Clinical significance of transmembrane 4 superfamily in colon cancer.

Cell motility is an important cellular function closely related to the processes of tumour progression and metastasis. Several members of transmembrane 4 superfamily (TM4SF) have been reported to be associated with cell motility and metastatic potential of solid tumour. The aim of this study is to clarify the clinical significance of the member of TM4SF (MRP-1/CD9, KAI1/CD82 and CD151) in human colon cancer. We studied 146 colon cancer patients who underwent curative surgery and studied the expression of MRP-1/CD9, KAI1/CD82 and CD151 using reverse transcriptase - polymerase chain reaction and immunohistochemistry. We found that 64 patients (43.8%) had MRP-1/CD9-positive tumours and that the overall survival rate of patients with MRP-1/CD9-positive tumours was much higher than that of patients with MRP-1/CD9-negative tumours (89.8 vs 50.8%, P<0.001). In contrast, 63 patients (43.2%) had KAI1/CD82-positive tumours and the overall survival rate of patients with KAI1/CD82-positive tumours was also higher than that of patients with KAI1/CD82-negative tumours (84.8 vs 54.9%, P=0.002). On the other hand, positive CD151 expression had a bad effect on the overall survival rate of patients with colon cancer (61.2 vs 74.9%, P=0.022). In a multivariate analysis, MRP-1/CD9 status was a good indicator of the overall survival (P=0.007). We have shown that the reduction of MRP-1/CD9 and KAI1/CD82 expression, and the increasing CD151 expression are indicators for a poor prognosis in patients with colon cancer. This is a first report describing about the relation between CD151 and colon cancer.

Comparison of three-field esophagectomy for esophageal cancer incorporating open or thoracoscopic thoracotomy.

BACKGROUND: Thoracoscopic esophagectomy for esophageal cancer has been performed as an alternative to open surgery to reduce surgical trauma. However, its effect on pulmonary function, exercise tolerability, and quality of life is unknown. METHODS: Fifty-one patients with esophageal cancer underwent thoracic esophagectomy with radical lymphadenectomy by posterolateral thoracotomy (29 cases) or thoracoscopic surgery (22 cases). Patients performed spirometry and exercise tolerance testing and completed a quality-of-life questionnaire before and 3 months after surgery. RESULTS: Pre-to-postoperative change in vital capacity was 74.3 +/- 10.6% in the thoracotomy group and 84.9 +/- 10.4% in the thoracoscopy group (p = 0.021). Maximum oxygen uptake was similar, but dyspnea was the more common factor limiting exercise tolerance postoperatively in the thoracotomy group. Change in pre-to-postoperative performance status was 1.20 +/- 0.62 in the thoracotomy group and 0.55 +/- 0.51 in the thoracoscopy group (p = 0.0003). CONCLUSIONS: Thoracoscopic esophagectomy for esophageal cancer has better preservation of pulmonary function and quality-of-life.

Usefulness of self-expandable metallic stent with an antireflux mechanism as a palliation for malignant strictures at the gastroesophageal junction.

BACKGROUND: Patients with unresectable malignant gastroesophageal strictures often are troubled with reflux esophagitis after stent placement. METHODS: A self-expandable metallic stent (SEMS) without an antireflux mechanism was placed in seven patients with unresectable malignant gastroesophageal strictures (group A), and SEMS with an antireflux mechanism was placed in five patients (group B). After we obtained monitoring systems, two patients in group A and all the patients in group B underwent measurement of bilirubin and pH in the esophagus using a 24-h bilirubin and pH monitor. RESULTS: The mean percentage of total time less than 0.14 for use of the bilirubin absorbance unit was 12.4% in group B and 64.0% in group A. The mean percentage of total time for a pH less than 4 was 2.9% in group B and 37.8% in group A. CONCLUSION: The placement of SEMS with the antireflux mechanism can be effective not only for palliation of gastroesophageal stricture, but also for prevention of reflux.

Clinical significance of CD151 gene expression in non-small cell lung cancer.

