Kazuhito Yajima

Heterogeneous expression of GAGE, NY-ESO-1, MAGE-A and SSX proteins in esophageal cancer: Implications for immunotherapy

Cancer/testis antigens (CTAs) elicit immune response in cancer patients and are therefore targets of immunotherapy. Current information on CTA expression is primarily based on mRNA assays and little is known about their expression at the protein level. The objectives of our study are to analyze GAGE, NY‐ESO‐1, MAGE‐A and SSX protein expression in esophageal cancer and to correlate their expression patterns with clinicopathologic parameters and survival. We examined CTA protein expression in 213 patients with esophageal cancer by immunohistochemistry. Antigen‐positive tumors were evaluated once and antigen‐negative tumors were evaluated 3 times by examining different parts of the cancer specimen. GAGE, NY‐ESO‐1 and MAGE‐A were heterogeneously expressed in 42 (20%), 44 (21%) and 111 (52%) tumors, respectively, whereas SSX expression was not detected. Of the 126 (59%) patients expressing CTAs, 70 (33%) expressed 1, 41 (19%) expressed 2 and 15 (7%) expressed 3 antigens. The expression of MAGE‐A was correlated with those of GAGE (p=0.001) and NY‐ESO‐1 (p=0.002), and the expression of GAGE was correlated with that of NY‐ESO‐1 (p=0.002). One hundred fifty‐six (79%) sections were positively stained in the first evaluation, whereas 37 (19%) and 4 (2%) positive sections were identified in the second and third evaluations, respectively. Particularly, MAGE and GAGE expression showed overlaps. GAGE, NY‐ESO‐1 and MAGE‐A protein expression was not correlated with the disease progression, TNM factors or survival. The detection of immunonegative cells in every specimen suggests addition of other drugs such as 5‐aza‐2′‐deoxycytidine to increase the therapeutic effect of CTA‐specific cancer vaccines.

Prospective Observational Study of Imatinib Therapy in Japanese Patients with Advanced Gastrointestinal Stromal Tumors: Long-term Follow-up and Second Malignancy

Abstract Objective Limited data are available concerning long-term results of imatinib therapy in patients with advanced gastrointestinal stromal tumors. We aimed to clarify the long-term outcomes of imatinib therapy in Japanese patients with advanced gastrointestinal stromal tumors. Methods A prospective, observational study of imatinib therapy for unresectable and metastatic gastrointestinal stromal tumors was conducted in our institution. Imatinib was initiated at a dose of 400 mg daily and continued until disease progression. Safety, efficacy and long-term tolerability and survival were evaluated in an intent-to-treat population. The median follow-up period in this study was 68 months. Results Seventy patients were enrolled between December 2001 and December 2009. Treatment-related Grade 3/4 adverse events occurred in 49 patients (70.0%). Although 14 patients required adverse effect management with hospitalization, only 5 patients (7.1%) withdrew from the treatment owing to imatinib intolerance. The tumor response and clinical benefit rates were 61.4 and 85.7%, respectively. Thirty-seven patients (52.9%) maintained the treatment at 400 mg daily imatinib, whereas 33 patients (47.1%) had their dose reduced to 300 mg daily or less. The overall survival rate at 5 years was 60.9% and the median survival time was 70 months. The median progression-free survival time of all the 70 enrolled patients was 30 months. Seven patients (10.0%) suffered from second malignancies, including three patients with genitourinary carcinomas. Conclusions Despite the need for dose reduction, the long-term results of imatinib therapy for advanced gastrointestinal stromal tumors were good in Japanese patients. Physicians should pay attention to the occurrence of second malignancies during imatinib therapy for gastrointestinal stromal tumor patients.

Gastric cancer surgery for patients with liver cirrhosis

AIM To elucidate the influence of liver cirrhosis (LC) on the prognosis of patients with gastric cancer (GC). METHODS Of the 1347 GC patients who underwent curative gastrectomy for GC between January 1984 and June 2007, 25 patients (21 men and 4 women with a median age of 67 years; range 54-77 years) with LC were enrolled in this study. Using the Child-Pugh classification, 15 patients were evaluated as grade A and 10 patients as grade B. No grade C patient underwent gastrectomy in this series. Clinical outcomes, including postoperative morbidity and survival, were retrospectively analyzed based on medical records and surgical files. RESULTS There was no significant difference in operative blood loss and perioperative blood transfusion between the two groups. The most common postoperative complication was intractable ascites, which was the single postoperative morbidity noted more frequently in grade B patients (40.0%) than in grade A patients (6.7%) with statistical significance (P = 0.041). Operative mortality due to hepatic failure was seen in one grade A patient. Three patients had hepatocellular carcinoma (HCC) at presentation and two patients developed HCC after surgery. Overall 5-year survival rate was 58.9% in patients with early GC and 33.3% in patients with advanced GC (P = 0.230). GC-specific 5-year survival rate of early GC patients was 90.0% while that of advanced GC patients was 58.3% (P = 0.010). Four patients with early GC died of uncontrolled HCC, of which two were synchronous and two metachronous. CONCLUSION The risk of postoperative intractable ascites is high, particularly in grade B patients. Early detection and complete control of HCC is vital to improve a patients prognosis.

