Novel surgical repair with bilateral gluteus muscle patching for intractable rectovaginal fistula.

We created a novel surgical repair for intractable rectovaginal fistula and treated four patients who had previously undergone unsuccessful surgery. An X-shaped skin incision was made on the perineum, and then the rectum was carefully divided from the vagina. Defects of both the rectum and the vagina were closed with vertical mattress sutures. The external sphincter muscle also was approximated. The gluteus muscle was identified through another skin incision to the buttock, and cut at the attachment to the femur. Bilateral gluteus muscles were approximated at the midline of the perineum so that the vagina was sufficiently separated from the rectum. Established anorectal angle was 92.5 degrees (SD=6.4 degrees ). Mean resting pressure was 101.3 cm H2O (SD=13.1). All patients retained complete anal function without soiling. The unusual problem of erosion of the posterior vaginal wall with fistulation in a sexually active woman justifies greater efforts, and this surgical technique offers good prospects in this small group of patients.

TI-201 SPECT compared with histopathologic grade in the prognostic assessment of cerebral gliomas.

PURPOSE: Although TI-201 SPECT has been used to evaluate the malignant grade of cerebral gliomas, the gold standard continues to be histopathologic examination. The authors assessed and compared the prognostic abilities of the two studies using survival analysis. MATERIALS AND METHODS: Twenty-nine patients underwent 34 sessions of TI-201 SPECT plus surgery for primary or recurrent cerebral gliomas 12 to 78 months before this analysis. Using conventional survival analyses, such as the log-rank test, Cox regression, and the Akaike cross-tab method, the authors evaluated the prognostic significance of 10 variables: histopathologic grade, TI-201 SPECT, Tc-99m HMPAO SPECT, tumor cell viability, radionecrosis, neurologic defects, clinical improvement, surgery, chemotherapy, and external beam radiotherapy. RESULTS: TI-201 SPECT was most strongly related to prognosis, followed by histopathologic grade. The other variables had little prognostic value. The Cox stepwise selection procedure indicated that TI-201 SPECT was the only independent predictor of outcome, whereas histopathologic analysis was eliminated from the prognostic model. However, the Kaplan-Meier survival curve and the Akaike method indicated that histopathologically low-grade tumors were more closely associated with longer-term survival than were TI-201 low uptake tumors. CONCLUSIONS: TI-201 SPECT is not only closely correlated with the histopathologic grade of tumor but is a significantly better predictor of outcome than histopathologic grade. However, histopathologic examination may provide additional information on longer-term survival. TI-201 SPECT is a valuable procedure, especially in patients in whom a histologic diagnosis of possible glioma cannot be made.

Novel control system for blood glucose using a model predictive method.

We developed a novel blood glucose control system, using a model predictive method, to achieve optimal control of the blood glucose level in severely diabetic or pancreatectomized patients. This system is designed to predict glucose level changes in advance, considering delayed response time and the administered doses of insulin. This method is also designed to calculate the most appropriate insulin infusion rate by considering differences in individual response to insulin. In this study, we compared our system with a conventional proportional and differential controller (PD controller) to determine whether the new system could regulate the glucose level efficiently in pancreatectomized dogs. The model predictive control method resulted in a significant reduction of mean insulin infusion rate compared with the conventional PD controller (0.71 mU/kg per min vs. 1.81 mU/kg per min, p = 0.0005), when the glucose level in both methods reached the planned target level (100 mg/dl). The new system also tended to have a reduced mean glucose infusion rate for compensating for overshooting of the glucose level compared with the PD controller (0.7 mg/kg per min vs. 1.1 mg/kg per min, p = 0.16). These results indicate that the new system should be a useful tool for regulating the glucose level in severely diabetic patients.

Pathologic significance of tumor progression in locally recurrent rectal cancer: different nature from primary cancer.

