Effects of liposome-encapsulated hemoglobin on gastric wound healing in the rat.

Liposome-encapsulated hemoglobin (LEH) may improve microcirculation and oxygen (O2 ) metabolism at a surgical wound to accelerate its healing. Ten mL/kg of LEH with high (h-LEH) or low O2 -affinity (l-LEH), homologous red blood cells (RBC), empty liposome or saline as a control was infused before a 10-mm incision and interrupted suture closure of the gastric wall in a total of 110 rats. Two and 4 days later, the stomach was excised for bursting pressure determination and histological sampling. The dose-response relationship was examined in 70 additional rats receiving progressively reduced doses of h-LEH. Hypoxia-inducible factor-1α (HIF-1α) was stained immunohistochemically in 54 other rats to examine its accumulation at the anastomotic sites. Bursting pressure of the surgical wound was significantly higher 2 days after surgery only in the h-LEH-treated rats (P < 0.05), but not at 4 days after surgery, when other rats showed increased bursting pressure to a nonsignificant level. Histological examination revealed less granulocyte infiltration, better granulation, and more macrophage infiltration in h-LEH-treated rats at 2 days, but no longer at 4 days postsurgery. Dose-response study revealed that 0.4 mL/kg of h-LEH (hemoglobin 24 mg/kg) was effective for elevating bursting pressure at 2 days. h-LEH-treated rats had significantly suppressed HIF-1α accumulation in the wound 6, 24, and 48 h after surgery as compared with control animals treated with homologous RBC or saline. In conclusion, the results suggest that h-LEH, but not l-LEH or homologous transfusion, may accelerate wound healing early after gastric incision and anastomosis in the rat. The mechanism(s) appears to be related to improved O2 supply, aerobic metabolism, and suppressed inflammation in the wound.

Fundic rotation technique: a useful procedure for laparoscopic exogastric resection of gastric submucosal tumors located on the posterior wall near the esophagogastric junction.

OBJECTIVE: To develope a new procedure for laparoscopic exogastric resection using a so-called "fundic rotation technique (FRT)" for gastric submucosal tumors (SMTs) on the posterior wall near the esophagogastric junction (EGJ). METHODS: Between April 2006 and February 2010, we performed laparoscopic resection for SMTs located near the EGJ (within 3.0 cm from the EGJ) in ten consecutive patients. Out of seven exogastric resections, an FRT was used in five patients with posterior tumors near the EGJ. RESULTS: The patients comprised three men and two women, with an average age of 65 years. The maximum tumor diameter averaged 3.8 cm (range, 2.0-8.0 cm), and the average distance from the EGJ was 1.5 cm (range, 0-2.5 cm). The pathological diagnosis was GIST in all cases. One case was converted to an open surgery due to its large size (8.0 cm) and the difficult access. All the patients quickly returned to their normal activities. No patient complained any symptoms of regurgitation, and endoscopic examination revealed no remarkable reflux esophagitis. No tumor recurrences occurred during a median follow-up period of 30 months. CONCLUSION: The indications for laparoscopic resection of SMTs located near the EGJ may be extended using an FRT.

Impact of difference in the definition of extranodal spread on the outcome of node-positive patients with gastric cancer.

PURPOSE: Previous studies have reported that extranodal spread is a prognostic factor in patients with several solid cancers. However, the definition of extranodal spread varies with the reporting investigator and has not been standardized yet. Therefore, we selected several widely used definitions from previous reports and comparatively assessed the clinicopathologic significance of these definitions. METHODS: Extranodal spread in the 103 node-positive patients who had received curative resections for gastric cancer was classified into two groups, viz., (a) capsule rupture, where cancer cells infiltrated into the perinodal fatty tissue beyond the capsule of the involved lymph node, and (b) no capsule rupture, where nests of cancer cells were detected demonstrable in adjacent tissues around the metastatic lymph node without rupture of the capsule. RESULTS: Sixty-five (63.1%) of the 103 patients showed extranodal spread. Of the 65 patients, 50 patients showed the capsule rupture type and 15 showed the no capsule rupture type of extranodal spread. The 5-year survival rate was significantly poorer in the capsule rupture group as compared with that in the no capsule rupture group and extranodal spread-negative group (P < 0.05 and P < 0.01, respectively). In regard to the mode of recurrence, the rate of peritoneal recurrence was significantly higher in the capsule rupture group (P < 0.01). CONCLUSIONS: In the assessment of patients with extranodal spread, it is considered important to classify the patients based on the status of extranodal spread into the capsule rupture group and no capsule rupture group.

