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Introduction: Small bowel tumors (SBTs) are difficult to diagnose because of limited opportunities and technical difficulties in evaluating the small bowel. Asymptomatic conditions or nonspecific symptoms make SBT diagnosis more challenging. In Asia, SBTs are reported to be more frequently malignant lymphoma (ML), adenocarcinoma, and gastrointestinal stromal tumor (GIST). In this study, we examined 66 patients diagnosed with SBTs and determined their clinical characteristics., Methods: This retrospective study was conducted from January 2013 to July 2020 at Kurume University Hospital. The modalities used to detect SBTs were computed tomography (CT), positron emission tomography, magnetic resonance imaging, and ultrasonography. Endoscopy was also performed in some cases to confirm SBT diagnosis. The study included 66 patients. The medical data collected included presenting symptoms, tumor location, underlying condition, diagnostic modalities, pathologic diagnosis, and treatment., Results: ML and adenocarcinoma were the most common tumors (22.7%), followed by GIST (21.2%) and metastatic SBT (18.2%). Symptoms that led to SBT detection were abdominal pain (44.5%), asymptomatic conditions (28.8%), hematochezia (12.1%), and anemia (10.6%). CT was the most used modality to detect SBTs. Nineteen patients were asymptomatic, and SBTs were incidentally detected in them. GISTs and benign tumors were more often asymptomatic than other malignant tumors., Conclusion: Abdominal pain was the main symptom for SBTs in particular adenocarcinoma, ML, and metastatic SBT. In addition, GIST, which was highly prevalent in Asia, had fewer symptoms. An understanding of these characteristics may be helpful in the clinical practice of SBTs., (© 2023 S. Karger AG, Basel.)

Microsatellite instability (MSI) is categorized by mutation frequency: high MSI (MSI-H), low MSI (MSI-L) and microsatellite stable (MSS). MSI-H tumors have a distinct immunogenic phenotype, with immunotherapies using checkpoint inhibitors already approved for the treatment of MSI-H gastroesophageal adenocarcinoma (GEA); this is not observed for MSI-L or MSS. Here, we tested the hypothesis that MSI-L tumors are also a distinct phenotype and potentially immunogenic. MSI-PCR assays (BAT25, BAT26, BAT40, D2S123, D5S346 and D17S250) were performed on 363 Epstein-Barr virus-negative, surgically resected esophagogastric junction (EGJ) adenocarcinoma samples. Tumors were characterized as MSI-H (≥2 markers), MSI-L (1 marker) or MSS (0 markers). CD8+ cell counts, PD-L1 and HER2 expression levels, TP53 mutations, epigenetic alterations and prognostic significance were also examined. All pathological and molecular experiments were conducted using serial, whole-tumor sections of chemo-naïve surgical specimens. MSI-H and MSI-L were assigned to 28 (7.7%) and 24 (6.6%) cases, respectively. Compared to MSS cases, MSI-L cases had significantly higher intratumoral CD8+ cell infiltration (P = .048) and favorable EGJ cancer-specific survival (multivariate hazard ratio = 0.35, 95% CI, 0.12-0.82; P = .012). MSI-L tumors were also significantly associated with TP53-truncating mutations as compared to MSI-H (P = .009) and MSS (P = .012) cases, and this trend was also observed in GEA data from The Cancer Genome Atlas (TCGA). Indel mutational burden among TCGA MSI-L tumors was significantly higher than that of MSS tumors (P = .016). These results suggest that MSI-L tumors may have a distinct tumor phenotype and be potentially immunogenic in EGJ adenocarcinoma., (© 2020 Union for International Cancer Control.)

Associations between treatment outcomes of immune checkpoint inhibitors and metastatic sites in advanced non-small cell lung cancer (NSCLC) are not well known. Therefore, this multicenter retrospective study aimed to investigate the predictive factors of metastatic sites after first-line pembrolizumab treatment for advanced NSCLC with a PD-L1 tumor proportion score (TPS) ≥50%. We retrospectively analyzed advanced NSCLC patients with a PD-L1 TPS ≥50% who underwent first-line pembrolizumab therapy at 11 institutions between February 2017 and April 2018. Clinical data collected from medical records included metastatic sites at the time of pembrolizumab treatment. Treatment outcomes of pembrolizumab were assessed according to the Response Evaluation Criteria in Solid Tumors, version 1.1. In total, 213 patients were included in the study. The median age was 71 years (range 39-91 years). Of the 213 patients, 176 (83%) were men and 172 (81%) had an Eastern Cooperative Oncology Group performance status (ECOG-PS) score of 0-1. The most common metastases were thoracic lymph node metastasis (77%), intrapulmonary metastasis (31%), bone metastasis (28%), and malignant pleural effusion (26%). On multivariate analysis, a poor ECOG-PS score (hazard ratio: 1.95, 95.0% confidence interval: 1.25-3.04; P = 0.003) and malignant pleural effusion (hazard ratio: 1.52, 95.0% confidence interval: 1.01-2.29; P = 0.043) were independent predictors of shorter progression-free survival in patients treated with pembrolizumab. For NSCLC patients with malignant pleural effusion, pembrolizumab monotherapy is not a suitable first-line treatment because of its insufficient effectiveness, even though their PD-L1 TPS was high.

Background: The incidence trend of esophagogastric junction (EGJ) adenocarcinoma in Japan has not been sufficiently investigated. Little is known about the microsatellite instability (MSI) status of this tumor., Summary: Previously published studies analyzing the trend of EGJ adenocarcinoma in Japan were reviewed. And a trend of surgically resected cases (Siewert type I-III) utilizing a retrospective multicenter cohort of 379 patients from 4 academic institutions in Japan investigated. Although an increasing trend in the last 2 reports was considered controversial, our cohort demonstrated a growing number of EGJ adenocarcinoma cases between 2006 and 2013. This trend was evident, especially in Siewert type I cases. In the previous 16 studies that performed MSI testing, MSI-high tumors ranged 0-8.3%, though there were no fixed microsatellite markers on EGJ adenocarcinoma. In a recent comprehensive genetic analysis by The Cancer Genome Atlas, MSI testing using the following 7 markers, BAT25, BAT26, BAT40, D2S123, D5S346, D17S250 and TGFR-II showed a favorable correlation with hypermutated tumors. We performed MSI testing using 6 of those markers, except TGFR-II, on 206 cases from one institution, and detected 15 cases (7.3%) with MSI-high. The prevalence of MSI-high was 0% in Siewert type I, 7.6% in type II, and 16.7% in type III. Key message: The number of surgically resected EGJ adenocarcinoma cases gradually increased, and MSI-high was infrequent in Siewert type I-II tumors in our Japanese cohort. Considering MSI-high as a predictive biomarker for emerging immune checkpoint inhibitors, MSI status is becoming more beneficial in EGJ adenocarcinoma., (© 2018 S. Karger AG, Basel.)

