Search

Background/aim: Clinical staging in the eighth edition of the Union for International Cancer Control TNM classification (TNM8) is reported to predict the prognosis of patients with gastric cancer. However, there have been no reports on using the TNM8 for prognostic stratification of patients with adenocarcinoma of the esophagogastric junction (AEG). This study aimed to investigate whether it was possible to stratify the prognosis of patients who underwent curative surgery for Siewert type II/III AEG according to the TNM8 clinical stage (cStage)., Patients and Methods: This study included patients with Siewert type II/III AEG who underwent curative surgery between 2000 and 2019 at Kanagawa Cancer Center. Those who received neoadjuvant chemotherapy were excluded. We investigated the survival of patients with AEG of each TNM8 cStage., Results: This study included 138 patients, among whom 102 (74%) had Siewert type II and 36 (26%) had Siewert type III AEG. A total of 50, 38, 43, and seven patients were classified with cStage I, II, III, and IV, respectively. The median duration of follow-up of the survivors was 54.7 months. The 5-year overall survival rate of the entire cohort was 65.8%, whereas for patients with cStage I, II, III and IV was 81.6%, 69.0%, 54.3% and 14.3%, respectively. The hazard ratio with reference to cStage I was 1.83, 3.07, and 8.13 for cStage I, III, and IV, respectively, increasing in a stepwise manner., Conclusion: TNM8 Clinical staging is able to stratify the prognosis of patients with Siewert type II/III AEG., (Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: The present study aimed to compare the efficacy and safety of nivolumab (NIVO) and irinotecan (IRI) and to identify clinical factors that facilitate treatment selection., Methods: Patients with advanced gastric cancer (AGC) who underwent NIVO or IRI treatment between November 2016 and June 2018 at three institutions were retrospectively reviewed. The inclusion criteria were histologically confirmed gastric/gastroesophageal adenocarcinoma pretreated with fluoropyrimidines and taxanes, no previous NIVO or IRI treatment, and adequate organ function. Main outcome measures were objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and adverse events. Interaction between treatment groups and clinical factors regarding OS were tested using a multivariate Cox proportional hazards model adjusted for relevant variables., Results: Both NIVO (n = 71) and IRI (n = 61) groups had similar baseline characteristics, except for sex distribution. NIVO and IRI groups had ORR of 20% and 6%, median PFS of 1.6 and 1.8 months, and median OS of 6.4 and 6.4 months, respectively. Interaction analysis did not reveal any significant interaction between NIVO and IRI related to OS for various factors. NIVO group tended to have fewer ≥ grade 3 adverse events than IRI group, especially neutropenia (3% vs. 28%) and febrile neutropenia (1% vs. 8%). In the NIVO group, one patient developed pneumonitis, and four patients developed skin reactions., Conclusions: Although no remarkable differences in efficacy were found between IRI and NIVO for AGC, NIVO had a better safety profile compared to IRI. We found no clinical markers that can assist treatment decisions., (© 2023. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Background: Splenic hilar lymphadenectomy is not recommended for advanced proximal gastric cancer that does not invade the greater curvature according to the results of the previous studies. The efficacy of splenic hilar lymphadenectomy for type II and type III adenocarcinomas of the esophagogastric junction and easy spread to the greater curvature of the stomach remains unclear. This study aimed to investigate the efficacy of splenic hilar lymphadenectomy and identify the risk factors for metastasis to splenic hilar nodes., Methods: We examined patients who underwent R0/1 gastrectomy for Siewert types II and III at a single high-volume center in Japan. We analyzed the metastatic incidence, therapeutic value index, and risk factors for splenic hilar lymph node metastasis., Results: We examined 126 patients (74, type II; 52, type III). Splenectomy was performed in 76 patients. Metastatic incidence and the therapeutic value index of splenic hilar lymph nodes in patients with type II and type III tumors were 4.5% and 0, and 21.9% and 9.4, respectively. In the patients who underwent splenectomy, we identified Siewert type III tumors (odds ratio: 6.93, 95% confidence interval: 1.24-38.8, p = 0.027) and tumor location other than the lesser curvature (odds ratio: 7.36, 95% confidence interval: 1.32-41.1, p = 0.023) to be independent risk factors. The metastatic incidence (46.2%) and therapeutic value index (15.4) were high in patients with both risk factors., Conclusions: Splenic hilar lymphadenectomy may contribute to the survival of patients with Siewert type III tumors, especially when the predominant location is not the lesser curvature., Competing Interests: Declaration of competing interest Yasushi Rino has received speaker honorariums and research grants from Daiichi Sankyo, Johnson & Johnson, Otsuka, Lilly, Taiho Pharmaceutical, Ono Pharmaceutical, Bristol-Myers Squibb, Abbott Nutrition, Asahi Kasei, Tsumura & Co., Covidien, Zeria Pharmaceutical and EA Pharma. The other authors declare that they have no conflict of interest., (Copyright © 2022 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: The phase 3 KEYNOTE-590 (NCT03189719) study showed first-line pembrolizumab plus chemotherapy significantly prolonged overall survival and progression-free survival versus placebo plus chemotherapy in patients with advanced unresectable or metastatic adenocarcinoma or squamous cell carcinoma of the esophagus or advanced/metastatic Siewert type I adenocarcinoma of the esophagogastric junction. We describe a subgroup analysis of Japanese patients from KEYNOTE-590., Methods: Eligible patients were randomly assigned 1:1 to pembrolizumab 200 mg intravenously every 3 weeks or placebo plus chemotherapy (cisplatin 80 mg/m 2 and 5-fluorouracil 800 mg/m 2 /day). Efficacy was evaluated in all Japanese patients and those with esophageal squamous cell carcinoma and programmed death ligand 1 combined positive score ≥ 10. Dual primary endpoints were overall survival and progression-free survival per RECIST v1.1 by investigator. Secondary endpoints included objective response rate per RECIST v1.1 by investigator and safety and tolerability., Results: At data cutoff (July 2, 2020), 141 Japanese patients were randomly assigned (pembrolizumab plus chemotherapy, 74; placebo plus chemotherapy, 67). In all Japanese patients, median overall survival was 17.6 months with pembrolizumab plus chemotherapy versus 11.7 months with chemotherapy (hazard ratio, 0.71; 95% confidence interval, 0.47-1.09), median progression-free survival was 6.3 versus 6.0 months (hazard ratio, 0.58; 95% confidence interval, 0.40-0.84), and objective response rate was 56.8% versus 38.8%. Grade 3-5 treatment-related adverse events were 74.3% and 61.2%., Conclusion: First-line pembrolizumab plus chemotherapy demonstrated improvement in overall survival and progression-free survival compared with placebo plus chemotherapy in Japanese patients with advanced/metastatic esophageal cancer; safety was comparable between treatment groups., Clinical Trial Registry: ClinicalTrials.gov, NCT03189719., (© 2022. Merck & Co., Inc., Rahway, NJ, USA and its affiliates and Takashi Kojima, Hiroki Hara, Akihito Tsuji, Hisateru Yasui, Kei Muro, Taroh Satoh, Takashi Ogata, Ryu Ishihara, Masahiro Goto, Hideo Baba, Tomohiro Nishina, Toshihiko Doi, Ken Kato.)