Transmembrane 4 superfamily (TM4SF) is a recently described gene family, and TM4SF members are known to play roles in the signal transduction pathways and to regulate cell activation, development, proliferation, and motility. MRP-1/CD9, KAI1/CD82, and ME491/CD63, members of the TM4SF, have been reported to suppress tumor progression or metastasis. Previously, we showed that MRP-1/CD9 suppressed cell motility and metastatic potential to lungs. Moreover, reduction of MRP-1/CD9 and KAI1/CD82 gene expression was found to be a factor in a poor prognosis for patients with non-small cell lung cancer. However, among TM4SF, CD151 is identical to an existing gene, PETA-3, which may promote tumor metastasis of malignant cells, and its expression may be involved in the malignant progression of cancer. The function of CD151 is opposite that of the metastasis suppressor genes, MRP-1/CD9 and KAI1/CD82. On the basis of these results, we used reverse transcription-PCR and immunohistochemical techniques for a retrospective study of CD151 gene expression in tumor tissues from 145 lung cancer patients; 72 tumors were stage I, 29 stage II, 27 stage IIIA, and 17 stage IIIB. Whereas 86 patients had tumors positive for the CD151 gene, 59 had tumors that were negative for the CD151 gene. The overall survival rate of patients with CD151-positive tumors was much lower than that of CD151-negative patients (51.9% versus 73.1%; P = 0.013). Our findings suggest that high CD151 gene expression in lung cancer may be associated with a poor prognosis. Assessment of CD151 could be instrumental for improvements in lung cancer diagnosis and therapies.

Neutral endopeptidase/CD10 and aminopeptidase N/CD13 gene expression as a prognostic factor in non-small cell lung cancer.

OBJECTIVES: Neutral endopeptidase modulates the growth of lung cancer, while aminopeptidase N degrades the extracellular matrix and is involved in cell motility. We studied the metastasis mechanism to detect novel metastasis-associated molecules and to evaluate them for clinical application. METHODS: We studied the relationship between the expression of neutral endopeptidase and aminopeptidase N by quantitative reverse transcript-polymerase chain reaction analysis in 132 patients with non-small cell lung cancer undergoing radical surgery from 1991 to 1996. RESULTS: Patients with neutral endopeptidase-positive and aminopeptidase N-negative tumors were defined as group A, those with neutral endopeptidase-positive and aminopeptidase N-positive or neutral endopeptidase-negative and aminopeptidase N-negative tumors as group B, and those with neutral endopeptidase-negative and aminopeptidase N-positive tumors as group C. The 5-year survival of group A patients (92.9%) was significantly better than that of group B patients (64.7%) and much better than that of group C patients (38.2%) (P = 0.0011). Neutral endopeptidase and aminopeptidase N thus have statistically significant P in overall survival in Cox regression (P = 0.019). CONCLUSION: Neutral endopeptidase and aminopeptidase N gene expressions are significant indicators of prognosis.

Suppression of pulmonary metastasis using adenovirally motility related protein-1 (MRP-1/CD9) gene delivery.

Previously we showed that MRP-1/CD9 might prevent tumor metastasis by suppression of cell motility and invasion of tissue barriers. The present study explored the possibility of preventing metastasis of mouse melanoma BL6 by expression of MRP-1/CD9 through gene transfer. A replication-deficient adenovirus vector was used for the in vivo transfer of MRP-1/CD9 cDNA. Intratumor injection of an adenovirus vector (rAd-MRP-1/CD9) expressing MRP-1/CD9 resulted in a 73.7% reduction in the number of pulmonary metastases of mice and the median survival time of mice treated with rAd-MRP-1/CD9 was significantly longer than those treated with the rAd-beta-gal vector (103.2 approximately plus;8.5 days vs 71.2 approximately plus;5.2 days, P<0.001 respectively). These results support the expression of MRP-1/CD9 through gene transfer as a therapeutic strategy for preventing metastases and prolonging survival, and support the feasibility of gene transfer in a clinically relevant setting.

