Search

The patient was a 61-year-old man with a diagnosis of carcinoma of the pancreatic head. Abdominal computed tomography( CT)showed no distant metastasis, and he underwent subtotal stomach-preserving pancreatoduodenectomy. Immediately after surgery, he received liver perfusion chemotherapy with 5-fluorouracil followed by systemic gemcitabine. Eighteen months after surgery, CT revealed liver metastasis in the S6 segment, and partial hepatectomy was performed. The pathological diagnosis was liver metastasis of pancreatic cancer. Postoperatively, the patient was treated with gemcitabine and S-1 therapy for 1 year and then switched to S-1 monotherapy for about 6 months. Four years after the initial surgery, CT showed 2 metastases in the right lung. After 2 months of S-1 monotherapy, wedge resection of the upper and lower lobes of the right lung was performed. Gemcitabine and nab-paclitaxel therapy were administered, after the metastasectomy, but pleural dissemination appeared on CT 5 years after the initial surgery. Modified FOLFIRINOX therapy was started and continued for 8 months, but CT revealed further disseminated lesions in the diaphragm. Palliative irradiation was provided, but the disease gradually progressed. After multidisciplinary treatment, the patient survived for 6 years and 3 months after the initial surgery.

A 66-year-old man was referred to our hospital with fever and abdominal pain. CT showed a mass in the intrapancreatic bile duct but no wall thickness in the perihilar bile ducts. Neither regional lymphadenopathy nor distant metastasis was observed. Biliary cytology showed adenocarcinoma. The diagnosis was distal cholangiocarcinoma, and pancreatoduodenectomy was performed. Intraoperative frozen section examination of the ductal resection margins at the right and left hepatic ducts was positive for carcinoma in situ, and the operation ultimately completed with R1 resection. Histological examination confirmed a diagnosis of cholangiocarcinoma with superficial spread and a single positive lymph node. Adjuvant chemotherapy with S-1 was administered for 1 year. Anastomotic recurrence at the hepaticojejunostomy was found 5 years after resection; biopsy specimens revealed adenocarcinoma. Thereafter, S-1 chemotherapy was resumed, and the patient remains alive and well 9 years and 1 month after resection.

Background: This study aimed to evaluate the adequate extent of regional lymphadenectomy according to tumor location and the impact of number-based nodal classification on survival in patients with non-ampullary duodenal adenocarcinoma (NADAC)., Methods: A total of 85 patients with NADAC who underwent surgery were enrolled. The frequency of metastasis was calculated for each node group in the respective tumor locations for 63 patients who underwent lymphadenectomy for pT2-pT4 tumor., Results: The frequency of metastasis in the pancreaticoduodenal (nos. 13 and 17) and superior mesenteric artery (no. 14) nodes was high (16.7 %-52.3 %) regardless of tumor location. Metastasis in the perigastric (nos. 3 and 4d) and right celiac artery (no. 9) nodes was not uncommon (14.3 %-22.2 %) for tumors in the first portion. The frequency of metastasis in the pyloric (nos. 5 and 6) and the other peripancreaticoduodenal (nos. 8 and 12) nodes varied depending on tumor location but could not be ignored for staging. When these nodes were classified as regional nodes, the 5-year survival in patients with pN0, pN1 (1-2 positive nodes), and pN2 (≥3 positive nodes) were 82.9 %, 51.7 %, and 19.2 %, respectively (p < 0.001). pN classification independently predicted survival (pN1, p = 0.022; pN2, p < 0.001)., Conclusions: Nos. 5, 6, 8, 12, 13, 14, and 17 nodes in all advanced NADAC and nos. 3, 4d, and 9 nodes in advanced NADAC in the first portion should be considered as regional nodes for accurate staging. The number-based nodal classification allows good patients' prognostic stratification., (© 2023 Published by Elsevier Ltd.)

A 75-year-old Japanese woman visited a hospital with a stomachache. The patient was diagnosed with localized mild acute pancreatitis. Blood tests revealed elevated serum IgG4 levels. Contrast-enhanced computed tomography showed a hypovascular mass, 3 cm in size, in the pancreatic body with dilation of the upstream duct. Additionally, it showed another tumorous lesion of 10 mm in size in the anterior wall of the stomach, and endoscopic examination confirmed a submucosal tumor (SMT) sized 10 mm in the anterior wall of the stomach. Endoscopic ultrasound-guided fine needle aspiration biopsy (EUS-FNAB) of the pancreas revealed an adenocarcinoma concomitant with marked IgG4-positive cell infiltration. Hence, distal pancreatectomy with local gastrectomy was performed, and the final diagnosis was concluded as pancreatic ductal adenocarcinoma (PDAC) complicated by IgG4-related diseases (IgG4-RD) in the pancreas and stomach. IgG4-RD of the digestive tract is exceedingly rare. The correlation between PDAC and autoimmune pancreatitis or malignancy and IgG4-RD is controversial. However, the clinical course and histopathological examination, in this case, provide valuable suggestive findings for further discussion., (© 2023. Japanese Society of Gastroenterology.)

Background/aim: Even though epithelial-mesenchymal transition markers in primary tumors are identified as a helpful indicator of cancer metastasis and prognosis, their expression in lymph node metastases (LNMs) remains poorly described. We aimed to investigate the difference between snail family transcriptional repressor 1 (SNAI1) and E-cadherin expression in primary tumors and LNMs, and how it affects prognosis., Patients and Methods: From 2010 to 2014, 127 patients who underwent radical surgery for stage III colonic adenocarcinoma without preoperative treatment were retrospectively reviewed for SNAI1 and E-cadherin expression in primary tumors and LNMs., Results: High SNAI1 expression was found in 76% and 70% of primary tumors and LNMs, respectively, and low E-cadherin expression was found in 73% and 84%, respectively. High expression of SNAI1 in LNMs significantly correlated with poor overall and relapse-free survival rates. Even though the rate of liver metastasis at 5 years was similar for the groups with high and low SNAI1 expression in LNMs, the incidence in the group with low SNAI1 expression in the second year was higher than that in the first year (33% vs. 17%), whilst in the group with high SNAI1 expression, the incidence in the first year was higher than in the second year (71% vs. 29%). The rate of recurrence of lung metastasis was significantly lower when SNAI1 expression in LNMs was low (p=0.031)., Conclusion: Low expression of SNAI1 in LNMs of colonic adenocarcinoma may indicate delayed recurrence in the liver and lung., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

A 69-year-old man was referred to our hospital because of appetite loss. Imaging showed a nodular tumor in the perihilar bile duct and a second flat lesion in the distal bile duct. Right hepatopancreaticoduodenectomy was performed, and the histopathological findings demonstrated that the perihilar and distal lesions were moderately and poorly differentiated adenocarcinoma, respectively, and anatomically separated. Furthermore, the resected specimens showed no pancreaticobiliary maljunction. Histological and TP53 gene analyses in a rare case of synchronous double bile duct cancers suggest that there are various genetic pathways through which bile duct cancer develops, highlighting the complexity of its pathogenesis.