PURPOSE: It has recently been demonstrated that the tumor growth rate is a stronger determinant of survival than the extent of the growth in local recurrence of rectal cancer. We studied which factors controlled the tumor growth rate using modern immunohistochemical methods. METHODS: In 51 patients who underwent extended resection for this condition, paraffin-embedded specimens were examined for 1) tumor angiogenesis by CD31 staining and microvessel counting, 2) apoptosis by terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling staining, and 3) cellular proliferative activity using anti-proliferative cell nuclear antigen antibody. The results were compared with carcinoembryonic antigen doubling time and survival. RESULTS: The five-year survival rate was 20 percent. The postoperative carcinoembryonic antigen doubling time, which was the strongest predictor of survival, correlated highly with proliferative cell nuclear antigen labeling index, but did not correlate with the apoptotic index or microvessel counts. CONCLUSION: Our study shows that cancer cell proliferation rather than apoptosis or angiogenesis is a major determinant of tumor growth rate and survival in patients with locally recurrent rectal cancer.

Clinical application of a blood pressure autoregulation system during hypotensive anesthesia.

A blood pressure autoregulation system based on the state-predictive control method was developed to minimize intraoperative blood loss and hence avoid blood transfusion. In this report, the system is further improved by incorporating fuzzy logic with a fail-safe function and an individual parameter-identifying function. The safety and stability of this system had been confirmed by preclinical experiments with dogs. Thereafter clinical application with 17 patients was conducted to maintain their mean arterial pressure at around 60 mmHg during major surgery. The use of this system resulted in decreased blood loss and more speedy and accurate surgery due to a clearer surgical field. Unwanted effects of hypotension were not observed clinically or in laboratory tests. This system is therefore safe, stable, and effective in reducing the blood loss during major surgery that otherwise might cause substantial blood loss.

Correlation of tensile strength with bursting pressure in the evaluation of intestinal anastomosis.

BACKGROUND: Although bursting pressure and tensile strength have long been measured to evaluate anastomotic techniques, it has yet to be clarified whether or not they are correlated, what implications they have, and which should be used as a gold standard. MATERIAL AND METHODS: Using an experimental model to estimate pressure and tension in the same colonic anastomosis, the following variables were measured in 48 rats between days 0 and 14: bursting pressure (BP); minimal tensile strength (MITS) necessary to break a part of the anastomosis, and maximal tensile strength (MATS) needed to disrupt the whole anastomosis. Also, circulatory wall tension (CWT) was derived from BP and the anastomotic circumference (AC), and longitudinal wall tension (LWT) from MITS and AC. These variables were compared using correlation and regression analysis. RESULTS: During the lag phase (days < or = 4) there was poor correlation between pressure-related and tension-related variables whereas highly significant correlations were noted in the subsequent fibroplastic phase (day > or = 5). It was shown by regression lines that positive MITS and MATS were expected when BP was zero. CONCLUSION: Contrary to the previous assumption, no correlation was found between BP and tensile strength in the critical postoperative period. Based on our present and previous studies, measurement of MITS is recommended to evaluate the healing of colonic anastomosis.

Significance of local recurrence of rectal cancer as a local or disseminated disease.

BACKGROUND: The nature of 'local recurrence' of rectal cancer remains unclear. METHODS: Fifty-nine patients with locally recurrent rectal cancer who underwent extended repeat resections including total pelvic exenteration (39) and sacrectomy (43) were reviewed. Twelve patients had distant metastases before or at the time of repeat resection. RESULTS: The 5-year survival rate was 25 per cent. A second recurrence occurred in 45 patients including five of the eight 5-year survivors. Thirty-six of these recurrences had locoregional manifestations and 29 had distant metastases. Of 18 prognostic factors examined, the most significant determinant was the postoperative carcinoembryonic antigen doubling time (CEADT), followed by the preoperative CEADT, carcinoembryonic antigen (CEA) level and occurrence of distant metastases, in decreasing order. Late onset of first recurrence was also a favourable indicator. Thus, the growth rate of the tumour had a more profound impact on survival than the current extent of tumour progression. After operation the CEADT was reduced in patients with second recurrence (P = 0.05). CONCLUSION: Locally recurrent rectal cancer is a manifestation of disseminated disease spreading locoregionally and often to distant organs with a low probability of long-term cure. However, survival varies widely depending on the tumour growth rate, which is biologically predetermined and is also influenced by surgery.

Cytokeratin 20 mRNA in peripheral venous blood of colorectal carcinoma patients.