[Preoperative bronchial arterial infusion of docetaxel for squamous cell carcinoma of the lung--clinical evaluation and correlation between anti-tumor effect and apoptosis].

As an induction therapy for advanced lung cancer, a patient received bronchial arterial infusion of 30 mg/m2 of docetaxel (TXT). Two weeks after infusion, although the tumor size was not reduced, the central necrotic area was significantly increased. There were no adverse effects. Nineteen days after infusion, we performed a right lower lobectomy and lymph nodal dissection. The resected specimen was examined by immunohistochemistry and biochemistry. The anti-tumor effects were evaluated clinically and the correlation between arterial TXT infusion therapy and apoptosis was studied. Hematoxylin and eosin staining demonstrated moderately differentiated squamous cell carcinoma associated with central necrosis, and cells with chromatin condensation scattered in both the necrotic areas and the margin of this area. It is thought that these findings were the result of this therapy, rather than just the self-necrosis seen in an untreated group.

Chylothorax after thoracoscopic esophagectomy.

Among 30 patients who underwent thoracoscopic esophagectomy with lymphadenectomy for thoracic esophageal cancer, from July 1995 to May 1997, chylothorax developed in 2 patients (7%). In Case 1, the ligation of the thoracic duct under conventional right thoracotomy was performed on the 9th day after esophagectomy. After ligation, the pleural effusion was decreased, and the patient was discharged from hospital on the 25th day after the second operation. In Case 2, massive pleural effusion developed on the 10th day after esophagectomy (at 3 days after thoracic drainage tube was removed). The thoracic duct was ligated at the level just cranial to the diaphragm thoracoscopically on the 14th day after esophagectomy. The patient was discharged from hospital on the 30th day after the second operation. Injury to the thoracic duct due to a magnification effect of the view of scopic surgery remains a pitfall in thoracoscopic esophagectomy. But thoracoscopic ligation of thoracic duct was effective and safe for these two cases of chylothorax after esophagectomy.

Acute acalculous cholecystitis complicated by penetration into the liver after coronary artery bypass grafting.

BACKGROUND: Perforation or penetration due to acute acalculous cholecystitis is a rare complication after open-heart surgery. The mortality rate of this disease is high. METHODS: A 71-year-old woman complained of a sudden onset of right upper abdominal pain with development of peritoneal signs at 21 days after coronary artery bypass grafting. Abdominal ultrasonography and laboratory examination performed at 1 day earlier had revealed no abnormalities. Neither anticoagulants nor antiplatelet agents were administered following the bypass operation. An exploratory laparotomy was performed to locate a presumed embolization to the superior mesenteric artery. RESULTS: Laparotomy revealed acute acalculous cholecystitis complicated by penetration into the liver, causing a subserosal hematoma. The hematoma had ruptured into the abdominal cavity. A cholecystectomy was performed. The gallbladder wall which was in contact with the liver was necrotic. Most of the gallbladder mucosa was necrotic. Microscopical examination revealed atherosclerosis of the cystic artery which was partially obstructed by thrombus. CONCLUSIONS: Given the atherosclerotic condition of the cystic artery, hypotension during the bypass in combination with postoperative total parenteral nutrition and hypovolemia may have induced the cystic artery thrombosis. Surgeons who manage patients with cardiovascular disease should be aware of this potentially lethal development.

Endobronchial stenting as a palliation for advanced esophageal cancer.

Three cases of airway invasion of esophageal cancer treated palliatively by endobronchial stenting are reported. In case 1 (a 60-year-old male) expandable metallic stents were inserted into the totally occluded left main bronchus. In case 2 (a 45-year-old male) a Dumon stent was inserted into the totally occluded left main bronchus. Both patients recovered from performance status 4 to performance status 1 or 0 and were in good condition before they died of cancer, 150 and 54 days after stenting in cases 1 and 2, respectively. In case 3, a Dumon stent was inserted into the left main bronchus before total occlusion. The patient recovered from performance status 3 or 2 to performance status 1 or 0 and survived 40 days after stenting with no signs of airway obstruction. Endobronchial stenting is a useful palliation for keeping the performance status at a good level in patients with esophageal cancer obstructing or narrowing the main airway.

