Yutaka Miyawaki

Genomic copy-number alterations of MYC and FHIT genes are associated with survival in esophageal squamous-cell carcinoma

Esophageal squamous‐cell carcinoma (ESCC) is one of the most common cancers and is associated with a poor prognosis. Studies are warranted on the clinical relevance of its genomic copy‐number alterations (CNA) as prognosticators for ESCC. In the present study, we first screened recurrent CNA by array‐based comparative genomic hybridization using an in‐house focused bacterial artificial chromosome‐based array for 108 loci in 45 ESCC specimens. We detected 14 regions showing recurrent (>20%) CNA (4 losses and 10 gains) by array‐based comparative genomic hybridization in the first cohort. Among them, loss of 3p14.2 and gain of 8q24.21 for the FHIT and MYC genes, respectively, and the accumulation of those two CNA (higher FM‐CNA scores) were significantly associated with a worse overall survival (OS) in the first cohort (P = 0.0273, P = 0.0356 and P = 0.0089, respectively). In the independent validation cohort of 92 resected ESCC cases, loss of FHIT, gain of MYC and higher FM‐CNA scores determined by a quantitative genomic PCR‐based copy‐number analysis were associated with a worse OS (P = 0.0011, P = 0.0104 and P = 0.0008, respectively) and disease‐free survival (P = 0.0038, P = 0.0132 and P = 0.0021, respectively). In addition, the Cox model showed the presence of either CNA to be an independent prognosticator for OS and disease‐free survival in the validation cohort (P = 0.0120 and P = 0.0255, respectively). These results suggest that CNA of MYC and FHIT are poor prognostic markers, and risk stratification based on the copy‐number status of those genes is useful to select the optimal treatment strategy in resected ESCC patients. (Cancer Sci, doi: 10.1111/j.1349‐7006.2012.02329.x, 2012)

Osteoplastic bone metastasis in esophageal squamous cell cancer : report of a case

This report presents a case of esophageal squamous cell cancer with osteoplastic bone metastasis. A 58-year-old male patient underwent multimodality treatment for esophageal cancer. Sclerotic changes resembling bone metastasis from prostate cancer were detected in the 4th thoracic and the 5th lumber vertebral body soon after the adjuvant chemoradiotherapy. Systemic examinations revealed no primary cancer as a cause of osteoplastic bone metastasis and no esophageal cancer recurrence. A needle biopsy revealed metastases of esophageal squamous cell cancer with osteoplastic changes. Multiple sclerotic changes were detected in the systemic bones at that time, and new carcinomatous bilateral pleural effusion developed. The drastic systemic progression of the cancer caused the rapid deterioration of the patient’s general condition.

Successful Anesthesia Management for 2-Stage Surgical Procedure of a Refractory Tracheogastric Tube Fistula After Esophagectomy.

Tracheogastric tube fistulas are rare but fatal complications after esophagectomy. Anesthetic management for a patient with this complication is challenging because air leakage and mechanical ventilation may cause aspiration. We present a case report of the anesthetic management of a patient having 2-stage surgical repair combined with endoscopic mucosal resection for a giant carinal tracheogastric tube fistula. The first stage was separation of the gastric tube above the fistula with spontaneous breathing under local anesthesia and sedation. The second stage was complete separation and reconstruction of the digestive tract under epidural and general anesthesia with spontaneous breathing and pressure support before insertion of a decompression tube.

Relationships between Micro-Vascular and Iodine-Staining Patterns in the Vicinity of the Tumor Front of Superficial Esophageal Squamous Carcinoma

OBJECTIVE The aim of the present study was to clarify differences between micro-vascular and iodine-staining patterns in the vicinity of the tumor fronts of superficial esophageal squamous cell carcinomas (ESCCs). METHODS Ten consecutive patients with ESCCs who were treated by endoscopic submucosal dissection (ESD) were enrolled. At the edge of the iodine-unstained area, we observed 183 sites in total using image-enhanced magnifying endoscopy. We classified the micro-vascular and iodine-staining patterns into three types: Type A, in which the line of vascular change matched the border of the iodine-unstained area; Type B, in which the border of the iodine-unstained area extended beyond the line of vascular change; Type C, in which the line of vascular change extended beyond the border of the iodine-unstained area. Then, by examining histopathological sections, we compared the diameter of intra-papillary capillary loops (IPCLs) in cancerous areas and normal squamous epithelium. RESULTS We investigated 160 sites that the adequate quality of pictures were obtained. There was no case in which the line of vascular change completely matched the whole circumference of the border of an iodine-unstained area. Among the 160 sites, type A was recognized at 76 sites (47.5%), type B at 79 sites (49.4%), and type C at 5 sites (3.1%). Histological examination showed that the mean diameter of the IPCLs in normal squamous epithelium was 16.2±3.7 μm, whereas that of IPCLs in cancerous lesions was 21.0±4.4 μm. CONCLUSIONS The development of iodine-unstained areas tends to precede any changes in the vascularity of the esophageal surface epithelium.

