Hisao Kanou

Immunomodulatory effects of low dose cis-Diaminedichloroplatinum (cisplatin) combined with UFT and PSK in patients with advanced colorectal cancer.

It is well known that cell-mediated immunity is suppressed in patients with neoplastic diseases. We have reported that soluble receptors for interleukin-2 (sIL-2R) and tumor necosis factor (sTNF-R1) are elevated in the serum of patients with advanced colorectal cancer. The presence of these soluble receptors and immunosuppressive cytokines, including interleukin-10 (IL-10), might be important in the mechanisms of immunosuppression. cis-Diaminedichloroplatinum (cisplatin) has been reported to immunomodulate, especially when used in low dose in combination with 5-Fluorouracil (5-FU). In this study, cisplatin and UFT, a form of uracil and tegafur which is a prodrug of 5-FU, were administered with immunomodulator Polysaccharide K (PSK) to ten patients with colorectal cancer, who showed distant metastasis in the liver or lung, and the serum levels of sIL-2R and sTNF-R1 and the production of γ-interferon (γ-INF) and interleukin-10 by peripheral blood mononuclear cells were measured. The serum concentrations of sIL-2R and the production of IL-10 were reduced (p<0.05) after 2 months of treatment. Thus, this combination appeared to have immunomodulative potential in patients with advanced colorectal cancer.

Development of Pyrrole-Imidazole Polyamide for Specific Regulation of Human Aurora Kinase-A and -B Gene Expression

Pyrrole-imidazole polyamide (PIP) is a nuclease-resistant novel compound that inhibits gene expression through binding to the minor groove of DNA. Human aurora kinase-A (AURKA) and -B (AURKB) are important regulators in mitosis during the cell cycle. In this study, two specific PIPs (PIP-A and PIP-B) targeting AURKA and AURKB promoter regions were designed and synthesized, and their biological effects were investigated by several in vitro assays. PIP-A and PIP-B significantly inhibited the promoter activities, mRNA expression, and protein levels of AURKA and AURKB, respectively, in a concentration-dependent manner. Moreover, 1:1 combination treatment with both PIPs demonstrated prominent antiproliferative synergy (CI value [ED(50)] = 0.256) to HeLa cells as a result of inducing apoptosis-mediated severe catastrophe of cell-cycle progression. The novel synthesized PIP-A and PIP-B are potent and specific gene-silencing agents for AURKA and AURKB.

Open Abdomen Management After Massive Bowel Resection for Superior Mesenteric Arterial Occlusion

PurposeMassive bowel resection is often performed for superior mesenteric arterial (SMA) occlusion, resulting in short bowel syndrome. We conducted this study to evaluate the effectiveness of open abdomen management to monitor the blood flow of the remnant bowel and anastomoses.MethodsWe treated five of seven patients with SMA occlusion by open abdomen management, with or without mesh, using a zipper, which we opened daily to monitor the blood flow around the anastomotic site.ResultsNone of the five patients treated by open abdomen management required re-resection of the remnant bowel and they were all discharged from hospital in a stable condition.ConclusionOpen abdomen management proved extremely useful for monitoring blood flow to the anastomotic site and for allowing complete drainage into the abdominal space. Using this method would assist in leaving as much remnant bowel as possible after resection for SMA occlusion.

Small intestinal perforation due to metastasis of breast carcinoma: Report of a case

A 79-year-old female patient underwent breast-conservation surgery following a diagnosis of right breast cancer in July 2007. In November 2008, the patient presented at our hospital with acute onset of lower abdominal pain. She was diagnosed with panperitonitis due to gastrointestinal perforation, and underwent an emergency operation. At the time of the operation, one site of free perforation was found in the small intestine, and a 2–3-cm nodule was found in the 50-cm anal side from the site of this perforation. Multiple metastases to the para-aortic lymph nodes and mesenteric lymph nodes were also found. The patient recovered without complications and was discharged from the hospital, but 3 months after surgery she succumbed due to multiple liver metastases. It is important to identify metastatic intestinal tumors in patients who have breast cancer.

Mediastinoscopy-assisted esophagectomy is useful technique for poor surgical-risk patients with thoracic esophageal cancer.

Elderly and poor surgical-risk patients with esophageal cancer experience several complications and often cannot undergo standard transthoracic esophagectomy. Mediastinoscopy-assisted esophagectomy (MAE) recently has been applied in patients with thoracic esophageal cancer. We herein report 2 poor surgical-risk patients of lower thoracic esophageal cancer treated with MAE. Patient 1 was a 60-year-old man with respiratory impairment due to pulmonary tuberculosis whereas patient 2 was an 80-year-old man with poor performance status and nutritional condition. In these patients, MAE was performed because standard esophagectomy by thoracotomy is too difficult to perform. We performed MAE using the mediastinoscope approaches via both the neck and hiatus. An approach via the hiatus is useful for mobilization of lower thoracic esophagus and via the neck is useful for direct visualization of recurrent nerve. These patients were successfully treated without complications. MAE enables the mobilization of the thoracic esophagus under the direct visualization in the mediastinum, and it may be considered to be safe and useful technique for elderly and poor surgical-risk patients.

