Takashi Akaishi

Thoracoscopic en bloc total esophagectomy with radical mediastinal lymphadenectomy

OBJECTIVE Total esophagectomy with en bloc mediastinal lymphadenectomy for cancer carries a substantial morbidity and mortality rate. To investigate the feasibility of thoracoscopic technique, we carried out an extensive laboratory study. Encouraged by our excellent results, we conducted a clinical trial. METHODS From September 1994 to September 1995, 39 patients thoracic esophageal cancer lesions not invading surrounding organs underwent total esophagectomy with mediastinal lymphadenectomy by means of thoracoscopy. Ages ranged from 47 to 86 years. The procedures were conventional except for the thoracic portion, which was performed as a thoracoscopic procedure with six trocar holes instead of thoracotomy. All harvested lymph nodes were counted for each station. Spirometric data and plethysmographically determined vital capacity were measured before and after operation for all patients. RESULTS All procedures were accomplished as scheduled, and none was converted to open thoracotomy. The operating time was 200 +/- 41 minutes (mean +/- standard deviation). Estimated blood loss was 270 +/- 157 ml. The harvested lymph nodes numbered 19.7 +/- 11.1 per patient. Seventeen patients (45%) had positive lymph nodes. There were no in-hospital deaths within 30 days. Twenty-two patients did not require postoperative ventilatory support. Vital capacity decreased to 85% +/- 11% of the preoperative values, and forced expiratory volume in 1 second decreased to 82% +/- 16%. CONCLUSIONS Thoracoscopic mediastinal lymphadenectomy is technically feasible, and its completeness is comparable to that of the open technique. The decline in pulmonary function is significantly less than that seen in our previous experience with the open technique.

The chimeric protein, PEBP2β/CBFβ-SMMHC, disorganizes cytoplasmic stress fibers and inhibits transcriptional activation

The chromosomal inversion 16(p13;q22) associated with human acute myeloid leukemia generates the chimeric PEBP2β/CBFβ-SMMHC gene. The PEBP2β/CBFβ portion of the chimeric polypeptide harbors most of the amino acid sequence of the PEBP2β/CBFβ protein, the non-DNA binding subunit of the heterodimeric transcription factor, PEBP2/CBF, whereas the SMMHC portion of the chimera consists of the rod domain of the smooth muscle myosin heavy chain molecule. In this study we examined the subcellular localization of the chimeric protein and its effect both on stress fibers and transcriptional activation by transfecting cDNA into tissue culture cells. The localization of the chimera was investigated by immunocytochemical staining of cells and was found to be both cytoplasmic and nuclear. One aspect of the effect of expression of the chimera was a drastic alteration of cell morphology. The cells appeared elongated and possessed long cytoplasmic processes. Double fluorescent labeling revealed disorganization of the stress fibers and an altered F-actin staining pattern in the transfected cells. Studies using a deletion mutant showed that both the PEBP2β/CBFβ and SMMHC domains are necessary for the induction of the morphological alteration. A significant proportion of the chimeric protein was retained in the cytoskeleton after detergent extraction of the cells and could be recuperated as a membrane fraction, suggesting that this is one of the probable sites of action of the PEBP2β/CBFβ-SMMHC protein. Another effect of the chimeric protein was inhibition of transcriptional activation dependent on the PEBP2/CBF binding DNA sequence. However, deregulation of PEBP2/CBF site dependent transcription by itself was not sufficient to induce cell morphological changes. Taken together, these results indicate that the PEBP2β/CBFβ-SMMHC chimeric protein acts at two levels, at the level of stress fiber organization and at the level of transcriptional activation. We suggest that the action of PEBP2β/CBFβ-SMMHC depends to a great extent on whether it is located in the cytoplasm or in the nucleus.

