Katsuyoshi Tabuse

Laparoscopic resection for gastrointestinal stromal tumors of the stomach.

BACKGROUND We reviewed our experience with primary gastrointestinal tumors (GISTs) after surgical treatment. METHODS Between 1998 and 2003, 56 patients who underwent surgical treatment for primary GIST of the stomach were enrolled in this study. Statistical analyses of the risk factors for recurrence were assessed. RESULTS The proportion of cases undergoing laparoscopic surgery was 25 of 56 (44%) in these retrospective data. The site of recurrence was only the liver in all cases. These recurrent cases were defined as high-risk category. Tumors measuring over 2 cm in size tended to recur earlier, namely within 32 months. A statistical analysis showed a statistically significant correlation between the disease progression and the pathological phenotype. CONCLUSIONS This retrospective study has shown that an initial laparoscopic resection of gastric GISTs is feasible even when the tumor size is relatively small (2-5 cm). The pathological phenotype (especially tumor mitosis) directly correlates to the patients survival even if the resected tumor size was relatively small.

A Wound Protector Shields Incision Sites from Bacterial Invasion

BACKGROUND Superficial surgical site infection (SSI) can be caused by bacterial invasion during surgery. We investigated whether bacteria are found at the wound margin during surgery and whether a wound protector (WP; Alexis® Wound Retractor; Applied Medical, Rancho Santa Margarita, CA) contributes to preventing invasion of the incision margin. METHODS We studied 272 patients who underwent gastrointestinal surgery (115 gastric, 157 colorectal, including emergency operations) between October 2005 and July 2007. The WP was used in all operations. After the intra-abdominal procedures were complete, bacterial swabs were taken from the abdominal cavity side of the WP and from the incision margin and used to prepare smears and cultures. After the swabbing, peritoneal lavage was performed using 3,000-5,000 mL of physiologic saline, and, after suture of the fascia, 500-1,000 mL of physiologic saline was used to irrigate the subcutaneous tissue. RESULTS Nine gastric surgery patients and 15 colorectal surgery patients had positive cultures from the abdominal cavity. No patients had positive cultures from the incision margin. Of the 24 patients with positive cultures, three suffered SSIs, all of whom had undergone colorectal surgery. Of the patients who had negative cultures, SSI occurred in only one patient, who had undergone colorectal surgery. CONCLUSIONS These results suggest that the WP protects an incision site from bacterial invasion.

The ratio between metastatic and examined lymph nodes is an independent prognostic factor for patients with resectable middle and distal bile duct carcinoma

BACKGROUND The lymph node ratio, defined as the ratio between the number of lymph node metastasis and the total number of lymph nodes examined, has been reported to be an important prognostic factor in other gastrointestinal carcinomas except middle and distal bile duct carcinomas. METHODS Between 1991 and 2004, 62 consecutive patients who underwent surgery for middle and distal bile duct carcinoma were retrospectively analyzed concerning prognostic factors. RESULTS The median number of lymph nodes examined was 12 (range 5 to 38). The overall 5-year survival rates of patients with lymph node ratio of 0, lymph node ratio of 0 to .2, and lymph node ratio >.2 were 62%, 41%, and 0%, respectively. A multivariate analysis revealed that a lymph node ratio >.2 and perineural invasion were independent predictive factors for survival. CONCLUSIONS Lymph node ratio >.2 is an important factor to predict survival after resected middle and distal bile duct carcinoma.

Assessment of liver function for successful hepatectomy in patients with hepatocellular carcinoma with impaired hepatic function

BACKGROUND/PURPOSE This study aimed to construct a formula for assessing liver function in order to prevent post-hepatectomy liver failure. METHODS A formula was constructed by analyzing data from 28 patients with hepatocellular carcinoma (HCC) with liver cirrhosis operated on between 1981 and 1984. Next, we evaluated the validity of this formula in 207 hepatectomy patients operated on from 1985 to 1999. For 145 hepatectomy patients operated on from 2000 to 2006, this formula was calculated before surgery in order to assess their risk of hepatectomy. RESULTS The formula for liver functional evaluation, constructed from preoperative hepatic function parameters, was: liver failure score = 164.8 - 0.58 x Alb - 1.07 x HPT + 0.062 x GOT - 685 x K. ICG - 3.57 x OGTT. LI + 0.074 x RW, where Alb is albumin (g/dl); HPT, hepaplastin test (%); GOT, glutamate oxaloacetate transaminase (U/l); K. ICG, K value of indocyanine green clearance test; OGTT. LI, 60-min/120-min glucose level in 75-g oral glucose tolerance test. linearity index of OGTT; and RW, weight of resected liver (g). We decided that a score below 25 would be safe for hepatectomy. CONCLUSIONS The mortality rate decreased from 3.9% in 1985--1999 to 1.3% in 2000--2006. This finding allows us to conclude that the formula is valid for assessing the risk of post-hepatectomy liver failure.

