Intraperitoneal chemotherapy for peritoneal metastases using sustained release formula of cisplatin-incorporated gelatin hydrogel granules.

PURPOSE: We previously reported the effectiveness of gelatin microspheres incorporating cisplatin in a mouse model of peritoneal metastases. In this study, we report our new complete sustained-release formula of gelatin hydrogel granules incorporating cisplatin (GHG-CDDP), which exerted a good anti-tumor effect with less toxicity. METHODS: GHG-CDDP was prepared without organic solvents to enable its future clinical use. The pharmaceutical characterization of GHG-CDDP was performed, and its in vivo degradability was evaluated. The anti-tumor effect was evaluated using a murine peritoneal metastasis model of the human gastric cancer MKN45-Luc cell line. RESULTS: Our new manufacturing process dramatically reduced the initial burst of CDDP release to approximately 2% (wt), while the previous product had a 25-30% initial burst. In intraperitoneal degradation tests, approximately 30% of GHG-CDDP remained in the murine abdominal cavity 7 days after intraperitoneal injection and disappeared within 3 weeks. GHG-CDDP significantly suppressed the in vivo tumor growth (p = 0.02) and prolonged the survival time (p = 0.0012) compared with the control. In contrast, free CDDP did not show a significant therapeutic effect at any dose. Weight loss and hematological toxicity were also significantly ameliorated. CONCLUSIONS: GHG-CDDP is a promising treatment option for peritoneal metastases through the complete sustained-release of CDDP with less systemic toxicity.

Laparoscopy endoscopy cooperative surgery for gastric plexiform fibromyxoma: a case report.

BACKGROUND: Gastric submucosal tumors are commonly treated by partial resection under laparoscopy. However, the surgical resection of gastric submucosal tumors sometimes causes deformation of the stomach, especially in the case of intraluminal tumors located near the pylorus or esophagogastric junction. Such deformations can result in impaired diet intake and reduced quality of life. Laparoscopic endoscopic cooperative surgery has been developed to overcome these problems. This is the first report to describe a case of gastric plexiform fibromyxoma, a rare gastric submucosal tumor, that was successfully resected by laparoscopic endoscopic cooperative surgery. CASE PRESENTATION: A 36-year-old Japanese woman presented with epigastric pain and anemia. Gastrointestinal endoscopy revealed a submucosal tumor in the gastric antrum. Because a definitive diagnosis could not be obtained and the tumor was located near the pylorus, we performed laparoscopic endoscopic cooperative surgery as diagnostic therapy. The postoperative course was favorable with no complications, such as delayed gastric emptying or outlet obstruction. The tumor was pathologically diagnosed as gastric plexiform fibromyxoma. CONCLUSIONS: Laparoscopic endoscopic cooperative surgery is a useful approach for diagnostic therapy for rare submucosal tumors to avoid the deformation of the stomach, especially when the tumor is located near the pylorus.

Aortoenteric fistula at the site of esophagojejunostomy after laparoscopic total gastrectomy: report of a case.

A fistula between the aorta and the digestive tract is a rare complication of gastrointestinal tract or vascular surgery. There are occasional reports of aortoesophageal fistula as a fatal complication after esophagectomy or esophageal stent implantation and of aortoenteric fistula (AEF) as a complication after aortic or other vascular procedures. However, AEF after gastrointestinal surgery is rare. We report a case of AEF after laparoscopic total gastrectomy for advanced gastric cancer, using the so-called overlap method of esophagojejunal anastomosis. The patient was a 77-year-old Japanese woman who underwent laparoscopic total gastrectomy and esophagojejunal anastomosis with Roux-en-Y reconstruction for advanced gastric cancer. Bacterial peritonitis was diagnosed 5 days after the operation, manifesting as partial necrosis and perforation of the small intestine. The patient was treated successfully with laparoscopic partial resection of the small intestine, but ultimately died of massive hematemesis caused by the AEF 30 days after her primary surgery.

A novel drug delivery system of intraperitoneal chemotherapy for peritoneal carcinomatosis using gelatin microspheres incorporating cisplatin.

BACKGROUND: Peritoneal carcinomatosis is a poor prognostic factor for patients with gastrointestinal, gynecologic, and pancreatic cancer. Cisplatin (CDDP) is among the most effective anti-cancer agents, although its adverse effects remain unresolved. For the treatment of peritoneal carcinomatosis with high-dose CDDP, it is necessary to design a new delivery system of CDDP that can decrease systemic toxicity and achieve a better targeted, high-dose chemotherapy. METHODS: Microspheres were prepared from gelatin of a nontoxic, biodegradable material for the sustained release of CDDP. The gelatin microspheres incorporating CDDP (GM-CDDP) were injected intraperitoneally into a mouse model of peritoneal carcinomatosis; their therapeutic efficacy and adverse effects were evaluated in comparison with intraperitoneal administration of free CDDP. RESULTS: GM-CDDP released CDDP in the peritoneal cavity as a result of gelatin biodegradation. Mice treated with microspheres in the peritoneal cavity lived longer than mice treated with free CDDP (74 ± 23 vs 40 ± 23 days; P < .05). The mice treated with GM-CDDP also lost no weight, whereas the free CDDP group lost approximately 20% body weight (106 ± 5% vs 80 ± 7%; P < .001; body weight on day 1 = 100%). GM-CDDP significantly decreased the nephrotoxicity and hematotoxicity of CDDP. CONCLUSION: GM decreased the adverse effects of CDDP and allowed high-dose intraperitoneal chemotherapy with the control of CDDP. This technique of gradual local release may allow us to provide a high-dose, targeted, intraperitoneal chemotherapy with CDDP, resulting in enhanced anti-cancer effects. These gelatin microspheres may be useful as a drug carrier for the treatment of peritoneal carcinomatosis.

