A novel triple secured technique for pancreatic reconstruction following pancreaticoduodenectomy for a soft pancreas.

BACKGROUND/AIMS: Soft pancreases are susceptible to developing pancreatic fistula following pancreaticoduodenectomy. To reduce the incidence of pancreatic fistula after pancreaticoduodenectomy in patients with a soft pancreas, we developed a triple secured technique. In this study, we describe the details of this technique and also report on the postoperative outcomes. METHODOLOGY: The triple secured technique employed an ultrasonic dissector for pancreatic transection with skeletonizing and ligating of the small pancreatic branch ducts, duct-invagination or duct-to-mucosa anastomosis for main pancreatic duct management, and, finally, four large stitches between the pancreatic stump parenchyma and the jejunal seromuscular layer to prevent minor pancreatic leakage. A total of 28 consecutive patients with a soft pancreas who underwent pancreaticoduodenectomy using our technique were included in this study. RESULTS: Postopetrative complications occurred in 16 patients. Grade B pancreatic fistula developed in 6 patients. However, no grade C pancreatic fistula occurred in this series. Neither any reoperation nor in-hospital mortality was observed in this series. CONCLUSIONS: Our triple secured technique after pancreaticoduodenectomy was feasible and safe, with an acceptable rate of grade B pancreatic fistula and no grade C pancreatic fistula for patients with a soft pancreas.

Prolonged recurrence-free survival following OK432-stimulated dendritic cell transfer into hepatocellular carcinoma during transarterial embolization.

Despite curative locoregional treatments for hepatocellular carcinoma (HCC), tumour recurrence rates remain high. The current study was designed to assess the safety and bioactivity of infusion of dendritic cells (DCs) stimulated with OK432, a streptococcus-derived anti-cancer immunotherapeutic agent, into tumour tissues following transcatheter hepatic arterial embolization (TAE) treatment in patients with HCC. DCs were derived from peripheral blood monocytes of patients with hepatitis C virus-related cirrhosis and HCC in the presence of interleukin (IL)-4 and granulocyte-macrophage colony-stimulating factor and stimulated with 0·1 KE/ml OK432 for 2 days. Thirteen patients were administered with 5 × 106 of DCs through arterial catheter during the procedures of TAE treatment on day 7. The immunomodulatory effects and clinical responses were evaluated in comparison with a group of 22 historical controls treated with TAE but without DC transfer. OK432 stimulation of immature DCs promoted their maturation towards cells with activated phenotypes, high expression of a homing receptor, fairly well-preserved phagocytic capacity, greatly enhanced cytokine production and effective tumoricidal activity. Administration of OK432-stimulated DCs to patients was found to be feasible and safe. Kaplan-Meier analysis revealed prolonged recurrence-free survival of patients treated in this manner compared with the historical controls (P = 0·046, log-rank test). The bioactivity of the transferred DCs was reflected in higher serum concentrations of the cytokines IL-9, IL-15 and tumour necrosis factor-α and the chemokines CCL4 and CCL11. Collectively, this study suggests that a DC-based, active immunotherapeutic strategy in combination with locoregional treatments exerts beneficial anti-tumour effects against liver cancer.

Augmentation of tissue ATP level during digestion using preoxygenated perfluorocarbon results in high islet yield-new strategy for islet isolation.

BACKGROUND: Recently, preservation using oxygenated perfluorocarbon (the two-layer method) has shown beneficial effects on islet yield and viability. In this paper, we apply this concept on isolation processes to examine the effectiveness of oxygenation. METHODS: Rat pancreata were digested using four different methods: (groups 1A, 1B, 2A, and 2B) with or without oxygenated perfluorocarbon in groups 1 and 2, respectively. Adenosine was added into the collagenase solution in subgroup A whereas it is not added in subgroup B. RESULTS: Tissue oxygen tension in group 1 was about 0 during digestion; whereas it rapidly reached about 300 mm Hg and was maintained in group 2. Tissue ATP level just after laparotomy (control) was 4.2 +/- 0.7 micromol/g dry weight. The ATP levels after digestion were 0.12 +/- 0.03 in group 1A (P < 0.01 vs control); 0.70 +/- 0.10 in group 1B (P < 0.01 vs control); 0.30 +/- 0.18 in group 2A (P < 0.01 vs control); and 2.90 +/- 0.80 in group 2B (P = 0.19 vs control). Islet yields (IEQ/pancreas) were 1600 +/- 400 in group 1B; 1400 +/- 400 in group 1B; 1300 +/- 400 in group 2A; and 2400 +/- 100 in group 2B. The amount in group 2B was significantly greater than that in the other three groups. CONCLUSIONS: Oxygen provision by preoxygenated perfluorocarbon itself showed no beneficial effect on islet yield. However, if oxygen provision was associated with adenosine administration into the pancreas, tissue ATP levels after digestion were well maintained, and a greater number of islets were retrieved.

