orabase and Peritoneal-Neoplasms

Nano-fibrillated bacterial cellulose (NFBC) is a safe, biocompatible material that can be prepared by culturing a cellulose-producing bacterium in a culture supplemented with carboxymethylcellulose (CMC) or hydroxypropylcellulose (HPC). CM-NFBC and HP-NFBC, prepared using CMC or HPC, show hydrophilicity and amphiphilicity, respectively, and thus they could be useful carriers for hydrophobic anticancer agents such as paclitaxel (PTX). In the present study, we prepared novel PTX formulations for intraperitoneal administration by associating PTX with either CM-NFBC or HP-NFBC and studied their therapeutic efficacy on peritoneally disseminated gastric cancer in a xenograft nude mouse model. Freeze-dried PTX formulations (PTX/CM-NFBC and PTX/HP-NFBC) were quickly reconstituted with saline without any foaming, compared to nanoparticle albumin-bound PTX (nab-PTX, Abraxane®). Both PTX/NFBC formulations extended the mean survival times in our xenograft murine models compared with either free PTX or nab-PTX. The PTX/NFBC formulations reduced systemic side effects of free PTX relating to weight loss. In our disseminated gastric peritoneal cancer model, the PTX/NFBC formulation increased the therapeutic index for PTX by increasing the therapeutic efficacy and decreasing toxicity. NFBCs should receive consideration as improved carriers for the clinical delivery of hydrophobic anticancer drugs such as PTX in malignancies in the abdominal cavity with peritoneal metastasis and dissemination.

Topics: Animals; Bacteria; Carboxymethylcellulose Sodium; Cellulose; Culture Media; Drug Compounding; Humans; Injections, Intraperitoneal; Male; Mice; Mice, Nude; Nanofibers; Paclitaxel; Peritoneal Neoplasms; Stomach Neoplasms; Treatment Outcome; Xenograft Model Antitumor Assays

To create anti-adhesive materials to be more effective and safer, we developed a thermally cross-linked gelatin film that showed superior anti-adhesive effects with excellent peritoneal regeneration. However, it may act as a convenient scaffold for tumor cell growth, thereby accelerating peritoneal dissemination when used in surgery for abdominal tumors. In this study, we tried to clarify this issue using mouse carcinomatous peritonitis models. First, we examined the in vitro tumor cell growth of mouse B16 melanoma or Colon26 cells on the gelatin film or the conventional hyarulonate/carboxymethylcellulose film. Tumor cell growth on each film was significantly lower than that of the control (no film). Next, we conducted the following in vivo experiments: After the parietal peritoneum was partially removed and covered with each film or without any film, mice were inoculated intraperitoneally with B16 melanoma or Colon26/Nluc cells expressing NanoLuc luciferase gene. At 7 days after the operation, we measured the weight of B16 melanoma tumors or the NanoLuc activity of Colon26/Nluc cells using in vivo imaging at the injured sites. There were no significant differences in the weight of the tumors and the NanoLuc activity among the three groups. We also observed the survival time of mice receiving the same operation and treatments. There was no significant difference in the survival time among the three groups. These results suggest that the gelatin film will likely not accelerate peritoneal dissemination as a convenient scaffold for tumor cell growth when used in surgery for abdominal tumors. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2122-2130, 2018.

Topics: Animals; Carboxymethylcellulose Sodium; Gelatin; Hyaluronic Acid; Male; Melanoma, Experimental; Membranes, Artificial; Mice; Neoplasm Metastasis; Peritoneal Neoplasms; Tissue Adhesions