Background/aim: Sulphite oxidase (SUOX) is a metalloenzyme that catalyses ATP synthesis via oxidative phosphorylation in the mitochondria. Although SUOX has been reported to affect the invasiveness and differentiation of cancer cells, its clinicopathological significance in pancreatic adenocarcinoma (PDAC) remains unclear. In this study, we investigated the utility of SUOX expression as a prognostic factor in PDAC., Patients and Methods: This study included 56 patients with PDAC who underwent pancreatic resection at the Kurume University Hospital between 2014 and 2018. SUOX immunohistochemistry was evaluated using tissue microarray specimens from patients. Patients were classified into a high SUOX expression group (≥10% of cells stained) or a low SUOX expression group (<10% of cells stained), and the associations of SUOX with clinicopathological characteristics and survival were analysed. Statistical analysis was performed using Cox regression analysis, the Kaplan-Meier method, and log-rank test., Results: SUOX was expressed in the cytoplasm of normal pancreatic ductal epithelium, pancreatic acinar cells, and islets of Langerhans. Although we did not find any significant correlation between SUOX expression and clinicopathological factors, SUOX was identified as an independent prognostic factor based on univariate and multivariate analyses. Pathological stage was also an independent prognostic factor. The high SUOX expression group showed a significantly poorer prognosis than the low SUOX expression group (p=0.018)., Conclusion: SUOX-mediated mitochondrial metabolism in PDAC may be a factor influencing prognosis and SUOX may be a potential novel prognostic biomarker., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Metastatic small bowel adenocarcinoma (SBA) is a rare disease with poor prognosis. This study aimed to explore the efficacy and safety of second-line chemotherapy for patients with SBA., Patients and Methods: We retrospectively reviewed the clinical characteristics of 27 metastatic patients with SBA after progression on first-line chemotherapy. The patients were divided into Cohort A, receiving second-line chemotherapy, and Cohort B, receiving best supportive care., Results: Patients in Cohort B had higher age, worse performance status, and higher neutrophil-to-lymphocyte ratio compared with those in Cohort A. Cohort A showed significantly better overall survival (OS) compared with Cohort B (median OS, 15.6 vs. 3.4 months; p=0.002). Objective response rate, disease control rate, and median progression-free survival (PFS) for Cohort A were 7%, 74%, and 5.0 months, respectively. Patients who underwent irinotecan-based chemotherapy showed longer PFS and OS compared with those who underwent taxane-based chemotherapy. No significant adverse events were reported., Conclusion: Second-line chemotherapy for metastatic SBA demonstrated clinical activity with acceptable toxicities., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Introduction: Laparoscopic gastrectomy has become a standard procedure for treatment of gastric cancer, and hence, the opportunity for trainees to perform open gastrectomies may decrease. We investigated whether laparoscopic distal gastrectomy, performed by surgical trainees without sufficient experience performing open gastrectomies, was feasible and safe., Patients and Methods: We compared short-term outcomes in patients when laparoscopic distal gastrectomies were performed by experienced trainees (ET group; n = 124) and inexperienced trainees (IT group; n = 98) from 2013 to 2019., Results: The operation time was significantly shorter in the ET group (median time: 253 minutes vs 286 minutes, P < 0.001). The incidence of grade ≥ 2 postoperative complications did not differ significantly between the groups. In the multivariate analysis, experience performing open gastrectomies was not an independent predictor of postoperative complications., Conclusion: Laparoscopic distal gastrectomies performed by trainees, with insufficient experience performing open gastrectomies, are as feasible and safe as that performed by ET., (© 2020 Asia Endosurgery Task Force and Japan Society of Endoscopic Surgery and John Wiley & Sons Australia, Ltd.)

Background/aim: Stanniocalcin2 (STC2) is associated with proliferation, invasion, and metastasis in various cancers. We examined the clinical significance of STC2 mRNA expression in patients with colorectal cancer (CRC)., Patients and Methods: Relative expression levels of STC2 mRNA in CRC tissues and corresponding normal mucosa obtained from 202 patients were measured using quantitative real-time reverse transcriptase-polymerase chain reaction., Results: Expression of STC2 mRNA was higher in the cancer tissue than in the adjacent normal mucosa. STC2 mRNA expression in cancer tissues was associated with tumour size, liver metastasis, venous invasion, and lymph node metastasis. High expression of STC2 mRNA was significantly associated with poorer postoperative survival (p=0.0003). Multivariate analysis showed that high expression of STC2 mRNA was an independent predictor of postoperative survival., Conclusion: High expression of STC2 mRNA in CRC tissue may be a useful prognostic marker in patients with CRC., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: The aim of this study was to evaluate the impact of postoperative infectious complications on long-term outcomes after curative resection of gastric cancer., Patients and Methods: Patients who underwent curative gastrectomy with lymphadenectomy for gastric cancer at Yokohama City University and Kanagawa Cancer Center from January 2000 to August 2015 were retrospectively selected from medical records. Clinicopathological factors between patients with and without infectious complications were compared. Prognostic factors of long-term survival were analyzed by univariate and multivariate Cox proportional hazards analyses., Results: A total of 2,254 patients were eligible for inclusion in the present study. Fifty-eight patients had postoperative infectious complications (IC group); 2,196 had no postoperative infectious complications (NC group). In the IC group, the median age (p=0.031), body mass index (p=0.004), American Society of Anesthesiologists physical status (p=0.006) and percentage of male patients (p<0.001) were higher in comparison to the NC group. The operation time was longer (p<0.001) and the incidence of intestinal-type histology was higher (p=0.017) in the IC group. The 5-year overall survival rates of the IC and NC groups were 59.8% and 83.2%, respectively (p<0.001). Univariate and multivariate analyses demonstrated that postoperative infectious complications were a significant risk factor for poorer overall survival (hazard ratio=2.38; 95% confidence interval=1.47-3.85, p<0.001)., Conclusion: Perioperative management is necessary to reduce the incidence of postoperative infectious complications and improve the survival of patients after curative resection of gastric cancer., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Cancer cells are often found postoperatively at surgical resection margins (RM) in patients with gastric cancer because of submucosal infiltration or hesitation to secure adequate RM. This study was designed to evaluate risk factors for microscopic positive RM and to clarify which patients should undergo intraoperative frozen section diagnosis (IFSD)., Methods: Patients who underwent R0/1 gastrectomy for gastric adenocarcinoma between 2000 and 2018 in a single cancer center in Japan were studied. We divided the patients into a positive RM group and negative RM group according to the results of definitive histopathological examinations. We performed multivariate analysis to analyze risk factors for positive RM by and used the identified risk factors to risk stratify the patients., Results: A total of 2757 patients were studied, including 49 (1.8%) in the positive RM group. The risk factors significantly associated with positive RM were remnant gastric cancer (odds ratio [OR] 4.7), esophageal invasion (OR 6.3), tumor size ≥80 mm (OR 3.9), and a histopathological diagnosis of undifferentiated type (OR 3.6), macroscopic type 4 (OR 3.7), or pT4 disease (OR 4.6). On risk stratification analysis, the incidence of positive RM was 0.1% without any risk factors, increasing to 0.4% with one risk factor, 3.1% with two risk factors, 5.3% with three risk factors, 21.3% with four risk factors, and 85.7% with five risk factors., Conclusions: The risk of macroscopically positive RM increased in patients who have risk factors. IFSD should be performed in patients who have four or more risk factors.