Background & Aims: In the West, early gastric cancer is increasingly managed with endoscopic resection (ER). This is, however, based on the assumption that the low prevalence and risk of lymph node metastases observed in Asian patients is applicable to patients in the United States. We sought to evaluate the frequency of and factors associated with metastasis of early gastric cancers to lymph nodes, and whether the Japanese ER criteria are applicable to patients in the US., Methods: We performed a retrospective study of 176 patients (mean age 68.5 years; 59.1% male; 58.5% white) who underwent surgical resection with lymph node dissection of T1 and Tis gastric adenocarcinomas, staged by pathologists, at 7 tertiary care centers in the US from January 1, 1999, through December 31, 2016. The frequency of lymph node metastases and associated risk factors were determined., Results: The mean size of gastric adenocarcinomas was 23.0 ± 16.6 mm-most were located in the lower-third of the stomach (67.0%), invading the submucosa (55.1%), and moderately differentiated (31.3%). Lymphovascular invasion was observed in 18.2% of lesions. Overall, 20.5% of patients had lymph node metastases. Submucosal invasion (odds ratio, 3.9; 95% CI, 1.4-10.7) and lymphovascular invasion (odds ratio, 4.6; 95% CI, 1.8-12.0) were independently associated with increased risk of metastasis to lymph nodes. The frequency of lymph node metastases among patients fulfilling standard and expanded Japanese criteria for ER were 0 and 7.5%, respectively., Conclusions: The frequency of lymph node metastases among patients with early gastric cancer in a US population is higher than that of published Asian series. However, early gastric cancer lesions that meet the Japanese standard criteria for ER are associated with negligible risk of metastasis to lymph nodes, so ER can be recommended for definitive therapy. Expanded criteria cancers appear to have a higher risk of metastasis to lymph nodes, so ER may be considered for select cases., (Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Endoscopic resection (ER) of superficial adenocarcinoma of the esophagogastric junction (AEGJ) has been shown to be safe and effective. However, long-term data in patients undergoing ER for superficial AEGJ in Japan are still limited. The aim of this study was to determine the effect of ER on survival and occurrence of metachronous cancer of patients with superficial AEGJ., Methods: A retrospective analysis of patients who underwent or endoscopic submucosal dissection (ESD) for superficial AEJG in 13 centers in Japan was performed. The patients were classified as either low risk or high risk for lymph node metastasis based on histologic features. The incidence of metachronous AEGJ as well as overall survival and disease-specific survival rates were calculated., Results: A total of 372 patients who underwent ER were included, in which 277 patients were low risk and 95 high risk for lymph node metastasis. Five-year cumulative incidences of local recurrence were 13% and .5% in the EMR and ESD groups, respectively (P < .01). Six AEGJ deaths were observed in the high-risk group and none in the low-risk group. The 5-year overall survival rates in the low-risk group without additional treatment, the high-risk group with additional treatment, and the high-risk group without additional treatment were 93.9%, 77.7%, and 81.6%, respectively. The 5-year disease-specific survival rates in the 3 groups were 100%, 94.4%, and 92.8%, respectively. The 5-year cumulative incidence of metachronous AEGJ in 316 patients without additional treatment was 1.1%., Conclusions: Favorable long-term outcomes with ER were observed in patients with AEGJ who met the low-risk criteria for lymph node metastasis. ESD was a reasonable and effective treatment in Japanese patients., (Copyright © 2019 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background: Although submucosal dissection is useful for treating laterally spreading colorectal tumors, there is little information regarding the endoscopic treatment of large protruding colorectal neoplasms. Here, we aimed to evaluate the clinical outcomes of endoscopic submucosal dissection for protruding colorectal neoplasms ≥ 20 mm in diameter., Methods: In total, 112 consecutive patients undergoing treatment between January 2005 and June 2017 were enrolled retrospectively. The study period was divided into six periods to evaluate any changes in outcomes over time. We reviewed all short-term clinical outcomes, including lesion characteristics, procedure time, and percentages of en bloc resection, curative resection, adverse events, and treatment discontinuation., Results: The percentages of en bloc, en bloc R0, and en bloc curative resections were 88 %, 82 %, and 59 %, respectively. Perforation occurred in 11 patients (10 %), and the endoscopic procedure was discontinued in five patients (4 %) because of technical difficulty. For lesions ≥ 40 mm in diameter, the procedure time showed a statistically significant decreasing trend in the latter half of the study period. However, the rate of cure did not improve along with enhancements to the procedure's technological aspects., Conclusions: Although endoscopic submucosal dissection for large protruding lesions has advanced in terms of its technical aspects, its ability to cure large protruding neoplasms has not shown gratifying results., Competing Interests: None., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Recently, lymphocyte-to-monocyte ratio (LMR) has attracted attention as a new marker of the chronic systemic inflammatory response and has been associated with patient prognosis in those who underwent chemoradiotherapy (CRT) for several solid cancers. This study aimed to evaluate the association between LMR and the prognosis of patients with rectal cancer., Methods: A total of 183 stage II-III rectal cancer patients who underwent preoperative CRT followed by surgical R0 resection were retrospectively reviewed. The LMR was calculated from pre- and post-CRT blood samples. To determine the optimal cutoff value for pre- and post-CRT LMR for predicting relapse-free survival (RFS) and overall survival (OS), a receiver operator characteristic curve was used. Cox's proportional hazard models were applied to identify risk factors for recurrence and overall mortality., Results: Low LMR was observed in 54 patients (pre-CRT <4.0) and 29 patients (post-CRT <1.5). Although pre-CRT LMR correlated with tumor size and ypT stage, post-CRT LMR showed no correlation to any pathologic features. Median follow-up term was 66.3 months; the 5-year RFS and OS of all patients were 72.5% and 88.7%, respectively. We found that a low pre-CRT LMR was an independent risk factor for OS (hazard ratio, 2.83; 95% confidence interval 1.03-8.13; P = 0.043)., Conclusions: In rectal cancer patients who have undergone preoperative CRT, a low pre-CRT LMR is a poor prognostic factor for OS., (Copyright © 2017 Elsevier Inc. All rights reserved.)

We report a case of occult breast cancer. A 61-years-old woman underwent tumorectomy of right axillary mass. Pathological diagnosis was adenocarcinoma. Two years after, right axillary mass was discovered again. Wide local excision, axillary lymph node dissection and radiation therapy of the breast was performed. Pathological findings showed lymph node metastasis of breast cancer, or primary cancer of the axially tail of the breast. Ten months after second operation, she presented an axillary mass again. She underwent resection of the axillary tumor. The pathological findings showed lymph node metastasis of breast cancer. There was no evidence of primary tumor of the breast during the period. We suspected lymph node metastasis of occult breast cancer. Irradiation was administered to the right axilla, and she is receiving endocrine therapy.

Podocalyxin (PODXL) is expressed in several cancers, including brain tumors and colorectal cancers. PODXL overexpression is an independent predictor of progression, metastasis, and poor outcome. We recently immunized mice with recombinant human PODXL, which was produced using LN229 glioblastoma cells, and produced a clone PcMab-47 that could be used for investigating PODXL expression by flow cytometry and immunohistochemical analysis. Herein, we produced a human-mouse chimeric PcMab-47 (chPcMab-47) and investigated its antitumor activity against PODXL-expressing tumors. chPcMab-47 reacted with LN229, LN229/PODXL, and Chinese hamster ovary (CHO)/PODXL cells, but it did not react with CHO-K1 or PODXL-knockout LN229 cell line (PDIS-13). chPcMab-47 exerted antitumor activity against a mouse xenograft model using CHO/PODXL. Furthermore, chPcMab-47 was reactive with colorectal cancer cell lines such as HCT-15, Caco-2, HCT-8, and DLD-1. chPcMab-47 also exhibited antitumor activity against a mouse xenograft model using HCT-15. These results suggest that chPcMab-47 could be useful for antibody therapy against PODXL-expressing cancers.

