Takashi Iwazawa

Effect of epidermal growth factor on cadherin-mediated adhesion in a human oesophageal cancer cell line.

Epidermal growth factor (EGF) mediates many pleiotrophic biological effects, one of which is alteration of cellular morphology. In the present study, we examine the possibility that this alteration in cell morphology is caused in part by the dysfunction of cadherin-mediated cell-cell adhesion using the human oesophageal cancer cell line TE-2R, which expresses E-cadherin and EGF receptor. In the presence of EGF, TE-2R changed its shape from round to fibroblastic and its colony formation from compact to sparse. Vanadate, a tyrosine phosphatase inhibitor, further potentiated the EGF response, whereas herbimycin A, a tyrosine kinase inhibitor, interfered with it. Moreover, EGF enabled the cells to invade in organotypic raft culture. These phenomena were accompanied not by decreased expression of the E-cadherin molecule but by a change in its localisation from the lateral adhesion site to the whole cell surface. Both alpha- and beta-catenin, cadherin-binding proteins, were also expressed at the same level throughout these morphological changes. Finally, we examined tyrosine phosphorylation of E-cadherin and alpha- and beta-catenin, and observed tyrosine phosphorylation of beta-catenin induced by EGF. These results suggest that EGF counteracts E-cadherin-mediated junctional assembly through phosphorylation of beta-catenin and modulates tumour cell behaviour to a more aggressive phenotype.

The usefulness of laparoscopy-assisted distal gastrectomy in comparison with that of open distal gastrectomy for early gastric cancer

Background. The technique of laparoscopy-assisted distal gastrectomy (LADG) was developed for early gastric cancer, but its feasibility and the associated clinical outcome remain unclear.Methods. We reviewed 24 patients who underwent LADG (LADG group) and 35 patients who underwent traditional open distal gastrectomy (ODG group) for early gastric cancer in our hospital, and compared the clinical data of the two groups.Results. The clinical and pathological backgrounds of the patients in the two groups were similar. The duration of surgery was not significantly different between the two groups, but the blood loss in the LADG group was significantly less than that in the ODG group. The number of removed lymph nodes was not significantly different between the two groups. The times to the first passing of flatus, first walking, and the restarting of oral intake; the length of hospital stay; and the duration of epidural analgesia were significantly shorter in the LADG group. The morbidity rate in the LADG group was lower than that in the ODG group.Conclusions. LADG is a safe and minimally invasive surgical technique, after which we can expect a faster recovery.

Immunohistochemical evaluation of alpha-catenin expression in human gastric cancer

E-cadherin (E-cad) plays a major role in the maintenance of cell-cell adhesion in epithelial tissues, and impaired E-cad expression correlates with tumour invasion and metastasis. Alpha-catenin (α-cat), an undercoat protein of adherens junctions, binds to the cytoplasmic domain of E-cad and is essential for linking E-cad to actin-based cytoskeleton. We investigated E-cad and α-cat expression in 60 human gastric cancers immunohistochemically. The 60 gastric cancers were classified into 18 (30%) in which α-cat expression was preserved, and 42 (70%) reduced cases. The reduction of α-cat expression was significantly related to dedifferentiation, depth of invasion, infiltrative growth and lymph node metastasis. We also examined the co-expression of α-cat and E-cad. Seventeen (28%) tumours preserved both molecules [α-cat(+)/E-cad(+)] and 33 (55%) tumours reduced both [α-cat(−)/E-cad(−)], whereas 9 (15%) tumours exhibited α-cat(−)/E-cad(+). The frequency of lymph node metastasis in α-cat(−)/E-cad(+) tumour (67%) was significantly higher than that in α-cat(+)/E-cad(+) tumours (24%) and was close to that in α-cat(−)/E-cad(−) tumours (82%). The frequency of haematogenous liver metastasis in α-cat(−)/E-cad(+) tumours (44%) was significantly higher than that in α-cat(+)/E-cad(+) tumours (6%) or α-cat(−)/E-cad(−) tumours (9%). Thus, in all E-cad(+) tumours, the frequency of lymph node and liver metastasis was higher in α-cat(−) tumours than in α-cat(+) tumours. α-Cat expression is apparently better at predicting tumour invasion and metastasis than E-cad expression.

