Noriyuki Shinoda

Expression of survivin in esophageal cancer: Correlation with the prognosis and response to chemotherapy

Survivin, a new member of the inhibitor‐of‐apoptosis (IAP) family, has been reported to be expressed in many cancers but not in differentiated normal tissue. Its expression in esophageal cancer, however, has not been reported. We investigated 51 esophageal cancers and their adjacent normal epithelial tissues for mRNA expression of survivin by RT‐PCR. The survivin expression in esophageal cancer tissue was significantly higher than that in normal esophageal tissue (0.211 ± 0.226 vs. 0.057 ± 0.135, p < 0.0001). pN4 tumors had significantly higher survivin expression than the pN0‐3 tumors (p = 0.0093). Fourteen patients with advanced esophageal cancer had received chemotherapy prior to surgery. The survivin expression in the cancer tissue in patients who achieved a partial response (PR) was significantly lower than that in patients with no change (NC) and in patients with progressive disease (PD; 0.099 ± 0.134 vs. 0.320 ± 0.222, p = 0.0434). The median survival for patients with high survivin expression (9.0 months) was less than that for patients with low survivin group expression (30.0 months, p = 0.0023). Survivin expression was one of the significant predictors of survival on univariate analysis (hazard ratio 2.471; 95% confidence interval 1.104‐5.533). The results suggest that survivin expression may provide prognostic information in patients with esophageal cancer.

Decreased expression of DFF45/ICAD is correlated with a poor prognosis in patients with esophageal carcinoma

DNA fragmentation factor 45 (DFF45)/inhibotor of caspase activated DNAse (ICAD) forms a complex with DFF40/CAD and inhibits its DNA cleaving function during apoptosis. DFF45 also functions as a chaperone for native DFF40 and is necessary for its function. It has been indicated that defects in the apoptotic pathway may exist in neoplastic cells.

Aberrant nuclear localization of β-catenin without genetic alterations in β-catenin or Axin genes in esophageal cancer

Backgroundβ-catenin is a multifunctional protein involved in two apparently independent processes: cell-cell adhesion and signal transduction. β-catenin is involved in Wnt signaling pathway that regulates cellular differentiation and proliferation. In this study, we investigated the expression pattern of β-catenin and cyclin D1 using immunohistochemistry and searched for mutations in exon 3 of the β-catenin gene and Axin gene in esophageal squamous cell carcinoma.Materials and methodsSamples were obtained from 50 esophageal cancer patients. Immunohistochemical staining for β-catenin and cyclin D1 was done. Mutational analyses of the exon3 of the β-catenin gene and Axin gene were performed on tumors with nuclear β-catenin expression.ResultsFour (8%) esophageal cancer tissues showed high nuclear β-catenin staining. Overexpression of cyclin D1 was observed in 27 out of 50 (54%) patients. All four cases that showed nuclear β-catenin staining overexpressed cyclin D1. No relationship was observed between the expression pattern of β-catenin and cyclin D1 and age, sex, tumor size, stage, differentiation grade, lymph node metastasis, response to chemotherapy, or survival. No mutational change was found in β-catenin exon 3 in the four cases with nuclear β-catenin staining. Sequencing analysis of the Axin cDNA revealed only a splicing variant (108 bp deletion, position 2302–2409) which was present in the paired normal mucosa.ConclusionA fraction of esophageal squamous cell carcinomas have abnormal nuclear accumulation of β-catenin accompanied with increased cyclin D1 expression. Mutations in β-catenin or axin genes are not responsible for this abnormal localization of β-catenin.

Use of omentum for mediastinal tracheostomy after total laryngoesophagectomy

BACKGROUND Carcinomas of the cervicothoracic esophagus frequently invade the trachea and complete removal of the tumor often requires mediastinal tracheostomy. Traditionally, this surgical management was associated with high morbidity and mortality. Several types of myoctaneous flaps have been used for mediastinal tracheostomy to reduce the complication. We present our experience with a new technique for construction of mediastinal tracheotomy after total laryngoesophagectomy and reconstruction with the stomach. METHODS The anterior chest wall was amply resected and the distal end of the trachea was placed low between the superior vena cava and aortic arch. We mobilized the entire omentum with the stomach and brought them up to the neck through the posterior mediastinum. The omentum was put around the trachea, main arteries, and the anastomosis. RESULTS Seven mediastinal tracheostomies were performed using this method. There was no hospital death. Complications included respiratory failure (2 patients) and pyothorax (1 patient). Anastomotic leakage and inominate artery rupture were not experienced. Postoperative survival was disease dependent. All patients were discharged with satisfactory oral food intake, good airway condition, and excellent cosmetic appearance. CONCLUSIONS We suggest the use of the omentum as a simple and reliable technique in constructing mediastinal tracheostomy following total laryngoesophagectomy for cervicothoracic esophageal cancer.