Background/aim: Endothelial cell-specific molecule-1 (ESM-1) is a soluble proteoglycan which has important role in various biological events. We investigated the impact of the ESM-1 expression in cancer tissues on outcomes in stage II/III gastric cancer patients who received adjuvant S-1 chemotherapy., Patients and Methods: The ESM-1 mRNA expression in cancerous tissues and adjacent normal mucosa from 253 patients was measured. The associations between the ESM-1 gene expression and the survival and clinicopathological features were investigated., Results: A significant association was observed between high ESM-1 expression and undifferentiated adenocarcinoma. The overall survival curve was significantly lower in patients with high ESM-1 expression than in those with low expression (p=0.005). High ESM-1 expression was a significant independent prognosticator (HR=2.291, p=0.007)., Conclusion: ESM-1 gene expression in cancerous tissues is an important prognosticator in stage II/III gastric cancer patients who received adjuvant S-1 chemotherapy., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

An 81-year-old man with esophageal cancer had undergone subtotal thoracic esophagectomy and retrosternal reconstruction using a gastric tube. He developed anemia. Gastrointestinal endoscopy was performed, which revealed a tumor in the posterior wall of the lower part of the gastric tube. Biopsy revealed well-differentiated adenocarcinoma. There was no lymph node metastasis and no distal metastasis on CT. We performed partial resection of the stomach tube because of his age and physical condition. We identified the position of the tumor by upper gastrointestinal series CT and gastrointestinal endoscopy. The tumor was located on the posterior wall of the lower part of the gastric tube and the back of the sternum lower border. Marking was performed by gastrointestinal endoscopy before operation. We simulated the operation and decided to perform laparostomy without sternotomy incision. We cut the anterior wall of the gastric tube in front of the tumor using the endoscope. We could then confirm the diagnosis of cancer, and clipped and removed the tumor from the posterior wall. The resected site was sutured with 4-0 absorbable thread. The pathological diagnosis was T1a(M)N0M0, ly0, v0, PM0, DM0, pStage ⅠA.

Background: Body weight loss (BWL) is frequently observed in gastric cancer patients who undergo gastrectomy for gastric cancer. The risk factors for severe BWL after gastrectomy remain unclear., Methods: The present study retrospectively examined patients who underwent curative gastrectomy for gastric cancer between January 2012 and June 2014 at Kanagawa Cancer Center. All patients received perioperative care based on the enhanced recovery after surgery protocol. The %BWL value was calculated based on the percentage of body weight at 1 month after surgery in comparison to the preoperative body weight. Severe BWL was defined as %BWL > 10%. The risk factors for severe BWL were determined by both univariate and multivariate logistic regression analyses., Results: There were 278 patients examined. The median age of the patients was 68 years. The operative procedures included total gastrectomy [n=97; open (n=61) and laparoscopic {n=36)] and distal gastrectomy (n=181). Surgical complications of grade ≥ 2 (as defined by the Clavien-Dindo classification) were observed in 37 patients, these included: pancreatic fistula (n=9), anastomotic leakage (n=5), and abdominal abscess (n=3). There were no cases of surgery-associated mortality. Both univariate and multivariate logistic analyses demonstrated that surgical complications, and total gastrectomy were significant risk factors for severe BWL., Conclusions: Surgical complications and total gastrectomy were identified as being significant risk factors for severe BWL in the 1 st month after gastrectomy. To maintain body weight after gastrectomy, physicians should pay careful attention to patients who undergo total gastrectomy and those who develop surgical complications., (Copyright © 2017. Published by Elsevier Taiwan LLC.)

Background: The therapeutic efficacy of dissection of the splenic hilar lymph nodes (#10) has not been fully evaluated in locally advanced proximal gastric cancer (LAGC) invading the greater curvature of the stomach., Methods: Patients with LAGC invading the greater curvature who underwent D2 total gastrectomy with splenectomy between January 2000 and May 2015 were retrospectively examined. The therapeutic value index was calculated by multiplying the metastatic rate of a station and the 5-year survival of patients with metastasis to that station; the metastatic rate and the index of each lymph node station were then compared., Results: In total, 82 patients were eligible for the present study. The most frequent metastatic node was #3, followed by #1, #4d and #7, #2, #4sa and #10, and #4sb and #9. These lymph nodes had a metastatic rate of more than 10%. The node station with the highest index was #3, followed by #7, #4d, #1, #4sb, #4sa, #2, and #9. The index of #10 was lower, but exceeded those of #8a and #11p., Conclusions: The metastatic rate of #10 was relatively high at 13%, and the therapeutic value index was as high as those of other suprapancreatic nodes. D2 dissection for proximal cancer located in the greater curvature should include removal of node #10.