A highly sensitive system was previously developed by us to detect the presence of colorectal carcinoma cells in blood in the form of cytokeratin 20 (CK20) mRNA. In the present study, we used an improved version of this system to analyse the peripheral blood of 28 patients with colorectal carcinoma, five patients with non-cancerous intestinal diseases and six normal controls for the presence or absence of CK20 mRNA and to investigate the relationship between the mRNA results and prognosis. All eight patients with recurrence were positive for CK20 mRNA, as were four patients in the Dukes' C stage with either distant metastasis or dissemination. Five of the nine patients in the Dukes' C stage with neither distant metastasis nor dissemination were positive, and three of these developed recurrence within 11 months after the analysis. Only one of the seven patients in the Dukes' A or B stage was positive, and none showed recurrence during the 1-19 months of observation. None of the five patients without carcinomas or of the six normal controls was positive. Although the follow-up period is limited and the recurrences were all local at present, these results suggest that the presence of CK20 mRNA in circulation may be a useful indicator for the screening of advanced colorectal carcinoma patients with a high risk of recurrence.

Expression of insulin-like growth factor-2 can predict the prognosis of human colorectal cancer patients: correlation with tumor progression, proliferative activity and survival.

Expression of insulin-like growth factor-2 (IGF-2) has been reported in tissue specimens and cell lines of human colorectal cancers. However, the effects of IGF-2 in colorectal cancer patients are not well known. In this study, IGF-2 staining was performed on tissue samples from 92 patients with colorectal cancer, and the relationship of IGF-2 staining to clinicopathological variables, proliferating cell nuclear antigen (PCNA) staining and patient survival was analyzed. IGF-2 staining was correlated with tumor progression, PCNA staining and patient survival. Our results suggest that IGF-2 plays an important role in tumor progression and that IGF-2 staining is useful as a prognostic factor in colorectal cancer patients.

Small intestinal cancer with extensive lymph node metastases showing complete remission by methotrexate/5-fluorouracil sequential therapy: report of a case.

A case of poorly differentiated adenocarcinoma of the small bowel with extensive lymph node metastases is herein presented, which responded to methotrexate/5-fluorouracil (MTX/5-FU) sequential therapy. The lymph node metastases disappeared completely after 10 months of treatment. After recurrence, combination therapy with radiation, hyperthermia, and cisplatinum were also effective in reducing the degree of nodal swelling while still allowing the patient to maintain her accustomed lifestyle for a prolonged period of time. Further multi-institutional studies are still needed, however, to fully assess this new therapeutic regimen for small bowel cancers.

A newly developed three-layer agarose microcapsule for a promising biohybrid artificial pancreas: rat to mouse xenotransplantation.

We examined the effectiveness of an improved version of a three-layer agarose microcapsule in islet xenotransplantation. The microcapsule is composed of a mixture of 5% agarose and 5% polystyrene sulfonic acid. The other two outer layers are polybrene and carboxymethyl cellulose. The agarose/polystyrene sulfonic acid membrane is for the purpose of immunoisolation, suppression of complement activity and reinforcement of the microcapsule. The polybrene layer suppresses the polystyrene sulfonic acid leakage by forming a polyionic complex at the surface of the agarose/polystyrene sulfonic acid membrane. The outermost layer, a carboxymethyl cellulose coating, improves the biocompatibility of the microcapsule. In vitro static incubation study showed that the insulin secretion from rat islets in microcapsules in response to 16.7 mM glucose stimulation was more than four times higher than that on 3.3 mM glucose stimulation (n = 8). In an in vivo study, 500 rat islets in microcapsules were xenogenically implanted in the abdominal cavity of mice with streptozotocin-induced diabetes. The graft survival times ranged from 2 to 5 mo, the average being 75 days (n = 5). Our results demonstrate that the improved version of the three-layer agarose microcapsule can effectively prolong the xenograft survival time without employing immunosuppressants, suggesting that this microcapsule could provide a promising biohybrid artificial pancreas for future clinical applications.

Application of a novel B cell line MIN6 to a mesh-reinforced polyvinyl alcohol hydrogel tube and three-layer agarose microcapsules: an in vitro study.

