Safety and feasibility of minimally invasive esophagectomy for elderly esophageal cancer patients.

The number of elderly patients with esophageal cancer has increased in recent years. The use of thoracoscopic esophagectomy has also increased, and its minimal invasiveness is believed to contribute to postoperative outcomes. However, the short- and long-term outcomes in elderly patients remain unclear. This study aimed to elucidate the safety and feasibility of minimally invasive esophagectomy in elderly patients. This retrospective study included 207 patients who underwent radical thoracoscopic esophagectomy for thoracic esophageal squamous cell carcinoma at Kobe University Hospital between 2005 and 2014. Patients were divided into non-elderly (<75 years) and elderly (≥75 years) groups. A propensity score matching analysis was performed for sex and clinical T and N stage, with a total of 29 matched pairs. General preoperative data, surgical procedures, intraoperative data, postoperative complications, in-hospital death, cancer-specific survival, and overall survival were compared between groups. The elderly group was characterized by lower preoperative serum albumin levels and higher American Society of Anesthesiologists grade. Intraoperative data and postoperative complications did not differ between the groups. The in-hospital death rate was 4% in the elderly group, which did not significantly differ from the non-elderly group. Cancer-specific survival was similar between the two groups. Although overall survival tended to be poor in the elderly group, it was not significantly worse than that of the non-elderly group. In conclusion, the short- and long-term outcomes of minimally invasive esophagectomy in elderly versus non-elderly patients were acceptable. Minimally invasive esophagectomy is a safe and feasible modality for elderly patients with appropriate indications.

C-reactive protein to albumin ratio is a prognostic factor for patients with cStage II/III esophageal squamous cell cancer.

C-reactive protein to albumin (CRP/Alb) ratio, a novel inflammation-based prognostic score, was first developed as a prognostic score for septic patients. Recent reports show that CRP/Alb ratio is also a prognostic score for cancer patients, including esophageal cancer. However, the role of CRP/Alb ratio for those with neoadjuvant chemotherapy (NAC) and the changes of CRP/Alb ratio around NAC have never been discussed. The aim of this study is to evaluate the significance of CRP/Alb ratio around NAC for patients with cStage II/III esophageal squamous cell cancer (ESCC). A total of 149 patients who were diagnosed as cStage II/III ESCC were enrolled between February 2007 and December 2014. We retrospectively investigated the relation between pre-NAC and post-NAC CRP/Alb ratio and short and long outcomes. The optimal cutoff level for pre-NAC and post-NAC CRP/Alb ratio was 0.030 and 0.048, respectively. There was no relation between CRP/Alb ratio level and postoperative outcomes. Post-NAC CRP/Alb ratio < 0.048 had a significantly higher overall survival rate than CRP/Alb ratio ≥0.048 (P< 0.001). Univariate analysis showed that cT, cN, pre-NAC CRP/Alb ratio < 0.030 and post-NAC CRP/Alb ratio < 0.048 was prognostic factors (P= 0.003, P= 0.022, P= 0.033, and P< 0.001, respectively). Multivariate analysis showed that cT and post-NAC CRP/Alb ratio < 0.048 was independent prognostic factors (P= 0.030 and P< 0.001, respectively). Post-NAC CRP/Alb ratio is an independent prognostic factor in patients with cStage II/III ESCC.

Surgical strategy of esophageal resection and reconstruction for aortoesophageal fistula.

Aortoesophageal fistula is a critical and life-threatening disease. The cardiovascular strategy for graft replacement has been widely discussed. However, the surgical strategy of esophageal resection and reconstruction for aortoesophageal fistula has rarely been discussed. The objective of this study is to establish a surgical strategy and procedure of esophageal resection and reconstruction for aortoesophageal fistula. Eleven patients with aortoesophageal fistula who underwent aortic graft replacement and esophagectomy between 2008 and 2015 at Kobe University Hospital were enrolled in this study. Patient characteristics, operative methods, and clinical outcomes were obtained by retrospective chart review. All 11 patients underwent graft replacement, esophagectomy, and omental wrapping. Ten esophagectomies were simultaneously accomplished in the same operative field as aortic graft replacement. Seven patients underwent subtotal esophagectomy from a left thoracotomy, and three patients underwent upper hemiesophagectomy from a median sternotomy. The other patient underwent staged esophagectomy from a right thoracotomy. Seven of 11 patients (63.6%) successfully underwent staged esophageal reconstruction. Pedicled jejunal transfer with supercharge and superdrainage were performed in six patients, and ileocecal reconstruction was performed in one patient. Median survival time in the patients with esophageal reconstruction was 21 months while that in the patients without esophageal reconstruction was 10 months. Six of 7 patients (85.7%) who underwent esophageal reconstructions were alive. Our surgical strategy for aortoesophageal fistula, which includes simultaneous graft replacement and esophagectomy in the same operative field and staged reconstruction by pedicled jejunal transfer to ensure omental wrapping, is feasible and promising.

