Ichiro Aikawa

Effect of Cyclosporine on the Endocrine and Exocrine Pancreas in Kidney Transplant Recipients

In order to assess whether cyclosporine (CsA) affects the endocrine and exocrine pancreas, 105 patient courses comprised of 87 living related donor (LRD) and 18 cadaver donor (CAD) transplants treated with cyclosporine and prednisolone (Pred) were compared with the results of historical controls of 170 LRD and 10 CAD transplants treated with azathioprine (Az) and Pred. All of the recipients were followed for over 6 months after transplantation. There were no differences in age, sex, Broca index, family history, and preoperative evaluation on diabetic dispositions between the two treatment groups. The incidence of diabetes mellitus (DM) requiring insulin therapy was higher in CsA-treated recipients (18/105, 17.1%) than in Az-treated recipients (23/180, 12.8%; P less than 0.05), although both the daily Pred and cumulative doses of methylprednisolone (MP) at the onset of DM were significantly smaller in the CsA group than in the Az group (26.1 +/- 2.2 mg v 41.4 +/- 3.4 mg, P less than 0.01 and 3,086 +/- 626 mg v 7,133 +/- 1,129 mg, P less than 0.01, respectively). Diabetic patients with CsA showed higher levels of blood glucose (401 +/- 46 mg/dL), but lower amounts of urinary glucose (40 +/- 4.3 g/d) compared with patients treated with Az (239 +/- 31 mg/dL, and 61.4 +/- 4.6 g/d, respectively, P less than 0.05). In the CsA group, the onset of DM was related to high CsA plasma trough levels (greater than 350 ng/mL) in 23% of patients. Insulin could be withdrawn within 3 months in six of eight patients who had been converted from CsA to Az.(ABSTRACT TRUNCATED AT 250 WORDS)

Experience with 247 living related donor nephrectomy cases at a single institution in Japan

There is currently much concern over the morbidity and mortality of donors undergoing nephrectomy for living related renal transplants. Between April, 1970 and July, 1986, 247 cases of living related renal transplants were performed at the Second Department of Surgery, Kyoto Prefectural University of Medicine. The average age of the donors was 50.3±9.7 years, 81 per cent of the donors being parents of the recipients. Minor abnormalities which did not affect the donors suitability were found in 71 cases. Nephrectomies were performed extraperitoneally in all cases. Peri-operative complications, including wound complications in 13 cases, urinary infection in 12 cases and pulmonary complications and arrythmia in 4 cases, were considered to be minor in nature. A variety of renal function tests, carried out two weeks after nephrectomy revealed normal levels, although they had become slightly worse than those estimated pre-operatively. Long-term sequalae in the follow-up period from 18 months to 16 years and 2 months, was studied on 124 donors who answered questionnaires. Currently, there are 5 late deaths, none of which are directly related to the nephrectomy. Of the 124 donors, 85.5 per cent stated that there had been no change in their physical states following surgery. Pain or a feeling of discomfort at the wound site was reported by 10 donors (8.1 per cent) and hypertension was observed only in 3 (2.4 per cent). No major complication directly related to the donor nephrectomy was found, except for one case of incisional hernia. The donor nephrectomy operation thus appeared to be quite safe, and successful long-term sequelae can be obtained if the donor is selected carefully, according to the strict prospective evaluation of medical state and renal functions.

A case of endoscopic injection sclerotherapy for a bleeding duodenal varix

SummaryA case of bleeding duodenal varix which was treated successfully with endoscopic injection sclerotherapy (EIS) is reported. The patient developed a hemorrhage from a varix in the descending portion of the duodenum two months after EIS for esophageal varices, and hemostasis was achieved using EIS with an intravariceal injection of 1% polidocanol. The duodenal varix decreased in size after EIS. Two months after EIS, a splenectomy was performed. During a 14-month follow up period after the EIS for the duodenal varix, there was no recurrent bleeding.

The Effect of Renal Transplantation on a Major Endogenous Ligand Retained in Uremic Serum

The effects of renal transplantation on serum concentrations of 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF) and indole-3-acetic acid (IAA), which are endogenous ligands retained in uremic serum, and on phenytoin binding to serum protein were investigated. IAA, a weakly bound ligand, was rapidly excreted by the transplanted kidney during the first one to three days after renal transplantation, but CMPF, a strongly bound ligand, was slowly excreted. The binding defect of phenytoin was partially corrected by transplantation during the period of study. The results suggested that the prolonged drug binding defect observed despite successful renal transplantation is caused by a slower decrease of strongly bound ligands such as CMPF retained in uremic serum; hypoalbuminemia, usually observed after transplantation, may also contribute to this phenomenon.

Infiltrating ductal carcinoma developing within cystosarcoma phyllodes —A case report—

Malignancy in cystosarcoma phyllodes is uncommon and often confined to the stromal element. An extremely rare case of infiltrating ductal carcinoma developing within the stroma of cystosarcoma phyllodes is reported herein. A breast tumor with a diameter of 15 cm, which was diagnosed as cystosarcoma phyllodes, was excised from the right breast of a 47-year old woman. The histopathological examination revealed that hyperplastic ductal epithelial cells with dark cytoplasm and enlarged hyperchromatic nuclei were infiltrating the stroma. Thus, a diagnosis of ductal carcinoma within cystosarcoma was made. Subsequently, a standard radical mastectomy was performed. No recurrence or metastasis has been observed over the post-operative period of 5 years and 6 months.

