Laparoscopic distal gastrectomy with intracorporeal handsewn Billroth-I anastomosis (ICHSA).

BACKGROUND: The number of cases of laparoscopic surgery has been increasing. Lymph node dissection has been standardized, and the enlarged view provided by laparoscopes allows for the procedure to be performed successfully entirely within the abdominal cavity, but many cases of reconstruction using the Billroth-I method are performed under direct vision through a small incision. In this study, by placing an anchor thread on a suture line on the lesser curvature of the stomach, we simplified the procedure for handsewn anastomosis and safely performed gastroduodenal anastomosis at low cost to obtain good results. METHODS: From January 2009 to December 2010, we performed handsewn gastroduodenal anastomosis in 18 cases. After performing lymph node dissection, the duodenum and the stomach were separated using an automatic stapling device. Anchor sutures were placed on the suture line of the lesser curvature of the stomach. First, the seromuscular layer of the stomach and the seromuscular layer of the duodenum were sutured by performing interrupted suturing using an extracorporeal knot-tying method. With the stomach and the duodenum in a fixed state, the anastomosis area was opened. The thread of the anchor suture was pulled toward the abdominal wall, and then all layers of the stomach and the duodenum at the posterior wall were continuously sutured. Similarly, for the anterior wall, all layers were continuously sutured from the lesser curvature toward the greater curvature. RESULTS: We performed this anastomotic procedure in 18 patients with early gastric carcinoma. The mean time required for the anastomosis was 64.6 ± 17.1 min, and the estimated blood loss was 53.1 ± 91 g. All operations were curative, and the mean number of retrieved lymph node was 27.1 ± 10.8. A nasogastric tube was removed on the first or second day. An upper gastrointestinal series performed on postoperative days 5-6 showed no anastomotic leakage and normal transit. Oral intake was started on days 6-7. Postoperative complications included one case of a ruptured suture, but this was resolved through a conservative approach. There was no mortality. Postoperative endoscopy revealed that the anastomosis area was extremely soft, and no abnormalities were observed. Moreover, the only costs related to the anastomosis were for the thread and needles, and although more time was required compared with mechanical anastomosis, the cost was extremely low. CONCLUSIONS: We performed gastroduodenal anastomosis under a total laparoscopic approach by handsewn. This method is economical, because it does not require the use of machinery for anastomosis, and the duodenal stump is short. We believe that this method, which can be performed in a similar manner even for obese patients, can be used as a standard method of anastomosis.

Long-term outcome of laparoscopic surgery for T1 cancer patients of the colorectum.

BACKGROUND/AIMS: Many reports of laparoscopic colorectal surgery (LCS) for advanced cancer have been published indicating that LCS is an optimal and less invasive surgical treatment. On the other hand, there are few reports that address the early stages of cancer, especially with regard to the long-term outcome. This study analyzed the short- and long-term outcomes after LCS in patients with T1 cancer. METHODOLOGY: Between 1994 and 2005, a total of 135 LCS, including 129 laparoscopic colectomies and 6 laparoscopic anterior resections were performed in patients with T1 cancer that was diagnosed after the operation. The median follow-up was 83.5 months (range, 33-165). RESULTS: Postoperative complications included 6 wound infections (4%), 3 bowel obstructions (2%), 2 anastomotic leakage (1.3%), 1 atelectasis (0.67%). None of the patients required a re-operation. Oral intake was started after a mean of 2.9 postoperative days and the mean postoperative hospital stay was 14.4 days. There was no mortality and the overall survival was 100% in long-term follow up. CONCLUSIONS: LCS for T1 cancer is technically and oncologically safe based on the long-term outcomes when performed by surgeons with sufficient experience in laparoscopic techniques.

Prospective randomized trial of a closed-suction drain versus a Penrose drain after a colectomy.

BACKGROUND/AIMS: Prospective studies in the gastroenterological surgery literature have shown fewer wound related complications with a closed-suction drainage than with an open passive drainage. This study compared the SSI and cost of closed-suction drainage and open passive drainage in a randomized trial. METHODOLOGY: This study involved 112 patients undergoing colectomy from December, 2003 through April, 2007. A closed-suction or an open (Penrose) drainage was used based on the surgeon's preference. The cost and the incidence of complications including SSI was compared in the two drain types. RESULTS: The SSI rate was 13/112 cases 11.6%, but there was no significant difference between the drain groups. In addition, 18 laparoscopic surgery cases did not show any wound infection or drain infections. The closed-suction drain was not expensive regarding personnel expenses and the cost of changing the dressings. CONCLUSIONS: No statistically significant postoperative differences were observed between a closed-suction drain or an open drain after a colectomy. However, a closed-suction drain management is useful for the reduction of a cost, labor saving, and the decrease of medical waste.