To evaluate the risk of postoperative complications related to HA-CMC use in patients undergoing optimal cytoreductive surgery for primary and recurrent ovarian, fallopian tube, and peritoneal cancers.. A single institution retrospective review identified all patients undergoing optimal (≤1 cm) cytoreductive surgery for primary or recurrent ovarian, fallopian tube, and peritoneal cancers between 1/95 and 12/08. Operative details and post-operative complications (<30 days) were extracted from the medical record. Fisher's exact test, Mann-Whitney-U, and multiple regression analyses were performed to identify factors, including HA-CMC use, associated with post-operative complications.. Three hundred seventy-five cases were analyzed: HA-CMC was utilized in 168 debulking procedures. There was no difference in the incidence of overall morbidity for patients with HA-CMC compared to those without HA-CMC (OR 1.07; 95% CI: 0.68-1.67). On univariate analysis, application of HA-CMC increased the risk of pelvic abscess (OR 2.66; 95% CI: 1.21-5.86), particularly in the primary surgery setting (OR 4.65; 95% CI: 1.67-12.98) and in patients undergoing hysterectomy (OR 3.36; 95% CI: 1.18-9.53). After controlling for confounding factors using multiple linear regression, HA-CMC use approached statistical significance in predicting an increased risk of pelvic abscess but not major postoperative morbidity.. HA-CMC adhesion barrier placement at the time of optimal cytoreductive surgery for ovarian, fallopian tube, and peritoneal cancer is not associated with major postoperative complications but may be associated with increased risk of pelvic abscess.

Topics: Carboxymethylcellulose Sodium; Fallopian Tube Neoplasms; Female; Gynecologic Surgical Procedures; Humans; Middle Aged; Ovarian Neoplasms; Peritoneal Neoplasms; Retrospective Studies

To determine whether HA-CMC was associated with the development of postoperative intra-abdominal collections in patients undergoing laparotomy for ovarian, fallopian tube, or primary peritoneal malignancies.. We retrospectively identified all laparotomies performed for these malignancies from March 1, 2005 to December 31, 2007. The use of HA-CMC was identified. Laparotomies for malignant bowel obstruction or repair of fistulae were excluded. Intra-abdominal collections, non-infected and infected, were defined as localized intraperitoneal fluid accumulations in the absence of re-accumulating ascites. All other complications were also captured. Appropriate statistical tests were applied using SPSS 15.0.. We identified 219 laparotomies with HA-CMC and 204 without HA-CMC. Upper abdominal resections were performed in 65/219 (30%) HA-CMC cases compared to 39/204 (19%) cases without HA-CMC (P=0.01). The rates of large bowel and/or rectal resections were similar in both cohorts. Intra-abdominal collections were seen in 18/219 (8.2%) HA-CMC cases compared to 5/204 (2.5%) cases without HA-CMC (P=0.009). HA-CMC was independently associated with the diagnosis of a postoperative intra-abdominal collection (P=0.01). All but 2 collections developed in patients undergoing debulking procedures.. HA-CMC appears to be associated with a higher rate of postoperative intra-abdominal collections. This seems to be greatest in patients who are undergoing a debulking procedure.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Ascites; Carboxymethylcellulose Sodium; Cohort Studies; Fallopian Tube Neoplasms; Female; Humans; Hyaluronic Acid; Laparotomy; Membranes, Artificial; Middle Aged; Ovarian Neoplasms; Peritoneal Neoplasms; Retrospective Studies; Tissue Adhesions; Young Adult

Hyaluronan mediates growth of SW620 colon cancer cells. Because hyaluronan is the active ingredient in Seprafilm, we hypothesized that Seprafilm would affect intraperitoneal tumor growth in a mouse model of peritoneal seeding.. Immunodeficient mice underwent laparotomy and intraperitoneal inoculation of 10(5) SW620 cells. Seprafilm (n = 22), Vicryl mesh (foreign body control; n = 24), or no material (sham; n = 19) was placed under the incision. Mice were killed after four weeks and tumors were dissected, counted, and weighed.. Ninety-five percent of mice in the sham group and 96 percent in the Vicryl group developed intraperitoneal tumors. In contrast, only 64 percent of mice in the Seprafilm group developed tumors (P = 0.024), and these tumors were smaller than those in the sham group; (Seprafilm = 42 +/- 9 mg vs. sham = 82 +/- 17 mg; P = 0.05). In contrast, tumors in the Vicryl group were dramatically larger (349 +/- 49 mg; P < 0.001 vs. sham or Seprafilm).. Despite previous data that suggested that hyaluronan increases colon cancer cell growth, we found that Seprafilm decreased tumor formation and tended to decrease size in this model. In contrast, Vicryl mesh increased tumor formation and size. Our results suggest that Seprafilm does not promote intraperitoneal tumor growth, especially compared with Vicryl mesh.