Neoadjuvant chemotherapy(NAC)is thought to be effective to improve the outcomes in patients with adenocarcinoma of the esophago-gastric junction(AEG). We encountered 3 patients who were confirmed as having a pathological complete response following gastrectomy after NAC. The first patient had Siewert type II and clinical Stage III AEG, the second patient had Siewert type I and clinical Stage III AEG, while the third had Siewert type II and clinical Stage II AEG. Two patients received NAC with 2 courses of S-1 plus cisplatin, while the third patient received 2 courses of docetaxel, S-1, and cisplatin. All of the patients were treated with D2 gastrectomy after the NAC, and remain alive at more than 40 months after initial chemotherapy treatment without recurrence. We report the details of these 3 cases and review the literature.

A 69-year-old woman who underwent laparoscopic assisted distal gastrectomy for early gastric cancer(pathological T1bN1M0)in June 2011was admitted to the hospital because of abdominal pain in May 2015.A n abdominal CT scan showed ileus caused by a transverse colon tumor and ascending colon perforation.We performed emergency right hemicolectomy and diverting ileostomy.The postoperative pathological findings revealed poorly differentiated adenocarcinoma and signetring cell carcinoma similar to the gastric cancer resected 4 years ago.Immunohistochemical findings showed that the colon tumor was positive for CK7, but negative for CK20 and expressed a gastric mucin phenotype.From these findings, the colon tumor was diagnosed as a metastasis from early gastric cancer.Colon metastasis from early gastric cancer is rare and the diagnosis is difficult in some cases.We herein report this case and discuss the clinical and pathologic features of colon metastasis from gastric cancer.

A 63-year-old man with dysphagia was referred to our hospital. He was found to have a type 2 tumor extending from the lower thoracic esophagus to the esophagogastric junction via upper gastrointestinal endoscopy. A biopsy revealed adenocarcinoma with overexpression of the human epidermal growth factor type 2(HER2). The tumor was type I according to Siewert's classification, as the epicenter of the tumor was 27mm to the oral side from the esophago-gastric junction. The clinical diagnosis was T3N1M1, stage IV according to the Japanese Classification of Gastric Carcinoma, and T3N2M0, stage III per the Japanese Classification of Esophageal Cancer. He was treated with neoadjuvant chemotherapy consisting of 6 courses of capecitabine(1,000mg/m / / 2: days 1-14)plus cisplatin(80mg/m2: day 1)and trastuzumab(8mg/kg: day 1 of the first course, 6mg/kg: day 1 after the second course). Computed tomography(CT)and upper gastrointestinal endoscopy showed shrinkage of the primary esophagogastric cancer and lymph node metastases. The patient had a partial response and underwent radical esophagectomy. The pathological findings revealed a T3N2M0, stage III tumor; the tumor was determined to be Grade 1b owing to the chemotherapeutic effect. At a follow-up examination 1 year and 7 months after the start of chemotherapy, the patient is alive without recurrence.

We report a case of advanced esophageal and gastric cancer that was successfully treated via multimodal therapy. A 65- year-old man with hoarseness was referred to our hospital. He was diagnosed with clinical T4aN2M0, Stage IV esophageal squamous cell carcinoma and clinical T3N1M0, Stage II B gastric adenocarcinoma. He was treated with 3 courses of chemotherapy, administered over 4weeks, with S-1(80mg/m / / 2: day 1-14), cisplatin(60mg/m2: day 1), and docetaxel(40mg/m2: day 1). Computed tomography(CT)revealed shrinkage of the primary esophageal tumor, gastric tumor, and lymph node metastases. Next, we selected definitive radiation chemotherapy(CRT), because lymph node metastases remained around the bilateral recurrent laryngeal nerves. After CRT with a total 60 Gy plus administration of 5-fluorouracil and cisplatin, CT showed that the primary esophageal tumor and lymph node metastases had disappeared. Then, distal gastrectomy was performed for the remaining gastric cancer, as part of the multimodal therapy. After gastrectomy, no systemic chemotherapy was performed. At a follow-up examination 5 years and 6 months after the start of chemotherapy, the patient is alive without recurrence.

Background: Sarcopenia is a decrease in both muscle mass and strength. It remains unclear whether sarcopenia is associated with morbidity after gastric cancer surgery. This study evaluated the impact of sarcopenia on the morbidity of gastric cancer surgery., Methods: A total of 293 gastric cancer patients who underwent curative surgery between May 2011 and June 2013 were retrospectively examined. Patients with performance status 3 or 4 were excluded. Preoperative lean body mass (LBM) was evaluated by bioelectrical impedance analysis and expressed as LBM index. Preoperative muscle function was measured by hand grip strength (HGS). The cutoff values were the gender-specific lowest 20 %. Grade 2 or higher morbidities, as retrospectively evaluated by the Clavien-Dindo classification, were obtained from the patient record. The risk factors for morbidity were examined by univariate and multivariate analyses., Results: Morbidity was observed in 39 patients (13.3 %), including 7 with pancreatic leakage, 12 with anastomotic leakage, and 4 with intraabdominal abscesses, but no mortality was observed. The univariate analysis showed that male gender, total gastrectomy, splenectomy, and a low HGS were significant risk factors for morbidity. A low LBM was not a significant risk factor. A low HGS, male gender, and total gastrectomy remained significant in the multivariate analysis., Conclusions: A low hand grip strength was a significant risk factor for morbidity after gastric cancer surgery. The importance of the hand grip strength as a risk factor should be examined in future prospective studies.

Background: Lean body mass loss after surgery, which decreases the compliance of adjuvant chemotherapy, is frequently observed in gastric cancer patients who undergo gastrectomy for gastric cancer. However, the risk factors for loss of lean body mass remain unclear., Methods: The current study retrospectively examined the patients who underwent curative gastrectomy for gastric cancer between June 2010 and March 2014 at Kanagawa Cancer Center. All the patients received perioperative care for enhanced recovery after surgery. The percentage of lean body mass loss was calculated by the percentile of lean body mass 1 month after surgery to preoperative lean body mass. Severe lean body mass loss was defined as a lean body mass loss greater than 5 %. Risk factors for severe lean body mass loss were determined by both uni- and multivariate logistic regression analyses., Results: This study examined 485 patients. The median loss of lean body mass was 4.7 %. A lean body mass loss of 5 % or more occurred for 225 patients (46.4 %). Both uni- and multivariate logistic analyses demonstrated that the significant independent risk factors for severe lean body mass loss were surgical complications with infection or fasting (odds ratio [OR] 3.576; p = 0.001), total gastrectomy (OR 2.522; p = 0.0001), and gender (OR 1.928; p = 0.001)., Conclusions: Nutritional intervention or control of surgical invasion should be tested in future clinical trials for gastric cancer patients with these risk factors to maintain lean body mass after gastrectomy.