[Isolated spontaneous dissection of the superior mesenteric artery in two cases treated with conservative therapy].

We report two cases of isolated spontaneous dissection of the superior mesenteric artery (SMA). Both patients complained of abdominal pain with sudden onset and were given diagnoses of dissection of the SMA based on abdominal CT scanning. CT showed dissention of the SMA with thrombosis of the false lumen and narrowing of the true lumen. Therefore there were no symptoms of bowel ischemia, and after hospitalization both cases received conservative therapy with anticoagulation and antiplatelet therapy. Spontaneous dissection of the SMA without aortic dissection is very rare, and only 53 cases have been recorded in Japan.

Laparoscopy-assisted combined resection for synchronous gastric and colorectal cancer: report of three cases.

In gastric cancer patients, the most common form of synchronous cancer is colorectal cancer. To reduce the invasiveness of the resection, a laparoscopy-assisted combined resection was performed in three patients with synchronous gastric and colorectal cancer. Although all gastric lesions were in the early stages, two colorectal lesions were advanced cases. In all cases, the laparoscopic gastric resection and reconstruction was performed first, followed by the colorectal resection. In the case of right-side colon cancer in addition to gastric cancer, it was relatively easy to perform the combined resection with lymph node dissection sharing the same ports used for the gastrectomy, although we needed an additional port. In one case, in which rectal cancer was present in addition to gastric cancer located in the upper portion of the stomach, a totally laparoscopic proximal gastrectomy was combined with a laparoscopy-assisted low anterior resection, leaving only a lower abdominal minilaparotomy wound. All patients quickly returned to normal activity without remarkable complications, with the exception of a wound infection in one patient. With a mean follow-up of 30.7 months, all patients survived without any sign of recurrence. This procedure represents a feasible option for minimally invasive treatment of synchronous gastric and colorectal cancer.

Endoscopy-assisted gastric resection: a safe and reliable procedure for tumor clearance during laparoscopic high distal or proximal gastrectomy.

BACKGROUND: Preoperative endoscopic tattooing or clipping is generally used to delineate the tumor-free margin in surgery for early gastric cancer. However, it is sometimes difficult to identify the line of resection during laparoscopic gastrectomy. METHODS: Between June 2003 and February 2008, we performed a total of 12 endoscopy-assisted gastric resections during laparoscopic gastrectomy for cancer, including four cases of high distal gastrectomy and eight cases of proximal gastrectomy. In the laparoscopic high distal gastrectomy cases, a surgeon performed transduodenal endoscopy to identify the clips before gastric resection. For totally laparoscopic proximal gastrectomy, an endoscopist performed transoral endoscopy to identify the clips placed in the distal margin of the lesion and to facilitate intracorporeal anastomosis. RESULTS: In all cases, we were able to observe clips as well as the primary lesion. Gastric resection was successfully performed with no positive margin. In the high distal gastrectomy group (n = 4), proximal and distal margins were 19.5 +/- 2.1 (range, 10-35) mm and 1,185 +/- 190.9 (range, 850-1,320) mm, respectively. In the proximal gastrectomy group (n = 8), proximal and distal margins were 21.3 +/- 7.1 (range, 5-38) mm and 47.5 +/- 3.5 (range, 15-75) mm, respectively. The intracorporeal side-to-side anastomosis during proximal gastrectomy was successfully performed using an endolinear stapler. CONCLUSIONS: Endoscopy-assisted gastric resection is a safe and reliable procedure for tumor clearance during laparoscopic high distal or proximal gastrectomy.