Treatment for Perforated Gastric Ulcer: a Multi-institutional Retrospective Review

BackgroundThe optimal treatment for patients with perforated gastric ulcer (PGU) remains controversial. This study therefore investigated the treatment status for this disease in clinical practice.MethodsWe retrospectively reviewed 183 patients with PGU from 1998 to 2007 across 15 institutions, and analyzed patient characteristics and short- and long-term outcomes according to treatments received.ResultsOf the 183 patients, 57 who were treated conservatively had less abdominal tenderness, lower levels of serum C-reactive protein, and shorter time to presentation than the 126 patients who underwent emergency surgery. There was no significant difference in baseline characteristics between the 41 successful patients and 16 failed patients in the conservative treatment group; however, the latter had a longer average hospital stay. Eighty-three of the emergency surgery patients who underwent gastrectomy had longer surgical times, greater blood loss, and shorter time to resumption of diet than the 57 patients undergoing stomach-preserving surgery; however, there was no significant difference in postoperative complications and hospital stay between these groups. Of 91 patients who received stomach-preserving treatment, only three had treatment failure in the long-term follow-up period.ConclusionStrictly selected patients should be initially considered for conservative treatment. The short-term outcomes of stomach-preserving surgery are comparable to gastrectomy; however, further evaluation of the long-term outcomes of stomach-preserving treatment is required.

Short-and long-term outcomes of surgery for diffuse peritonitis in patients 80 years of age and older

PurposeWe evaluated the impact of advanced age on the morbidity, mortality, and long-term outcome after emergency surgery for diffuse peritonitis.MethodsWe retrospectively evaluated the mortality and morbidity rates in 36 patients who were 80 years of age or older and who had undergone emergency surgery for diffuse peritonitis, and calculated 5-year survival by the Kaplan-Meier method. Factors compromising prognosis were identified by univariate and multivariate analyses.ResultsThe median patient age was 84 years (range, 80–97 years); 16 patients were men and 20 were women. Preoperative concomitant disease was present in 81% of patients; cardiac disease was most common. Sites of visceral perforation were in the upper gastrointestinal tract in five patients, colon or rectum in 30, and gallbladder in 1. The postoperative morbidity rate was 72%, the surgical mortality rate was 11%, and the in-hospital mortality rate was 28%. The median hospital stay was 56 days. The median survival was 41 months, with a 5-year survival rate of 23%. A multivariate analysis identified number of failing organs as the only independent adverse prognostic factor (P < 0.001; relative risk 5.51, 95% confidence interval 1.97–15.4).ConclusionsElderly patients with diffuse peritonitis had an unsatisfactory rate of short-term morbidity and mortality compared with those undergoing elective surgery. Postoperative organ failure was most likely to compromise survival.

Radio‐guided sentinel node mapping in patients with superficial esophageal carcinoma: Feasibility study

The aim of this study was to assess whether the sentinel node concept could be applicable to clinically early carcinoma of the esophagus. We studied ten consecutive cT1N0 patients who underwent radical esophagectomy with regional lymph node dissection. On the day before surgery, 99m‐Tc tin colloid was injected endoscopically around the primary tumor. Lymphoscintigraphy was also performed about three hours after injection. Immediately after surgery, the radioactivity of all dissected lymph nodes was measured with a hand‐held gamma probe. The radioactivity and the metastatic status assessed by routine histopathologic examination were compared. A total of six patients had hot spots detected by lymphoscintigraphy, of which the detection rate was 60% (6 of 10). The ex vivo hot node detection rate was 90% (9 of 10). Three patients were found to have metastatic nodes. In one patient, sentinel node mapping failed to identify any hot spot or hot node. In the other two patients, the metastatic nodes did not correspond to hot nodes. The accuracy of hot node status was 77.8% (7 of 9), and the false‐negative rate was 100% (2 of 2). The present study showed that radio‐guided sentinel node detection is insufficiently reliable at present due to the high false‐negative rate and low accuracy.