To clarify the prognostic value of the postoperative blood neutrophil-to-lymphocyte ratio (NLR) in patients undergoing pancreatectomy for pancreatic carcinoma (PAC). A high preoperative NLR has been reported to be a predictor of poor survival in patients with various cancers including PAC. However, it has not been extensively examined in postoperative NLR after pancreatectomy for PAC. This retrospective study enrolled 86 patients who underwent pancreatectomy without preoperative therapy for PAC from 2005 to 2013. Clinicopathological parameters, including postoperative NLR, were evaluated to identify predictors of the overall and recurrence-free survival of patients after pancreatectomy. Univariate and multivariate analyses were performed, using the Cox proportional hazards model. Univariate and multivariate analyses showed that postoperative NLR at one month was an independent prognostic factor in the overall and recurrence-free survival of patients. The 3-year survival rate after pancreatectomy was as follows: 33.9 per cent in patients with a postoperative NLR of less than 3.0 at one month; and 7.3 per cent in those with a postoperative NLR of 3.0 or more at one month (P < 0.001). The overall survival rate after pancreatectomy in the NLR at one month ≥3.0 group was significantly lower than in the NLR at one month <3.0 group: one year, 42.6 versus 81.9 per cent; three year, 7.3 versus 33.9 per cent (P < 0.001). The results of the study suggest that the postoperative NLR at one month is an independent predictor of survival after pancreatectomy in patients with PAC.

Objective: The objectives of this retrospective study were to elucidate the clinicopathological features and recent surgical results of cervical esophageal cancer., Summary Background Data: Cervical esophageal cancer has been reported to have a dismal prognosis. Accurate knowledge of the clinical characteristics of cervical esophageal cancer is warranted to establish appropriate therapeutic strategies., Methods: The clinicopathological features and treatment results of 63 consecutive patients with cervical esophageal cancer (Ce group) who underwent surgical resection from 1980 to 2013 were analyzed and compared with 977 patients with thoracic or abdominal esophageal cancer (T/A group) who underwent surgical resection during that time., Results: Among the patients who received curative resection, the 5-year overall and disease-specific survival rates of the Ce patients were significantly better than those of the T/A patients (overall: 77.3% vs 46.5%, respectively, P = 0.0067; disease-specific: 81.9% vs 55.8%, respectively, P = 0.0135). Although total pharyngo-laryngo-esophagectomy procedures were less frequently performed in the recent period, the rate of curative surgical procedures was markedly higher in the recent period (2000-1013) than that in the early period (1980-1999) (44.4% vs 88.9%, P = 0.0001). The 5-year overall survival rate in the recent period (71.5%) was significantly better than that in the early period (40.7%, P = 0.0342)., Conclusions: Curative resection for cervical esophageal cancer contributes to favorable outcomes compared with other esophageal cancers. Recent surgical results for cervical esophageal cancer have improved, and include an increased rate of curative resection and decreased rate of extensive surgery.

The immunological characteristics of carcinoma of unknown primary site (CUP) are not well established due to inclusion of heterogeneous types of metastatic tumors with the absence of any detectable primary site. We evaluated the immune responses in patients with histologically unfavorable CUP during personalized peptide vaccination (PPV). Ten patients with histologically unfavorable CUP who had been treated by PPV after chemotherapy failure were analyzed. In PPV treatment, up to four human leukocyte antigen-matched peptides of a total 31 peptides were selected according to preexisting host immunity before vaccination and administered subcutaneously. Peptides derived from the Lck antigen were most often chosen for use among all patients. CTL responses were increased in 8 of the 10 and 5 of the five patients tested at the end of the first and second PPV cycles, respectively. Increases in humoral responses after vaccination, including IgG, IgG1, IgG3, IgA, and IgM, were observed against not only the vaccinated peptides but also the non-vaccinated peptides. Severe adverse events due to PPV were not observed. Median overall survival was 13.9 months (95 % CI 4.0-22.5 months). PPV activated both cellular and humoral immune responses to short peptides derived from CTL epitopes in the majority of CUP patients. PPV with Lck-derived peptides may be a feasible, new treatment modality for histologically unfavorable CUP patients due to its safety and strong ability to boost immune responses, although its clinical efficacy remains to be investigated in larger-scale trials.

Background: Molecular profiling in gastric cancer (GC) is important for diagnosis and treatment. In this study, we investigated signal transduction pathways that might induce chromosomal instability in GC., Methods: Epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), and p-AKT expression were analyzed using immunohistochemistry, and chromosomal instability was assessed by DNA aneuploidy using laser scanning cytometry, in a total of 202 GC cases., Results: The rate of EGFR expression and p-AKT expression was 70.3 and 34.2 %, respectively, in GC patients. In total, 57.5 % of GC patients exhibited DNA aneuploidy, and p-AKT positively correlated with EGFR and HER2 (p = 0.0127 and p = 0.00031, respectively). Patients with EGFR overexpressing GC showed shorter disease-specific survival than the other cases (hazard ratio 2.00, 95 % confidence interval 1.19-3.53; p = 0.0104). Moreover, EGFR and p-AKT expression was significantly correlated with DNA aneuploidy (p = 0.0002 and p = 0.0302, respectively)., Conclusions: Our data showed that both EGFR and p-AKT overexpression were clearly associated with DNA aneuploidy. Aneuploidy could be a useful marker for therapies that target EGFR.

This study is a case report on a 49-year-old woman who had a gastrectomy and lymphadenectomy for pStage IIIa gastric cancer. Shortly after a 12-month course of adjuvant chemotherapy, CT showed a nodule adjacent to the gallbladder. High (18) F-fluorodeoxyglucose accumulation was detected, with a standardized uptake value of 10. Therefore, laparoscopic excision was performed for diagnosis and treatment. The histopathological finding was suture granuloma. Suture granulomas with high standardized uptake values on PET scans are uncommon and often cause surgeons to provide an inaccurate diagnosis. Our study suggests that suture granuloma should be included in the differential diagnosis of a new or recurrent mass detected in patients with a history of prior surgery; however, surgeons must bear in mind that false-positive fluorodeoxyglucose-PET results can be observed in suture granuloma., (© 2015 Japan Society for Endoscopic Surgery, Asia Endosurgery Task Force and Wiley Publishing Asia Pty Ltd.)