New method of laparoscopic incisional hernia repair with double circumferential transfascial sutures.

BACKGROUND: Although, laparoscopic incisional hernia repair (LIHR) provides an alternative method for managing incisional hernias, the ideal procedure for reducing the incidence of postoperative complications remains unclear. PATIENTS AND METHODS: We have developed a new method of LIHR that involves a double transfascial suture and does not require the use of spiral tackers. We performed this procedure consecutively in five patients (four males and one female with a mean age of 65.6 years). We describe our new method of LIHR, and present preliminary clinical results. RESULTS: The mean defect size was 26.2 ± 15.8 cm(2), and the mesh size that was used was 121.7 cm(2) in all cases. An occult hernia was found in one patient during laparoscopic observation. The mean operative time was 198.4 ± 49.3 minutes with a blood loss of 12.2 ± 24.6 mL. Postoperative courses were uneventful with a median postoperative hospitalization period of 8 days. No patient required mesh removal and none developed a recurrent hernia during the median follow-up period of 13 months. CONCLUSION: Although, larger number of patients and longer follow-up will be required to prove the operative adequacy of our new procedure, it appears to represent a feasible option for LIHR.

Liposome-encapsulated hemoglobin accelerates gastric wound healing in the rat.

BACKGROUND: Liposome-encapsulated hemoglobin, a nanometer-sized artificial O2 carrier with a high O2 affinity (h-LEH), may facilitate O2 delivery to surgical wounds and thereby accelerate healing after gastrointestinal surgery. METHODS: Ten mL/kg of h-LEH (n = 25), empty liposome (n = 21) or homologous washed red blood cells (RBC, n = 22) was intravenously infused prior to the creation of a 10 mm incision and interrupted suture closure of the gastric wall in rats. After two and four days, the stomach was excised and the bursting pressure was determined by gradually inflating the stomach with air. This procedure was followed by histological examinations. RESULTS: The bursting pressure of the surgical wound was significantly higher two days after surgery in the h-LEH-treated rats in comparison to the control rats that received either empty liposome or RBC transfusion (P < 0.05). The three groups displayed similar bursting pressures four days after surgery. Histological examinations revealed less neutrophil infiltration, better granulation, and more macrophage infiltration in the h-LEH-treated rats after two days; however, these differences were no longer significant four days after surgery. CONCLUSION: The results suggest that h-LEH, but not a homologous transfusion or empty liposome, may accelerate early wound healing after a gastric incision and anastomosis in a rat model.

Clinical outcome of jejunal pouch double-tract reconstruction after total gastrectomy.

BACKGROUND/AIMS: The importance of the duodenal passage and the need for pouch reconstruction after total gastrectomy are matters of controversy. METHODOLOGY: Twenty consecutive patients with early gastric cancer were studied 20who underwent jejunal pouch double-tract (JPD) reconstruction after total gastrectomy. Nutritional variables were examined for > or =10 years postoperatively. RESULTS: The mean operation time was 204 minutes. There was no anastomotic leakage and no hospital mortality. Anastomotic stenosis between the esophagus and a jejunal pouch developed in 2 patients (10%), and reflux esophagitis was observed in 4 (20%). Symptoms were controlled by conserva tive treatment within 3 years after surgery. Body mass indices in all patients were significantly decreased from 1 month (p<0.05) to 10 years (p<0.005) after the operation. The mean body weight decrease occurring during the first to the tenth postoperative year was 12.7% overall, but 17.8% and 9.1% in patients aged > or =60 years and <60 years, respectively. The body weight decreases from 3 (p<0.05) to 6 (p<0.01), and at 9 years (p<0.01) were significantly lower before 60 years of age than after. CONCLUSIONS: JPD reconstruction facilitates long-term recovery of body weight after total gastrectomy and should be considered before the aged of 60.