Successful islet transplantation from a single pancreas harvested from a young, low-BMI, non-heart-beating cadaver.

BACKGROUND: Young donors, donors with low body mass index (BMI), and non-heart-beating (NHB) donors are considered nonideal for islet transplantation. In this report, we successfully used a pancreas from a young, low-BMI, NHB donor for islet transplantation. METHODS: The donor was a 15-year-old adolescent boy whose cause of death was rupture of a primary brain tumor. According to Japanese regulations, his pancreas was procured after cardiac arrest. Warm ischemic time was 3 minutes and cold ischemic time was 300 minutes. The pancreas was digested by the automated method of Ricordi, followed by purification using continuous Euro-Ficoll gradients on a Cobe 2991 device. The recipient was a 35-year-old woman with unstable type 1 diabetes mellitus. Her pretransplant C-peptide level was null. She suffered frequent hypoglycemic unawareness. Her pretransplant M value, which is a good marker for glucose instability, was 125. Islet yield was 252,816 IEQ. There were no signs of contamination. Viability of islets assessed by FDA/PI staining was 83%. Stimulation index was 2.7. RESULTS: The patient received 5160 IEQ/kg of islets via the portal vein under local anesthesia. There were no transplant-related complications. Although she required minimal exogenous insulin, her C-peptide level increased to 0.7 ng/mL at postoperative day (POD) 14. Her M value at POD 15 to 19 decreased dramatically to 23.6, indicating good glycemic control. At 3 months posttransplant, episodes of hypoglycemia disappeared. CONCLUSIONS: Although an additional transplant is mandatory to wean patients from insulin, this case shows the possibility of using marginal donors, such as a young, low-BMI, NHB donor, for pancreas islet transplantation.

Effect of relative humidity on the photocatalytic activity of titanium dioxide and photostability of famotidine.

Titanium dioxide (TiO2) has been widely used as a pharmaceutical excipient and is also known to be a strong photocatalyst. An investigation into the relationship between the photocatalytic activity of TiO2 and the photostability of famotidine, which is known as an H2-blocker, is presented. The photocatalytic activity of the anatase form of TiO2, as measured by the four-probe method, is approximately 1.5 times higher than that of the rutile form. Discoloration of famotidine in a binary system containing TiO2 depends significantly on both the wavelength of the irradiating light and the crystal form of the TiO2, with the degree of discoloration of anatase higher than that of the rutile form. Discoloration of famotidine also depends on relative humidity. The relationship between discoloration rate constant and water vapor pressure is linear. These results demonstrate that famotidine is easily discolored by the photocatalytic activity of TiO2 and suggest that the solid-state photocatalytic activity of TiO2 is strongly affected by relative humidity.

[Percutaneous endoscopic gastrostomy (PEG) for the management of dysphagia: experiences in the neurosurgical care unit].

This report concerns percutaneous endoscopic gastrostomy (PEG) administered in the neurosurgical care unit to a patient with dysphasia. This reliable nutrition route has the major advantage of minimal surgical invasion and can be expected to become a standard nutritional method. Since patients with neurological disorders account for the majority of those who need PEG, neurosurgeons need to be aware of the importance of PEG.

[Clinical studies of varicocele. 3: A rare venous return via Santorini's plexus in a varicocele patient. Report of a case].