Background and Aims: Compliance with S-1 adjuvant chemotherapy is not satisfactory, and the aim of the present study was to clarify risk factors for the continuation of S-1 after gastrectomy., Methods: This retrospective study selected patients who underwent curative D2 surgery for gastric cancer, were diagnosed with stage II/III disease, had a creatinine clearance >60 ml/min, and received adjuvant S-1 at our institution between June 2010 and March 2014. The time to S-1 treatment failure (TTF) was calculated., Results: Fifty-eight patients were selected for the present study. When the TTF curves stratified by each clinical factor were compared using the log-rank test, lean body-mass loss (LBL) of 5 % was regarded as a critical cutoff point. Univariate Cox's proportional hazard analyses demonstrated that LBL was a significant independent risk factor for continuation. The 6-month continuation rate was 91.7 % in patients with an LBL < 5 %, and 66.3 % for patients with an LBL > 5 % (p = 0.031)., Conclusions: The present study demonstrated that LBL might be an important risk factor for a decrease in compliance to adjuvant chemotherapy with S-1 in patients with stage II/III gastric cancer who underwent D2 gastrectomy. A multicenter, double-blinded, prospective cohort study is necessary to confirm whether LBL would affect adjuvant S-1 continuation.

Background: Clinical T1 gastric cancer has low metastatic potential to lymph nodes and is generally curable by local treatment. Endoscopic resection can preserve the whole stomach and does not impair the patient's quality of life; however, its indication is strictly limited to the subset of patients without nodal metastasis. The study was designed to predict reliably the patients without nodal metastasis based only on the clinical information., Methods: We examined patients with clinical T1 disease who were treated with surgery. The clinically available information was evaluated for its ability to predict nodal metastasis by logistic regression model. Then, the predictive ability of the logistic regression model using the risk factors for nodal metastasis was evaluated by a receiver operating characteristic curve., Results: A total of 511 patients were entered into this study. The clinical depth (cT1a or cT1b), maximal tumor diameter, and pathological type were confirmed to be significantly different between patients with and without nodal metastasis. The cutoff value of the tumor diameter differed depending on the histology and clinical depth: 79 mm for differentiated type and 48 mm for undifferentiated type in cT1a tumors, and 43 mm for differentiated type and 11 mm for undifferentiated type in cT1b tumors. According to these criteria, 348 of the 511 patients (68.1 %) were classified to have predictive N0 status. The negative predictive value was 95.7 % (95 % confidence interval 94.0-97.5 %)., Conclusions: The predictive criteria based on the multivariate logistic model identified that almost two-thirds of the patients with clinical T1 gastric cancer were possible candidates for endoscopic treatment.

Background: Postoperative infectious complications increase disease recurrence in colorectal cancer patients. We herein investigated the impact of infectious complications on gastric cancer recurrence after curative surgery., Methods: In total, 502 patients who underwent R0 resection for gastric cancer were reviewed. Patients were classified into those with infectious complications (IC group) and those without infectious complications (NO group). The risk factors for recurrence-free survival (RFS) were identified., Results: Infectious complications, which occurred in 52 patients (10.4%), included pneumonia, ileus with a systemic inflammatory reaction, anastomotic leakage, and intraperitoneal abscess. The overall 5-year RFS rate was 83% in the NO group and 58% in the IC group (p = 0.000). Multivariate analysis demonstrated that age, ASA score, stage, and infectious complications were significant predictors of RFS., Conclusions: Infectious complications were a risk factor for gastric cancer recurrence. To avoid causing infectious complications, the surgical procedure, surgical strategy, and perioperative care should be carefully planned.

Harvesting lymph nodes (LNs) after gastrectomy is essential for accurate staging. This trial evaluated the efficiency and quality of a conventional method and a methylene blue-assisted method in a randomized manner. The key eligibility criteria were as follows: (i) histologically proven adenocarcinoma of the stomach; (ii) clinical stage I-III; (iii) R0 resection planned by gastrectomy with D1+ or D2 lymphadenectomy. The primary endpoint was the ratio of the pathologic number of harvested LNs per time (minutes) as an efficacy measure. The secondary endpoint was the number of harvested LNs, as a quality measure. Between August 2012 and December 2012, 60 patients were assigned to undergo treatment using the conventional method (n=29) and the methylene blue dye method (n=31). The baseline demographics were mostly well balanced between the 2 groups. The number of harvested LNs (mean±SD) was 33.6±11.9 in the conventional arm and 43.4±13.9 in the methylene blue arm (P=0.005). The ratio of the number of the harvested LNs per time was 1.12±0.46 LNs/min in the conventional arm and 1.49±0.59 LNs/min in the methylene blue arm (P=0.010). In the subgroup analyses, the quality and efficacy were both superior for the methylene blue dye method compared with the conventional method. The methylene blue technique is recommended for harvesting LNs during gastric cancer surgery on the basis of both the quality and efficacy.

We report the case of a solitary pulmonary tumor, which was diagnosed as recurrent early gastric cancer by detailed pathological examinations. A 59-year old man initially underwent total gastrectomy for gastric adenocarcinoma located at the esophago-gastric junction. A pathological examination indicated a papillary adenocarcinoma (pap ) that had invaded the submucosal layer (sm²), but had not metastasized to the regional lymph nodes (n0). The final diagnosis was P0H0M0T1bN0, Stage IA. Chest computed tomography (CT) 30 months after primary surgery indicated a solitary tumor with a diameter of 9 mm at S3 of the left lung. A positron emission tomography (PET)-CT scan showed an accumulation of ¹⁸F-fluordeoxy-glucose (FDG18) at the same location. Lung cancer was suspected and the patient was given a left upper lobectomy. The resected tumor was diagnosed as gastric cancer metastatic adenocarcinoma by permanent pathological examination. The tumors showed similar histology and immuno histochemical findings for CK7, CK20, TTF-1, SP-A, CDX-2, and HER2 . Early gastric cancer is an almost curable disease and recurrence is very rare. We report the details of this case and review the literature.