Background: Little is known about the specific risks of metastasis in esophageal adenocarcinoma in relation to invasion depth or other pathologic factors., Methods: We conducted a multicenter retrospective study in 13 high-volume centers in Japan from January 2000 to October 2014 to elucidate the risk of metastasis of esophageal adenocarcinoma. A total of 458 patients (217 surgically resected and 241 endoscopically resected) with esophageal adenocarcinoma or esophagogastric adenocarcinoma involving the esophagus were included. Metastasis was considered positive if there was histologically confirmed metastasis in the surgical specimen or clinically confirmed metastasis during follow-up. Metastasis was considered negative if no metastasis was identified in resected specimens and during follow-up in patients treated surgically or no metastasis during follow-up for >5 years in patients treated by endoscopic resection., Results: Metastasis was identified in 72 patients. Multivariate analysis confirmed lymphovascular involvement [odds ratio (OR) 6.20; 95 % confidence interval (CI) 3.12-12.32; p < 0.001], a poorly differentiated component (OR 3.69; 95 % CI 1.92-7.10; p < 0.001), and lesion size >30 mm (OR 3.12; 95 % CI 1.63-5.97; p = 0.001) as independent risk factors for metastasis. No metastasis was detected in patients with mucosal cancer without lymphovascular involvement and a poorly differentiated component (0/186 lesions) or in patients with cancer invading the submucosa (1-500 µm) without lymphovascular involvement, a poorly differentiated component, and ≤30 mm (0/32 lesions)., Conclusions: Mucosal and submucosal cancers (1-500 µm invasion) without risk factors have a low incidence of metastasis and may thus be good candidates for endoscopic resection.

Background and Aims: Although the number of gastric cancer patients aged ≥85 years indicated for endoscopic submucosal dissection (ESD) has increased, little is known about the outcomes and prognostic factors. This study aimed to investigate the clinical outcomes and prognostic factors for overall survival (OS) of patients aged ≥85 years who underwent ESD for gastric cancer., Methods: We retrospectively reviewed 108 patients aged ≥85 years with 149 gastric cancers treated by ESD between 1999 and 2014 at our institution. The clinical outcomes and prognosis were evaluated. Furthermore, the relationships between patient and lesion characteristics with OS were determined using the Kaplan-Meier method and a Cox proportional hazards model., Results: All patients had Eastern Cooperative Oncology Group performance status (PS) of 0 to 1. En bloc, R0, and curative resections were achieved in 98.0%, 91.3%, and 72.7%, respectively, without severe adverse events requiring surgery. During a median follow-up period of 40.2 months (range, 1.8-108.7 months), 23 patients died, including 2 of gastric cancer. The 3-year (54.3% vs 95.9%) and 5-year (54.3% vs 76.3%) OS rates were significantly lower in patients with a low (<44.6) as opposed to a higher (≥44.6) prognostic nutritional index (PNI) (P < .001). The PNI was independently prognostic of OS (hazard ratio, 7.0; 95% confidence interval, 2.2-22.9; P = .001)., Conclusions: ESD is feasible for gastric cancer patients aged ≥85 years with good PS. However, low PNI was found to be prognostic of reduced OS, indicating the need to evaluate the PNI in determining whether to perform ESD., (Copyright © 2017 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Early gastric cancer (ECG) can be difficult to diagnose endoscopically. Endoscopists should be familiar with subtle changes and endoscopic features of EGC. Chromoendoscopy and image-enhanced endoscopy improve diagnostic accuracy and facilitate endoscopic resection. Endoscopic submucosal dissection is a preferred endoscopic technique for resection of EGC and offers a comparable overall survival to surgical resection. Endoscopic management of benign gastric epithelial polyps (fundic gland polyps, hyperplastic polyps, and gastric adenoma) depends on patient symptomatology, patient's comorbidities (eg, familial syndromes), lesions' characteristics, and risk of malignant transformation. This article provides an overview of endoscopic management of EGC and common premalignant gastric lesions., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Although preoperative carcinoembryonic antigen (pre-CEA) and carbohydrate antigen 19-9 (pre-CA 19-9) are reportedly prognostic indicators for colorectal cancer (CRC), the prognostic roles of postoperative CEA (post-CEA) and CA 19-9 (post-CA 19-9) shortly after surgery have not been clarified in patients with curatively resected stage IV CRC. The aim of this study was to evaluate the predictive abilities of post-CEA and post-CA 19-9., Methods: A total of 129 consecutive patients who had stage IV CRC and underwent R0 resection were retrospectively analyzed. Pre-CEA and post-CEA and CA 19-9 levels were measured within 1 mo before and 3 mo after surgery, respectively. Relapse-free survival (RFS) and overall survival were estimated using the Kaplan-Meier method, and multivariate analysis was performed using the Cox proportional hazards model., Results: Pre-CEA was elevated (≥5.0 ng/mL) in 73.6% of the patients and remained elevated after surgery in 32.7% of the patients. Elevated post-CA 19-9 (≥50 U/mL) was observed in 9.5% of the patients. Neither elevated pre-CEA nor elevated pre-CA 19-9 was significantly associated with RFS but both elevated post-CEA and elevated post-CA 19-9 were associated with markedly reduced RFS (P = 0.0002 and P = 0.0004, respectively). When considered in combination, post-CEA and post-CA 19-9 significantly stratified RFS and was an independent predictive factor for recurrence (P = 0.0035), as was lymphatic invasion (P = 0.0015). Post-CA 19-9 was the only evident independent predictive factor for overall survival (P = 0.0336)., Conclusions: In patients with stage IV CRC who underwent curative resection, the combination of post-CEA and post-CA 19-9 at 3 mo after surgery was a potent prognostic indicator for recurrence., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background and Study Aims: As more early gastric cancer (EGC) patients are being treated with endoscopic submucosal dissection (ESD), it is important to understand the outcomes of patients who develop metachronous gastric cancer (MGC). The aim of this study was to evaluate the long-term surveillance and treatment outcomes of MGC after curative gastric ESD., Patients and Methods: The study included 1526 consecutive patients who underwent curative ESD resection of EGC. They were generally followed by annual or biannual esophagogastroduodenoscopy. The risk factors and treatment outcomes for MGC were assessed along with the 5-year, 7-year, and 10-year cumulative incidence functions of MGC and disease-specific survival (DSS)., Results: During a median follow-up period of 82.2 months, 238 patients developed MGC post-ESD resection of EGC. The 5-year, 7-year, and 10-year cumulative incidence functions of MGC were 9.5%, 13.1% and 22.7%, respectively. Male sex and multiple initial EGCs were independent risk factors for MGC in the Cox proportional hazard model. Of the 238 patients with MGC, 215 were treated with endoscopic resection, of which 183 achieved curative resection, although one patient later died of his initial EGC. A further 14 patients were treated surgically, three had metastatic disease and received palliative chemotherapy, and the remaining six were observed without any intervention. A total of seven patients died of MGC, five at least 5 years after their index ESD. The 5-year, 7-year, and 10-year DSSs were 99.2%, 98.6%, and 92.5%, respectively., Conclusions: The incidence of MGC increases with time after curative gastric ESD, therefore surveillance endoscopy should be continued indefinitely., (© Georg Thieme Verlag KG Stuttgart · New York.)