Clinical outcomes and advantages of laparoscopic surgery for primary Crohn's disease: are they significant?

BACKGROUND/AIMS: The clinical outcomes and advantages of laparoscopic surgery for Crohn's disease have not yet been recognized in general. The aim of this study was to critically assess the clinical outcomes, safety, cosmesis, quality of life (QOL) and feasibility of laparoscopic surgery for primary Crohn's disease. METHODOLOGY: The study subjects consisted of 48 patients who had primary surgical treatment for Crohn's disease, 28 through conventional laparotomy and 20 in whom surgery was laparoscopically assisted. The short-term and long-term outcomes, cosmesis, and postoperative QOL were evaluated in both groups. RESULTS: There were no statistically significant differences in the patient characteristics between the two groups. In the laparoscopic group, non-resected procedures were significantly more frequent (p < 0.05), blood loss was less (p < 0.05), oral intake was started earlier (p < 0.05) and the length of the skin incision was shorter (P < 0.01). The C-reactive protein values and leukocyte counts were not significantly different in the two groups. The cosmetic results were very satisfactory in 11 patients (64.7%). There were no severe complications and no increase of the recurrence rate for laparoscopic surgery. Moreover, there was no definite clinical disadvantage and no prolonged operating time in the laparoscopic procedures. CONCLUSIONS: Laparoscopic surgery for primary Crohn's disease is safe and feasible in selected patients without severe adhesion, fistula or abscess, and was associated with better cosmesis than conventional open surgery. Therefore, laparoscopic procedures should be considered as the preferred operative approach for a primary bowel resection.

Inhibitory effect of linoleic acid on transformation of IEC6 intestinal cells by in vitro azoxymethane treatment.

The effect of linoleic acid (LA) on growth and transformation of IEC6 intestinal cells was examined. IEC6 cells expressed mRNAs of 15-lipooxygenase (LOX15) and peroxisome proliferator-activated receptor (PPAR)gamma but not COX-2. Cell growth was suppressed by LA in a dose-dependent manner in IEC6 cells. Three-week treatment with LA provided IEC6 cells a quiescent state. LA-induced growth inhibition was abrogated by exposure to antisense S-oligodeoxynucleotides (S-ODNs) for LOX15 and/or PPARgamma. In an in vitro carcinogenesis model, IEC6 cells, which had confirmed CYP2E1 expression and activity, were continuously treated with AOM and/or LA for 40 weeks. DNA injury in AOM-treated cells was suppressed to the control level by concurrent LA treatment. Colony formation of AOM-treated cells in soft agar was suppressed by treatment with LA, which was reversed by exposure to antisense S-ODNs for LOX15 and/or PPARgamma. AOM-treated IEC6 cells formed s.c. tumors in 9 of 12 mice, whereas AOM+LA-treated cells formed no tumor. IEC6 cells showed no remarkable alteration of protein production by AOM treatment, whereas cells treated with AOM+LA showed decreased epidermal growth factor receptor (EGFR) and phospho-EGFR and increased BAX. These findings suggest that LA inhibited AOM-induced transformation of COX-2-negative IEC6 cells, which was possibly mediated with PPARgamma ligands generated by LOX15 from LA.

Peritoneal metastasis inhibition by linoleic acid with activation of PPARgamma in human gastrointestinal cancer cells.

The effect on peritoneal metastasis of linoleic acid (LA) was examined using in vitro treatment of cancer cells and mouse peritoneal metastasis models. Firstly, cell growth of MKN28 human gastric cancer cells and Colo320 human colon cancer cells was suppressed by LA in a dose-dependent manner with increment of apoptosis. LA-induced growth inhibition was recovered by the exposure to antisense S-oligodeoxynucleotide for peroxisome proliferator-activated receptor gamma (PPARgamma) or 15-lipoxygenase-1, which converts LA to PPARgamma ligands. LA significantly inhibited invasion into type-IV collagen-coated membrane of MKN28 and Colo320 cells (p<0.05). BALB/c nu/nu mice inoculated with MKN28 and Colo320 cells into their peritoneal cavities were administrated with LA intraperitoneally (weekly, four times). The LA treatment significantly diminished the number of metastatic foci of both cells in the peritoneal cavity (p<0.05). Protein production in MKN28 and Colo320 cells treated with LA showed a decrease of epidermal growth factor receptor and an increase of Bax. These findings suggest that LA inhibits invasion and metastasis of human gastric and colon cancer cells by nondietary administration.

Discrepancy between E-cadherin protein expression and morphology in human gastric carcinoma cells.