An 82-year-old man underwent radiotherapy (brachytherapy, external beam radiotherapy) for prostate cancer, followed approximately five years later by endocrine therapy for biochemical recurrence, which controlled the prostate-specific antigen (PSA) level. His later admission due to severe gross hematuria and dysuria is described. Computed tomography and magnetic resonance imaging findings revealed a cystic tumor continuous with the prostate between the prostate and rectum, and this tumor was thought to be the cause of the hematuria and dysuria. Transrectal biopsy and transurethral resection of the prostate were performed for pathological diagnosis and improvement of dysuria. The pathological diagnosis was remnant prostate cancer, and the cystic tumor was thought to have developed as a result of prostate cancer recurrence. Although chemotherapy using docetaxel was considered postoperatively, the patient refused this treatment. Even though the PSA level was under control, the patient's condition progressed rapidly, with onset of pulmonary and cervical lymph node metastases within a short period of time, and the patient subsequently died.

Background: More effective treatment is necessary to improve the poor prognosis for patients with unresectable gastric cancer. We investigated the efficacy and feasibility of adjuvant surgery following chemotherapy., Patients and Methods: Records of 70 patients with unresectable stage IV gastric cancer who underwent induction chemotherapy were reviewed retrospectively. Patients who developed an absence of non-curative clinical factors during chemotherapy underwent gastrectomy [adjuvant surgery (AS) group]; the others continued chemotherapy [non-AS group]., Results: Non-AS and AS groups contained 56 (80%) and 14 (20%) patients, respectively. In the AS group, 92.9% of patients had one non-curative clinical factor, while 48.2% of patients in the non-AS group had two or more non-curative clinical factors (p=0.0386). In the AS group, operative outcomes, including the postoperative complication rate (21.4%), were acceptable. The 3-year overall survival rate in the AS group was 65.6% versus 7.7% in the non-AS group (p<0.0001). In patients with one non-curative clinical factor of peritoneal dissemination, the median survival of the AS group was 29.5 months versus 11.4 months in the non-AS group (p=0.0230)., Conclusion: Adjuvant surgery for initially unresectable stage IV gastric cancer was safe and feasible, and may improve the prognosis for patients with one non-curative clinical factor, such as peritoneal dissemination., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Purpose: This study clarifies age differences in clinicopathologic characteristics and risk factor exposure of patients who have undergone esophagectomy for esophageal cancer (EC)., Methods: Clinical results of esophagectomy were compared between 22 patients younger than 50 years of age (Group I) and 327 patients older than 50 years of age (Group II) with esophageal squamous cell carcinoma., Results: The two groups did not significantly differ in clinicopathological characteristics, including prognosis. Postoperative pulmonary complication incidence rates were 4.2 % (Group I) and 14.4 % (Group II). In Group I, the incidence of multiple ECs was 36.4 %, and association with head and neck cancer was 31.8 %, which were significantly higher than in Group II (13.4 %, p = 0.021; and 9.2 %, p = 0.015, respectively). Furthermore, the patients in Group I with multiple cancers were almost all heavy smokers and/or users of alcohol., Conclusions: These results suggest that multiple upper aerodigestive tract cancers are associated with heavy exposure to risk factors in patients younger than 50 years of age.

Background: A gastrectomy for gastric cancer is sometimes required in patients older than 80 years due to the continuously increasing age of society. However, if a gastrectomy worsens the postoperative quality of life and daily activity in elderly patients because of poor nutrition, the procedure may not always be a useful treatment strategy., Patients and Methods: Clinicopathological data of patients with gastric cancer who underwent a gastrectomy at our Department between 1998 and 2008 (N=471) were collected and analyzed. The results of treatment for patients older than 80 years (N=41) were analyzed and compared against those of patients younger than 80 years (N=430)., Results: Patients older than 80 years had a higher frequency of preoperative co-morbidities than patients younger than 80 years. However, there was no statistical difference in postoperative complications regarding nutrition between the two groups., Conclusion: Older age is not a determinant of poor nutrition following gastrectomy. Gastrectomy for gastric cancer is, therefore, a useful treatment strategy, regardless of ageing., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

A 44-year-old woman who was diagnosed with anaplastic lymphoma kinase-positive lung adenocarcinoma developed brain metastases, multiple spinal metastases and meningeal dissemination. Crizotinib was administered after the failure of first-line chemotherapy. Esophagitis and liver damage were induced by the twice-daily administration of crizotinib at 250 mg and 200 mg, respectively. The alternate-day administration of crizotinib (250 mg, twice daily) was able to control disease progression without any adverse effects for several months. We evaluated the relationship between the serum concentration of crizotinib and the development of esophagitis and liver damage. The alternate-day administration of crizotinib is one of the strategies for managing the severe toxicity of crizotinib.

A 55-year-old man had laparoscopic cholecystectomy for acute cholecystitis and unexpected gallbladder cancer, followed by a liver bed resection and lymph node dissection. Eleven years later, he had a port-site recurrence of gallbladder cancer requiring resection; at that time, no other site of recurrence was observed. The patient has survived for 20 months without another recurrence. Although a rare finding, clinicians should be alert to the possibility of such a recurrence even 11 years after complete cure of the primary tumor, particularly in patients who have undergone laparoscopic cholecystectomy for unexpected gallbladder cancer., (© 2014 Japan Society for Endoscopic Surgery, Asia Endosurgery Task Force and Wiley Publishing Asia Pty Ltd.)

Purpose: Our goal was to create a multimodal treatment strategy for patients with locally advanced esophageal cancer (EC)., Methods: A retrospective review identified a total of 193 patients with clinical T3 thoracic EC were categorized into 3 groups: 81 who had surgery only (group I); 102 who had planned neoadjuvant chemoradiotherapy (NACRT; group II); and 10 who had salvage esophagectomy after definitive chemoradiotherapy (dCRT; group III)., Results: Postoperative complications developed in 27, 45, and 80 % of patients in group I, group II, and group III, respectively. NACRT and dCRT were independent risk factors associated with postoperative complications; the odds ratios for group II and group III, compared with group I, were 2.1 and 8.8, respectively. The respective mortality rates were 4, 2, and 20 % (group I vs. group III, p < 0.05; group II vs. group III, p < 0.01). The 5-year survival rate was 25.2 % in group I and 41.6 % in group II. The 5-year survival rate in group II patients with markedly effective NACRT (89.2 %) was significantly better than in patients with ineffective/slightly effective (11.8 %; p < 0.0001) and moderately effective treatment (51 %; p < 0.05). Four patients who had noncurative surgery died within 4 months after salvage esophagectomy, whereas four of six patients were still alive after curative surgery., Conclusions: A pathological complete response to NACRT is critical for improving survival in patients with clinical T3 thoracic EC. Salvage surgery should be considered only in carefully selected patients with locally advanced EC.