An 80-year-old man was under annual surveillance esophagogastroduodenoscopy after endoscopic submucosal dissection (ESD) for early gastric cancer (EGC). Two years after the initial ESD, a 0-IIc type metachronous EGC lesion, 8 mm in size, without an ulcer scar, was found in the gastric antrum. The estimated tumor depth was up to the mucosa, and biopsy revealed well and poorly differentiated adenocarcinoma. ESD was performed for this lesion and en bloc resection with negative margins was achieved. Histopathological examination revealed an adenosquamous carcinoma 8 mm in size invading the deep submucosal layer (1600 μm), with lymphovascular invasion, consistent with the diagnosis of non-curative resection. Additional gastrectomy was recommended for this patient; however, two months after the ESD, preoperative computed tomography revealed multiple liver metastases, and the patient was considered as an unsuitable candidate for surgical resection. Systemic chemotherapy was therefore started; however, the patient died of gastric cancer 27 mo after the second ESD. Early gastric adenosquamous carcinoma localized to the mucosa and submucosa is extremely rare and its clinical behavior is not well known. The present report is very significant in that it underscores the distinct possibility of gastric adenosquamous carcinoma being very aggressive and fatal even when detected at an early cancer.

Cetuximab-containing treatments for metastatic colorectal cancer have been shown to have higher overall response rates and longer progression-free and overall survival than other systemic therapies. Cetuximab-related manifestations, including severe skin toxicity and early tumor shrinkage, have been shown to be predictors of response to cetuximab. We hypothesized that early skin toxicity is a predictor of response and better outcomes in patients with advanced colorectal carcinoma. We retrospectively evaluated 62 patients with colorectal adenocarcinoma who had unresectable tumors and were treated with cetuximab in our institution. Skin toxicity grade was evaluated on each treatment day. Tumor size was evaluated using computed tomography prior to treatment and 4-8 weeks after the start of treatment with cetuximab.Patients with early tumor shrinkage after starting treatment with cetuximab had a significantly higher overall response rate (P = 0.0001). Patients with early skin toxicity showed significantly longer overall survival (P = 0.0305), and patients with higher skin toxicity grades had longer progression-free survival (P = 0.0168).We have shown that early tumor shrinkage, early onset of skin toxicity, and high skin toxicity grade are predictors of treatment efficacy and/or outcome in patients with advanced colorectal carcinoma treated with cetuximab.

Background and Study Aims: Compared with any other location in the gastrointestinal tract, the duodenum presents the most challenging site for endoscopic resection. The aim of this study was to analyze the clinical outcomes of duodenal endoscopic resection and to assess the feasibility of the technique as a therapeutic procedure., Patients and Methods: A total of 113 consecutive patients with 121 nonampullary duodenal tumors underwent endoscopic resection by endoscopic submucosal dissection (ESD), endoscopic mucosal resection (EMR), or polypectomy between January 2000 and September 2013. Long-term outcomes were investigated in patients with more than 1 year follow-up., Results: The median tumor size was 12 mm (range 3 - 50 mm). Lesions consisted of 63 adenocarcinomas/high-grade intraepithelial neoplasias (53 %) and 57 adenomas/low-grade intraepithelial neoplasias (48 %). Endoscopic resection included 106 EMRs (87 %), 8 ESDs (7 %), and 7 polypectomies (6 %). En bloc resection was achieved in 77 lesions (64 %), and 43 lesions (35 %) underwent piecemeal resection; one procedure was discontinued due to perforation. There were 14 cases of delayed bleeding after EMR (12 %), 1 perforation (1 %) during ESD, and 1 delayed perforation (1 %) after ESD, which required emergency surgery. Of the 76 patients who were followed for more than 1 year, none of the patients died from a primary duodenal neoplasm, and there were no local recurrences during the 51-month median follow-up period (range 12 - 163 months)., Conclusions: Duodenal endoscopic resection was feasible as a therapeutic procedure, but it should only be performed by highly skilled endoscopists because of its technical difficulty. Piecemeal resection by EMR is acceptable for small lesions, based on these excellent long-term outcomes., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background and Study Aims: After noncurative endoscopic submucosal dissection (ESD) for differentiated-type early gastric cancer (EGC), close observation is often preferred when a cancer-positive lateral margin is the only noncurative factor. However, sometimes recurrence is found during the observation period. This study aimed to examine risk factors for recurrent cancer based on the long-term clinical outcomes after noncurative ESD in which the only noncurative factor was a cancer-positive lateral margin., Patients and Methods: Among 3784 EGCs (3316 patients) treated by ESD between 1997 and 2010, 77 noncurative differentiated-type EGCs (75 patients) were retrospectively analyzed after meeting the following inclusion criteria: 1) the only noncurative factor was a cancer-positive lateral margin; 2) close observation was selected after the ESD; and 3) > 1 year follow-up after ESD., Results: Locally recurrent cancer was found in 10 lesions within a median follow-up period of 59.8 months; no metastasis or gastric cancer-related death occurred. The cumulative incidence of local recurrence 5 years after ESD was 11.9 %. All locally recurrent cancers were mucosal differentiated-type adenocarcinomas. Multivariate analysis indicated that a cancer-positive lateral margin length of ≥ 6 mm was significantly associated with local recurrence (hazard ratio 20.8; 95 % confidence interval 5.2 % - 82.9 %; P < 0.001). The cut-off value of 6 mm was determined by the receiver operating characteristic curve; the sensitivity and specificity for 5-year risk of developing local recurrence were 66.7 % and 95.6 %, respectively., Conclusions: A cancer-positive lateral margin length of ≥ 6 mm was an independent risk factor for local recurrence, and this may be a useful criterion for selecting high-risk cases for stricter management., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background and Study Aims: Intramucosal undifferentiated early gastric cancer (EGC) up to 2 cm in size without ulceration has been treated by endoscopic submucosal dissection (ESD) because the incidence of lymph node metastasis is negligible. The aim of this retrospective study was to clarify the short-term and long-term outcomes of ESD carried out to treat undifferentiated EGC., Patients and Methods: Between January 1999 and September 2011, 113 patients with poorly differentiated adenocarcinoma or signet ring cell carcinoma on preoperative biopsy underwent ESD. In 16 patients differentiated EGC had been diagnosed after the ESD and these patients were excluded from the study. Short-term outcomes were evaluated in the remaining 97 patients with undifferentiated EGC, and long-term outcomes analyzed in the 79 patients with undifferentiated EGC who had undergone ESD between 1999 and 2008., Results: En bloc and R0 resection were achieved in 99.0 % and 90.7 % of patients, respectively. Median procedure time was 45 minutes. Postoperative bleeding, perforation during the procedure, and delayed perforation were noted in 4.1 %, 3.1 %, and 1.0 % respectively. Curative resection was achieved in 63.9 %. Additional surgery was performed in 21 of 35 patients in whom resection was noncurative: one (4.8 %) had local residual tumor and two (9.5 %) had lymph node metastases. Of the 46 /79 patients in the long-term outcome group who had curative resection, none had local recurrence or lymph node or distant metastasis during a median follow-up of 76.4 months. The 5-year overall mortality rate after curative resection was 7.0 %, and no patient died of gastric cancer., Conclusions: ESD for undifferentiated EGC can achieve curative resection with an excellent 5-year mortality rate., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background and Study Aim: Close observation after noncurative endoscopic resection for early gastric cancer (EGC) is an acceptable option if a positive horizontal margin or piecemeal resection of differentiated-type adenocarcinoma is the only noncurative factor. When locally recurrent EGC is subsequently detected, endoscopic submucosal dissection (ESD) may be performed, although only limited research has been reported regarding the outcomes. We aimed to evaluate the effectiveness, safety, and long-term clinical outcomes of ESD performed for locally recurrent EGC., Patients and Methods: Endoscopic resection was performed in 3704 patients with a total of 4216 EGC lesions between January 1997 and December 2011 at our institution. During this period, 95 patients with 95 locally recurrent EGCs following their endoscopic resection underwent ESD performed by experts, which we retrospectively reviewed. The prior endoscopic resection procedures were endoscopic mucosal resection in 75 cases and ESD in 20., Results: Of the 95 cases, en bloc resection was achieved in 90.5 %, R0 resection in 84.2 %, and curative resection in 81.1 %. Median procedure time was 70 minutes; no bleeding requiring blood transfusion was seen. There were six perforations (6.3 %), with one necessitating emergency surgery. Within a median follow-up period of 76.4 months (range, 10.5 - 170.0 months), second local recurrences occurred in three patients. Five-year overall and disease-specific survival rates were 92.8 % and 100 %, respectively., Conclusions: ESD was safe and effective with favorable long-term clinical outcomes for locally recurrent EGC following endoscopic resection., (© Georg Thieme Verlag KG Stuttgart · New York.)