BACKGROUND/AIMS: The E-cadherin-mediated cell adhesion system is now considered to be an "invasion suppressor system" in cancer cells. The purpose of this study is to examine the effect of E-cadherin on morphogenesis of MKN28 human gastric carcinoma cell line in the course of E-cadherin antisense S-oligodeoxynucleotide (ODN) treatment. METHODOLOGY: The effect of E-cadherin antisense or random S-ODN treatment on cell growth, morphology in monolayer culture, and E-cadherin protein expression of MKN28 cells were evaluated. Further, immunohistochemical examination was performed. RESULTS: Cell growth under 3-microM and 6-microM E-cadherin antisense S-ODN treatment did not differ from that under random S-ODN treatment. Although the expression of E-cadherin was decreased assuredly at the time of 6 days after 3-microM E-cadherin antisense S-ODN treatment by immunohistochemical examination, cell-cell adhesion was still observed until Day 10 after the treatment. On Day 15, the cells lost the cell-cell adhesion and showed the detachment and intercellular slits at least. Expression of the insoluble fraction of E-cadherin protein decreased in E-cadherin antisense S-ODN treatment cells at 6 days. CONCLUSIONS: In this study, we demonstrated that discrepancy between E-cadherin protein expression and morphology exists in MKN28 cells treated with E-cadherin antisense S-ODN treatment.

Effect of Nma on growth inhibition by TGF-betaa in human gastric carcinoma cell lines.

Non-metastatic gene A (nma) has a homologue DNA sequence to a gene of bone morphogenetic proteins and activin membrane-bound inhibitor (BAMBI), which negatively regulates TGF-beta signaling. In this study, we analyzed the functional homology between Nma and BAMBI in human gastric carcinoma cell lines. Various levels of nma mRNA expression were detected by the RT-PCR technique in all human gastric carcinoma cell lines. Then, Nma antisense and sense S-oligodeoxynucleotide (ODN) were used to analyze the response of TGF-beta to cell growth and invasion gastric carcinoma cell lines. The cell growth was inhibited by TGF-beta in Nma antisense S-ODN treatment gastric carcinoma cell lines, MKN28, MKN1, MKN74 and TMK1. TGF-beta reduced cell growth and invasive activity of MKN28 treated with Nma antisense S-ODN in a dose and time-dependent manner. Furthermore, lysates of Nma sense or antisense S-ODN treated MKN28 cells were immunoprecipitated with anti-TGFbetaR-I or anti-TGFbetaR-II antibody. The 29 kDa signal considered as Nma appeared in sense S-ODN treated MKN28 cells immunoprecipitated with anti-TGFbetaR-I. These results indicate that Nma negatively regulates TGF-beta signaling, consequently playing an important role as one of the escape mechanisms from TGF-beta-mediated growth control similarly to BAMBI, and induce cell growth and invasion in human gastric carcinoma cell lines.

Gallbladder cancer treatment using adenovirus expressing the HGF/NK4 gene in a peritoneal implantation model.

Gallbladder cancer cells are stimulated by hepatocyte growth factor (HGF) in vitro and in vivo. We constructed an adenovirus vector, AdCMV.NK4, carrying the HGF antagonist HGF/NK4 (NK4) and evaluated whether or not this vector can suppress the peritoneal implantation of gallbladder cancer in a novel peritoneal injury mouse model. A human gallbladder cancer cell line (GB-d1) and human peritoneal mesothelial cells infected with the adenovirus vector produced a substantial level of NK4 protein. An invasion of GB-d1 cells was determined by a coculture with AdCMV.NK4-infected human mesothelial cells in vitro. Both the invasion and migration of GB-d1 cells were dramatically inhibited by this vector in a multiplicity of infection (MOI)-dependent manner. GB-d1 cells were intraperitoneally injected into the nude mice with peritoneal injury, followed by either AdCMV.NK4 or a control vector (AdCMV.LacZ). The incidence and the size of the metastatic tumor drastically decreased by AdCMV.NK4 (MOI 100: n=4, P<.0001). Real-time PCR analysis revealed a transient elevation of mouse HGF mRNA expression at the peritoneal injury sites. AdCMV.NK4 has been suggested to induce the inhibition of the implantation and growth of gallbladder cancer cells in vivo through its anti-HGF activity, and the use of NK4 gene transfer could be an effective modality for preventing peritoneal metastasis of gallbladder cancer.

Effect of human noxa on irinotecan-induced apoptosis in human gastric carcinoma cell lines.