A Prospective Study of Nutritional Supplementation for Preventing Oral Mucositis in Cancer Patients Receiving Chemotherapy

BACKGROUND AND OBJECTIVES Patients undergoing chemotherapy often develop distressing adverse effects such as oral mucositis and diarrhea. Nutritional support with elemental diet is effective against various gastrointestinal complications and may exert protective effects against adverse effects induced by chemotherapy. To evaluate the influence of elemental diet on chemotherapy-induced oral mucositis and diarrhea, we conducted a randomized control trial in patients with esophageal cancer undergoing chemotherapy. METHODS AND STUDY DESIGN Twenty esophageal cancer patients receiving chemotherapy with 5-fluorouracil plus cisplatin were assigned randomly to one of the following two groups: (1) receiving elemental diet with Elental (one pack per day) for 14 days and (2) not receiving Elental during chemotherapy. The severity of oral mucositis and diarrhea was graded using clinical examination by doctors and a standard questionnaireon days 1-14. RESULTS Based on the analysis of the standard questionnaire, the distribution of the maximum severity of oral mucositis showed a statistically significant reduction in the Elental group (p=0.020), while clinical examination showed insignificant reduction but shift toward lower grade. In the Elental group, the incidence of oral mucositis (grade >=2) reduced consistently and the median grade was lower at all-time points. Regarding diarrhea, no difference was observed between the two groups based on the analysis of the standard questionnaire and clinical examination results. CONCLUSIONS This study illustrates the effectiveness of oral elemental diet in preventing oral mucositis during chemotherapy. This is a preliminary report and further study with larger patients groups should be devoted to optimization of efficacy.

Lobar torsion after thoracoscopic esophagectomy, and prevention method to detect its incidence during the operation

Abstract Introduction: Lobar torsion is a rare but fatal complication, with such cases being mostly treated with pulmonary resection. Only a few cases of pulmonary torsion following esophagectomy h...

Esophageal Squamous Cell Carcinoma Developed 11 Years After Allogeneic Bone Marrow Transplantation for Acute Lymphatic Leukemia

Younger patients (aged <30 years) presenting with esophageal cancer are rare. Bone marrow transplantation offers a curative therapy in patients with malignant and nonmalignant lymphohematopoietic diseases and other disorders. However, one important late complication in transplantation survivors is the development of secondary malignancies including solid tumors. Although some solid cancers have been demonstrated to occur after bone marrow transplantation, only a few cases of esophageal squamous cell carcinoma have thus far been reported. We herein describe the case of a 27-year-old male with esophageal squamous cell carcinoma, who was diagnosed with T-cell-type acute lymphatic leukemia at the age of 12 and relapsed 5 years later. He achieved a second complete remission and underwent bone marrow transplantation at the age of 17. A genetic analysis revealed germ-line lineage-derived chimeric cellular populations of the donor and patient on both the esophageal squamous cell carcinoma and non tumorous portions of the patients esophageal mucosa with a preponderance of the patients germ-line lineage-derived cells, suggesting that repopulated donor-derived hemopoietic stem cells in the esophageal epithelia only partially contributed to the carcinogenesis of esophageal squamous cell carcinoma several years after bone marrow transplantation. Multiple events occurring during the course of treatment for primary hematological disorder may play an important role in the development of esophageal squamous cell carcinoma.

The current status of recurrent and residual treatment after an esophagectomy: what method of treatment should be performed and how?

AimThis study investigated the present status of patients with recurrent and residual disease after an esophagectomy, and examined the ideal clinical course and method for patients with recurrent or residual esophageal cancer.Patients and methodsSeventy-five patients who developed recurrence between April 2005 and May 2009, and 14 patients who showed macroscopic residual tumors following tumor resection, were included in this study. At the same time, the staging of the recurrent or residual tumors was determined and analyzed.ResultsSeventy-two patients received first-line treatment, and the response rate was 61.1%. Second-line treatment was administered for 50 patients, and most selected chemotherapy. The response rate was 36.0% and the response rate to chemotherapy was 23.3%. Third-line, fourth-line, fifth-line, and sixth-line treatment was performed for 28, 13, 9, and 5 patients, respectively, and the response rate was 30.8%, 15.4%, 22.2%, and 25.0%, respectively. Additional treatments were not administered because of the patients’ requests as a result of their poor performance status and tumor progression. No significant difference was observed in survival between patients with recurrent and residual tumors, nor among the number of the treatment methods administered. There was no significant difference in survival among stage III, IVa, and IVb patients, although the stage III patients achieved better clinical responses to the first-line treatment.ConclusionsAggressive additional treatments should be performed early after operations for residual tumors. Control of distant metastasis is considered the primary issue in recurrent and residual treatment. Therefore, the establishment of effective chemotherapeutic agents and molecular targeting agents or combination therapy is necessary. In addition, further surgery should be pursued aggressively in cases in which tumor progression can be controlled. Continued treatment did not necessarily prolong survival; thus, physicians must respect the patient’s wish to continue the treatment and select suitable treatments that do not compromise the patient’s quality of life.