Breast cancer arisingde novo in recipients of kidney allograft

Immunosuppressive therapy is not only an etiologic factor ofde novo malignant disease but it also accelerates progression of the already developed malignant disease in immunosuppressed recipients. Two cases ofde novo breast cancer arising in kidney transplant recipients are reported herein. A 25 year-old woman, transplanted one haploidentical kidney transplant 4 years and 9 months ago, developed a left breast tumor. Within one month the tumor had rapidly enlarged from 3.5 cm to 8 cm in diameter by the time she underwent a radical mastectomy. Nine axillary lymph nodes were positive for metastasis. Although her graft function had been poor due to chronic rejection, she was treated with standard immunosuppressive therapy, but not adjuvant therapy. Since local recurrent disease appeared two months postoperatively, the immunosuppressive therapy was ceased and60Co therapy started. Recurrent disease progressed rapidly, however, and she died 7 months after her operation. A 27 year-old woman, having allograft from an identical sibling, noted a right breast tumor, 8 years and 7 months later. Again the tumor had grown rapidly from 1.8 cm to 3 cm in diameter within one month. She underwent a standard radical mastectomy. One axillary lymph nodes was positive for metastasis. She has been treated with standard immunosuppressive therapy and adjuvant endocrinochemotherapy. Presently, she is alive with a well functioning graft and no disease.

Successful resection of advanced pancreatic tail cancer after neoadjuvant gemcitabine chemotherapy: report of a case.

Pancreatic cancer with distant metastasis is not an indication for surgery, and the median survival of these patients is less than 3 months. We report the case of a patient who has survived for 21 months without any signs of recurrence after resection of advanced pancreatic cancer following a course of chemotherapy with gemcitabine (GEM). A 75-year-old man was hospitalized for anorexia and emaciation. Examinations showed pancreatic cancer with distant peritoneal metastasis. After the main tumor and metastasis had been shrunk by GEM chemotherapy, we performed distal pancreatectomy combined with splenectomy. Microscopically, the main tumor was confirmed as moderately differentiated tubular adenocarcinoma with interstitium and fibrosis. The radicality of the surgery was R0, according to the TNM classification of the UICC. The patient recovered well and has had no clinical symptoms for 40 months since the initial chemotherapy. This case suggests that multidisciplinary treatment with GEM may prolong the survival of some patients with unresectable pancreatic cancer.

Improved outcome of renal transplantation with cyclosporine compared with azathioprine —Experience in 33 recipients followed for over one year—

Long-term clinical aspects after kidney transplantation using cyclosporine (CsA) were studied in 33 patients who received kidney grafts from one haplotype identical living related donor and who were followed for at least one year. Both actual graft and patient survival rates were 97 per cent at one year. Incidence and severity of acute rejection were reduced to a greater extent in patients treated with CsA than in patients treated with azathioprine (AZ). The incidence of infections was low, and no serious bacterial infection occurred in these 33 patients. In 17 of 33 patients with a deteriorative graft function caused by intractable nephrotoxicity, CsA was converted to AZ. The mean serum creatinine level of converted patients was significantly higher than that of patients maintained with CsA at each time when a dose of CsA was stepwise reduced from 14 mg/kg/day to 6 mg/kg/day. Conversion to AZ improved graft function dramatically, although it resulted in reversible acute rejections in 4 patients. CsA induced hepatotoxicity occurred in 10 patients, but in all normal liver function was restored with decrease in the dose. The potent immunosuppressive effect of CsA compensates for its side effects. However, CsA should be converted to AZ when the chronic nephrotoxicity persists at a late stage of post-transplantation.

Cyclosporine-associated microangiopathic hemolytic anemia in a renal transplant recipient.

A case of microangiopathic hemolytic anemia (MHA) associated with the immunosuppressive agent, cyclosporine, is reported herein. The patient manifested anemia with red blood cell fragmentation, hypertension, thrombocytopenia, elevation of serum LDH levels and glomerular capillary thromboses within a few days of his transplantation. Extensive treatments with urokinase and heparin proved ineffective and graftectomy was performed 7 days after his transplantation. Immunofluorescent staining failed to show immunoglobulin (IgG or IgM) or complement (C3) deposition within the glomeruli, which discriminated MHA from acute humoralvascular rejection.

Quantitative Analysis of Microvasculature of Rat Pancreas Transplants in Acute Rejection

The changes of the microvasculature of rat pancreas transplants during acute rejection were investigated and quantitatively analyzed. The vessels in pancreas transplants increased in caliber and decreased in density during acute rejection. These changes were marked in the exocrine pancreas, especially in central zones, whereas changes in islets were mild. These results indicate that the early deterioration of exocrine function is closely related to vascular destruction.