Background: T1 gastric cancer can be diagnosed only by endoscopy and is almost curable by local treatment. It has been unclear how a multidetector-row computed tomography (CT) evaluation is valuable for clinical T1 patients., Methods: Patients with clinical T1 disease, as diagnosed by endoscopy and treated with endoscopic submucosal dissection (ESD) or surgery between October 2000 and October 2007, were examined. The efficacy of CT was evaluated by the reversal rate of endoscopic T1 by CT, the incidence of clinical M1 disease, and the accuracy of diagnosing pathological N+ disease in patients who received surgery. To confirm metachronous distant and nodal metastases, the disease-free survival (DFS) also was evaluated., Results: A total of 761 patients, 236 treated by ESD and 525 treated with surgery, were examined. None of the patients had an endoscopic diagnosis of clinical T1 reversed by CT. No clinical M1 disease was found. Among the 525 patients who underwent surgery, 8 showed clinical N+ disease (1.5 %), while 47 demonstrated pathological N+ disease (8.9 %). The accuracy, sensitivity, specificity, positive predictive value, and negative predictive values were 90.3, 4.3, 98.7, 25, and 91.3 %, respectively. The 5-year DFS rate was 93.6 % (95 % confidence interval 91.4-95.8 %)., Conclusions: The present study suggests that diagnostic value of CT is limited for staging of clinical T1 gastric cancer patients, because the reversal rate of endoscopic T1 by CT was very low, clinical M1 disease was rare, the diagnosis of N+ status was unreliable, and metachronous M1 and N+ findings were rare.

Background: The factors that affect the 6-month continuation of adjuvant chemotherapy with S-1 have not been fully evaluated. The objective of this retrospective study was to clarify the risk factors for 6-month continuation of S-1 adjuvant chemotherapy., Methods: The study selected patients who underwent curative D2 surgery for gastric cancer, were diagnosed with stage 2 or 3 disease, had a serum creatinine level of ≤ 1.2 mg/dl, and received adjuvant S-1 between June 2002 and March 2011., Results: One hundred of these patients were eligible for the present study. A comparison of 6-month continuation of S-1 stratified by various clinical factors, using the log-rank test, revealed a marginally significant difference in creatinine clearance (CCr) between those patients who continued for 6 months and those who did not. A CCr of 60 ml/min was regarded as the critical point. Uni- and multivariate Cox's proportional hazard analyses demonstrated that CCr was the only significant independent factor for the prediction of 6-month continuation. The 6-month continuation rate was 72.9 % in the patients with CCr ≥ 60 ml/min, and 40.0 % in patients with CCr <60 ml/min (P = 0.015). Adverse events occurred more frequently and earlier in the patients with CCr <60 ml/min than in those with CCr ≥ 60 ml/min., Conclusions: CCr <60 ml/min was a significant risk factor for 6-month continuation of S-1 adjuvant chemotherapy, even though the renal function was judged as normal by the serum creatinine level. Careful attention is therefore required for S-1 continuation in patients with CCr <60 ml/min.

We report a case of advanced gastric carcinoma treated successfully by four courses of neoadjuvant chemotherapy (NAC) with paclitaxel and cisplatin. The patient was a 43-year-old man with advanced gastric cancer, clinically diagnosed as P0H0M0CY0T3N2, which had invaded the upper body of the stomach and esophagus. He was entered into a clinical trial and received the following NAC regimen: paclitaxel 80 mg/m(2), and cisplatin 25 mg/m(2), on days 1, 8, and 15, followed by a rest on day 22, as one course. The lymph nodes had reduced in size to 59% after two courses and to 40% after four courses, with no sign of severe toxicity. Subsequently, he underwent D2 total gastrectomy with pancreatico-splenectomy. On microscopic examinations, no tumor cells were detected in the ulcer scar of the resected stomach or the regional lymph nodes. Thus, we discuss the potential of long-term NAC, especially for responders to two initial courses.

Background: The risk of surgery for gastric cancer has not been fully evaluated, and this study aimed to assess the severity of postoperative complications after D2 or modified D2 gastrectomy in elderly patients., Methods: Eligible patients were retrospectively selected from the Kanagawa Cancer Center database between 1990 and 2009 based on the following criteria: age ≥80 years and D2 or modified D2 gastrectomy as a primary treatment for gastric cancer. The severity of complications was evaluated using the Clavien-Dindo classification., Results: A total of 83 patients with a median age of 82 years (range 80-88 years) were entered in this study. Sixty (72 %) had at least one co-morbid condition. American Society of Anesthesiologists scores were 2 in 66 patients and 3 in 17 patients. The extent of gastrectomy was distal in 65 (78 %) and total in 18 (22 %) patients. The procedure used for lymphadenectomy was modified D2 in 38 (46 %) and D2 in 45 (54 %) patients. Altogether, 18 complications were observed in 15 patients. The overall morbidity rate was 18 % [95 % confidence interval (CI) 9.7-26.2 %], and the mortality rate was 3.6 % (95 % CI 0-7.6 %). Complications were classified as grade 2 (n = 9), grade 3a (n = 1), grade 3b (n = 4), grade 4 (n = 1), and grade 5 (n = 3). Severe complications (≥ grade 3) occurred in 8.4 % (95 % CI 2.4-14.4 %)., Conclusions: The morbidity rate was acceptable, but that of severe complications was high, suggesting that surgery for gastric cancer in elderly patients is risky and should be limited.

Background: Some patients experience a recurrence of cancer even after curative D2 gastrectomy followed by adjuvant S-1 chemotherapy. The objective of this retrospective study was to clarify the survival and prognosticators in these patients., Methods: The study selected patients who underwent curative D2 surgery, were diagnosed with stage II, IIIA, or IIIB cancer, received adjuvant S-1 for more than 4 weeks, and experienced recurrence confirmed by an imaging study., Results: A total of 34 patients were evaluated. The median overall survival (OS) was significantly longer in the 26 patients who received palliative chemotherapy than that in the 8 who did not (8.5 vs. 2.5 months, P = 0.002). Only 1 patient received S-1, 21 received taxane-containing regimens, and 4 received irinotecan plus cisplatin as the first-line chemotherapy. Univariate and multivariate analyses showed that the histological type was only independent significant prognosticator., Conclusions: These results suggested that the survival did not reach the level expected for first-line chemotherapy. The histological type was a significant prognosticator in patients who experienced recurrence after adjuvant S-1 therapy and thereafter received palliative chemotherapy.