Patients with esophageal cancer are susceptible to other primary cancers, but multiple primary cancers involving the esophagus and jejunum are rare. We herein report a case of primary jejunal cancer as a component of metachronous triple primary cancers including esophageal cancer and ascending colon cancer. A 63-year-old male patient with a history of surgery for esophageal cancer and ascending colon cancer was admitted to our hospital after experiencing 1 month of repeated vomiting and epigastric abdominal pain. Esophagogastroduodenoscopy, duodenography, and computed tomography revealed a jejunal tumor located 2 cm from the ligament of Treitz on the anal side. Partial resection of the jejunum with lymph node dissection was performed. The postoperative course was uneventful, and the patient remains well with no signs of recurrence 10 months after the operation. This is the first report of curative resection of triple primary cancers of the esophagus, jejunum, and colon. Patients with a history of esophageal cancer are susceptible to other primary cancers, and it is important to perform surveillance for the subsequent development of other cancers.

Aim: To investigate the associations between dietary intake of polyphenols and colorectal cancer., Methods: The study subjects were derived from the Fukuoka colorectal cancer study, a community-based case-control study. The study subjects were 816 cases of colorectal cancer and 815 community-based controls. The consumption of 148 food items was assessed by a computer-assisted interview. We used the consumption of 97 food items to estimate dietary intakes of total, tea and coffee polyphenols. The Phenol-Explorer database was used for 92 food items. Of the 5 foods which were not listed in the Phenol-Explorer Database, polyphenol contents of 3 foods (sweet potatoes, satoimo and daikon) were based on a Japanese study and 2 foods (soybeans and fried potatoes) were estimated by ORAC-based polyphenol contents in the United States Department of Agriculture Database. Odds ratios (OR) and 95%CI of colorectal cancer risk according to quintile categories of intake were obtained by using logistic regression models with adjustment for age, sex, residential area, parental history of colorectal cancer, smoking, alcohol consumption, body mass index 10 years before, type of job, leisure-time physical activity and dietary intakes of calcium and n-3 polyunsaturated fatty acids., Results: There was no measurable difference in total or tea polyphenol intake between cases and controls, but intake of coffee polyphenols was lower in cases than in controls. The multivariate-adjusted OR of colorectal cancer according to quintile categories of coffee polyphenols (from the first to top quintile) were 1.00 (referent), 0.81 (95%CI: 0.60-1.10), 0.65 (95%CI: 0.47-0.89), 0.65 (95%CI: 0.46-0.89) and 0.82 (95%CI: 0.60-1.10), respectively (P trend = 0.07). Similar, but less pronounced, decreases in the OR were also noted for the third and fourth quintiles of total polyphenol intake. Tea polyphenols and non-coffee polyphenols showed no association with colorectal cancer risk. The site-specific analysis, based on 463 colon cancer cases and 340 rectal cancer cases, showed an inverse association between coffee polyphenols and colon cancer. The multivariate-adjusted OR of colon cancer for the first to top quintiles of coffee polyphenols were 1.00 (referent), 0.92 (95%CI: 0.64-1.31), 0.75 (95%CI: 0.52-1.08), 0.69 (95%CI: 0.47-1.01), and 0.68 (95%CI: 0.46-1.00), respectively (P trend = 0.02). Distal colon cancer showed a more evident inverse association with coffee polyphenols than proximal colon cancer. The association between coffee polyphenols and rectal cancer risk was U-shaped, with significant decreases in the OR at the second to fourth quintile categories. There was also a tendency that the OR of colon and rectal cancer decreased in the intermediate categories of total polyphenols. The decrease in the OR in the intermediate categories of total polyphenols was most pronounced for distal colon cancer. Intake of tea polyphenols was not associated with either colon or rectal cancer. The associations of coffee consumption with colorectal, colon and rectal cancers were almost the same as observed for coffee polyphenols. The trend of the association between coffee consumption and colorectal cancer was statistically significant., Conclusion: The present findings suggest a decreased risk of colorectal cancer associated with coffee consumption.

Aim: To justify esophagectomy for elderly patients., Patients and Methods: A total of 1,002 patients with thoracic esophageal cancer who underwent esophagectomy were divided into three groups: I (≤ 74 years old, n=898); II (75-79 years, n=81); and III (≥ 80 years, n=23). Historical changes were compared between the first surgical period (1964-1989) and the second period (1990-2011)., Results: The morbidity rates were 40%, 41% and 26% in the respective groups. Pulmonary complications decreased historically in groups II and III (36% to 15% and 43% to 0%, respectively). The mortality was higher in the older groups (4.8%, 8.6% and 13.0%, respectively); however, there was a marked historical decrease in groups II (18.2% to 5.1%) and III (28.6% to 6.3%). The 5-year survival improved from 5% to 35% in group II and from 0% to 17% in group III., Conclusion: The outcomes of esophagectomy for elderly patients have markedly improved, with acceptable mortality even in octogenarians.

Purpose: We investigated the relationship between the p53-dependent apoptotic pathway and the survival of patients with gastric cancer, retrospectively, to elucidate new biomarkers of uracil/tegafur (UFT) chemotherapy., Methods: We examined the expression of p53, p21, Bax, and myeloid cell leukemia 1 (Mcl-1) proteins immunohistochemically in 105 patients who underwent curative gastrectomy for gastric cancer invading the serosa. Postoperative oral UFT was prescribed for 1 year. Kaplan-Meier survival curves were compared with the two-sided log-rank test., Results: Positive staining for p53, p21, Bax, and Mcl-1 proteins was found in 63.8, 52.4, 39.0, and 72.4% of the subjects, respectively. Survival time did not differ significantly between the patients with and those without p53, p21, and Bax expression. However, patients with Mcl-1- tumors survived longer than those with Mcl-1+ tumors. Postoperative UFT treatment did not improve survival; however, adjuvant UFT significantly prolonged the survival of patients with p53-, p21-), Bax+, or Mcl-1+ tumors, but not of patients with p53+, p21+, Bax-, or Mcl-1- tumors., Conclusions: The efficacy of adjuvant chemotherapy for gastric cancer may be affected by the status of apoptosis-related proteins such as p53, p21, Bax, and Mcl-1. However, because susceptibility to apoptosis did not explain the sensitivity of chemotherapeutic agents, further investigation of the mutual interaction between apoptosis-related proteins is required.