Effects of rikkunshito, a kampo medicine, on quality of life after proximal gastrectomy.

BACKGROUND: The loss of the gastroesophageal junction after proximal gastrectomy (PG) induces various gastrointestinal symptoms, such as regurgitation, anorexia, and body weight loss, leading to impairment of the postoperative quality of life. In the present study, we investigated the long-term quality of life and the effects of rikkunshito, a traditional Japanese medicine (kampo), on the gastrointestinal symptoms and plasma ghrelin levels in patients with gastric cancer who had undergone PG. METHODS: Nineteen patients who had undergone PG> 6 mo before entry into the present study were enrolled. The plasma ghrelin levels, body weight, appetite, and Gastrointestinal Symptom Rating Scale (GSRS) scores were examined before and after the 4-wk administration of rikkunshito. A subgroup analysis was performed of patients showing a GSRS score of ≥ 2 before treatment, indicating the presence of gastrointestinal symptoms. RESULTS: The patients' body weight increased significantly after the administration of rikkunshito. Neither their appetite nor plasma acylated and deacylated ghrelin levels were significantly affected. In the subgroup analysis, the mean total GSRS score improved significantly from 2.6 ± 0.6 before the administration of rikkunshito to 1.9 ± 0.7 after administration because of the significant improvement in the subscale scores for abdominal pain, acid reflux, diarrhea, and constipation. CONCLUSIONS: The long-term quality of life was well preserved in the patients who had undergone PG at our hospital. In the patients with a baseline GSRS score of ≥2, rikkunshito significantly improved the symptoms of postgastrectomy syndrome, and its effect was possibly independent of the plasma ghrelin levels.

Successful outcome after laparoscopic surgery for sporadic colonic desmoid tumor with ß-catenin mutation: a case report.

INTRODUCTION: Desmoid tumors (also called aggressive fibromatosis) are histologically benign, but have a strong tendency to recur locally after resection. They are rare neoplastic tumors that may occur sporadically or in association with familial adenomatous polyposis caused by a germline mutation in the adenomatous polyposis coli gene. The etiology of desmoid tumors is unknown, but their association with a history of abdominal surgery, trauma, and estrogen therapy is well known. CASE PRESENTATION: A 36-year-old Asian woman was referred complaining of an abdominal tumor. She had no history of familial adenomatous polyposis, abdominal surgery, trauma or pregnancy. A laparoscopy-assisted right hemicolectomy with a minilaparotomy was conducted for resection of her right-side colon and the anterior wall of her duodenum. The histopathological diagnosis was a desmoid tumor that grew from the transverse mesocolon. Mutational analysis indicated a mutation of the ß-catenin gene (CTNNB1), consisting of a substitution of threonine for alanine at codon 41. The patient has been followed postoperatively for more than 3 years without any sign of recurrence. CONCLUSION: We report a case of sporadic colonic desmoid tumor which was resected by laparoscopic surgery. A successful outcome was achieved because there has been no local recurrence for more than 3 years. The tumor grew from the transverse mesocolon, and harbored a mutation of the CTNNB1 gene. Mutational analysis of CTNNB1 gene may play an important role as a prognostic marker of desmoid tumors.

Uneventful splenectomy and cholecystectomy in a patient treated with anti-interleukin-6 receptor antibody therapy.

INTRODUCTION: Interleukin-6 (IL-6) is a multifunctional cytokine that regulates various aspects of the immune responses, acute phase reactions, and hematopoiesis. In rodent models, IL-6 has been suggested to be one of the essential mediators for optimal acute phase responses to infection and tissue damage. However, in humans, the roles of IL-6 in acute phase responses after surgery remain poorly understood. CASE REPORT: We present the first case report of successful splenectomy and cholecystectomy in a severe autoimmune-associated hemolytic anemia patient during treatment with a humanized anti-IL-6 receptor antibody. DISCUSSION: This unique case suggests that IL-6 is not an essential cytokine to safely perform surgical intervention and to prevent postoperative complications and that surgical intervention may not be contraindicated but can be selected as a therapeutic modality in patients treated with anti-IL-6 receptor antibody therapy.