Safety and benefit of curative surgical resection for esophageal squamous cell cancer associated with multiple primary cancers.

BACKGROUND: Enhancements in surgical techniques have led to improved outcomes for esophageal cancer. Recent findings have showed that esophageal cancer is frequently associated with multiple primary cancers, and surgical resection is usually complicated in such cases. The aim of this study was to clarify the clinical significance of surgery for patients with esophageal squamous cell cancer associated with multiple primary cancers. METHODS: The clinical outcomes of surgical resection for esophageal cancer were compared among 79 patients with antecedent and/or synchronous cancers (Multiple cancer group) and 194 patients without antecedent and/or synchronous cancers (Single cancer group). RESULTS: The most common site of multiple primary cancers was the pharynx (36 patients; 29.7%), followed by the stomach (24 patients; 19.8%). The reconstruction method was more complicated in the Multiple cancer group as a result of the prolonged surgery time and increased blood loss. However, postoperative morbidity and overall survival (OS) did not differ between the two groups. After esophagectomy, metachronous cancers were observed in 26 patients, with 30 regions in total, and 93.1% were found to be curable. Sex was the only independent risk factors for developing metachronous cancer after esophagectomy. CONCLUSIONS: The presence of antecedent and synchronous cancers complicates the surgical resection of esophageal cancer; however, no differences were found in the OS and postoperative morbidity between the two groups. Therefore, surgical intervention should be selected as a first-line treatment. Because second primary cancers are often observed in esophageal cancer, we recommend a close follow-up using esophagogastroduodenoscopy and contrast-enhanced computed tomography.

Transcriptional targeting of adenovirus vectors with the squamous cell carcinoma-specific antigen-2 promoter for selective apoptosis induction in lung cancer.

Squamous cell carcinoma antigens SCCA1 and SCCA2 are highly homologous serine proteinase inhibitors which have been widely utilized as serological markers for squamous cell cancers, but it has recently been demonstrated that only SCCA2 is truly specific for certain forms of lung cancer. Using a construct containing the 5'-flanking region of the SCCA2 gene between -460 and +0 bp and the luciferase reporter gene, SCCA2 promoter activity was detected in SCCA2-producing SCC cell lines (LK-2, LC-1), but not in SCCA2-nonproducing lung adenocarcinoma cell lines (A549, ABC-1, and RERF-LC-MS) or normal cells (WI-38, SAEC, and NHEK-Adult). Infection with a recombinant adenovirus vector, Ad-SCCA2-DsRed, resulted in cell-specific expression of the SCCA2 promoter-driven DsRed marker gene only in LK-2 and LC-1 cells. The same strategy was used for SCCA2-driven expression of a proapoptotic gene, (KLAKLAK)2, which can cause mitochondrial disruption by triggering mitochondrial permeabilization and swelling, resulting in the release of cytochrome c and induction of apoptosis. Infection with Ad-SCCA2-KLAKLAK2 specifically reduced the growth of the two human lung SCC cell lines compared to the SCCA2 nonproducing cell lines both in vitro and in vivo, suggesting that the SCCA2 promoter had a tumor-specific effect. These results suggest that transduction of SCCA2 promoter-controlled suicide genes by adenoviral vectors can confer transcriptionally targeted cytotoxicity in SCCA2-producing lung SCC cells, and represents a novel strategy for gene transfer specifically targeted to SCC in the lung.

Concurrent infiltration by CD8+ T cells and CD4+ T cells is a favourable prognostic factor in non-small-cell lung carcinoma.

The purpose of this study was to clarify the relationship between the number of tumour-infiltrating T lymphocytes and the clinicopathological features and clinical outcome in patients with non-small-cell lung cancer (NSCLC). Tissue specimens from 109 patients who underwent surgical resection for NSCLC were immunohistochemically analysed for CD4 and CD8 expression. Patients were classified into two groups according to whether their tumours exhibited a 'high' or 'low' level of CD8(+) or CD4(+) lymphocyte infiltration. Although the level of infiltration by CD8(+) T cells alone had no prognostic significance, the survival rate for patients with both 'high' CD8(+) and 'high' CD4(+) T-cell infiltration was significantly higher than that for the other groups (log-rank test, P=0.006). Multivariate analysis indicated that concomitant high CD8(+) and high CD4(+) T-cell infiltration was an independent favourable prognostic factor (P=0.0092). In conclusion, the presence of high levels of both CD8(+) T cells and CD4(+) T cells is a significant indicator of a better prognosis for patients with NSCLC, and cooperation between these cell populations may allow a significantly more potent antitumour response than either population alone.