A 12-year-old man was referred to our clinic because of sanguineous discharge. At the out-patient department, bilateral varicocele was found. Urinalysis showed microscopic hematuria, but no other laboratory data were abnormal. Excretion urography was normal. The retrograde phlebograph showed a rare venous return via Santorini's plexus and lumbar veins. After varicocelectomy, urinalysis improved.

[Clinical studies of varicocele. 2: Radiographic examination and measurement of spermatic vein pressure in varicocele patients].

There are two types of internal spermatic veins (ISV) by radiographic examinations. In type 1, ISV is dilated with some collateral venous branches. On the other hand, ISV of type 2 is narrowed with increased collateral venous branches or abnormalities such as the circumaortic renal are seen. In these groups, pressure of renal vein and ISV were measured. As a result, renal vein pressure was about the same in type 1 as in the controls at 9.5 +/- 2.3 cmH2O but was higher in type 2 at 17.0 +/- 2.8 cmH2O. As for ISV, it was also about the same in type 2 as in the controls at 13.9 +/- 6.8 cmH2O but was markedly higher in type 2 at 33.3 +/- 3.9 cmH2O. When selective renal venography was performed, a contrast medium back-flow was seen in 9 out of 11 type 1 varicocele patients, but it was not seen in any of the cases with the nutcracker phenomenon. These results suggested that type 1 may be caused by the structural and functional disorders in the valve between the renal vein and ISV. In contrast, pathogenesis of type 2 varicocele may be due to an abnormality of the ISV in the embryo.

[Clinical efficacy of flucytosine on urinary candidiasis].

An antifungal agent (Flucytosine) was used to treat urinary candidiasis in 9 patients who had an indwelling catheter and developed fungal colony counts greater than 10(4). Among 9 patients with catheter drainage, urologic underlying diseases were benign prostatic hyperplasia in 7 and a neurogenic bladder in one patient all of whom had accompanied diabetes mellitus. Only one patient was supravesically diverted from the upper urinary tract through an indwelling catheter of bilateral ureterocutaneostomy after the removal of a tumorous bladder. All patients had previously received antimicrobials. Isolated strains of Candida were Candida albicans in 6, Candida tropicalis in 2, and Candida parapsilosis in one patient. Out of 9 patients having received daily administration of 1,500 mg Flucytosine for 2 weeks, 7 patients subsequently had no yield of fungal colony after the treatment. Minimum inhibitory concentration (MIC) of this agent was determined at the range of 0.1 to 0.2 microgram/ml in 5 patients with C. albicans and 0.2 microgram/ml in both patients with C. tropicalis. Otherwise, a high MIC of over 100 micrograms/ml indicating resistance to this agent was observed in only 2 patients with C. albicans and C. parapsilosis. Three of the 7 patients had recurrent urinary Candida infection even 2 weeks after the discontinuation of this antifungal therapy despite rapid and excellent eradication of urinary candidiasis. From these results, Flucytosine may be one of the most promising antifungal agent with a low MIC in the treatment of compromised urinary Candida infection and should be occasionally supplemented with a topical instillation of amphotericin B without any serious complication in the prevention of recurrence.

[Clinicopathological examinations of sinus reactions of lymph nodes from tumor-bearing patients].

The sinus reaction of lymph nodes from tumor-bearing patients was classified into 5 categories, normal (N), sinus histiocytosis (SH), mixed sinus reaction (M), sinus catarrh (SC) and not classified (NC), according to the definition of Thoresen (1982). As a result, at the low stage, 93.8% were N and SH, while at the high stage, 97.0% were M, SC and NC. The same results were also obtained, when the transfer of the lymph nodes was taken into consideration. On the other hand, when the lymph nodes were studied from the distant lymph nodes area (DLA) and regional lymph node area (RLA) according to the position of the pathogen, SC was the most with DLA, since all cases were at the high stage. With RLA, SH was the most at 47.6% at the low stage, while at the high stage. SC and NC indicated 66.0%. Therefore, the sinus reaction can be used to estimate the degree of the response to the cancer and the diagnosis of tumor-bearing patients.

[Renal papillary necrosis cured with endourological treatment].