The usefulness, indications, and complications of laparoscopy-assisted colectomy in comparison with those of open colectomy for colorectal carcinoma

The technique of laparoscopy-assisted colectomy (LAC) was developed for benign and malignant diseases of the colon and rectum; however, its feasibility and the associated clinical outcome remain unclear. We reviewed 45 patients who underwent LAC (LAC group) and 62 patients who underwent traditional open surgery (Open group) for colorectal carcinoma in our hospital, and compared the clinical data between the two groups in an effort to determine whether LAC is really minimally invasive and if it enhances the quality of life. So that the backgrounds of the patients in both groups were almost the same, we only compared data of patients with colorectal carcinoma of stages 0, I, and II. The duration of surgery in the Open group was significantly shorter for all procedures except sigmoid resection, but the blood loss was not significantly different between any of the procedures except for right colectomy. The time to the first passing of flatus and restarting oral intake, length of hospital stay, and duration of epidural analgesia were significantly shorter in the LAC group. The morbidity and mortality rates in the LAC group were almost the same as those in the Open group at 29.5% and 3.3% versus 22.6% and 1.6%, respectively. However, five major complications of LAC for advanced colorectal carcinomas might be prevented by performing an open procedure. In conclusion, LAC is a safe and minimally invasive surgical technique following which we can expect a faster recovery; however, patients with advanced colorectal carcinomas must be carefully selected for this operation.

Solitary splenic metastasis from ovarian cancer successfully treated by hand-assisted laparoscopic splenectomy: report of a case.

Abstract.Solitary splenic metastasis is an extremely rare phenomenon for which splenectomy is generally indicated because a good prognosis can be achieved if chemotherapy is given postoperatively. We report herein a case of solitary splenic metastasis from ovarian cancer, which was completely removed by hand-assisted laparoscopic surgery.

Efficacy of Absorbable Clips Compared with Metal Clips for Cystic Duct Ligation in Laparoscopic Cholecystectomy

Abstract.Purpose: This study was conducted to examine the usefulness and safety of absorbable clips in laparoscopic cholecystectomy (LC). Methods: We retrospectively compared the clinical data of 328 patients who underwent LC using absorbable clips for cystic duct ligation and 444 patients who underwent LC using metal clips for cystic duct ligation. Results: The mean operative time in the absorbable clip group was significantly shorter than that in the metal clip group. The mean intraoperative blood loss and hospital stay were not significantly different between the two groups. The rate of conversion to open laparotomy in the absorbable clip group was significantly higher than that in the metal clip group, at 6.7% vs 2.3%, respectively. The most common reason for conversion was difficult adhesions and inflammation around the gallbladder. The morbidity of the metal clip group was significantly higher than that of the absorbable clip group, at 8.4% vs 4.0%, respectively. The incidence of major postoperative complications requiring laparotomy did not differ between the two groups. There were no deaths in the absorbable clip group, but 1 of the 444 patients (0.23%) in the metal clip group died from disseminated intravascular coagulation on postoperative day 3. Conclusion: The results of this study suggest that absorbable clips are as safe and effective as standard metal clips for vessel and duct ligation in LC.

Hand-assisted laparoscopic surgery for a large gastrointestinal stromal tumor of the stomach.

We report two cases of large gastrointestinal stromal tumor (GIST) of the stomach that were successfully treated by hand-assisted laparoscopic surgery (HALS). Two patients, a 56-year-old woman and a 60-year-old man, were admitted to our department for the treatment of a large submucosal tumor of the stomach. After gastrointestinal endoscopy, ultrasonography, computed tomography, and magnetic resonance imaging, we suspected that the masses, measuring 7.0 cm and 8.0 cm in diameter, respectively, were GISTs in the stomach. However, preoperatively, we could not rule out the possibility of malignant neoplasms, because they had been bleeding or gradually growing. Hand-assisted laparoscopic wedge resection was safely performed for the diagnosis and treatment of the submucosal tumor of the stomach. The immunohistochemical diagnosis in both patients was GIST of the stomach with intermediate-grade malignancy. HALS may be a good indication for large GISTs of the stomach that are difficult to diagnose preoperatively, whether they are malignant or benign, because it is safe and minimally invasive, promoting rapid recovery.