Background: X-ray cross-complementing group 1 (XRCC1) polymorphisms affect DNA repair capacity and may therefore be of importance in colorectal carcinogenesis. Alcohol consumption, an important risk factor for colorectal cancer, may induce carcinogenesis through DNA damage caused by the toxic effects of alcohol or its metabolites. Therefore, we examined the associations of XRCC1 Arg399Gln, Arg280His, and Arg194Trp polymorphisms with colorectal cancer and the impact of the association between alcohol consumption and colorectal cancer risk., Methods: This case-control study in Fukuoka, Japan including 685 cases and 778 controls. The cases were incident patients with histologically confirmed colorectal adenocarcinoma. The controls were randomly selected community subjects., Results: The XRCC1 399Gln/Gln genotype was significantly associated with colorectal cancer risk (adjusted odds ratio [OR] 1.57, 95% CI 1.01-2.42; relative to 399Arg/Arg genotype). The association was strongest in individuals with high alcohol consumption. The Arg280His polymorphism modified the association between alcohol consumption and colorectal cancer risk (interaction P = 0.049). The OR of colorectal cancer in individuals with the 280His allele was 0.45 (95% CI 0.26-0.78) as compared with the 280Arg/Arg genotype limited to the 399Gln allele (interaction P = 0.001). The adjusted ORs for 399Gln/Gln-280Arg/Arg-194Arg/Arg and 399Arg/Gln-280Arg/Arg-194Arg/Trp were 1.71 (95% CI 1.02-2.87) and 1.57 (95% CI 1.05-2.33), respectively, with 399Arg/Arg-280Arg/Arg-194Arg/Arg as reference (interaction P = 0.418)., Conclusions: The findings are additional evidence that individuals with the XRCC1 399Gln/Gln genotype have an increased risk of colorectal cancer, and that XRCC1 polymorphisms have an important role in colorectal cancer risk associated with alcohol consumption or gene-gene interaction.

Purpose: An esophagectomy followed by reconstruction for esophageal cancer is a highly aggressive operation. The purpose of this study was to justify a two-stage operation for high-risk patients with esophageal cancer., Methods: The clinical results of 27 patients who underwent two-stage operation were compared with 118 patients who underwent a simultaneous resection and reconstruction (control subjects). The reasons for the selection of the two-stage operation were underlying general disease in 13 patients (liver dysfunction, n = 6; pulmonary disease, n = 3; poor performance status, n = 2; diabetes and renal failure, n = 1 each) and high-risk operation in 14 other patients (colon interposition, n = 7; salvage operation after definitive chemoradiotherapy, n = 4; and intraoperative events, n = 3). The patients initially underwent an esophagectomy and a cervical esophagostomy. Reconstruction was usually performed 2-3 weeks later., Results: The patients in the two-stage group were older than the control patients (mean 67.8 vs. 61.6 years old). The morbidity rate of the two-stage operation was 29.6%, which was not statistically different than control patients (32.2%). Postoperative complications in the two-stage operation were anastomotic leakage in 5 patients, and pneumonia and wound infection in 1 patient each. No patient experienced in-hospital death. The survival rates were not statistically different between the two groups., Conclusion: A two-stage operation is a safe operation that prevents the occurrence of critical postoperative complications, and it thus may be considered an important treatment strategy for high-risk patients with esophageal cancer.

Background: Resections for esophageal cancer are invasive, with high mortality and morbidity rates. The object of this study was to clarify the factors associated with in-hospital death while also evaluating any associated historical changes in the characteristics of such deaths., Methods: The factors associated with mortality were examined by logistic regression analysis in 1106 patients who underwent an esophagectomy for esophageal cancer. The historical changes in the characteristics of in-hospital deaths were also evaluated., Results: A multivariate analysis revealed that not only undergoing an esophagectomy before 1979, but also a patient's age (odds ratio 1.070 for every increase in age by year) and an incomplete resection (odds ratio 2.265) were independent factors associated with in-hospital death. The in-hospital mortality rates were 16.1%, 5.8%, 2.5%, and 3.1%, while the 30-day mortality rates were 9.2%, 2.2%, 0.8%, and 0.3% during 1964-1979, the 1980s, the 1990s, and the 2000s, respectively. Eight patients had preoperative comorbidities among 11 patients who died in the hospital after 1997. The mortality rate was 5.5% in patients with any comorbidities, while it was 1.3% in patients without any comorbidities (P = 0.026). The most common direct cause of in-hospital death was previous pulmonary complications; however, cancer progression has recently become the most common cause., Conclusions: To prevent in-hospital mortality after an esophagectomy, strict indications for surgery and careful perioperative management are important, especially in high-risk patients with advanced esophageal cancer.

We herein present the case of a 66-year-old man with both gastric cancer and an infrarenal abdominal aneurysm. The patient's medical history included bladder cancer, chronic renal failure, and ischemic heart disease. We performed a simultaneous endovascular aneurysm repair (EVAR) and total gastrectomy. Following the procedure, the patient remained in the intensive care unit for 3 days. Oral feeding was resumed on postoperative day 7, and the patient was discharged from the hospital on postoperative day 13 with no complications. Despite the patient's medical problems and higher operative risk, he tolerated simultaneous EVAR and total gastrectomy, and had a good outcome after undergoing these simultaneous procedures.

A 68-year-old man was scheduled for pancreaticoduodenectomy under general anesthesia. He was suffering from Charcot-Marie-Tooth disease (CMTD) for 34 years, and complicated with liver cirrhosis. Anesthesia was induced with propofol and fentanyl, and maintained with oxygen-air-sevoflurane and remifentanil. Epidural block was not used because the patient had coagulation abnormality and thrombocytopia. Rocuronium was injected intravenously for tracheal intubation, supplemented as required using an electrical nerve stimulator. The longer duration of action of rocuronium was observed in this case because the patient was complicated with CMTD and liver cirrhosis. We suggest that monitoring neuromuscular function may be necessary to detect subtle residual neuromuscular blockade when rocuronium is used in a patient with CMTD and liver dysfunction.

Second mitochondria-derived activator of caspases/direct inhibitor of apoptosis-binding protein with low pI (Smac/DIABLO) is released by mitochondria in response to apoptotic stimuli and is thought to regulate apoptosis by antagonizing inhibitors of apoptosis proteins, which play an important role in sensitization of cancer cells to various therapeutic regimens. The expression of Smac/DIABLO has been demonstrated in various cancer cells, though little is known about its clinical significance with respect to colorectal cancer. The current study was designed to evaluate the relationship between prognosis and Smac/DIABLO expression by clinicopathological analysis of patients with colorectal cancer. Smac/DIABLO expression was evaluated using immunohistochemical staining in 121 consecutive patients with colorectal cancer and the relationship between Smac/DIABLO expression and clinicopathological factors was analyzed. Smac/DIABLO-positive expression was detected in 80 of the 121 patients (66%). The incidence of lymph node and distant metastasis in Smac/DIABLO-negative cancer was significantly higher than that in Smac/DIABLO-positive cancer (P=0.0004 and P=0.003, respectively). While univariate analysis showed that survival in patients with Smac/DIABLO-negative expression was significantly poorer than in Smac/DIABLO-positive cases (P<0.0001), Smac/DIABLO-negative expression was a prognostic indicator independent of Dukes' staging and lymph node metastasis by multivariate analysis. This study proposes that the decrease of Smac/DIABLO expression is an independent factor determining the poorer prognosis of patients with colorectal cancer.