BACKGROUND/AIMS: A protein BH3-only member bcl-2 family, Noxa is a proapoptotic mediator for p53-induced apoptosis. We analyzed the effect of Noxa on p53-induced apoptotic gastric carcinoma cell lines. METHODOLOGY: The expressions of human Noxa (hNoxa) mRNA on human gastric carcinoma cell lines were assessed with RT-PCR. Further, hNoxa antisense and sense S-oligodeoxynucleotide (ODN) were used to analyze the effect of hNoxa on p53-induced apoptotic gastric carcinoma cell lines. RESULTS: Various levels of hNoxa mRNA expression were detected in all gastric cell lines. MKN45 that has wild-type p53 showed severe inhibition by irinotecan compared with MKN28, which has mutated p53. Cell growth under hNoxa antisense S-ODN treatment did not differ from that under sense S-ODN treatment in MKN28. On the other hand, the suppression of cell growth in MKN45 decreased with hNoxa antisense S-ODN treatment as compared to hNoxa sense S-ODN treatment. MKN45 cells exhibited DNA fragmentation clearly after 24 hr of 3 mM hNoxa sense S-ODN treatment. The DNA fragmentation in MKN45 was inhibited by hNoxa antisense S-ODN treatment. CONCLUSIONS: It seems that hNoxa plays an important role in induction of apoptosis on p53 wild type gastric carcinoma cell lines.

Protection of trocar sites from gallbladder cancer implantation in a murine model by physically covering the sites.

Laparoscopic surgery for malignant diseases is associated with a risk for port site recurrence (PSR), and this problem remains to be resolved. This study was performed to evaluate the role that Seprafilm and Interseed (TC7) play in the prevention of PSR, using a nude mouse model of PSR. Nude mice with 2-mm port sites were created. The resultant peritoneal defects were covered with either Seprafilm or Interseed (TC7). The protective effect of Seprafilm and Interseed (TC7) on GB-dl (a human gallbladder cancer cell line) implantation at port sites was assessed after 7 days. In addition, the effects of Seprafilm and Interseed (TC7) on wound healing at the port sites were also observed. The Seprafilm and Interseed (TC7) groups showed a significantly lower incidence of PSR than the control group. Both Seprafilm and Interseed (TC7) changed into a gel form and covered the ruptured muscle layer and injured peritoneum for 3-5 days. When the peritoneal defect, produced by trocar insertion, was physically covered with either Seprafilm or Interseed (TC7), the incidence of PSR was observed to significantly decrease. These materials seem to be promising modalities for the prevention of PSR.

Laparoscopic treatment of a gastric duplication cyst: report of a case.

Gastric duplications are rare benign tumors that are mainly discovered in relatively young patients. Although laparoscopic surgery, a less invasive surgical procedure, should be used for this condition, its application in the treatment of this disease has not yet been reported. A 14-year-old girl visited our hospital with the chief complaint of repeated episodes of upper abdominal pain. Because diagnostic imaging revealed a cystic tumor in the dorsal stomach, laparoscopic surgery was performed. The cystoma was intraoperatively found to contiguous with the posterior wall of the gastric cardia and was thus diagnosed to be a gastric duplication. With the intraoperative aid of gastroscopy, we were able to remove the cystoma from the continuous gastric wall safely without causing either a perforation or any other injury to the stomach. Gastric duplication is a congenital disease, and thus the majority of such cases are diagnosed in childhood. A laparoscopic resection of a duplicated stomach is less invasive and esthetically superior to other methods, and therefore it is considered to be a useful therapeutic modality.

Gamma interferon gene transfection efficiently inhibits proliferation of neurofibroma cell lines in vitro.

Primarily isolated neurofibroma cell lines and a human dermal fibroblast cell line were transfected with human gamma interferon gene in vitro, and changes in the cell proliferation rates were investigated. The proliferation rates of both cell lines were remarkably suppressed after the gene transfection. In particular, the neurofibroma cell lines almost stopped proliferating five days after gene transfection. The tritium thymidine uptake of the fibroblast cell line was almost abolished three days after gene transfection. The culture media from both of the gene-transfected cell lines contained a measurable gamma interferon concentration as late as five days after transfection, this was detected by an enzyme-linked immunosorbent assay. These data suggest that gamma interferon gene therapy might be a possible treatment for intractable or inoperable neurofibromas in patients with von Recklinghausen's disease in the future.

Inhibition of the proliferation of a malignant peripheral nerve sheath tumor cell line by gamma interferon gene transfection.

A solitary malignant peripheral nerve sheath tumor was resected, and a tumor cell line was obtained using an explant culture. The morphology of this cell line was quite similar to those of cell lines of dermal neurofibromas of neurofibromatosis 1, except for the fact that the malignant peripheral nerve sheath tumor cell line could be cultured for more than two months. When the tumor cell line was transfected with human gamma interferon gene, the growth rate was remarkably abolished, as previously observed in neurofibroma cell lines transfected with the gamma interferon gene. This new finding suggests the potential for treating either solitary or neurofibroma-related, inoperable, malignant peripheral nerve sheath tumors by local gamma interferon gene transfection in vivo.