We previously showed that carbon ion irradiation can inhibit the expression of the anillin (ANLN) gene, which is regulated by the activation of the phosphatidylinositol-3-kinase (PI3K)/Akt signaling pathway associated with metastasis. The purpose of this study is to compare the effects of carbon ion irradiation on the PI3K/Akt signaling pathway to those of photon irradiation. Our study showed that carbon ion irradiation of human lung adenocarcinoma cells A549 decreased their invasion more effectively than photon irradiation did. We found that carbon ion irradiation reduced the nuclear localization of ANLN at lower dose, but did not affect its expression. Low-dose carbon ion irradiation also reduced the level of phosphorylated Akt compared to untreated controls, whereas photon irradiation did not. These results suggest that carbon ion irradiation effectively suppresses the metastatic potential of A549 cells by suppressing the PI3K/Akt signaling pathway.

Background: Thymidylate synthase (TS) catalyzes the methylation of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP) and is a key enzyme for DNA synthesis. High expression of TS is thought to be associated with poor prognosis in some kinds of cancers. However, this association has not been clarified for nonsmall cell lung carcinoma. In the current study, the authors investigated the clinicopathologic significance of TS mRNA levels and the correlation with cellular proliferation in patients with lung adenocarcinoma., Methods: The expression levels of TS mRNA were measured in 47 lung adenocarcinoma tissues using the Taq-Man real-time reverse transcriptase-polymerase chain reaction (RT-PCR) method and examined the clinicopathologic significance of TS expression. To clarify the correlation between TS expression level and cell proliferation, the Ki-67 labeling index was also examined using immunohistochemical staining., Results: A positive correlation was observed between the expression levels of TS mRNA and stage of disease, lymph node metastasis, or tumor differentiation (P = .015). The higher expression group of TS mRNA showed a significantly poorer prognosis than the group with lower expression (P = .042). Moreover, there was a strong correlation noted between the expression levels of TS mRNA and the Ki-67 labeling index (P = .009)., Conclusions: The results of the current study demonstrated that TS may be associated with stage of disease, lymph node metastasis, tumor differentiation, prognosis, and tumor cell proliferation. These results suggest that the expression levels of TS mRNA may be useful for predicting the malignant potential in patients with lung adenocarcinoma., (Copyright 2006 American Cancer Society.)

A 62-year-old man was revealed to have type 2 gastric cancer with synchronous liver metastasis. We considered liver metastasis to be a prognostic factor, and performed two courses of combination thermochemotherapy consisting of hepatic arterial infusion of MMC and TS-1 and thermotherapy. Partial response was observed in the liver metastases,but the primary lesion showed no changes; therefore, we performed four courses of combination thermochemotherapy consisting of TS-1/CDDP therapy and thermotherapy. By the end of three courses of this therapy,the primary lesion had cicatrized,and endoscopic biopsy revealed no cancer cells. These results suggest that gastric cancer,in which liver metastasis is considered to be a prognostic factor,can be effectively treated by combination therapy with hepatic arterial infusion therapy, followed by thermochemotherapy for the primary lesion.

The Noguchi criteria are useful in assessing the prognosis of patients with small lung adenocarcinoma. Although there is a significant difference in prognosis between type A or B and type C, it is difficult in some cases to distinguish these types accurately by microscopy. In this study, we used immunohistochemistry to examine alpha-smooth muscle actin (alpha-SMA) produced by active fibroblasts in 25 pulmonary adenocarcinomas less than 2 cm in diameter. Eleven of type C (61%) showed positive staining for alpha-SMA, whereas no positive cases were seen in type A or B. The incidence of cancerous blood vessel and lymphatic invasion were significantly higher in alpha-SMA positive cases than in negative cases, and the positive cases showed poorer prognosis. These findings indicate that immunohistochemical detection of alpha-SMA is useful and essential for histological typing by the Noguchi criteria.

Autonomous or continuous granulocyte colony-stimulating factor. (G-CSF)-production in malignant neoplasms is considered to induce leukocytosis without apparent infection. We examined G-CSF gene expression in human non-small cell lung cancer (NSCLC) and discussed its clinicopathological significance. Northern blot analysis revealed G-CSF gene expression in 14 of 84 surgical specimens (16.7%, 10/30 squamous cell carcinoma, 3/50 adenocarcinoma, 1/4 large cell carcinoma). Eight patients (57.1%, 8/14) with NSCLC showing G-CSF gene-expression had peripheral blood leukocytosis (> 8,000/microliter). The prognosis was significantly worse in 10 stage I or II NSCLC showing G-CSF gene expression (p < 0.01, Cox-Mantel test). These findings suggest that G-CSF gene expression is common event in the early stage of primary NSCLC, while it cannot completely explain the leukocytosis induced by lung cancer.

Skeletal muscle is one of the most unusual sites of metastasis from any malignancy. We report on a case of skeletal muscle metastasis from colonic carcinoma, and review seven previously reported cases. The patient was a 66-year-old man who exhibited a painful metastatic mass in the right major teres muscle six months after surgery for colonic carcinoma. He underwent three operations and one course of arterial infusion chemotherapy, but died of carcinoma after two years and seven months. In seven previous cases and in the present case (3 males and 5 females, aged between 30 and 75 years), the sites of the primary lesion and metastatic lesion in skeletal muscle were diverse. The interval between primary carcinoma and relapse ranged from synchronous to 5 years. Spontaneous pain in the recurrent region was a characteristic symptom. Surgical removal of the metastatic lesions relieved pain. Prognosis was considered poor. However, complete resection of the metastatic lesion at a time when no other recurrent lesions were present might have cured the patient.

Production of cathepsin B by tumor cells has been linked to metastatic potential in several experimental models. Sections of 95 primary lung adenocarcinomas were examined for expression of cathepsin B using a standard avidin-biotin immunohistochemical technique. Staining for cathepsin B was observed in 22.1% of all cases and 28.0% of those of the Clara cell type. In Clara cell adenocarcinomas, cathepsin B expression correlated with positive lymph node status, presence of distant metastases, and poor prognosis (P < 0.05). However, no correlation with clinical outcome was observed in other cell types. Our data suggest that cathepsin B may be involved in invasion and metastasis in Clara cell lung adenocarcinoma.