Role of interleukin-2 and interferon-γ in induction of activated natural killer cells from mice primed in vivo and subsequently challenged in vitro with the streptococcal preparation OK432

SummaryThe natural-killer(NK)-cell-mediated cytotoxicity to syngeneic tumor cells can be augmented by in vivo priming and subsequent in vitro challenge with the streptococcal preparation OK432. Supernatants of cocultures of spleen cells with OK432 contained interleukin-2 (IL-2) and interferon (IFN), mainly IFN-γ. As the anti-(mouse IFN-γ) monoclonal antibody but not anti-(mouse IFN-α) antibody inhibited the induction of activated NK cells with OK432, the IFN-γ participated in this response. The enhancement of NK cell activity and production of IL-2 were partially inhibited by the pretreatment of spleen cells with mitomycin C or irradiation, and were completely abolished by pretreatment with actinomycin D. The IL-2 activity after treatment with various metabolic inhibitors ran parallel to the NK activity in a system augmented with OK432. The activity of incubated spleen cells with IL-2 receptors was increased by OK432 treatment, and the NK cell and IFN activities of supernatants were also abrogated by the treatment with anti-(mouse IL-2 receptor) monoclonal antibody, to block the interaction between IL-2 and these receptors of effector cells. The panning method clarified that the incubated spleen cells with IL-2 receptors are responsible for the production of IFN-γ. These results suggest that IL-2 plays a major role in inducing the activated NK cells from murine spleen cells primed in vivo and subsequently challenged in vitro with OK432, by the production of IFN-γ.

Microwave cell death: Enzyme histochemical evaluation for metastatic carcinoma of the liver

We have reported that microwave cell death is a unique cell death preserving not only cell and nuclear shapes but also immunohistochemical antigenicity. However, their enzyme activity was lost, which indicated cell dysfunction and death. This peculiar observation implies that the microwave effect is likely an ‘in situ’ tissue fixation and that this type of cell death is morphologically different from cell death, by either oncosis or apoptosis, as previously known. To confirm whether this peculiar cell death was observed also in human tissue samples, we examined clinical samples from patients with metastatic liver cancer, which were treated with microwave irradiation. They were examined immunohistochemically for human Ki‐67 antigen and proliferating cell nuclear antigen and enzyme histochemically for alkaline phosphatase, and the same morphological changes that were observed in microwave‐treated rat liver were found. In conclusion, we believe that routine hematoxylin‐eosin stain alone is not a suitable method to evaluate microwave treatment for cancer because microwave coagulation therapy‐treated cells preserved their nuclei and cellular architectures, even after 3 months. For microwave‐treated tumors, enzyme histochemistry is helpful to determine its effectiveness.

Impact of lymph node metastasis on survival in patients with pathological T1 carcinoma of the ampulla of vater

To determine the prognostic factors for patients with pathological T1 (pT1) carcinoma of the ampulla of Vater, 36 consecutive patients with carcinoma of the ampulla of Vater who underwent surgery were retrospectively analyzed in terms of clinicopathological features. The overall 5-year Kaplan-Meier survival in all patients was 50.2%, and the median survival of all patients was 64.0 months. Factors favorably influencing a long-term outcome were the absence of lymph node metastasis (P<0.0001), the absence of ulcer formation of the tumor (P=0.0062), and the absence of tumor invasion into the duodenum (P = 0.0025) and the pancreas (P=0.0098). In a multivariate analysis, lymph node metastasis was the only predictor of survival (P=0.0023). In the pT1 stage patients, 20% of the patients had lymph node metastasis, and their survival was statistically poor compared to the pT1 patients without lymph node metastasis (P=0.017). As for survival after the operation, there was no significant difference between pancreatoduodenectomy and pylorus-preserving pancreatoduodenectomy.