Objective: This phase II study evaluated the toxicity and efficacy of a novel dosing schedule of docetaxel and S-1 as treatment for advanced gastric cancer., Methods: Patients with measurable advanced or recurrent gastric cancer and no prior exposure to the investigational drugs were treated with intravenous docetaxel 35 mg/m(2) on days 1 and 15, and oral S-1 80 mg/m(2)/day on days 1-14 every 4 weeks. The primary endpoint was objective response., Results: Thirty-five eligible patients were enrolled and received a total of 151 cycles of treatment (median 3, range 1-19). One complete response and 13 partial responses were observed, with an overall response rate of 40% (95% CI: 24-56%). Median progression-free survival and median overall survival times were 4.5 and 14.2 months, respectively. The most common grade 3-4 toxicities were neutropenia (23%) and leukocytopenia (15%)., Conclusion: Biweekly docetaxel combined with S-1 is active in advanced or recurrent gastric cancer, and can be administered with proper management of adverse events in an outpatient clinic., (Copyright 2009 S. Karger AG, Basel.)

This report describes the case of a patient who had undergone surgery to resect bilateral ovarian tumors and then presented with colon metastasis 20 years later. A 69-year-old woman was admitted to the hospital for a clinical survey. She had been operated on for bilateral ovarian cancer in 1987 and was treated by postoperative adjuvant chemotherapy. The patient's follow-up showed no abnormality until 2006. Colonoscopy revealed an elevated irregular lesion in the cecum. A biopsy of the lesion showed a group V, moderately differentiated adenocarcinoma. A right hemicolectomy with a partial resection of the ileum and a lymphadenectomy was performed. Immunohistochemical staining during the pathological diagnosis showed the lesion to be colon metastasis from a serous papillary adenocarcinoma of the ovary. Immunohistochemical staining was positive for cytokeratin 7, carbohydrate antigen (CA)-125, and estrogen receptors, and negative for cytokeratin 20, carcinoembryonic antigen, and CA19-9. The use of immunohistochemistry demonstrated the tumor to be of ovarian origin.

Colorectal cancer (CRC) frequently develops in patients with ulcerative colitis (UC). We report a case of CRC treated successfully by proctocolectomy 8 months after living donor liver transplantation (LDLT) for primary sclerosing cholangitis (PSC). The lesion was detected early, probably as a result of colonoscopic surveillance after LDLT. Thus, patients with a long history of UC, who undergo LDLT for PSC, should be followed up with regular surveillance colonoscopy. Moreover, surgery, such as radical resection of the colon and rectum should be performed without delay, even shortly after LDLT. To our knowledge, this is the first report of a patient undergoing proctocolectomy after LDLT.

Background: In Japan, most esophageal cancers are squamous cell carcinomas, and the results of esophagectomy have improved remarkably in recent years. The object of this study was to evaluate advances in operative therapy for esophageal cancer in Japan., Method: We evaluated mortality, morbidity, and prognosis in 1000 consecutive patients who underwent esophagectomy for esophageal cancer at a single institution in Japan. The patients were divided into 3 groups according to the period when esophagectomy was performed: Group I (n = 197), 1964-1980; group II (n = 432), 1981-1993; and group III (n = 371), 1993-2006., Results: The incidence of squamous cell carcinoma was 94%. The morbidity rates were 62%, 38%, and 33 %, in groups I, II, and III, respectively (P < 0.01, groups I vs II and III), and the in-hospital mortality rates were 14.2%, 5.1%, and 2.4%, respectively (P < 0.01, between each group). The 5-year overall survival rate was 30% (14%, 27%, and 46% in groups I, II, and III, respectively; P < 0.0001). Multivariate analysis revealed age, gender, depth of invasion, node metastasis, distant metastasis, curability, extent of lymphadenectomy, resectability, and the period when the operation was performed as independent prognostic factors., Conclusion: Generally, esophagectomy has been performed safely without critical complications; however, the prognosis has improved remarkably with advances in surgical techniques and treatment modalities.

Somatically acquired mutations in the epidermal growth factor receptor (EGFR) gene in lung cancer are associated with significant clinical responses to gefitinib, a tyrosine kinase inhibitor that targets EGFR. We screened the EGFR in 469 resected tumours of patients with lung cancer, which included 322 adenocarcinomas, 102 squamous cell carcinomas, 27 large cell carcinomas, 13 small cell carcinomas, and five other cell types. PCR with a specific condition was performed to identify any deletion in exon 19, while mutant-allele-specific amplification was performed to identify a mutation in codon 858 of exon 21. EGFR mutations were found in 136 cases (42.2%) with adenocarcinoma, in one case with large cell carcinoma, and in one case with pleomorphic carcinoma. An in-frame deletion in exon 19 was found in 62 cases while an L858R mutation was found in 77 cases. In the 322 cases with adenocarcinoma, these mutations were more frequently found in women than in men (P=0.0004), in well differentiated tumours than in poorly differentiated tumours (P=0.0014), and in patients who were never smokers than in patients who were current/former smokers (P<0.0001). The mutation was more frequently observed in patients who smoked

A case of pulmonary collision tumor is herein reported. An abnormal shadow was discovered in the right lung of a 53-year-old man. A right upper lobectomy with a mediastinal lymph node dissection was performed. Based on the findings of a postoperative pathologic examination, this tumor was considered to be a collision tumor of large cell carcinoma and adenocarcinoma, as the distribution of each tumor was clearly separated. This case is the first report of a primary pulmonary collision tumor consisting of large cell carcinoma and adenocarcinoma.

A novel histone deacetylase inhibitor, FK228, is a promising anticancer agent and has been proposed to modulate intracellular signaling, in addition to regulating gene transcription. We evaluated the effect of this agent on Akt-mediated signaling in relation to its cytotoxic activity using lung adenocarcinoma cell lines. Based on MTT assay and the appearance of cleaved poly (ADP-ribose) polymerase (PARP), we regarded A549 and PC14 cells as relatively sensitive and resistant cell lines, respectively. In A549 cells, FK228 suppressed the phosphorylation of Akt at Ser-473 and glycogen synthase kinase-3 without affecting these protein levels, indicating inhibition of the Akt-mediated signaling pathway. On the other hand, in PC14 cells, these biochemical reactions were not detected after treatment with FK228. The combination of FK228 and a phosphatidylinositol 3-kinase (PI3K)/Akt pathway inhibitor, LY294002, was determined to be synergistically cytotoxic in PC14 cells by isobologram analysis. This synergistic effect was attributable to the enhancement of apoptosis, as judged by flow cytometric analysis, and the appearance of cleaved PARP. The combination of FK228 with UCN-01, another PI3K/Akt pathway inhibitor, also exerted a synergistic effect. We concluded that FK228 suppresses the PI3K/Akt signaling pathway in a cell-specific manner, and this effect is a determinant of sensitivity to FK228.