Clinical significance of immune cell infiltration within gallbladder cancer.

To investigate the pathophysiological significance of infiltrating antitumour immune cells, we evaluated the quantity of immune cell intratumoral infiltration in 110 surgically resected gallbladder specimens by immunohistochemistry. We examined 45 cases of gallbladder cancer and 65 cases of benign gallbladder diseases for CD4(+) T cells, CD8(+) T cells, natural killer cells (NKCs), and dendritic cells (DCs). High levels of CD4(+) T cell, CD8(+) T cell, NKC, and DC infiltration were recognised in 51.1% (23 out of 45), 37.8% (17 out of 45), 33.3% (15 out of 45), and 48.9% (22 out of 45) of cancer specimens, respectively. High numbers of infiltrating CD4(+) and CD8(+) T cells correlated with decreasing tumour invasion, and high numbers of infiltrating DCs correlated with decreasing lymph-node tumour metastasis. Furthermore, increased infiltration of CD4(+) and CD8(+) T cells and DCs exhibited a significant correlation with prolonged survival. NKC infiltration, however, did not correlate with any of the clinicopathological factors examined. Additionally, high levels of infiltration were not identified in specimens from benign diseases, consistent with the cancer-specific activity of CD4(+) and CD8(+) T cells and DCs. In this study, we demonstrate that CD4(+) and CD8(+) tumour-infiltrating lymphocyte and DCs, but not NKCs, are important factors in the accurate prognosis of survival after surgical removal of gallbladder adenocarcinoma.

Caveolin-I overexpression is a favourable prognostic factor for patients with extrahepatic bile duct carcinoma.

Extrahepatic bile duct carcinoma (EBDC) is a malignancy well known for its poor prognosis. Some clinicopathological prognostic markers have been proposed, but genetic factors have not been well investigated. We have examined expression patterns of caveolin-1, which has been shown to function as a tumour suppressor in vitro, in EBDC using immunohistochemistry. Normal tissues adjacent to the tumour cells did not show immunoreactivity for caveolin-1. A total of 22 of the 60-carcinoma tissue samples (36.7%) studied were positive for caveolin-1. Caveolin-1 immunostaining negatively correlated with the patient's age and pathological T factor (pT) in a statistically significant manner. Multivariate analysis using Cox's proportional hazards model identified caveolin-1 expression as an independent positive prognostic factor. Thus, our study suggests that caveolin-1 expression may be a useful prognostic marker for EBDC.

Impact of caveolin-1 expression on prognosis of pancreatic ductal adenocarcinoma.

Caveolin-1 is a major component of caveolae and plays a regulatory role in several signalling pathways. Caveolin-1 was recently identified as a metastasis-related gene in prostate cancer. The clinical effects of caveolin-1 expression in pancreatic carcinoma, however, remain unknown. In this study, we have investigated the relationship between caveolin-1 expression and the clinicopathologic variables and clinical outcome in 79 patients with pancreatic adenocarcinoma undergoing surgical resection. Caveolin-1 expression was determined by immunohistochemistry, using a polyclonal anti-caveolin-1 antibody. Patients were divided into two groups based on the extent of caveolin-1 expression: a negative expression group (immunoreactivity in less than 50% of cells) and a positive expression group. Positive caveolin-1 immunostaining was detected in 32 cases (40.5% of total), while non-neoplastic ductal epithelium showed little or no staining. Positive caveolin-1 expression was correlated with tumour diameter (P=0.0079), histopathologic grade (P=0.0272) and poor prognosis (P=0.0008). Upon multivariate analysis with Cox's proportional hazards model, positive caveolin-1 expression was shown to be an independent negative predictor for survival (P=0.0358). These results suggest that caveolin-1 overexpression is associated with tumour progression, thereby indicating a poor prognosis for certain patients undergoing surgical resection for pancreatic carcinoma.

RCAS1 as a tumour progression marker: an independent negative prognostic factor in gallbladder cancer.