This study examines the function of a novel B cell line (MIN6) enclosed in hybrid bioartificial pancreas with mesh-reinforced polyvinyl alcohol hydrogel tube (MRPT) or with improved, three-layer agarose microcapsules. MIN6 was established from insulinomas obtained by targeted expression of the simian virus 40 T-antigen gene in transgenic mice. MIN6 retains the ability to secrete insulin in response to physiological glucose concentrations. The MRPT and the three-layer agarose microcapsules, which were developed to act as an artificial pancreas, were readily permeated by insulin, glucose, and other nutrients. Both can immunoisolate enclosed MIN6 cells from the recipient's humoral and cellular immunosystems, which causes a xenogeneic rejection response. MIN6 cells (5.0 x 10(6) or 1.5 x 10(6)) were enclosed in MRPT or in a hundred three-layer microcapsules and subjected to an in vitro perifusion study or a static incubation study to observe the insulin release from each bioartificial pancreas in response to glucose stimulation. In vitro study revealed that the insulin secretion in response to 16.7 mM glucose stimulation was twice that with 3.3 mM glucose stimulation with both MRPT and the three-layer agarose microcapsules. The present study demonstrates that MIN6 effectively functions as a bioreactor for the hybrid bioartificial pancreas. The application of MIN6 cells to the hybrid bioartificial pancreas may offer a solution to the current serious dearth of organs.

Association between preoperative plasma CEA levels and the prognosis of gastric cancer following curative resection. Tumor Marker Committee, Japanese Foundation for Multidisciplinary Treatment of Cancer, Tokyo, Japan.

A large-scale retrospective study was undertaken to evaluate the association between preoperative plasma carcinoembryonic antigen (CEA) levels and the prognosis of 2768 gastric cancer patients who underwent curative gastrectomy between 1983 and 1984 at 66 leading medical institutions in Japan Postoperative follow-up was at least 5 years. Preoperative plasma CEA levels were also analysed against other prognostic factors. Preoperative plasma CEA levels showed strong correlations to the degree of lymph node metastasis (P < 0.001), TNM stage (P = 0.004) and the histopathology of the gastric cancer (P < 0.001). Preoperative CEA levels were also evaluated against survival, after being adjusted for the effect of clinically important factors by multivariate analysis. Patients with lower preoperative plasma CEA levels survived significantly longer than patients with higher CEA levels (P = 0.0001). This analysis demonstrates that curatively resected gastric cancer patients with higher preoperative plasma CEA levels have a poorer prognosis than those with lower levels, despite the adjustment for the effects of major prognostic factors.

Blood pressure control during surgical operations.

In order to reduce intraoperative blood loss and spare blood transfusion, we developed a blood pressure control system using a state-predictive controller. Using adult mongrel dogs, the mean arterial pressure (MAP) was recorded from a femoral artery while trimethaphan camsilate was infused at constant rates. A pure delay plus a first-order delay model was then derived from the dose-response curves and the values of plant parameters (gain, time-constant, dead-time, and so on) were estimated based on the experimental data. For this model, a state-predictive servo system was designed to cope with the pure delay existing in the model, and simulated. In order to evaluate the accuracy and reliability of this system, we experimented on dogs. With a reference MAP set at 60 mmHg, the MAP reached the reference level in 5.8 to 26.5 min. The duration of error from the reference MAP (+/- 10%) was 2.3 +/- 3.9 min/h (n = 7). These results indicated the safety and stability of our system.

[Effect of systemic calcium antagonist on a model of ocular circulation disturbance induced by endothelin-1].

We studied the effect of generally applied calcium antagonist on endothelin (ET-1) treated rabbit eyes. Nicardipine (20 micrograms/kg) was injected intravenously 15 minutes before intravitreal injection of 10 microliters of ET-1 at 10(-6) M. We measured the relative caliber of the retinal artery (the caliber of the retinal artery at the edge of the optic nerve head (ONH)/that of ONH), the capillary blood flow in ONH, visual evoked potential (VEP), intraocular pressure (IOP), and blood pressure (BP). In the control group (0.4 ml/kg of saline), administration of ET-1 caused contraction of the retinal artery, decrease of the capillary blood flow in ONH, prolongation of the VEP latency, and reduction of IOP. But these effects were significantly reduced in the calcium antagonist group. These results showed that generally applied calcium antagonist inhibits the disturbance of ocular circulation induced by ET-1. However, it also caused significant reduction of BP until 45 minutes after application, so we will have to work to find the optimum dose of calcium antagonist.