Microwave cell death: Immunohistochemical and enzyme histochemical evaluation

In Japan, microwave coagulation therapy (MCT) has been used for the management of primary and metastatic liver cancer. Needle biopsy examination from the lesion has frequently shown the presence of nucleated cancer cells in histopathological examinations, prompting the conclusion that cancer cells are not completely eliminated by microwave therapy, whereas computed tomography and ultrasonography examinations show tumor regression. To determine whether microwave‐treated tissue contains functionally viable cells, an examination of the Na+‐K+‐ATPase protein and its activity using immunohistochemical and enzyme histochemical methods were carried out in microwave‐treated rat liver. Four concentric, morphologically identifiable zones around the microwave probe needle appeared 2 days after treatment. Zone A, which was between the innermost spongy zone and the outer necrotic zone, contained only slight morphological alterations in the hepatocytes, which had slightly hyperchromatic nuclei and mildly eosinophilic cytoplasm. The hepatocytes in zone A were found to be positive for the Na+‐K+‐ATPase antigenicity but negative for enzyme activity, indicating that zone A was undergoing cell death, although morphologically this was not discernible. This type of cell death caused by microwave treatment is morphologically different from previously known types of cell death, either oncosis or apoptosis.

Clinical impact of a macroscopically complete resection of colorectal cancer with peritoneal carcinomatosis

BACKGROUND So far, few reports have focused on the clinicopathological features and patterns of recurrence after a complete resection of peritoneal carcinomatosis (PC) of colorectal origin. The purpose of the present study was to show the clinicopathological features of a macroscopically complete resected tumor and the pattern of recurrence after the curative resection of colorectal PC. METHODS In 153 patients with colorectal PC, 31 patients who underwent a complete resection of a synchronous primary lesion of a colorectal PC between 1998 and 2007 were assessed retrospectively. RESULTS Clinicopathological differences were observed in the tumor location, presence of extraperitoneal metastases, extent of PC, and presence of lymph node metastases between a macroscopically complete resection and noncomplete resection patients (P = .045, P < .0001, P < .001, and P = .039, respectively). Tumor recurrence after the complete resection of colorectal PC was observed in 24 patients (77.4%). The 5-year survival rate after complete resection was 36.0%. The survival rate in the macroscopically complete resection group was higher than in the incomplete resection group (P < .001). The 5-year intra- and extraperitoneal recurrence survival rates were 63.9% and 33.8%, respectively. No significant clinicopathological factors affected intraperitoneal recurrence-free survival. Conversely, a univariate analysis using the log-rank test revealed that extended PC and presence of lymph node metastases were poor factors affecting extraperitoneal recurrence (P = .009 and P = .023, respectively). Eleven of 31 patients survived for 5 years after resection. Two of the 4 patients with liver metastases had received a hepatectomy. CONCLUSION Although the 5-year survival rate after a macroscopically complete resection for colorectal PC approached 36.0%, 77.4% of patients developed intra- and extraperitoneal recurrence. Extended PC and presence of lymph node metastases were poor factors affecting extraperitoneal recurrence.

Induction of activated natural killer cells from murine spleen cells primed in vivo and subsequently challenged in vitro with the streptococcal preparation OK432.

SummaryThe present study shows that natural killer cell-mediated cytotoxicity of BALB/c mouse spleen cells to syngeneic tumor cells was augmented by in vivo priming or in vitro stimulation with the streptococcal preparation OK432. The augmentation of spleen cell cytotoxicity to syngeneic tumor cells by in vivo priming alone with OK432 was lower than that obtained by in vitro stimulation alone with OK432. When the murine spleen cells primed in vivo with OK432 were rechallenged in vitro with OK432 at various intervals, the natural cytotoxicity was more strongly enhanced than that seen with in vitro stimulation alone. The cell surface phenotype of killer cells activated with OK432 was Thy 1+ and asialo GMinf1sup+, suggesting the activated natural killer cell. Next, mice were transplanted with syngeneic colon adenocarcinoma cells, and primed in vivo with OK432. These spleen cells were subsequently challenged in vitro with OK432. These spleen cells displayed a strong cytotoxic activity not only to the transplanted adenocarcinoma cells but also to other syngeneic tumor cells.