A cumurative operation for apical invading lung cancer was performed in a 49-year-old man. Left upper lobectomy was combined with resection of the chest wall, left subclavian artery and brachial nerve, following reconstruction of the left subclavian artery with an artificial vessel graft. Our approach involved sternotomy, antero-lateral thoracotomy and cutting of the clavicle. This approach is useful for apical lung cancer without wide invasion of the posterior chest wall, as in this patient. Although radiotherapy and chemotherapy were administered, the patient succumbed to hematogenous metastases 15 months after the operation. We suggest that adjuvant therapy may be needed for apical invading lung cancer, even if the tumor is believed to be completely resected.

The three-dimensional structure of the collagen network of normal mucosa, hyperplastic polyps, tubular adenoma, villous adenoma and adenocarcinoma of the human large intestine was examined by scanning electron microscopy after cell-maceration with a low temperature NaOH solution. In the normal large intestine, the surface of the sub-basal laminar collagen sheath lining the crypts was generally smooth. In hyperplastic polyps, the crypts extended and the sub-basal collagen network protruded from the surrounding normal tissue. The sub-basal laminar collagen sheath was more densely arranged near the openings of the crypts and on the luminal surface than in deeper regions of the crypts. In tubular adenoma, the tumor glands showed meandering, bending, and divisions. The sub-basal laminar collagen sheath was composed of densely packed collagen fibrils. In villous adenoma, the sub-basal laminar collagen sheath formed foliate or linguiform villous cores projecting sharply into the lumen. In adenocarcinoma, the sub-basal laminar collagen sheath exhibited a dense arrangement of fibrils in the central region of the tumor. Toward the marginal region, the collagen sheaths surrounding tumor glands became thinner, and at the edge of the marginal region, basket-like collagen sheaths were observed around individual tumor cells infiltrating the interstitium. Such a tumor lesion was frequently surrounded by a thick collagen fiber zone.

We delivered preoperative radiotherapy with intratumoral injection (ITI) of radiosensitizer, 5-bromodeoxyuridine for patients with locally advanced cancer originating in lower rectum. We identified immunohistochemically the tumor cells that incorporated BrdU, and evaluated the radiosensitizing effect of BrdU histopathologically. (1) BrdU-labeled nuclei of cancer cells were identified in twenty-three cases out of 24 (96%). Mean labeling index was 18.5%, and tended to decrease as time progressed. (2) The parameters representing volume of residual tumor nests (Tumor Nest Index) or degrees of tumor extension (Depth of Extramural Tumor and Depth of Extramural Fibrosis) for patients with ITI were compared to those for patients without ITI. Those parameters tended to decrease when ITI was combined with radiotherapy. However, the difference was not significant statistically. Intratumorally injected BrdU can incorporate with cancer cells, but a methodological invention is required for yielding clinically measurable radiosensitization.

Among 287 patients underwent pulmonary resection between Mar 1978 and Dec 1989, 49 were proved pathologically to have their primary tumor of 3 cm or less in the greatest dimension. Twelve of these 49 classified to stage III A by the modiastinal lymph node metastasis or stage IV by the pulmonary metastasis. The histologic type of tumor was adenocarcinoma in 10 and squamous cell carcinoma in 2. Mode of surgical treatment consisted of pneumonectomy in 2, lobectomy in 8, segmentectomy or wedge resection in 2, and complete mediastinal lymph node dissection was performed in all but 2. Survival rate in 1, 3, 5 year was 100%, 38.1% and 38.1% in 9 with stage III A disease, and 100%, 100% and 50% in 3 with stage IV disease, respectively, and significant difference was noted in comparison with control group with larger tumor in each stage (p less than 0.05). From these results, we concluded that patients with small primary tumor could expect longer survival after surgical treatment, even if mediastinal lymph node metastasis or pulmonary metastasis was present.

Between August 1982 and February 1985, 13 patients with pathological stage I non-small cell lung cancer received postoperative chemotherapy with ACNU, ADM and 5-FU. Nine patients had squamous cell carcinoma, two adenocarcinoma, and two large cell carcinoma. All patients were alive in August, 1985, but four of them had recurrent disease. The site of recurrence was the brain in three and the contralateral lung in one. Of these four patients, three had t2n0(-) p0 squamous cell carcinoma and one t1n0(-) p1 large cell carcinoma. In a control group consisting of six squamous cell carcinoma and six adenocarcinoma, recurrence occurred in one patient with t1n0(-) p0 squamous cell carcinoma. Although the treated group had unfavorable conditions of cell type and tumor size, there was no evidence that this combination chemotherapy could control recurrence of the tumor under these conditions.

Thirty-five peripheral carcinomas of human lungs were morphologically examined in comparison with the bronchiolar nonciliated epithelium. Clara cell granules were found not only in 21 cases of papillary adenocarcinoma, including three of classical bronchiolo-alveolar carcinoma, but also two of acinar and four of solid carcinoma. The granules of tumor cells were identical to those of bronchiolar nonciliated cells on histochemical and ultrastructural levels. Most granules consisted of a monotonous and finely granular matrix, but there were variants containing fingerprint-like lamellae and small vesicles. These variants were also found in nonciliated cells of normal bronchiolar epithelium. The amount of granules was related to the degree of tumor differentiation. It is suggested that most peripheral carcinomas of the lungs have a potential for Clara cell differentiation, irrespective of whether they exhibit any histologic appearances.

A 46-year-old man had a general health check including an upper gastrointestinal series, gastric endoscopy and biopsy. He was diagnosed as advanced gastric cancer and hospitalized for surgery. Preoperative abdominal CT scan examination was performed, and a mass was incidentally detected in the left kidney. Further examination, ultrasound survey and selective renal angiography, confirmed a renal cancer. The patient had had no macroscopic or microscopic hematuria. Gastric resection with lymph node dissection and left nephrectomy were performed and then both cancers were radically removed. Pathologically, gastric cancer was poorly differentiated adenocarcinoma and renal cancer was carcinoma of the clear cell type.

A case of early esophageal cancer, 2.5 cm in length, located just above the esophagogastric junction is presented. This cancer seemed to originate from the fundic gland of the esophagus, because it consisted of the submucosal invasion of well-differentiated adenocarcinoma which was almost completely covered with the squamous cell mucosa of the esophagus. This patient was referred to our clinic because of lower to be a small-cell carcinoma of the lung extending to the mediastinum. He died of the lung cancer one year after operation.