To assess the roles of the extent of gastric resection and duodenal food passage reconstruction in gastric cancer, we examined a consecutive series of 1,061 patients who underwent total or partial (proximal and distal) gastrectomies with or without duodenal food passage reconstruction between August of 1974 and January of 2002, and received gastrectomies with D2-3 lymph node dissection. Patients who underwent distal or proximal gastrectomy were found to have significantly better survival rates than those who underwent total gastrectomy in stages 1A (10-year survival: 86.6 and 78.9 vs. 61.6%), 2 (56.5 and 65.6 vs. 34.4%), 3A (45.9 and 33.3 vs. 15.2%), and 4 (5-year survival rates: 23.7 and 50.0 vs. 7.1%). Additionally, patients with duodenal food passage reconstruction or double tract reconstruction also showed significantly better survival rates than those without duodenal food reconstruction in stages 1A (10-year survival: 86.4 and 82.5 vs. 61.7%), 1B (69.9 and 90.6 vs. 54.1%), 2 (60.5 and 63.3 vs. 16.5%), and 3A (39.9 and 47.4 vs. 23.1%). In multivariate analysis, the independent prognostic factors were age at operation, depth of tumor, duodenal food passage reconstruction, and lymph node metastasis. Our results indicate that both the extent of gastric resection and duodenal food passage reconstruction were important factors in the outcome of gastric cancer patients, and that surgeons should perform minimal gastric resection with preservation of the duodenal food passage when the gastric stump is tumor-free., (Copyright (c) 2005 S. Karger AG, Basel.)

A 73-year-old woman came to our hospital because of poor appetite, and careful examination revealed a Borrmann type 2 tumor on the posterior wall of the lower body of the stomach as well as enlarged para aortic-lymph nodes. Surgery was performed in November 2000, but because the para-aortic lymph nodes were densely adherent to the aorta, it was impossible to dissect the lymph nodes from the wall (N3, Stage IV). Postoperatively, a course of TS-1 100 mg/day for 4 weeks and discontinuation for 2 weeks was started. After one course of TS-1, the enlarged para-aortic lymph nodes were no longer seen on abdominal computed tomography (CT). The dose of TS-1 was subsequently reduced to 80 mg/day because of adverse effects. Although the patient is still taking TS-1, she is well with no signs of recurrence 34 months after surgery.

Background: We compared the prognostic efficacy between the Japanese General Rules of Prostatic Cancer (JGRPC) and the Gleason grading system (GGS) by applying them to a single set of patients and assessing the survival outcome., Methods: One hundred and seventy-six patients with previously untreated prostate cancer were studied. One experienced Japanese pathologist graded the slides with JGRPC. Another experienced American pathologist graded the same slides with the Gleason grading system. The JGRPC grades were correlated with the Gleason scores (GS) grouped into three (GS 2-4, 5-7 and 8-10) or four (GS 2-4, 5-6, 7 and 8-10) tiers., Results: The highest cancer death rates were seen in the higher grade groups in both systems. Comparison of JGRPC grade and three-tiered grouping of the GS showed identical grades in 81 of 176 cases (46.0%). The overall kappa value of agreement was only 0.151. The 96 cases of JGRPC moderately differentiated carcinoma group contained two nearly equal-sized groups by the Gleason grading system, those with GS 5-7 (47cases) and GS 8-10 (49 cases). There was a significant difference in survival rate between the GS 5-7 and GS 8-10 groups. No significant differences were noted in the reverse analysis of survival by JGRPC groups within patients with the same GS three-tiered groups. Similar trends were seen when JGRPC was compared with the four-tiered grouping of the GS., Conclusion: Both JGRPC and the Gleason grading system are useful in estimating the prognosis of prostate cancer, but only a mild correlation was found between the two systems. The Gleason grading system may provide more prognostic information than JGRPC in the moderately differentiated group.

To assess the mechanism of the anticancer effect of doxifluridine (5'-DFUR), a clinicopharmacological study was performed. So far, no comparative study has been reported between the thymidylate synthase (TS) inhibition rate and the 5-FU concentration in colorectal cancer after oral administration of 5'-DFUR. In 37 patients with colorectal cancer, 5'-DFUR was administered orally/preoperatively (800 mg/day x more than 4 days before operation and 300 mg on the day of operation). The mean total dosage was 6.9 g. Specimens of tumor and normal intestinal tissue were obtained 4.4 hours on average after final administration. The TS inhibition rate as well as the 5-FU concentration and the activity of pyrimidine nucleoside phosphorylase (PyNPase) were analyzed in both tissues. The PyNPase activity was significantly higher in the tumor tissue than in the normal tissue (137.9 +/- 10.8 vs. 31.0 +/- 4.7 micrograms FU/mg protein/hr, p < 0.0001). The 5-FU concentration was also significantly higher in the tumor tissue than in the normal tissue (101.3 +/- 30.6 vs. 23.2 +/- 5.5 ng/g, p = 0.024). The TS inhibition rate correlated with the 5-FU concentration in the tumor tissue (r = 0.527, p = 0.047). These findings suggest that the TS inhibition rate may be an index of the anticancer effect of 5'-DFUR in colorectal cancer.

We studied 148 colorectal adenocarcinomas to clarify any correlation between HLA-DR antigen expression on tumor cells and histopathological features. Paraffin sections of formalin-fixed tissues were stained with HLA-DR antigen using the indirect immunoperoxidase technique. All the tumor tissues were divided into two groups, depending on the incidence of HLA-DR-positive cells (greater and lesser than 50%). Carcinoma tissues with a higher incidence showed less mural invasion, lymphoductal invasion, venous invasion, lymphonodular metastasis, and peritoneal metastasis. Tissues with a high HLA-DR reactivity were more often observed for Dukes' A and B stages, whereas those with a low HLA-DR positivity were frequently Dukes' C and D stages. As for the cumulative survival rate, the group with high HLA-DR expression demonstrated significantly better survival. We speculate that HLA-DR expression by colorectal cancer cells exerts a favorable influence on clinical course.