Endoscopy-assisted totally laparoscopic resection of a submucosal tumor of the duodenum.

Although, endoscopic polypectomy is one of the first options for diagnosis and treatment of submucosal tumors of the duodenum, it is sometimes difficult for large or sessile tumors. Therefore, local excision or more extended surgery is performed under open laparotomy. In this paper, we present a laparoscopic resection of Brunner's gland hyperplasia of the duodenum which demonstrated rapid interval size change. A 73-year-old male with a histologically unproven submucosal tumor underwent endoscopy-assisted laparoscopic resection of the tumor and intracorporeal suturing of the defect. Simultaneous duodenoscopy and laparoscopy were performed to identify the line of resection. A duodenotomy was performed and the tumor was excised after everting the tumor toward the abdominal cavity. The defect was handsewn with the greater curvature side rolled caudally with an exteriorized stay suture. Postoperative pain was minimal and the patient quickly returned to normal activity. Our new technique provides a minimal invasive treatment for tumors of the duodenum.

A case of the primary small intestinal cancer which performed operation under laparoscopy after ileus decompression.

The patient was a 66-year-old man with repeated episodes of abdominal pain resulting in a diagnosis of ileus, and he was admitted to this hospital. During hospitalization, the pain symptoms improved after the insertion of an ileus tube, but there was a recurrence of ileus after the patient was started on a liquid diet. An adhesive intestinal obstruction was thus suspected, and laparoscopy was performed. A diagnosis of small intestinal carcinoma was made based on the intraoperative findings. A partial resection of the small bowel and a regional lymphadenectomy were performed through a minor laparotomy. The incidence of primary small intestinal cancer has been relatively rare, and it is difficult to differentiate the disease in most cases. A laparoscopy is considered useful to diagnose and treat ileus after decompression of the intestinal tract, and this article describes the case with some discussion.

Clinical outcome of proximal gastrectomy in patients with early gastric cancer in the upper third of the stomach.

OBJECTIVE: To determine whether clinical outcomes after proximal gastrectomy are better than those after total gastrectomy with Roux-en Y reconstruction. METHODS: We studied 10 consecutive patients with early gastric cancer who underwent esophagogastrostomy after proximal gastrectomy (PG group). Nutritional variables in these patients were compared with those in 10 consecutive patients who underwent Roux-en Y reconstruction after total gastrectomy (TG group). Patients were followed up for 5 years after operation. RESULTS: There was no anastomotic leakage. The total cholesterol level 1 year after operation was higher in the PG group than in the TG group (p< 0.05). Body mass index was significantly lower than the preoperative value between 1 month and 2 years postoperation in the PG group, whereas the TG group showed decreases between 3 months to 5 years postoperation. The percent decreases in body weight at 3 and 4 years in the PG group were lower than those in the TG group (both p< 0.05). Postoperative weight loss was thus milder in the PG group than in the TG group. CONCLUSION: Esophagogastrostomy after PG may produce better clinical outcomes than Roux-en Y reconstruction after TG in patients with early gastric cancer arising in the upper third of the stomach.

Esophagogastrostomy before proximal gastrectomy in patients with early gastric cancers in the upper third of the stomach.