Elevated serum concentration of interleukin-1 receptor antagonist (IL-1ra) is correlated to interleukin-6 and to hypoalbuminemia in cachectic patients with colorectal cancer

AbstractBackground. The mechanisms leading to the development of cancer cachexia are still not well understood. Some important factors, including cytokines and growth factors, are involved, and recently, cytokines such as interleukin-1 and interleukin-6 have been reported to be involved as mediators of this disorder. Methods. In patients with colorectal cancer, serum concentrations of interleukin-1 receptor antagonist (IL-1ra) and interleukin-6 (IL-6) were measured by enzyme-linked immunosorbent assay (ELISA) and analyzed in relation to the patients nutrition (in terms of albumin concentration [percentage of total protein] in the serum) and the tumor load. Results. The concentration of IL-1ra was significantly increased in cachectic patients compared with that in healthy volunteers and in the non-cachectic patients, and the concentration was correlated to the serum concentration of IL-6 and inversely correlated to the concentration of albumin (%). These concentrations, however, did not correlate to levels of tumor markers tested, ie, carcinoembryonic antigen (CEA) and carbohydrate antigen (CA)19-9. Conclusion. It was shown that the serum concentration of IL-1ra was a useful indicator for cancer cachexia and hypoalbuminemia; IL-1ra seems to be produced by immune-regulating host cells rather than by neoplastic cells.

Laparoscopic transhiatal approach for cardiac cancer with lower esophageal invasion for patients with compromised respiratory function.

BACKGROUND/AIMS The thoracoabdominal approach with extended abdominal incision and a left thoracotomy is the traditional approach for the treatment of cardiac cancer with lower esophageal invasion. However, this procedure entails high morbidity and mortality. We evaluated the effectiveness of the laparoscopic transhiatal approach without a thoracotmy. METHODOLOGY We retrospectively analyzed the data obtained from 40 patients who underwent total gastrectomy with lower esophagectomy for cardiac cancer with lower esophageal invasion. These patients were divided into 2 groups: patients who underwent surgery via the conventional thoracoabdominal approach with extended abdominal incision and a left thoracotomy group (CTA group) and patients who underwent surgery via the laparoscopic transhiatal approach without a thoracotomy group (LTH group). RESULTS All the LTH group patients were successfully treated without a thoracotomy. The 1- second forced expiratory volume was significantly lower in LTH group than in CTA group. No difference was observed between the groups with respect to the mean length of resected esophagus. The LTH group patients did not develop postoperative pneumonia. CONCLUSIONS The laparoscopic transhiatal approach is safe and feasible for the resection of gastric cardiac cancer with lower esophageal invasion in patients with compromised respiratory function.

Laparoscopic excision for an enlarged ciliated hepatic foregut cyst as a minimally invasive procedure.

Ciliated hepatic foregut cyst (CHFC) is a very rare cystic lesion of the liver. Although CHFC has traditionally been considered to lack malignant potential, recent reports have shown the malignant transformation of this lesion into squamous-cell carcinoma. It is difficult to differentiate CHFC from malignant tumor, and it is important to consider in aspiration cytology for the evaluation of possible neoplastic disease. In this paper, we describe the case of a 57-year-old female who underwent a laparoscopic excision of an enlarged CHFC that was diagnosed by fine-needle aspiration cytology. Laparoscopic excision may be adopted as a minimally invasive surgical procedure for CHFC.

A long-surviving patient with unresectable advanced gastric cancer responding to S-1 after receiving improved gastrojejunostomy

Conventional gastrojejunostomy has been employed for unresectable advanced gastric cancer with pyloric stenosis; however, it is often not fully effective. We report a patient with unresectable gastric cancer who was effectively treated with an anticancer drug, S-1, after receiving an improved gastrojejunostomy. The patient was a 55-year-old woman who was referred to our hospital for epigastric pain. Upper gastrointestinal endoscopy showed a Borrmann III tumor in the antrum of the stomach, and gastric roentgenography showed pyloric stenosis. Preoperative findings were T3N2H0P0, stage III b. At operation, the tumor was found to have invaded the duodenum and the head of the pancreas, and disseminated nodules were found in the mesenterium of the small intestine, the left diaphragm, and the round ligament of the liver. A curative operation was impossible for the advanced gastric cancer. Therefore, an improved gastrojejunostomy was performed to allow oral intake. Oral intake started 7 days after the operation, and she left our hospital 20 days after the operation. She started treatment with 80 mg/day of S-1, given orally, for 28 days, followed by 14 days’ rest, as 1 course. During 16 courses of the treatment, she maintained a performance status of 0 to 1 and maintained quality of life. However, she died because of pelvic dissemination and genital bleeding (caused by tumor invasion into the uterus) 2 years and 4 months after the surgery. This case suggested that the improved gastrojejunostomy was a useful method for treating unresectable gastric cancer, allowing the possibility of oral intake, and the use of S-1.

Fixation of the round ligament to the peritoneum and wrapping of the cut surface of the liver for prevention of early delayed gastric emptying after hepatic lateral segmentectomy.

PurposeLeft-sided hepatectomy occasionally leads to early delayed gastric emptying (EDGE). We developed a new fixation procedure of the round ligament to the peritoneum to prevent EDGE after hepatic lateral segmentectomy and evaluated its efficacy.MethodsWe retrospectively studied 42 patients who underwent hepatic lateral segmentectomy. They were divided into two groups: a fixation group (N = 15) and a nonfixation group (N = 27). The round ligament of the liver was divided at the umbilicus and detached from the abdominal wall from the umbilicus to the liver. The cut surface of the liver was wrapped by the round ligament, and the distal part of the round ligament was then fixated to the peritoneum.ResultsEDGE was found to be 0% in the fixation group versus 15% in the nonfixation group.ConclusionsFixation of the round ligament to the peritoneum is a useful technique to prevent EDGE after hepatic lateral segmentectomy.