We report a case of adenocarcinoma of the minor duodenal papilla, a rare type of duodenal neoplasm. A 76-year-old man with a history of surgery for rectal cancer and gastric cancer was referred to us after a follow-up upper gastrointestinal endoscopy revealed an abnormal elevation in the minor duodenal papilla. The pathological diagnosis of a biopsy specimen was adenocarcinoma. Preoperative examination of other organs revealed a tumor in the ascending colon, which was also identified as adenocarcinoma. We performed synchronous pancreatoduodenectomy and ileocecal resection with lymph node dissection. Histopathological examination of the resected specimen revealed that the papilla tumor arose from the duodenal mucosa and infiltrated the submucosa of the duodenal wall, but not the pancreatic parenchyma. Based on these findings, we diagnosed primary adenocarcinoma of the minor duodenal papilla. To our knowledge, this is only the sixth such case reported in the English-language literature, and we review all six cases after this case report.

Background: Although correlations between endoscopic macroscopic type and tumor depth have been reported for superficial esophageal squamous cell carcinoma and early gastric and early colorectal adenocarcinomas, there is no published study investigating the correlation between endoscopic macroscopic type and invasion depth for mucosal (M) and submucosal (SM) adenocarcinomas located at the esophagogastric junction (EGJ). We decided to analyze, therefore, the relationship between endoscopic macroscopic type and tumor depth for such cancers., Methods: We retrospectively reviewed 73 early EGJ adenocarcinomas (M/SM = 33/40; differentiated/undifferentiated type = 70/3) in 73 consecutive patients treated endoscopically and/or surgically between January 2000 and December 2008. The mean age of the patients was 63.9 years (range 37-85 years) and the male/female ratio was 62:11. EGJ adenocarcinoma was defined as junctional carcinoma (type II) according to the Siewert classification., Results: We found polypoid type lesions (0-I) in 14 patients, non-polypoid type without mixed type (0-IIa, 0-IIb, or 0-IIc) in 39, and mixed type (0-IIa + IIc or 0-IIc + IIa) in 20 patients. Non-polypoid type without mixed type (31%; 12/39) lesions had a significantly lower risk for SM invasion compared to polypoid type (79%; 11/14; p < 0.01) and mixed type (85%; 17/20; p < 0.01) lesions. In polypoid type lesions, the risk of SM invasion was significantly lower for the pedunculated subtype (0-Ip) than for the sessile subtype (0-Is) lesions (0%; 0/2 vs. 92%; 11/12; p < 0.05). M lesions (mean size 14.5 ± 7.5 mm) were significantly smaller than SM lesions (24.5 ± 7.7 mm; p < 0.01)., Conclusions: Determination of endoscopic macroscopic type may be useful in accurately diagnosing early EGJ adenocarcinoma invasion depth.

Following the trend of the digitalization of the modalities used for diagnostic imaging, the devices for such imaging have increasingly included monitors. The present study was undertaken to evaluate the usefulness of soft-copy (liquid crystal display; LCD) images of phantoms of small adenocarcinomas using receiver operating characteristic (ROC) analysis of two different display systems: LCD and hard copy (film). A two-tailed paired t-test and the jackknife method (parametric methods) were performed, and no significant differences were found in the area under the ROC curve (AUC) for the pulmonary fields, lungs, ribs, or mediastinum between the film and LCD display systems, and the detectability did not differ between the film and LCD monitors. A Mann-Whitney U test, which is a non-parametric method that applies to the analysis of a small sample, also showed no significant differences in the AUC. The results of this study suggest that LCDs can replace hard-copy film as a display system if the signals.

We report a rare case of lung adenocarcinoma exhibiting Garcin syndrome due to skull base metastasis. A diagnosis of lung adenocarcinoma and intraperitoneal lymph node metastases was given to a 50-year-old man after pathological examination of a superclavicular lymph node biopsy. After systemic chemotherapy with cisplatin plus docetaxel, he had left hearing loss and vertigo. Since auditory nerve damage might occur due to cisplatin, the chemotherapy regimen was changed. However, facial paralysis occurred and his auditory nerve disorder progressed to deafness. He was diagnosed with Garcin syndrome due to the skull base and spinal cord metastases by brain and spine MRI, and cytological examination of the spinal fluid. After intrathecal administration of methotrexate and cranial irradiation, the progression of facial paralysis and auditory nerve disorder were halted. It is important to consider Garcin syndrome as a possible complication in lung cancer patients who have central nervous system symptoms.

A 70-year-old man was admitted for tranverse colon cancer with multiple liver metastases. Hepatic arterial infusion chemotherapy and systemic chemotherapy (FOLFOX 4) were conducted postoperatively. Thirteen months after the first surgery, liver metastases became resectable and hepatectomy was performed. Though multiple liver metastases were unresectable at the time of the first examination, hepatectomy was possible followed by hepatic arterial infusion chemotherapy and systemic chemotherapy.

Amyotrophic lateral sclerosis (ALS) is a degenerative disease involving both upper and lower motor neurons and the pathogenesis of this disorder is still unknown. To date, few reports have suggested that motor neuron diseases may have a paraneoplastic origin. However, it is still under discussion whether ALS occurring in cancer patients is paraneoplastic. A 60-year-old man with rectal cancer (Stage IV) having multiple lung, liver and para-aortic lymph node metastases underwent anterior resection of the rectum as palliative surgery. He was referred to our hospital for adjuvant chemotherapy. Lung and lymph node metastases decreased after 2 courses of chemotherapy using CPT-11 and 5-FU/LV but liver metastases were enlarged, following up increase in CEA. Thereafter, he suffered from muscle weakness in hands, arms, and legs and results of neurophysiologic studies were compatible with primary lateral sclerosis (ALS). For second line chemotherapy, he was treated with low-dose CDDP/5-FU over 6 courses. As a result, the size the of metastatic lesions markedly reduced and CEA was decreased to the normal level. Although significant tumor reduction was observed, his neurological symptoms rapidly progressed. He died of aspiration pneumonia 8 months after onset of the disease. Autopsy revealed that his neuropathological findings were compatible with ALS, and it was thought to be the primary cause of death in the because of absence of cancer progression. In this case the neurological syndrome was not affected by cancer therapy. Thus our case does not support the hypothesis that ALS in associated with cancer and the relationship between both disorders remains uncertain.

