncologists. The questionnaires gathered data on background (age, gender, years in practice, specialty, and knowledge of cancer CAM), perception (effectiveness/ineffectiveness, scientific evidence, and drug interactions), and attitude (experience with and response to CAM users). Questions about oncologists' perceptions and attitudes to CAM were limited to herbs and other natural products that were sold over the counter., Results: One hundred sixty-six questionnaires were returned as undeliverable. Of the remaining questionnaires, 751 were returned (a response rate of 39%). Two-thirds of the responders were surgical oncologists and most of the remaining responders were medical oncologists. The majority of oncologists (82%) believed that CAM products were ineffective against cancer. The main reason for this belief was a lack of reliable information (as cited by 85% of oncologists). Only 13% of oncologists had experienced CAM-associated disease improvement in their cancer patients. Of all the oncologists, 84% considered the possibility of drug interactions between anticancer drugs and CAM products. The majority of oncologists (80%) replied that they could neither promote the use of CAM products nor recommend quitting the products, when they were asked about the use of CAM products by cancer patients., Conclusions: Negative perceptions of CAM products persist among clinical oncologists. A lack of proven effectiveness of CAM products and concerns about drug interactions with anticancer treatment suggest a need for both accurate information on CAM products and clinical trials., (Copyright 2003 American Cancer Society.)

Purpose: To compare fluorouracil (FU) alone with FU plus cisplatin (FP) and with uracil and tegafur plus mitomycin (UFTM) for patients with advanced gastric cancer in a prospective, randomized, controlled trial., Patients and Methods: A total of 280 patients with advanced gastric cancer were randomly allocated and analyzed for survival, response, and toxicity. The survival curves were compared between groups by log-rank test on an intent-to-treat basis., Results: At the interim analysis, the UFTM arm showed a significantly inferior survival with higher incidences of hematologic toxic effects than did control arm FU alone, and the registration to UFTM was terminated. Both investigational regimens, FP and UFTM, had a significantly higher incidence of hematologic toxic effects than FU alone, although the effects were manageable. The overall response rates of the FU-alone, FP, and UFTM arms were 11%, 34%, and 9%, respectively. The median progression-free survival was 1.9 months with FU alone, 3.9 months with FP, and 2.4 months with UFTM, respectively. Although FP demonstrated a higher response rate (P <.001) and longer progression-free survival than did FU alone (P <.001), no differences in overall survival were observed between the arms. The median survival times and 1-year survival rates were 7.1 months and 28% with FU, 7.3 months and 29% with FP, and 6.0 months and 16% with UFTM, respectively., Conclusion: Neither investigational regimen, FP nor UFTM, showed a survival advantage as compared with FU alone. FU alone will remain a reference arm in our future trial for advanced gastric cancer.

Background: Because docetaxel and cisplatin are both active against gastric cancer and have different mechanisms of action, this combination may provide additive or synergistic effects against gastric cancer. This article presents a phase I study designed to determine the recommended dose of cisplatin combined with a fixed dose of docetaxel, and a subsequent phase II study that evaluated the clinical efficacy and feasibility of this combination regimen., Methods: Patients enrolled in the study had to have histologically confirmed advanced or recurrent gastric cancer with measurable disease and adequate organ function, and to be aged 20 to 75 years, with a performance status (PS) of 0 to 2. In the phase I study, docetaxel was administered at a fixed dose of 60 mg/m(2) on day 1. Cisplatin was also administered on day 1, at dose levels of 60, 70, and 80 mg/m(2). Where dose-limiting toxicities were not observed in more than 33.3% of patients, three patients were accrued for each dose level., Results: Recommended doses for the phase II evaluation were determined to be 60 mg/m(2) of docetaxel and 80 mg/m(2) of cisplatin. Although grade 3 or more severe leukopenia and neutropenia were observed in 71.4% and 82.1% of the patients, respectively, nonhematological toxicities were not severe. The overall response rate at the recommended dose level was 25.0% (7/28 patients), and the rate was 40% (6/15) for patients with liver metastases. The median survival time was 9.7 months and the 1-year survival rate was 39.3%., Conclusion: Although this study failed to demonstrate a high response rate, this regimen was feasible and might be of value in further investigations in respect to the relatively high response rate in patients with liver metastasis and the favorable survival.

Since there are no large-scale surveys of how cancer patients perceive unproven therapy in Japan, we wanted to clarify this issue by means of a cross-sectional questionnaire conducted among cancer patients. The survey revealed that 32% of cancer patients used unproven therapy without having sufficient information about it. There was a lack of communication between cancer patients and their physicians on topics relating to alternative medicine. Issues that we have to solve are concerned with the education of cancer patients, lay people and physicians on the meaning and role of alternative medicine and on the necessity for scientific evaluation of medical treatments in Japan.

The incidence of hepatitis A (HA), hepatitis B (HB), and non-A, non-B hepatitis (NANBH) was 27%, 30% and 43% among 73 patients with sporadic hepatitis. Epidemiological data (geographical distribution, seasonal variation, age, sex, and occupation) were not distinguishing of the type of hepatitis. Neither intrafamilial infection nor previous contact with viral hepatitis patients could be demonstrated in the NANBH cases. Fever and jaundice were less frequent in NANBH than in HA. Maximum levels of SGPT, serum bilirubin, ZTT, and gamma-globulin were significantly lower in NANBH than in HA and HB. Ten of 29 NANBH patients (35%) presented abnormal SGPT activities for more than 6 months, and four (14%) more than 12 months. In the ten patients with prolonged courses, jaundice was more frequent and maximum levels of SGPT were higher than in patients with transient courses. Histopathologic findings were not markedly different from those of HA and HB. Bile duct damage, fatty deposition, and giant multi-nucleated cells were recognized in 6, 12, and 2 NANBH patients, respectively. There were no characteristic ultrastructural changes in NANBH.