Anatomic segmental resection of the lung by thoracoscopy: An experimental study

In patients who are unable to undergo a lobectomy for a small peripheral lung cancer, a partial thoracoscopic resection appears to be one viable alternative. However, since the regional lymphatics are disrupted in an anatomical fashion with a segmentectomy, it appears superior to a wedge resection. This experimental study was conducted to determine whether or not an anatomical segmental resection is feasible by thoracoscopy. A segmental resection of porcine lungs was performed using thoracoscopy. The segmental vessels were divided between ligatures. The segmental bronchus was divided by an endoscopic stapler. The intersegmental lung parenchyma was divided using a cotton dissector and a contact neodymium-yttrium aluminum garnet laser. Forty-three pigs were divided into seven groups as follows. Group 1: S1+2; group 2: S3; group 3: upper division; group 4: lower division; group 5: S6; group 6: S8; and group 7: S9+10. The operating times ranged from 145±15 min to 191±47 min. Blood loss ranged from 36±35 ml to 151±48 ml in all groups. The blood loss in the group with a resection of S6 and S9+10 was significantly greater than that of the other five groups. Most of the blood loss occurred during the division between the intersegmental planes. In conclusion, a thoracoscopic segmentectomy is considered to be technically feasible; however, further fefinements in this technique are warranted before beginning clinical trials.

How Should Therapies for Superficial Cancer of the Esophagus Be Performed

In Japan, superficial cancer of the esophagus is defined as cancer limited to the submucosa. Recently, detection of such cancer has improved due to the development of a slender fiberscope and techniques of chromo-endoscopy [1].

Long-term Survival After Curative Resection of Carcinoma of the Thoracic Esophagus

Since Torek first successfully performed radical surgery for esophageal carcinoma in 1913, the results of esophageal surgery have been somewhat disappointing. A high operative mortality rate and a low 5-year survival rate were consistent features of surgery for esophageal cancer for a long time. The results of surgery, however, have shown marked improvement in Japan in the last 15 years. In the 12-year period from 1969 to 1980,10113 cases of esophageal carcinoma were registered in Japan. Among these cases, resection was carried out on 6130, and re-sectability was 67%. The operative mortality rate was 8.0%. Of these cases, 1953 survived 5 years or more after surgery, and the 5-year survival rate was 23.7% (Table 1).

Do Postoperative Radiochemotherapy and/or Aggressive Chemotherapy for Patients with Cancer of the Esophagus Who Have Undergone Curative Surgery Contribute to Improvement of Prognosis?

The most frequent sites of tumors after curative surgery of the thoracic esophagus are in the cervical region and/or mediastinum. Detailed analysis of 187 cases in our hospital showed that postoperative adjuvant therapy, namely, radiochemoimmunotherapy, improved the survival rate of patients undergoing such surgery. This indicates that such therapy prevents the recurrence of micrometastasis after curative surgery. However, the prognosis of patients with positive nodes did not improve, in spite of extensive radical surgery including lymph-adenectomy. In order to improve the prognosis in such cases with positive regional nodes, a newly devised protocol of radiochemocytokine therapy including tumor necrosis factor (TNF), interleukin 2 (IL-2) and a-interferon (α-INF) has recently been performed. For patients with distant node metastasis, conventional postoperative aggressive chemotherapy under active nutritional support has been found to prolong survival. The 5-year survival rate of patients treated with aggressive chemotherapy and radiochemocytokine therapy was analyzed.

Histopathological Studies of Esophageal Cancers Using Various Monoclonal and Polyclonal Antibodies

Different types of esophageal cancers have different characteristics, although they are all histologically classified as squamous cell carcinomas. To evaluate their characteristics we applied polyclonal and monoclonal antibodies and performed immunohistochemical examination of esophageal epithelia and cancers.

Renal dysfunction following surgery for carcinoma of the thoracic esophagus.

X過去10年間の胸部食道癌277例のうち術後の腎機能障害 (血清クレアチニン2.0mg/dl以上) は15例 (5.4%) に発生した. 15例中9例は第1病日に異常値を示した. 70歳以上と未満 (10.9: 4.3%), 高血圧の既往の有無 (8.0%: 3.7%) について発生率に約2倍の差がみられた. 術前の腎機能では, 血清クレアチニンが1.5mg/dl以上と未満 (35.7%: 3.8%, p<0.01), PSP試験15分値が20%以上と未満 (20.7%: 3.0%, p<0.01), Fishberg尿濃度試験で500mOsm/kg以上と未満 (17.4%: 4.0%, p<0.05) についてそれぞれ発生率に有意差がみられた. 腎機能障害の原因となった合併症の治療が困難であった3例を除き, 他の12例では保存的治療により腎機能障害は回復した.