A giant subcutaneous leiomyosarcoma arising in the inguinal region

BackgroundSubcutaneous leiomyosarcoma is a rare condition that accounts for 1% to 2% of all superficial soft tissue malignancies. Approximately 10% of cases arise in the trunk, although the extremities are the most commonly affected.Case presentationWe report herein the case of a 31-year-old man with a subcutaneous leiomyosarcoma, measuring 124 × 105 mm, arising in the left inguinal region. A wide local excision (with a resection margin ≥ 20 mm) was performed. Histological examination of the resected specimen revealed a leiomyosarcoma with high cellularity and two mitoses per 10 high-power fields. The patient remains well with no evidence of disease 5 years and 8 months after the operation.ConclusionThis is the first reported case of subcutaneous leiomyosarcoma arising in the inguinal region and also one of the largest tumors reported. The experience of this case and a review of the English-language literature (PubMed, National Library of Medicine, Bethesda, MD, USA) suggest that a resection margin of ≥ 10 mm is recommended when excising this rare tumor.

Endobronchial metastasis from adenocarcinoma of gastric cardia 7 years after potentially curable resection

Endobronchial metastasis (EBM) is a rare form of metastasis from extrapulmonary malignant tumors, although there are few reports of EBM from gastric cancer specifically. We report the case of a 51-year-old woman who had undergone gastrectomy for advanced gastric cancer seven years previously but was diagnosed with a solitary lung tumor by follow-up computed tomography. On diagnosis of primary lung cancer, she underwent pulmonary lobectomy, but immunohistochemical examination confirmed the resected tumor to be an EBM from the gastric cancer. Six months later, she was diagnosed with peritoneal metastases and underwent chemotherapy with gastric cancer regimen. She is still alive at 33 mo after the lobectomy. Generally, the prognosis for EBM is poor although multidisciplinary treatment can lead to long-term survival. Precise diagnosis on the basis of detailed pathological and immunohistochemical evaluation can contribute to deciding the most effective treatment and improving prognosis.

Gastrojejunostomy as induction treatment for S-1-based chemotherapy in patients with incurable gastric cancer

PurposeThe development of new generation anticancer agents, including the oral drug, S-1, may alter the clinical importance of gastrojejunostomy in the treatment of incurable gastric cancer. We reviewed a series of patients who underwent gastrojejunostomy for this reason between 2002 and 2005.MethodsFourteen patients underwent gastrojejunostomy followed by S-1-based chemotherapy for incurable gastric cancer with obstruction or stenosis of the gastric outlet at Niigata University Medical and Dental Hospital and two affiliated hospitals. The safety of gastrojejunostomy, outcome of palliation, and survival time were analyzed retrospectively. We compared the survival times with those of patients who underwent palliative gastrectomy or exploratory laparotomy between 1987 and 2001.ResultsThe median operative time and blood loss were 153 min and 66 ml, respectively. There were no major complications. The median starting time for chemotherapy after gastrojejunostomy was 15.5 days. All patients were discharged after gastrojejunostomy, and the median postoperative home stay ratio was 68%. The median survival time after gastrojejunostomy was 354 days, which was significantly longer than that of patients who underwent palliative gastrectomy or exploratory laparotomy.ConclusionGastrojejunostomy for incurable gastric cancer contributes not only to improving quality of life (QOL), but to prolonging survival through the induction and maintenance of S-1-based chemotherapy.

Risk factors influencing the pleural drainage volume after transthoracic oesophagectomy.

OBJECTIVES The objective of this study was to clarify the factors influencing pleural drainage volume after transthoracic oesophagectomy and to determine criteria for the selection of patients who would benefit from the early removal of chest drains. METHODS Clinicopathological characteristics of 155 patients who underwent transthoracic oesophagectomy were prospectively collected, and the daily drainage volume of each patient was retrospectively reviewed. Potential risk factors were compared between the high-output group (n = 39) and low-output group (n = 116), which were dichotomized using the 75th percentile of total pleural drainage volume of the total study population. Multivariate logistic regression analyses were used to identify independent risk factors. RESULTS The median duration of drainage was 10 days, with a median total drainage volume of 2258 ml. Of 27 potential risk factors influencing the drainage volume, creatinine clearance (P = 0.04), operative approach (P = 0.03) and thoracic duct removal (P = 0.01) were significantly associated with the total pleural drainage volume. The removal of the thoracic duct (P = 0.02; odds ratio, 4.02; 95% confidence interval 1.20-13.41) and lower creatinine clearance (P = 0.04; odds ratio, 1.02; 95% confidence interval 1.00-1.04) was independent risk factors for increased pleural drainage volume after transthoracic oesophagectomy. CONCLUSIONS The early removal of chest drains may be possible in patients without these risk factors.