Receptor-binding cancer antigen expressed on SiSo cells (RCAS1) induces apoptosis in immune cells bearing the RCAS1 receptor. We sought to determine RCAS1 involvement in the origin and progression of gallbladder cancer, and also implications of RCAS1 for patient survival. RCAS1 expression was examined immunohistochemically in 110 surgically resected gallbladder specimens. The gallbladders represented 20 cases of cholecystitis with no associated pancreaticobiliary maljunction; 23 cases of cholecystitis with pancreaticobiliary maljunction; 14 cases of adenomyomatosis; 7 adenomas; and 46 cancers. High expression of RCAS1 (immunoreactivity in over 25% of cells) was observed in 32 of the 46 cancers (70%), but not in other diseases, including pre-cancerous conditions. RCAS1 immunoreactivity was associated with depth of tumour invasion (P = 0.0180), lymph node metastasis (P = 0.0033), lymphatic involvement (P = 0.0104), venous involvement (P = 0.0224), perineural involvement (P = 0.0351) and stage by the tumour, nodes and metastases (TNM) classification (P = 0.0026). Thus, RCAS1 expression may be a relatively late event in gallbladder carcinogenesis, possibly promoting tumour progression. Cox regression multivariate analysis demonstrated RCAS1 positivity to be an independent negative predictor for survival (P = 0.0337; risk ratio, 12.690; 95% confidence interval, 1.216-132.423). High expression of RCAS1 significantly correlated with tumour progression and predicted poor outcome in gallbladder cancer.

Five cases of the lymphangioma of the mediastinum in adult.

Mediastinal lymphangioma is rare disease. Above all cavernous type of mediastinal lymphangioma is very rare. We report 5 cases of mediastinal lymphangioma including cavernous type. CT was performed in all and revealed that they were smoothly marginated and cystic. All were surgically resected and specimens were classified pathologically into cystic type (3 cases), cavernous type (1 case) and mixed type of the two (1 case). MRI was performed in the cavernous type and suggested that the mass was lymphangioma because of pathognomonic lesion. Despite preoperative diagnosis of mediastinal lymphangioma is difficult, MRI is able to useful examination. In the follow-ups there has been no recurrence in our series.

[An experience with omentopexy for the repair of postoperative bronchopleural fistula].

Postoperative bronchopleural fistula has been the most troublesome complications in the thoracic surgery. In this report, we presented a case of bronchopleural fistula successfully closed by omentopexy. A 51-year-old man had undergone left upper lobectomy and S6 segmentectomy for primary lung cancer. Bronchopleural fistula due to postoperative pneumonia was developed and completion pneumonectomy with the intercostal-musclo-pexy was performed. Post-re-operative course was unsuccessful, bronchopleural fistula remained, so we tried re-closure of the bronchial stump by omentopexy without thoracoplasty or muscle flap plombage. About a half year after 3rd operation, he relapsed into bronchopleural fistula. Then fibrin gluing was performed via a flexible fiberoptic bronchoscope without hospitalization, and the omental flap was fixed completely to the bronchial stump. We believe the omentopexy a useful procedure for treating postoperative bronchopleural fistula which can't make any chest-wall deformation.

[The relation between the time and the fatigue of skeletal muscle ventricle].

It is generally recognized that if skeletal muscle is stimulated corresponding with the heart rate to assist the cardiac performance, the contraction power of the skeletal muscle decreases in a few minutes. It becomes necessary that the skeletal muscle is electrically stimulated in 6-9 weeks to lead into the transformation or that the muscle is laid without working after operation in 6-9 weeks to wait for growing of the collateral vessels. The observation time of the fatigue phenomenon in many studies is, however, short and it is not understandable that the contraction power decreases near to zero although the type I fibers remain. So we studied the relationship between the time and the pressure assist of the skeletal muscle ventricle (SMV). It was concluded that 1) the cause of the power decrease is not only the fatigue but the operative invasion. 2) in our setting, when SMV was stimulated in the ratio of 1:4 or 1:10 to the heart rate, the power recovered within 3 hours. 3) if the initial setting of the drive is light enough, the preconditioning or the vascular delay will be unnecessary and the working transformation or the in situ training will practicable.

A human gastric choriocarcinoma cell line with human chorionic gonadotropin and placental alkaline phosphatase production.

A gastric choriocarcinoma cell line synthesizing human chorionic gonadotropin (HCG) was established in 1971 by Oboshi et al. and was found to possess human placental alkaline phosphatase. The present paper also deals with the relationship between the cell growth and HCG secretion and with cellular localization of HCG and human placental alkaline phosphatase by cytochemical and ultrastructural methods. This cell line was found to secrete HCG during cellular proliferation, with the maximum secretion in the stationary phase (about 1 muIU/cell/48 hr), and the hormone could be detected in a small proportion of mono- and/or multinuclear cells in both logarithmic and stationary phases. The organ-specific, heat-stable, L-phenylalanine-sensitive, immunoreactive human placental alkaline phosphatase was localized on the cell membrane of many cells. Ultrastructurally, the line consisted mainly of cytotrophoblastic and intermediate cells in the process of syncytial formation, with more or less squamous metaplasia. From these findings it was concluded that the cell line maintained the properties of trophoblastic cells from morphological and functional aspects, i.e., it was a cell line with two distinct marker substances.