Perforated duodenal diverticulum: report of two cases.

Duodenal diverticula may be complicated by diverticulitis, perforation, hemorrhage, pancreatitis, or biliary obstruction. Two cases of perforated duodenal diverticulum are reported. Both patients were elderly females. Computed tomography of the abdomen showed retroperitoneal air around the duodenum in the first case, and an enterolith in a duodenal diverticulum and a retroperitoneal abscess in the second case. Laparotomy and diverticulectomy with two-layer closure of the duodenum was performed in the first case. The second patient was treated conservatively with antibiotics, percutaneous abscess drainage, and endoscopic lithotomy. Both recovered well. Computed tomography is useful in the diagnosis of a perforated duodenal diverticulum. Although surgical intervention is the standard treatment, conservative therapy is also an option. Duodenal enteroliths are rare but may cause perforation of a diverticulum or biliary obstruction. The duodenal blind loop created by a Billroth II gastrectomy provides a static environment for the formation of enteroliths in duodenal diverticula.

Utility of endoscopic ultrasonography in assessing the indications for endoscopic surgery of submucosal esophageal tumors.

BACKGROUND: The submucosal tumor (SMT) of the esophagus presents good indications for minimal invasive surgery, such as endoscopic or thoracoscopic resection. However, it is essential that the layer of origin be ascertained. The SMT can be detected as hypoechoic lesions in the wall of the esophagus, and the intramural location can be estimated in terms of destruction or deviation of the ultrasonic layer structure of the esophagus. METHODS: To test the efficacy of this approach, a series of patients were examined by an endoscopic ultrasonography (EUS). RESULTS: In one patient, the lesion was diagnosed as located in the muscularis mucosa, and endoscopic resection was performed. In another four patients, the lesions appeared to be in the proper muscle layer, and enucleation was carried out under thoracoscopy or open surgery. Histologically, all of the lesions were leiomyomas, and the EUS diagnosis was correct in all of the patients. CONCLUSIONS: Thus, the intramural condition of SMTs can be estimated and indications for endoscopic or thoracoscopic resection assessed by this approach.

Case of spontaneous regression of metastatic lesions of leiomyosarcoma of the esophagus.

A rare case of spontaneous regression of esophageal leiomyosarcoma is reported. A 63-year-old woman underwent esophagectomy and reconstruction at our hospital after diagnosis of leiomyosarcoma. Nineteen months after esophagectomy, a coin lesion was detected in the right lung and right thoracotomy revealed pleural dissemination. The lesion in the right lung was resected and was confirmed histologically as recurrence of leiomyosarcoma. During further surgery, metastatic lesions were found in the spleen and pleura. However, all metastatic lesions were found to decrease without any anti-cancer therapy.

[Changes of serum cytokine levels after thoracoscopic esophagectomy].

We introduced thoracoscopic esophagectomy with extended lymphadenectomy for reduction of respiratory dysfunction and less surgical intervention in July 1995. In this study, we investigated the changes in serum interleukin-6 (IL-6) and interleukin-1 receptor antagonist (IL-1ra) levels in 8 patients (TS Group) who underwent thoracoscopic esophagectomy with extended lymphadenectomy and compared them with the changes in patients who underwent conventional thoracotomy (CT Group). The duration of the operation and intrathoracic procedure in the TS group were significantly longer than in the CT group. However, the amount of blood loss and intrathoracic blood loss of the TS group were not significantly higher than in the CT group. The number of dissected lymph nodes was not significantly larger. The serum IL-6 levels reached maximum levels 3 hours from the end of operation. In the TS group, the changes in IL-6 levels were significantly larger (p < 0.05). On the other hand, the changes in CRP levels were also significantly larger (p < 0.01). Significant correlation was observed between the duration of the intrathoracic procedure and the maximum levels of IL-6. On the other hand, serum IL-1ra levels were not significantly. At present, these results suggest that the surgical intervention of thoracoscopic esophagectomy are more larger than that of conventional thoracotomy. We think that the length of intrathoracic procedure of thoracoscopic esophagectomy may make more large surgical stress.