OBJECTIVE: This study was designed to assess the outcome of esophagogastrostomy before proximal gastrectomy in patients with early gastric cancers in the upper third of the stomach. METHODS: From 1997 through 2004, we studied 10 consecutive patients. A stapler was introduced into the stomach, and an esophagogastrostomy was performed before proximal gastrectomy. Hill's posterior gastropexy and Dor's anterior fundic wrap were performed to prevent reflux esophagitis. RESULTS: The operation time was 171 ± 44 minutes, and the intraoperative bleeding volume was 294 ± 228 mL. There was no anastomotic leakage. Anastomotic stenosis, occurring in 40% of the patients, required endoscopic balloon dilatation. Symptoms of reflux esophagitis, occurring in 40% of the patients, resolved within 2 years after operation. As compared with the preoperative value, body mass index was significantly decreased 1 and 2 years after operation, but was similar at 3 to 5 years. The percent decrease in body weight after operation fluctuated between 6% and 8% between 2 and 5 years. Postoperative weight loss was thus mild. CONCLUSIONS: Esophagogastrostomy before proximal gastrectomy may be less invasive, simpler, and produce better outcomes than conventional procedures for the surgical treatment of early gastric cancer in the upper third of the stomach.

Multiple gastric carcinoids associated with hypergastrinemia. A review of five cases with clinicopathological analysis and surgical strategies.

Previously, total gastrectomy was regarded as the treatment for multiple gastric carcinoids because of the unknown biological characteristics of this disease. Recent studies, however, have revealed that type 1 gastric carcinoids have a low potential for malignancy. In this study, five patients with hypergastrinemia and multiple gastric carcinoids, who underwent gastrectomy with regional node dissection, were analyzed. On serum chemistry examinations, the serum gastrin level was found to be high (515.5-over 3000 pg/ml) in all patients pre-operatively, but returned to a normal range (40-50 pg/ml) in all three cases examined post-operatively. Histopathological examination of our five cases revealed multiple gastric tumors, i.e. three to five tumors in Cases 1-4 and numerous tumors in Case 5. The multiple tumors were histologically carcinoid tumors up to 15 mm in size, limited to the submucosa, and no lymph node metastasis was identified in any of the cases. The patients were followed-up at outpatient clinics with no additional adjuvant therapy, and there was no evidence of recurrence during follow-up. Recently, minor invasive surgery such as endoscopic mucosal resection or laparoscopic antrectomy has been performed to treat type 1 gastric carcinoids. Our data provide important insights into understanding the biological behavior of multiple gastric carcinoids.

Focus on the conditions of resection and reconstruction in gastric cancer. What extent of resection and what kind of reconstruction provide the best outcomes for gastric cancer patients?

To assess the roles of the extent of gastric resection and duodenal food passage reconstruction in gastric cancer, we examined a consecutive series of 1,061 patients who underwent total or partial (proximal and distal) gastrectomies with or without duodenal food passage reconstruction between August of 1974 and January of 2002, and received gastrectomies with D2-3 lymph node dissection. Patients who underwent distal or proximal gastrectomy were found to have significantly better survival rates than those who underwent total gastrectomy in stages 1A (10-year survival: 86.6 and 78.9 vs. 61.6%), 2 (56.5 and 65.6 vs. 34.4%), 3A (45.9 and 33.3 vs. 15.2%), and 4 (5-year survival rates: 23.7 and 50.0 vs. 7.1%). Additionally, patients with duodenal food passage reconstruction or double tract reconstruction also showed significantly better survival rates than those without duodenal food reconstruction in stages 1A (10-year survival: 86.4 and 82.5 vs. 61.7%), 1B (69.9 and 90.6 vs. 54.1%), 2 (60.5 and 63.3 vs. 16.5%), and 3A (39.9 and 47.4 vs. 23.1%). In multivariate analysis, the independent prognostic factors were age at operation, depth of tumor, duodenal food passage reconstruction, and lymph node metastasis. Our results indicate that both the extent of gastric resection and duodenal food passage reconstruction were important factors in the outcome of gastric cancer patients, and that surgeons should perform minimal gastric resection with preservation of the duodenal food passage when the gastric stump is tumor-free.

Enhancement of amphotericin B activity against Candida albicans by superoxide radical.