Oxaliplatin (L-OHP) is a new third-generation platinum which is efficacious in treating advanced unresectable recurrent colorectal cancer as a first-line regimen. The marketing authorization was given in Japan in March, 2005. Its increased use has resulted in rare serious adverse effects, including anaphylactic shock. We experienced a case that developed anaphylactic shock by L-OHP. We report a 69-year-old man who was treated for recurrent colorectal cancer who underwent systemic chemotherapy with FOLFOX 4. After eight cycles he developed severe L-OHP associated neuropathy and lung metastases was a progressive tendency. The FOLFOX 4 regimen was discontinued and another modality, FOLFIRI regimen, was used. After eight cycles of FOLFIRI regimen, lung and liver metastases showed progressive disease for response assessment by RECIST criteria. Although a patient was stopped L-OHP for neurotoxicity, neuropathy was disappeared after 4 months interval. Therefore, we reintroduced L-OHP, FOLFOX 4 regimen. Anaphylactic shock occurred in the second cycle of reintroduction of the FOLFOX 4 regimen (total 10 cycles), 30 minutes after infusion of L-OHP. L-OHP infusion was immediately withdrawn and he was treated with intravenous hydroxyzine hydrochloride and methylprednisolone. The anaphylaxis symptoms resolved in 30 minutes. Chemotherapy based on L-OHP for unresectable recurrence colorectal cancer causes anaphylactic shock as a rare severe complication. The prediction factor is not proved. We should take steps for early detection of anaphylactic reaction and perform the appropriate treatment.

The aim of the present study was to compare the usefulness of the peripheral airway cell markers, naspin A and surfactant protein A (SP-A), for distinguishing primary lung adenocarcinoma from adenocarcinomas of other organs in various clinical conditions. Immunohistochemical expression of napsin A and SP-A was analyzed at primary sites of 120 lung carcinomas and 40 adenocarcinomas of other organs, at lung metastatic sites of 32 adenocarcinomas of other organs, and in metastatic lymph nodes of 21 lung adenocarcinomas and 45 adenocarcinomas of other organs. Napsin A and SP-A expressions were compared between primary and recurrent sites in 8 lung adenocarcinomas. Napsin A and SP-A expressions were noted in 84.3% and 53.0% of primary sites of 83 lung adenocarcinomas, respectively, but neither napsin A nor SP-A was expressed at primary sites of other histological types of lung carcinomas or at primary or metastatic sites of adenocarcinomas of other organs. In lung adenocarcinomas, napsin A and SP-A were expressed in metastatic lymph nodes in 81.0% and 19.0%, respectively, and at recurrent sites in 87.5% and 37.5%, respectively. Napsin A is superior to SP-A for distinguishing primary lung adenocarcinoma from adenocarcinomas of other organs at primary, metastatic, and recurrent sites.

Members of the inhibitor of apoptosis protein (IAP) family including survivin, are expressed in many tumors. However, age-related changes in their expression in cancer have not been clarified. Thus, we investigated the expression of mRNA-coding for IAP family proteins in colon cancer samples from young (<70 years of age) and elderly (>70 years) patients by real-time quantitative RT-PCR. Samples were collected from cases with well-differentiated adenocarcinoma or moderately differentiated adenocarcinoma and their adjacent normal epithelial tissue. Well-differentiated adenocarcinoma tended to express higher levels of survivin than normal mucosa, and expression in moderately differentiated adenocarcinoma was significantly greater than in normal mucosa in samples from both groups of patients ( p<0.05, respectively). When samples were compared between the different age groups, the normal mucosa exhibited similar levels of survivin expression. However, samples from older patients showed a significantly higher level of expression than those from younger patients in well and moderately differentiated adenocarcinomas ( p<0.05, respectively). In contrast, the levels of expression of cIAP1, cIAP2, and NAIP in the cancerous tissues were lower than those found in normal mucosa regardless of age. As for age-related changes, the expression of cIAP2 in normal mucosa and moderately differentiated adenocarcinoma was stronger in the elderly group than the young group ( p<0.05, respectively), and NAIP expression in well-differentiated adenocarcinoma was higher in the young group than the elderly group ( p<0.05). XIAP expression was similar in normal and cancerous tissues in both the young and elderly groups. These results suggest that the expression of IAP family proteins, especially survivin, is associated with the age-related biological characteristics of colon cancer.

Mast cells accumulate in angiogenesis-dependent situations of lung adenocarcinoma. Human mast cells are divided into two major subsets: MCT (mast cells with immunoreactivity for tryptase but not chymase) and MCTC (reactive for tryptase and chymase). Chymase is an important mediator of tissue remodeling, but research into chymase-containing mast cell subpopulations has been hampered by the lack of reagents suitable for use with formalin-fixed tissue. We stained chymase using CC1 antibody in 66 cases of small sized lung adenocarcinoma as well as CD34 and tryptase. There were significant positive correlations of microvessel counts with MCT-type and MCTC-type mast cell counts in lung adenocarcinomas. When analyzed according to Noguchi's classification, MCT-type and MCTC-type mast cells were significantly increased in Noguchi type-C tumors [localized bronchioloalveolar carcinoma (LBAC) with active fibroblastic proliferation] compared with in Noguchi type-A (LBAC) plus type-B tumors (LBAC with alveolar collapse). Members in the high-count group of MCTC-type but not MCT-type mast cells showed a significantly worse outcome than those in the low-count group in LBACs. Counting chymase-positive (MCTC-type) mast cells in tumor stroma may be a good prognosis predictor for LBACs, especially Noguchi type-C tumors.

Ultrastructural studies have shown that Clara cell-type is a more common type of adenocarcinoma than alveolar type II cell-type, and that both types may provide better prognosis than other types, indicating an importance of differentiation toward peripheral airway cells. Pulmonary surfactant protein (SP)-A is a specific marker for both alveolar type II cells and Clara cells in peripheral lung tissues, while SP-C and Clara cell 10 kD protein (CC10) may be particularly and highly specific to alveolar type II cells and Clara cells, respectively. The aims of this study were to assess the differentiation of adenocarcinoma cells in pleural effusions by evaluating the expression of these cell markers and to evaluate their values as diagnostic tools for judging the cause of pleural effusion. We examined pleural effusions from 52 patients; 20 with primary lung adenocarcinomas, 6 with small cell lung carcinomas, 11 with metastatic malignant tumors and 15 with non-neoplastic diseases. The cell pellets from effusions were subjected to immunocytochemical staining for SP-A, proSP-C, a precursor of SP-C, and CC10. By this immunocytochemical study for SP-A and proSP-C, 10 (50%) and 6 (30%) of 20 adenocarcinomas, respectively, showed a positive immunoreactivity in their effusion cells, while none of them expressed CC10. Alveolar type II cells therefore may be the main progenitor cells of some adenocarcinomas. In pleural effusions from patients with primary lung adenocarcinomas, reverse transcriptase-polymerase chain reaction (RT-PCR) for SP-A mRNA showed a sensitivity of 83%, while, in all remaining patients, these assays were negative. In conclusion, we demonstrated that lung adenocarcinomas, which are partially differentiated toward alveolar type II cells, are not as rare as previously thought, and that both the RT-PCR and immunocytochemical analyses for SP-A and pro-SP-C could be worthy indicators of differential diagnosis.