Long-term outcome for 120 Japanese patients with Takayasu's disease. Clinical and statistical analyses of related prognostic factors.

BACKGROUND: Patients with Takayasu's disease, a chronic inflammatory arteriopathy of unknown cause, have variable clinical courses, and predictors of the long-term outcome are not well understood. We studied prognostic factors of this disease, based on follow-up results, and a new prognostic classification was proposed. METHODS AND RESULTS: Life-table methods and Cox regression analyses were applied to clinical data on 120 patients who had been prospectively followed for a median of 13 years (range, 1 month to 34 years). The overall survival rate at 15 years after the diagnosis was 82.9% and remained the same for the remainder of the follow-up period. Univariate Cox analyses revealed that of the six dichotomous variables evaluated at diagnosis, four were statistically significant predictors, including complications (Takayasu's retinopathy, hypertension, aortic regurgitation, and aneurysm), pattern of the past clinical course, age of the patient, and calendar year of diagnosis. Thus, the 15-year survival was 66.3% versus 96.4% for patients with and without a major complication, 67.9% versus 92.9% for patients with and without a progressive course, 58.3% versus 92.7% for age > 35 years and < or = 35 years, and 79.9% versus 96.5% for patients diagnosed in 1957 through 1975 and in 1976 through 1990, respectively. The delay in diagnosis and the erythrocyte sedimentation rate (ESR) were of marginal significance. The multivariate Cox analysis showed that only two of the above variables were statistically independent predictors, ie, the major complication and the progressive course. In addition to these two factors, ESR was the third predictor, if the Cox stepwise elimination procedure was performed. These three predictors used in various combinations made a total of 1822 classifications theoretically feasible. Of these, a three-stage classification was selected as the best one, based on the Akaike information criterion. The presence of both major complication and progressive course (stage 3) was the worst prognostic indicator (43% survival at 15 years). In contrast, no patient died who had neither of these manifestations or who had a progressive course but an elevated ESR as well (stage 1). CONCLUSIONS: The long-term outcome for patients with Takayasu's disease seems best predicted by two major prognostic factors, ie, complications and the pattern of the past clinical course, as well as by ESR. Aggressive medical and surgical treatment may be considered for patients with a major complication and a progressive course (stage 3).

[Posterior proctomucosectomy and ileal pull-through reconstruction: a new restorative procedure after total proctocolectomy].

We reported a new method of restorative proctocolectomy using posterior approach and pull-through reconstruction. This method obviated transanal manipulation, a major factor causing damage to the internal sphincter, thus preventing fecal incontinence due to sphincter dysfunction. Also, temporary ileostomy was not necessary because the spout of an S-pouch was pulled down below the anal verge and its distal free end acted as a diverting stoma while the more proximal, healing zone (future anastomotic line) was kept from fecal contamination. This method was applied to a 32-year-old woman with familial polyposis coli and a 50-year-old woman with ulcerative colitis. Their bowel movements steadily decreased to three times and five times a day, respectively. There was no fecal leakage or perianal excoriation. The advantages as well as disadvantages of this method compared with the conventional techniques were discussed.

[A case of a huge malignant lymphoma in the lesser omentum showing a long-term survival after combined treatment of surgery and VEP-THP chemotherapy].

A 33-year-old house wife with malignant lymphoma in the lesser omentum was treated with a combination of surgery and VEP-THP chemotherapy (consisting of pirarubicin, cyclophosphamide, fildesin and predonine). Complete remission has been observed by reduction surgery and subsequent chemotherapy of VEP-THP. Although mild bone marrow suppression was seen during the chemotherapy, gastrointestinal toxicity and alopecia were minimal, which led to 10 complete courses of VEP-THP regimen. The patient has been in good health 5 years after the operation with no sign of recurrence. This case indicates that even advanced malignant lymphoma may be successfully treated with a combination of surgery and proper chemotherapy.