The effectiveness of palliative resection for advanced esophageal carcinoma: Analysis of 24 consecutive cases

Abstract.Purpose: In some patients who already have advanced esophageal cancer at the time of presentation, symptoms like the inability to eat, and complications such as bronchoesophageal fistula are so debilitating that palliative resection may be beneficial. However, resection of the esophagus is associated with significant risk, and whether this operation should be performed for palliation remains controversial. Because few reports have been published on this subject, we retrospectively analyzed 24 patients with esophageal cancer who underwent palliative resection.Methods: Esophageal resection was performed with palliative intent in 12 patients and with curative intent in another 12 who were left with residual cancer.Results: There was no operative death. All of the ten patients who had been unable to eat preoperatively were able to eat after the operation, and four patients with a life-threatening bronchoesophageal fistula were free of symptoms after the operation. Two patients died in hospital during the postoperative chemotherapy but the other 22 were discharged. The mean survival period was 264 days.Conclusions: With improved postoperative care, the risk of palliative esophageal resection is no longer considered unacceptable.

Effect of Whole Body Hyperthermia on Ischemia and Reperfusion Injury of Rat Intestine: Real-Time ATP Change Studied Using 31P-MRS

We studied the effect of hyperthermia pretreatment on subsequent small intestinal ischemia and reperfusion (I/R) injury in the rat. Systemic hyperthermia has been reported to induce heat shock proteins (HSPs) in several organs [1-6]. We examined the expression of HSP72 in the small intestinal mucosa using Western blotting and immunohistochemistry. We monitored energy metabolism using magnetic resonance spectroscopy continuously during a 60-min ischemia and the following 120 min of reperfusion. Expression of HSP72 in the small intestine was significantly increased at 6–8 h after hyperthermia. Intestinal ischemia was induced by clamping the superior mesenteric artery. Heating of the rat conferred substantial resistance to the I/R injury. In the untreated rats, β-ATP decreased during ischemia (37.1 ± 15.5% of the pre-ischemic value) and recovered on reperfusion, but reached only ∼50% of the pre-ischemic value after 120 min of reperfusion. However, β-ATP in the pretreated rats was maintained during ischemia at significantly higher levels and on reperfusion reached ∼80% of the pre-ischemic value. These results indicate that hyperthermia protects the rat intestine from the I/R injury by unknown mechanisms which may include the induction of HSPs.

A Case of Peritonitis Chronica Fibrosa Incapsulata Presenting as lleus after Irradiation.

放射線照射後にイレウスにて発症した腸管膜様包衰症の1例を経験したので報告する.症例は, 子宮頸癌のため広範子宮全摘術と術後放射線照射を受けた既応を持つ62歳の女性で, 腹部膨満感, 嘔気を主訴に来院した.放射線障害による腸管癒着性イレウスの診断で腸切除術を施行した.終末回腸が厚さ約1mmの被膜に覆われた10.8×7.6×7.4cmの腫瘤を形成しており, 腸管膜様包裏症と診断した.腸管膜様包裏症は比較的まれな疾患で, 本邦では1970年以降現在までに本例を含め23例の報告があるのみで, 放射線照射に起因した本症の報告は本例が初めてである.また, 本症の術前診断は困難であるが, 本例では腹部CTがその特徴的な所見をとらえていた.

A case of Early Synchronous Double Cancer of Esophagus and Stomach.

息者は56歳の男性.検診時に胃体上部のI型早期胃癌を指摘され当科初診.精査にて胸部下部食道の表在陥凹型早期食道癌も発見され, 同時性食道胃早期重複癌の診断にて入院.食道亜全摘, 噴門側胃切除, 胃管再建術を施行した。同時性食道胃早期重複癌はまれで, 本邦報告例は自験例を含め37例にすぎない。今回, 本邦報告例を集計し臨床的に検討した。男性32例, 女性4例, 平均年齢62歳.食道癌は胸部中下部食道, 深達度smの表在隆起型または陥凹型が多く, 胃癌はA領域のHc型が多く認められた, 多発食道癌3例 (8%), 多発胃癌8f/11 (22%) と多発癌の合併は高率に認められた。手術術式は, 食道亜全摘十胃全摘が21711 (57%) と多用されている。予後の明らかな21例中44/1 (19%) が術後1年以内に死亡しており, 同時性食道胃早期重複癌の手術においては, 最小限の手術侵襲で, さらに根治性が得られる手術術式の選択が重要と考えられる。