The patient was a 64-year-old male. On November 21, 1991, he underwent gastric resection on the pyloric side for early gastric cancer in the authors' hospital, and did not experience recurrence for many years thereafter. However, endoscopic examination of the upper gastrointestinal tract performed on June 11, 1999 revealed advanced cancer in the posterior wall of the residual stomach which was accompanied by invasion of the esophagus. Thus, the residual stomach was completely removed on July 5, 1999. The histopathological findings were tub1, se, ly3, v2, aw(-), ow(+) and ew(+), and a portion of the esophageal stump and the serosa of the lesser curvature were positive for cancerous tissue. Endoscopic examination was performed one month after the operation, on August 7, 1999. A forceps biopsy taken from an elevated lesion of the esophagus at the posterior wall of the anastomosis revealed adenocarcinoma cells in the lower layer of the squamous epithelium. A residual esophageal lesion was thus diagnosed. Beginning on August 9, 1999, TS-1 was administered in a dosage of 50 mg bid, but it was later learned that the patient had ingested only half of that TS-1 dosage (i.e., 50 mg/day). After completion of one course of this therapy, endoscopy was again performed. It was found that the prominence on the esophageal mucosa at the anastomosis, which had been diagnosed as being cancerous tissue, had shrunk in size, while a forceps biopsy taken from the same site yielded no findings of malignancy. The patient was followed for 18 months thereafter, and endoscopy was performed three times during that interval but continued to yield no evidence of malignancy. As of February 2001, this patient had completed 12 courses of TS-1 at one-half its usual dosage. There have been no findings of recurrence, and the patient's course continues to be good. In summary, this was an interesting case in which residual cancer was detected in the esophageal stump following resection for gastric cancer, and it can be concluded that TS-1 therapy was effective in spite of being incomplete (i.e., half-dose), eradicating the residual cancer tissue.

Background: Thymidine phosphorylase (TP) has chemotactic activity in endothelial cells in vitro and angiogenic activity in vivo. However, the clinical significance of TP and cooperative roles of TP with other angiogenic factors have remained unclear in nonsmall cell lung carcinoma (NSCLC)., Methods: The authors stained for TP, vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (bFGF) in 132 tumors from patients with Stage I NSCLC. They compared TP, VEGF, and bFGF expression levels with microvessel counts (MVCs), macrophage counts, mast cell counts, and clinical outcomes of patients with Stage I NSCLC., Results: In adenocarcinoma samples, only stromal cell-TP expression and tumor cell-VEGF expression were associated with MVCs and mast cell counts but not with macrophage counts. In squamous cell carcinoma samples, there were no significant associations of the expression of any examined angiogenic factors with MVCs, mast cell counts, or macrophage counts. More importantly, only among patients with Stage I adenocarcinoma of the lung did patients in the stromal cell-TP positive tumor group and in the tumor cell-VEGF positive tumor group have a significantly worse prognosis compared with patients in the stromal cell-TP negative tumor group and in the tumor cell VEGF negative group, respectively. In addition, among patients with Stage I adenocarcinoma, patients in the stromal cell-TP positive and tumor cell-VEGF positive tumor group had a significantly worse prognosis among the four groups., Conclusions: TP induction in tumoral stroma, but not in tumor cells, and tumor cell-VEGF induction may promote angiogenesis cooperatively in adenocarcinoma of the lung. Stromal cell-TP expression and tumor cell-VEGF expression may be important prognostic factors in adenocarcinoma of the lung, and stromal cell-TP expression may be a marker of active remodeling stroma in adenocarcinoma of the lung., (Copyright 2002 American Cancer Society. DOI 10.1002/cncr.10352)

A 54-year-old man was diagnosed as having pancreatic cancer and disseminated intravascular coagulation. His plasma tissue factor level on the 11th hospital day was 996 pg/ml (normal range, 120-270 pg/ml). He was treated with gabexate mesilate, antithrombin III, and low-molecular-weight heparin. However, he died of multiple organ failure on the 17th hospital day. The histological finding was poorly differentiated ductal adenocarcinoma of the pancreas, and the production of tissue factor in this lesion was revealed. Tissue factor is a factor that initiates blood coagulation; thus, its expression in pancreatic cancer is one of the causes of coagulation abnormalities in this disease. Although one report has demonstrated immunoreactivity for tissue factor in pancreatic cancer, the patient's detailed clinical course was not mentioned in that report. This is the first report to prove that pancreatic cancer produced tissue factor in a patient with disseminated intravascular coagulation.

We evaluated the relationship between Noguchi's classification for small adenocarcinomas of the lung and tumor markers in serum (CEA, Cyfra, SLX, CA 19-9, CA 125). Fifty surgically resected small peripheral adenocarcinomas measuring 2 cm or less in greatest diameter were examined. The tumors were divided into three groups on the basis of Noguchi's classification: group AB of tumors belonging to Noguchi's classification A or B, group C of tumors belonging to Noguchi's classification C, and group DEF of tumors belonging to Noguchi's classification D, E, or F. The level of serum CEA was higher in group DEF (5.9 +/- 7.6 ng/ml) than in group AB (2.3 +/- 2.4 ng/ml) and group C (2.0 +/- 1.3 ng/ml). There were no differences in the levels of the other serum tumor markers among the three groups. The incidences of anormality in serum CEA and Cyfra were higher in group DEF (6/18 and 6/18, respectively) than in group AB (1/7 and 0/7) and group C (1/25 and 1/25). Although a high level of serum CEA or Cyfra is a strong indication that the tumor is Noguchi's classification D, E, or F of pulmonary adenocarcinoma, it is difficult to classify small adenocarcinomas by Noguchi's classification using a serum tumor marker level.

We reviewed 33 patients who underwent a limited operation for primary lung cancer between 1980 and 1998. These cases were divided into three groups; a poor risk group consisting of 18 patients who had a high risk such as pulmonary or cardiac dysfunction and who underwent partial resection of a lung, a reduction group consisting of 9 patients who had advanced lung cancer or uncontrolled cancer of an organ other than the lung and who underwent partial resection, and an active limited operation group consisting of 6 patients who underwent segmentectomy with lymphoadenectomy for the treatment of early lung cancer. The 1 and 3-year survival rates in the poor risk group, reduction group and active limited operation group were 73.9, 60.0, 100%, and 63.4, 0.0, 100%, respectively. The results of limited operations performed for poor risk cases were satisfactory in terms of both functional state and prognosis. Limited operations performed to reduce tumor in advanced lung cancer cases did not improve the prognosis. Although an active limited operation for a case of early lung cancer remains controversial with respect to indication, it is thought that this operation is not inferior to a standard radical operation (lobotomy with mediastinal lymphoadenectomy) in selective cases in which the maximum tumor diameter is 2 cm or less. The indication for a limited operation must be further examined from aspects of tumor size, tumor histology and the other factors of the tumor.