Topics: Adjuvants, Immunologic; Animals; Carboxymethylcellulose Sodium; Female; Hyaluronic Acid; Immunocompromised Host; Membranes, Artificial; Mice; Mice, SCID; Models, Animal; Neoplasm Seeding; Peritoneal Neoplasms; Polyglactin 910; Surgical Mesh; Tumor Cells, Cultured

The risk of port site metastasis in laparoscopic surgery for cancer patients is a problem that has yet to be resolved. We examined the protective effect of a sodium hyaluronate-based bioresorbable membrane (Seprafilm) on tumor cell implantation at laparoscopic trocar sites.. Four 2-mm trocar sites were created in nude mice, and the peritoneal wounds were covered with different-sized pieces of Seprafilm. The protective effect of Seprafilm on the implantation of GB-d1 (a human gallbladder cancer cell line) at the trocar sites was assessed after 7 days. In addition, the effects of sodium hyaluronate and Seprafilm on the growth and motility of GB-d1 were examined in vitro.. Seprafilm significantly decreased the incidence of implantation compared with the control group. Histologically, Seprafilm was observed on days 1 and 3, as a sheet of gel that covered the injured peritoneum and muscle layer. In an invasion assay using Seprafilm, no cells were found to infiltrate through the gel sheet.. Seprafilm protects peritoneal wounds by physically covering the injured peritoneum. Therefore, if Seprafilm were attached to the injured peritoneum after laparoscopic surgery for cancer patients, it might reduce port site metastasis.

Topics: Adenocarcinoma; Animals; Biocompatible Materials; Carboxymethylcellulose Sodium; Cell Line, Tumor; Cholecystectomy, Laparoscopic; Gallbladder Neoplasms; Gels; Humans; Hyaluronic Acid; Implants, Experimental; Male; Membranes, Artificial; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Seeding; Peritoneal Neoplasms; Surgical Instruments; Xenograft Model Antitumor Assays

Auto-crosslinked polysaccharide hyaluronan-based solution (Hyalobarrier-gel) prevents postoperative adhesions. However, its effect on tumour growth is still unknown. The aim of the present study was therefore to investigate the impact on survival of intra-abdominally administered Hyalobarrier-gel, native hyaluronan (HA) and hyaluronan/carboxymethylcellulose (HA/CMC), after intraperitoneal tumour implantation.. After receiving an intraperitoneal inoculum of the human HT29 colorectal cell line, 615 athymic nude mice were assigned randomly to five groups: groups 1 and 2 received Hyalobarrier-gel 20 mg/ml (n = 124) and 40 mg/ml (n = 126) respectively; groups 3 and 4 received HA (n = 120) and HA/CMC film (Seprafilm) (n = 123) respectively. The survival of each treated group was compared with that of group 5, the control, which had no treatment (n = 122).. As 34 of the 615 mice were not eligible, 581 animals were considered for the analysis. At 120 days, 136 animals (23.4 per cent) were still alive. At autopsy there was macroscopic absence of tumour in 75 cases (12.9 per cent). No statistically significant differences were found between the treatment and the control groups with respect to postoperative death and absence of tumour implantation. There was no difference in survival rate between the control group and groups treated with Hyalobarrier-gel, HA or HA/CMC.. Hyalobarrier-gel, HA and HA/CMC had no negative impact on the survival rate in mice that received an intraperitoneal implantation of HT29 colorectal human tumour cells.

Topics: Animals; Anticarcinogenic Agents; Carboxymethylcellulose Sodium; Colorectal Neoplasms; Drug Combinations; Gels; HT29 Cells; Humans; Hyaluronic Acid; Male; Mice; Mice, Nude; Neoplasm Transplantation; Peritoneal Neoplasms; Random Allocation; Survival Analysis; Tissue Adhesions