We recently experienced a case of renal papillary necrosis which we removed by endourological treatment. A 58-year-old female diabetic patient complaining of left flank pain, fever and chills was admitted to our clinic. She had no past history of analgesic abuse or atypical vasculitis. Physical examination revealed a body temperature of 38 degrees C and tenderness in the left costovertebral angle. Pyuria was noted, and urine cultures grew more than 100,000 colonies of Escherichia coli per cubic millimeter. DIP revealed a diminished renal function, hydronephrosis, distorted middle and lower calyces and filling defect in the dilated ureter. However, there was no evidence of obstruction or ureteral reflux. Retrograde pyelography confirmed distortion and irregularity of the calyces and hydronephrosis due to a shadow defect which was movable during radiographic examinations. Laboratory studies revealed anemia, leucocytosis and hyperglycemia, but no elevation of BUN. Therefore, the patient was diagnosed as renal papillary necrosis. We succeeded in its endourological removal through nephrostomy with a choledochoscope (Olympus Co.) under epidural anesthesia. After surgery, the patient made a satisfactory recovery.

[Changes in N-acetyl-beta-glucosaminidase (NAG) in prostatitis patients].

NAG was measured before and after treatment and compared in 11 acute prostatitis patients, 13 chronic prostatitis patients and 10 healthy volunteers. Urinary NAG before treatment was 34.1 +/- 18.4 U/l in the acute prostatitis patients and was significantly higher than that in the healthy volunteers, which was 5.1 +/- 1.2 U/l. It was 8.5 +/- 3.2 U/l in the chronic prostatitis patients. Urinary NAG after treatment decreased and was 7.6 +/- 4.4 U/l and 6.7 +/- 1.7 U/l in the acute and chronic prostatitis groups, respectively. These results suggest that urinary NAG is useful in evaluating the changes in the condition of prostatitis and in diagnosing prostatitis, especially acute prostatitis.

[Urinary tract infection : clinical significance of antibody-coated bacteria].

More attention should be directed to upper urinary tract infections as they cause renal parenchymal damage. Recently, many reports on antibody-coated bacteria (ACB) in urological diseases have been made. We performed ACB tests in 68 cases of urological infectious diseases. The tests were made according to Thomas' method. Anti-human immunoglobulin IgG, IgA, and IgM rabbit sera were used. The results were compared using the chi-square analysis. ACB-positive were 0 approximately 15% of the cases of acute cystitis, 33 approximately 67% of the cases of chronic cystitis, 30 approximately 60% of the cases of prostatitis and urethritis, and 60 approximately 90% of the cases of pyelonephritis. The percentage was higher in the patients who had indwelling catheters than in those who did not. The ACB test was suggested to be helpful in diagnosing upper urinary tract infection in the female patients who did not have indwelling catheters. But there was the danger of making an incorrect diagnosis with this test on male patients who had indwelling catheters, and those with prostatitis or urethritis, and on female patients with indwelling catheters.

Urinary tract infection and blood P1 antigen: preliminary report.

A clinical study was made on the relationship between the blood type P1 antigen and urinary tract infection (UTI). The blood type P1 antigen could be detected in 3 out of 11 healthy Japanese volunteers (27.2%), and in 54% of the UTI patients as a whole. Classified by the type of infection, it could be detected in 3 out of 4 patients with upper UTI (75%) and in 11 out of 22 patients with lower UTI (50%). These incidences were higher than that of healthy volunteers, the difference being statistically significant. The relationship between the annual frequency of UTI and the positive detection of P1 antigen was examined. The patients who had been exposed to UTI twice or more a year proved to have a higher detection rate (61%), than the other group of patients, the difference being statistically significant. Two of the patients with E. coli detected as a clinical isolate proved to have the P1 antigen.

[Clinical effect on tumor regression and tissue concentration of peplomycin treated with peplomycin emulsion in hydroxypropylcellulosum].