Angiogenesis is in part related to mast cells. However, the biological significance of mast cells within lung carcinoma remains unclear. Immunohistochemistry was used to stain for tryptase, CD34 and vascular endothelial growth factor (VEGF) in 85 cases of stage I nonsmall cell lung carcinoma. VEGF was found in 33 of 53 adenocarcinomas and 14 of 32 squamous cell carcinomas. Cases of adenocarcinoma had significantly higher mast cell counts than those of squamous cell carcinoma. In adenocarcinoma, mast cell counts in VEGF-positive tumours were significantly higher than in VEGF-negative tumours, whereas in squamous cell carcinoma they were not. Good correlation was observed between intratumoural mast cell counts and microvessel counts. Double staining showed most intratumoural mast cells expressed VEGF. Importantly, only in lung adenocarcinoma, members in the high mast cell count group had significantly worse prognosis than those in the low mast cell count group. It is concluded that tumour-released vascular endothelial growth factors may be related to mast cell accumulation, intratumoural mast cells may produce vascular endothelial growth factor, and stromal mast cells correlate with angiogenesis and poor outcome in stage I lung adenocarcinoma.

Tumor growth and metastasis are angiogenesis-dependent processes initiated and regulated by a number of cytokines. Vascular endothelial growth factor (VEGF) is a potent angiogenic protein with a selective mitogenic effect on vascular endothelial cells. Osteopontin (OPN) induces endothelial cell migration and upregulates endothelial cell migration induced by VEGF. To clarify the cooperative role of VEGF and OPN in tumor angiogenesis, we stained VEGF, OPN, and CD34 immunohistochemically in 87 cases of stage I non-small cell lung cancer (adenocarcinoma, 55, and squamous cell carcinoma, 32). Of the 87 patients studied, 27 patients had postoperative relapse and 60 patients did not. VEGF was found in 34 of 55 cases of adenocarcinomas and 14 of 32 squamous cell carcinomas, and OPN was found in 30 of 55 adenocarcinomas and 10 of 32 squamous cell carcinomas. In adenocarcinoma, microvessel counts of VEGF-positive and OPN-positive tumors were significantly higher than VEGF-negative and OPN-negative tumors, respectively, whereas in squamous cell carcinoma they were not. More importantly, patients with VEGF- and OPN-positive stage I lung adenocarcinoma had significantly worse prognosis as compared with other groups. Cooperation of OPN is important in VEGF-mediated tumor angiogenesis in stage I lung adenocarcinoma.

Ever since the identification of the colony-stimulating factor (CSF), granulocyte-CSF (G-CSF)-producing tumors have often been reported, and have been attracting attention, especially in pulmonary cancer. However, there have been only a small number of reports of G-CSF-producing tumors in cases of gastrointestinal cancer, and only four cases of G-CSF-producing gallbladder cancer have been reported so far. Recently, we encountered a 73-yr-old man with G-CSF-producing gallbladder cancer. The leukocyte count in the peripheral blood increased to the maximum of 75,200/mm3 during the course of observation, and mature neutrophils accounted for 97% (segmented forms: 89%, band forms: 8%). The serum G-CSF concentration was high (129 pg/ml). The leukocyte count became normalized postoperatively, and the serum G-CSF concentration also decreased (50 pg/ml). The tumor was diagnosed as undifferentiated adenocarcinoma of the pleomorphic type on the histopathologic examination. Numerous tumor cells were stained with the anti-G-CSF antibody. Detailed findings of the patient are presented here together with some discussion of the literature.

Vascular endothelial growth factor (VEGF) is one of the most important factors for angiogenesis in various malignant tumors. However, the biological significance of VEGF in lung adenocarcinoma remains unclear. We stained intratumoral microvessels immunohistochemically using anti-CD34 antibody and analyzed VEGF expression using anti-VEGF antibody in 44 cases of stage I lung adenocarcinoma. Of the 44 patients studied, 14 patients had a postoperative relapse, and 30 patients did not. The mean microvessel count (MVC) in stage I lung adenocarcinoma was 79.5 +/- 26.9 per x200 microscopic field. Immunohistochemical expression of VEGF was found in 27 of 44 cases of stage I lung adenocarcinoma. The mean MVC in cases of VEGF-positive lung adenocarcinoma (86.4 +/- 28.2) was significantly higher than that in cases of VEGF-negative lung adenocarcinoma (68.6 +/- 21.4; P < 0.05). The high-MVC group patients (MVC > 80) had significantly worse survival rates than those in the low-MVC group (MVC < or = 80; P < 0.01), and patients with VEGF-negative tumors had significantly better survival rates than those with VEGF-positive tumors (P < 0.05). We conclude that angiogenesis, as assessed by intratumoral MVCs, is a significant prognostic factor in stage I lung adenocarcinoma, and that VEGF is an important angiogenic factor in stage I lung adenocarcinoma.

Although experimental studies indicate that overexpression of metallothionein (MT), glutathione-S-transferase-pi (GST-pi), or P-glycoprotein (P-GP) is related to the drug resistance of cancer cells, the clinical significance of the overexpression remains to be elucidated. The expressions of MT, GST-pi, and P-GP wre evaluated immunohistochemically in 74 specimens of gastric adenocarcinoma in T1-3N1-2 stages which were resected with curative intent. Fluorinated pyrimidines, mitomycin C, and Adriamycin were prescribed in 73, 54, and 2 patients, respectively. The staining characteristics were investigated in relation to the clinical results. The cell-proliferative activity was studied with anti-proliferating cell nuclear antigen antibody. Expressions of GST-pi and P-GP correlated with the staining intensity of normal mucosa. Five-year disease-free survival rates (DFSRs) of GST-pi-negative and GST-pi-positive groups were 75.0 and 49.0%. The 5-year DFSRs of P-GP-negative and P-GP-positive groups were 68.2 and 38.6%. Concurrent expression among the three proteins was associated with the survival: 5-year DFSR of no- or one-protein-positive group was 75.0%, while those of 2- and 3-protein-positive groups were 56.0 and 38.9%, respectively. Tumors concurrently expressing 2 or 3 proteins have a high proliferative activity. Expressions of MT, GST-pi, and P-GP by the tumor are associated with a poorer prognosis of the patients.

Unlabelled: To clarify differences in accumulation in 201 Tl scintigraphy, we examined the relationship between uptake of 201 Tl, histopathological differentiation and Na-K ATPase., Methods: Thallium-201 SPECT was performed twice: 15 min (early scan) and 120 min (delayed scan) after intravenous injection of 3 mCi 201 Tl-chloride. The uptake ratio of 201 Tl was calculated and compared with the grade of differentiation and the staining pattern of Na-K ATPase., Results: The sensitivity of 201 Tl SPECT for well-differentiated adenocarcinomas was lower than that for moderately and poorly differentiated ones. The uptake ratio on the delayed scan was significantly lower in the well-differentiated group than that in the moderately and poorly differentiated groups. This parameter was also significantly higher in the Na-K ATPase-positive group than the -negative group., Conclusions: These results indicate that the uptake ratio of 201 Tl SPECT may be a noninvasive indicator of the grade of pathological differentiation of adenocarcinoma and provide insight into the relationship among 201 Tl SPECT, malignancy and Na-K ATPase.

We report the unusual case of identical male twins developing early gastric cancers that were found almost simultaneously. A 39-year-old man underwent a barium-swallow examination to investigate the cause of right hypochondrial discomfort; the examination revealed evidence of gastric cancer in the upper body of the stomach. A diagnosis of adenocarcinoma was confirmed by endoscopic biopsy, and a total gastrectomy was performed. Subsequent screening of the patient's asymptomatic identical twin revealed gastric cancer in the lower body of the stomach, for which distal gastrectomy with Billroth I reconstruction was performed. The histopathological types of the two cancers were similar and both had infiltrated the submucosa. The relevant etiological factors contributing to the development of gastric adenocarcinoma in these identical twins is discussed, following the case report.