This study aimed to examine the involvement of oxidative damage in amphotericin B (AmB) activity against Candida albicans using the superoxide (O2-) generator paraquat (PQ). The effects of PQ on AmB activities against growth, viability, membrane permeability and respiration were examined in a wild-type parent strain (K) and a respiration-deficient mutant (KRD-19) since PQ-induced superoxide generation depends on respiration. In the parent strain, the minimal inhibitory concentration (MIC) of AmB, 0.25 microg/ml, tested with a liquid culture was lowered to 0.025 microg/ml by 1 mM PQ. Such a PQ-induced decrease in the MIC value of AmB was minimal in the mutant. Similar PQ-induced enhancement of AmB activity toward the parent strain was also observed with growth on an agar medium. In viability tests, when candidal cells were exposed to AmB (0.1 microg/ml) for I h, the lethality of AmB was enhanced by 1 mM PQ only in the parent strain. Exogenous superoxide dismutase and catalase failed to diminish the enhancing effect of PQ on the growth inhibitory activity of AmB in the parent strain, suggesting an interaction between superoxide and AmB in candidal cells. The enhancement of AmB activity by PQ, observed preferentially in the wild-type strain, can be explained by extensive superoxide generation depending on respiration. These results suggest that oxidative damage induced by superoxide is involved in AmB activity against C. albicans.

[A case of advanced gastric cancer with multiple liver metastases responding to TS-1 and CDDP].

A 44-year-old male presented to our hospital with abdominal pain. The upper endoscopy revealed advanced gastric cancer. On the abdominal CT, there was evidence of multiple, massive liver metastases. After total gastrectomy, the patient was treated with daily oral administration of 120 mg TS-1 for 4 weeks followed by 2 weeks' rest and 6 weekly infusions of 10 mg CDDP in an intra-hepatic artery as 1 cycle. On the follow-up CT, the liver metastases had decreased significantly both in size and number after 2 cycles. The current case suggests that TS-1 and CDDP may have a potent therapeutic efficacy in cases of advanced gastric cancer with multiple liver metastases.

Sentinel lymph node detection with Tc-99m tin colloids in patients with esophagogastric cancer.

BACKGROUND: The aim of this study was to determine by radioisotope use whether the sentinel lymph node concept is applicable to esophagogastric cancers. In addition, we examined radioactivities of hot nodes and compared them with the sensitivity of a gamma probe. METHODS: The subjects were 44 patients, 23 with esophageal cancer and 21 with gastric cancer. The day before surgery, patients underwent endoscopic submucosal injection of 184 MBq of Tc-99m tin colloids into sites surrounding the tumor. Radioisotope activities of lymph nodes dissected at surgery were measured with a well-typed gamma detector and each lymph node was categorized as a hot or cold node. Histopathology of the lymph nodes was examined by hematoxylin and eosin staining. Radioisotope activities and histopathological results were compared to determine whether radioisotope flow reflects lymphatic flow to regional lymph nodes. The sensitivity of a gamma probe was measured in a laboratory study and the relation between the radioisotope activities of hot nodes and the detection sensitivity of the gamma probe was examined. RESULTS: Histopathological examination revealed lymph node metastasis in 18 of the 44 patients. In 15 of these 18 patients, metastatic foci were recognized in at least one hot node. Subsequent analysis was performed on the 36 patients in whom tumor invasion was confined to the muscle layer and in whom endoscopic clippings had not been applied. Lymph node metastases were observed in 12 of these 36 patients. In these 12 patients, at least one hot node was positive for metastasis. The laboratory study revealed that the gamma probe was able to detect radioisotope activities of >/=0.02 micro Ci. Thirty-two of 63 (51%) esophageal cancer hot nodes and 16 of 86 (19%) gastric cancer hot nodes showed radioisotope activities below the detection sensitivity of the gamma probe. CONCLUSION: The sentinel lymph node concept is applicable to patients with esophageal and gastric cancers; however, further studies are necessary to identify hot nodes accurately using gamma probes.