A simple one-step double staining with DAPI and hematoporphyrin (HP) was used for UV-microspectrophotometric (UV-MSPM) and flow cytometry (FCM) analysis of the same samples. The specimens analyzed included fresh biopsy and/or surgical materials, trimmed 50 microns-thick paraffin sections and smears (with the latter not available for FCM). We provided the special technology for preserving the cytoplasm as far as possible to permit measurement of cell size and N/C ratio. DAPI indicates DNA content under 365 nm and HP of total protein content under 670 nm UV-MSPM. The DAPI can measure the nuclear size and the latter the cell size. DAPI/HP staining yielded much more accurate measurements than staining with FITC and PI. The use of both MSPM and FCM with cell sorting on the same samples is very helpful in cytology and histopathology for evaluating and differentiating borderline lesions and grade of malignancy, as well as oncostatic effectivity. Our goal is to combine this technology with the automated cytologic screening system CYBEST, which was developed by Tanaka et al, based on a morphometric device.

A review of data on 360 patients with esophageal squamous cell carcinoma who underwent esophageal resection revealed 14 cases (3.9%) and 16 lesions with synchronous gastric carcinomas. Among the 16 lesions, there were 14 (87.5%) early gastric carcinomas and two advanced carcinomas. Of the 14 early gastric carcinomas, two were minute (less than 5 mm in the largest diameter) early gastric carcinomas and four small (6-10 mm in the largest diameter). These gastric carcinomas were in a relatively early stage. The six early gastric carcinomas were not detected preoperatively. However, a thorough observation of the gastric mucosa could not be done in four of those due to stenosis which had developed as a result of the esophageal carcinoma. Therefore, intraoperative gastric observation should be done in cases in which the findings of the preoperative endoscopic examination of the stomach are inadequate and the upper gastrointestinal series reveal certain gastric abnormalities.

The c-erbB-2 proto-oncogene is known to encode a 185,000 molecular weight glycoprotein. This protein has been detected immunohistochemically in several human adenocarcinomas, suggesting that it may play a role in the development of these malignancies. In the otolaryngological field none of the adenocarcinomas expressing c-erbB-2 protein has yet been described. In this article we presented a case of parotid adenocarcinoma expressing the c-erbB-2 protein. In this case the adenocarcinoma was thought to have originated from pleomorphic adenoma. Immunohistochemically, the adenocarcinoma cells were stained and the remaining pleomorphic adenoma cells were not stained by polyclonal antibody against the c-erbB-2 protein. The expression of c-erbB-2 protein may have been related to the malignant development of the pleomorphic adenoma.

A resected case and an autopsied case of an adenosquamous carcinoma and two autopsied cases of a squamous cell carcinoma of the liver are presented. With regard to the first case, a 58-year-old male underwent an operation, based on the diagnosis of a hypovascular hepatoma or a cholangioma. The resected material showed a nodular whitish gray tumor at the S4 region which histologically proved to be an adenosquamous carcinoma. In the two autopsied cases, found was a huge, grayish necrotic mass at the right lobe of the liver and a defect of gall-bladder. The tumor, in both cases, proved to be squamous cell carcinoma originating in the liver.

Background Afatinib is a 2nd generation EGFR-TKI and has been a standard first line treatment for patients (pts) with advanced NSCLC with EGFR mutations. Afatinib has good efficiency, whereas afatinib has severe adverse events (AEs) and often lead to discontinuation of treatment or a dose reduction. NJLCG1601 was conducted to evaluate the efficacy of low-dose afatinib maintenance treatment. Methods EGFR-TKI-naïve stage III / IV / recurrent NSCLC pts harboring EGFR mutations (exon 19 deletion or exon 21 L858R or minor mutation) were enrolled. Pts received afatinib 40mg orally once a day. When prescribed AEs (grade ≧ 2 in CACAE ver 4.0) or unacceptable AEs occurred, a dose of afatinib was reduced from 40mg to 30mg, 30mg to 20mg. The treatment was continued until disease progression, occurrence of intolerable severe AEs, or withdrawal of consent. The primary endpoint was 1-year progression free survival (PFS) rate. Secondary endpoints were PFS, overall response rate (ORR), the incidence of AEs, and the incidence of grade ≧ 3 AEs. Assuming a threshold 1-year PFS rate of 42% and an expected 1-year PFS rate of 63%, a total of 26 pts was required to have 90% power at a two-tailed alpha of 0.05. This is a subset analysis of patients with adenocarcinoma in NJLCG1601 study (Trial Identifier, UMIN000020688). Results Between Apr 2016 and Sep 2017, 30 pts were enrolled. Among 30 patients, 28 patients (93%) were adenocarcinoma. Pts characteristics were as follows: median ages, 70 years (range 46-79 years); proportion of males, 43%; clinical stage, IV 61% and post-op 39%; EGFR mutation types, exon 19 deletion 54%, ex21 L858R 36%, and minor mutations 11%. 1-year PFS rate was 53.6% (95% CI, 33.8-69.8), median PFS was 13.0 months, and ORR was 78.6%. Dose reductions occurred in 86% (24/28). Incidence of all cause grade ≧ 3 was 60% which is smaller than the frequency of Japanese subset in LUX-Lung 3. ILD was occurred in 3 patients and 1 patients died. Treatment-related deaths were observed in 2 pts. Conclusions Low-dose afatinib maintenance treatment reduced treatment-related adverse events without detracting from the therapeutic efficacy. Legal entity responsible for the study UMIN000020688. Funding Has not received any funding. Disclosure A. Nakamura: Honoraria (self): MSD; Honoraria (self): Chugai; Honoraria (self): AstraZeneca. S. Inoue: Honoraria (self): AstraZeneca; Honoraria (self): Eli Lilly; Honoraria (self): MSD; Honoraria (self): Otsuka Pharmaceutical; Honoraria (self), research funding: Kyorin Pharmaceutical; Honoraria (self): Ono Pharmaceutical; Honoraria (self): GlaxoSmithKline; Honoraria (self): Daiichi Sankyo Company; Honoraria (self): Taiho Pharmaceutical; Honoraria (self): Chugai Pharmaceutical; Honoraria (self): Teijin Pharma; Honoraria (self), research funding: Novartis Pharma; Honoraria (self): Pfizer Inc; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Meiji Seika Pharma. S. Sugawara: Honoraria (self): AstraZeneca; Honoraria (self): Chugai Pharma; Honoraria (self): Nippon Boehringer Ingelheim; Honoraria (self): Taiho Pharmaceutical; Honoraria (self): Pfizer; Honoraria (self): Eli Lilly; Honoraria (self): Novartis; Honoraria (self): Kyowa Hakko Kirin; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Ono Pharmaceutical; Honoraria (self): MSD. All other authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]