An oral anticancer drug, TS-1, enabled a patient with advanced gastric cancer with Virchow's metastasis to receive curative resection.

Abstract.We encountered a patient with advanced gastric cancer, with Virchows lymph node metastasis, who subsequently underwent curative resection after neoadjuvant chemotherapy with the newly developed oral anticancer drug, TS-1. The patient was a 67-year-old woman who had a type 2 tumor in the middle third of the stomach, and Virchows lymph node metastasis, which was diagnosed by fine-needle aspiration cytology; she also had swollen paraaortic lymph nodes. Curative resection was considered impossible, and TS-1 (100 mg/day) was administered for 28 days in one course, mainly in the outpatient clinic. Although grade 2 stomatitis interrupted the therapy on day 21 of the second course and on day 7 of the third course, the type 2 tumor showed marked remission (partial response; PR) and the metastasis in the Virchows and paraaortic lymph nodes had completely disappeared after the third course (complete response; CR). Eleven weeks after the completion of the TS-1 treatment, total gastric resection with D3 lymph node dissection was performed. Histopathological examination revealed tumor involvement only in the mucosal and submucosal layers of the stomach and the no. 4d lymph node. Most of the tumor was replaced with fibrosis with granulomatous change in the muscularis propria of the stomach and in the no. 3, no. 6, and no. 7 lymph nodes. This may be the first report of a patient with advanced gastric cancer with Virchows lymph node metastasis who successfully received curative resection following neoadjuvant chemotherapy with a single oral anticancer drug.

Primary squamous cell carcinoma of the stomach.

Primary squamous cell carcinoma (SCC) of the stomach is extremely rare; only 32 cases are found in the Japanese literature. The pathogenesis of this neoplasm remains obscure and controversial. Furthermore, the optimal treatment, including adjuvant chemotherapy, remains unclear. We report herein a case of SCC of the stomach in a 70-year-old male with amazing effectiveness of neoadjuvant chemotherapy, low-dose FP chemotherapy. To our knowledge, no case of this disease has ever been reported that was given neoadjuvant chemotherapy and histologically showed its effectiveness. Our case demonstrated a striking effectiveness of chemotherapy in the neoplasm both radiologically and histologically.

Hand-assisted laparoscopic splenectomy for splenic tumors.

Background: The feasibility of hand-assisted laparoscopic splenectomy (HALS) for splenic tumors including benign or malignant neoplasms and the associated clinical outcome of the patients remain unclear. Methods: A total of 10 patients with splenic tumors undergoing HALS were retrospectively analyzed in this study. The intraoperative course, postoperative course, and postoperative recovery were evaluated. Results: Ten patients with splenic tumors consisted of 5 with benign tumors and 5 with malignant tumors. HALS was not converted to an open splenectomy in any of the patients. Mean operative time was 170 min (range 100–310 min). Mean estimated blood loss was 105 g (range 10–900 g). Mean splenic size and splenic weight was 13 cm and 478 g, respectively. Splenomegaly based on size or weight occurred in 50% of the patients. There were no intra- or postoperative complications. Postoperative chemotherapy was given to 4 patients with malignant tumors including metastatic carcinomas and malignant lymphomas. All the patients were alive at a mean follow-up of 26 months, ranging from 15 to 43 months after surgery. There was no port-site recurrence after surgery in our study. Mean time to first flatus, mean time to first walking, mean time to resumption of oral intake, mean length of hospital stay, and mean duration of epidural analgesia were 1.8, 1, 1.5, 10.8 and 3.1 days, respectively. The results were equal in terms of intra- and postoperative course to those seen with a standard laparoscopic splenectomy for 13 patients with idiopathic thrombocytopenic purpura. Conclusion: HALS may be a good indication for malignant tumors as well as benign tumors of the spleen.