Peplomycin emulsified in hydroxypropyl cellulosum (HPC-PEP) was prepared for intravesical chemotherapy. Clinical efficacy of HPC-PEP and tissue concentration of peplomycin (PEP) were studied in 12 patients with bladder tumor. Histopathology showed transitional cell carcinoma; 2 in grade 1,8 in grade 2, and 2 in grade 3. The total volume of 30 ml HPC-PEP was prepared from a mixture of 2% HPC and 90 mg PEP in 15 ml saline, and was intravesically administered through a urethral catheter and retained for two hours. Clinical evaluation 7 days after the initial instillation demonstrated good tumor regression in 2, good response in 5, and no change in 5. The mean PEP level in tumor tissue was 0.36 microgram/gr after 7 days and 0.19 microgram/gr even after 14 days. These clinical observations and tissue levels of PEP suggest that HPC-PEP might be useful as an intravesical instillation agent for bladder tumor.

[Effect of metoprolol in patients with renal hypertension].

Eighteen patients with renal hypertension were treated with metoprolol (Seloken) for more than 3 months. Compared with the pretreatment value, the mean blood pressure decreased by 6.0, 11.2, 9.2 and 12.2 mmHg, after 2 weeks and 3, 6 and 12 months of treatment with metoprolol, respectively. All the differences observed were statistically significant (p less than 0.01). The blood pressure lowering effect of metoprolol was observed in 12 of the 17 patients (70.6%) examined. Decrease in plasma renin activity was seen in most of the responders. Although the number of patients was limited, the plasma level of metoprolol was also measured. The results indicated no sign of accumulation of metoprolol in the body. Moderate deterioration in renal function was observed in 1 patient but the treatment with metoprolol could be continued. Metoprolol administration had to be discontinued in 1 patient, who developed asthma. There were no other serious side effects.

[Comparison of urinary and seminal N-acetyl-beta-glucosaminidase isoenzymes].

N-acetyl-beta-glucosaminidase (NAG) and its isoenzymes were measured in the urine and seminal plasma of healthy volunteers. Urinary NAG level was 2.62 +/- 1.30 U/L (mean +/- standard deviation), 1.99 +/- 0.77 U/g creatinine and seminal NAG level was 2370 +/- 1007 U/l. Urinary NAG level was 2.59 +/- 1.44 U/l, 1.93 +/- 0.80 U/g creatinine in males and 2.67 +/- 1.15 U/l, 2.08 +/- 0.78 U/g creatinine in females, and there was no significant sex difference. NAG isoenzymes in the urine and seminal plasma were divided into two major peaks, A and B. The A:B ratio was 78.0 +/- 6.5: 21.9 +/- 6.5 in the urine and 24.7 +/- 3.2: 75.2 +/- 3.2 in the seminal plasma, and was significantly different. Urinary NAG isoenzyme was 80.3 +/- 6.7: 19.6 +/- 6.7 in males and 74.1 +/- 4.3: 25.9 +/- 4.3 in females, and there was no significant difference between the sexes. These results indicated that urinary and seminal NAG can be differentiated by measuring the isoenzymes. Furthermore, the comparison of seminal NAG isoenzymes before and after vasectomy indicated that seminal NAG may be affected not only by the sperm but also by the prostatic fluid.

[Studies of enzymuria and proteinuria: Report 1: N-acetyl-beta-glucosaminidase in urological diseases].

N-Acetyl-beta-glucosaminidase (NAG) exists in renal tubules and seminal tract. We measured the NAG level in patients with urinary tract and seminal tract diseases and evaluated its clinical significance. The urinary NAG level was high in renal tubular function disorders such as glomerulonephritis, diabetic nephropathy and hydronephrosis. In these patients, NAG-isoenzyme studies indicated that the A-type isoenzyme decreased while the B-type isoenzyme increased. On the other hand, in the seminal tract disease patients, the urinary NAG level was high in benign prostatic hypertrophy with a catheter indwelling and in prostatitis. Urinary and seminal NAG-isoenzymes were measured in normal subjects. The isoenzyme patterns for urinary NAG and seminal NAG differed. The urinary NAG isoenzymes were measured in acute prostatitis patients, we found that the A-type isoenzyme decreased and the B type increased. In conclusion, when the A/B ratio of the NAG-isoenzyme is close to 24.9/75.0 in the urine, the presence of urological diseases in which seminal plasma could be mixed in, especially prostatic diseases, should be suspected.