[Thoracoscopic enucleation of esophageal leiomyoma].

We treated four cases of thoracoscopic enucleation of esophageal leiomyoma. All four cases were asymptomatic, but either barium swallow or esophagofiberscopic examination revealed esophageal submucosal tumor. The locations of the tumors were middle and lower in one case and middle in the other three cases. All patients were intubated with a double lumen endotracheal tube under general anesthesia. Two patients required thoracotomy due to the tumor surrounding the esophageal wall in one case and severe adhesion to the esophageal mucosa in the other. The mini-thoracotomy was used in three cases. In the other two cases, we used four and three trocars, respectively. The balloon catheter, which had been inserted into the esophageal lumen, was useful for removing the tumor. The tumor was pulled up using the traction suture and dissected from the mucosa and muscular layer. After enucleation of the leiomyoma, the split muscular layer was sutured. The postoperative course was uneventful. These two patients were discharged on the 12th and 15th postoperative days, respectively. We conclude that the thoracoscopic enucleation of the esophageal leiomyoma is useful for reduction of surgical stress and is a more feasible approach for the treatment of esophageal leiomyoma.

[Five cases of peptic ulcer of gastric tube after radical esophagectomy for esophageal carcinoma and analysis of Helicobacter pylori infection at gastric tube].

The peptic ulcer of gastric tube using for esophageal reconstruction is rare. We report herein five cases of peptic ulcer of gastric tube used for esophageal reconstruction after esophagectomy for esophageal carcinoma. The reconstructive route, in all cases, was posterior mediastinum. In one case, 10 days after esophagectomy, he had high grade fever and pneumonia of right lower lobe of lung. Endoscopic examination revealed a deep ulcerative lesion on anterior wall of gastric tube and fistula formation on membranous part of trachea. The partial resection of gastric tube was performed for closing to tracheo-gastro fistula. In other four cases, the location of ulcer was middle or lower third of gastric tube. One had multiple peptic ulcer and other had single. Two cases of four underwent post irradiation therapy. One case of then, the Helicobacter infection detected using by rapid urease test and histological examination. We analyzed of Helicobacter pylori infection and serum gastrin level of gastric tube in outpatients who have used gastric tube for esophageal reconstruction after radical esophagectomy. Helicobacter pylori infection was positive at 56% (9/16) of all patients. The serum gastrin level of patients who was positive of Helicobacter pylori infection is not significantly higher than that of patients who was negative. We consider that post operative irradiation therapy and Helicobacter infection might play in development of peptic ulcer of gastric tube.

[Surgical treatment of esophageal cancer in four patients after gastrectomy for gastric cancer].

The incidence of another cancer in subjects with esophageal cancer is high. Gastric cancer is the most common. We report surgical treatment for esophageal cancer in four patients who underwent gastrectomy for gastric cancer earlier. Extended lymphadenectomy of the neck, mediastinum, and abdomen was performed together with subtotal esophagectomy for three patients with thoracic esophageal cancer. In the two patients who had undergone subtotal gastrectomy and Billroth II reconstruction, the esophagus was reconstructed with part of the colon from the left side, perifused by the left colic artery. In a third patient, who had undergone total gastrectomy and jejunal interposition, reconstruction was done with part of the colon from the right side. In the remaining patient, who had cervical esophageal cancer and who had undergone total gastrectomy, cervical esophagectomy and total laryngectomy were done, followed by free jejunal interposition. One patient with thoracic esophageal cancer died of pulmonary metastasis of the esophageal cancer 24 months after surgery. The three other patients were not found to have recurrence in the most recent follow-up. Esophagectomy and reconstruction are more risky and complicated in patients who have already undergone gastrectomy for malignancy. However, in patients who have undergone curative surgery for gastric cancer, curative treatment for esophageal cancer such as esophagectomy together with extended lymphadenectomy is indicated.