A Polymorphism rs6726395 in Nrf2 Contributes to the Development of Emphysema-Associated Age in Smokers Without COPD.

INTRODUCTION: Several studies have reported that single nucleotide polymorphisms (SNPs) in the gene encoding NF-E2-related factor 2 (Nrf2) contribute to airflow limitations in smokers without COPD. Although small airway lesions and emphysema contribute cooperatively to airflow limitation, the relationship between Nrf2 SNPs and the development of emphysema in smokers without COPD is not well understood. METHODS: Healthy subjects who underwent an annual health checkup with computed tomography (CT) of the chest at Osaka City University Hospital were prospectively recruited. The percentage of low-attenuation area (%LAA) on chest CT was quantified, and correlations between %LAA, Nrf2 SNP [rs6726395 (G/A)] genotypes, and clinical characteristics were examined. RESULTS: A total of 245 subjects without COPD [non-/light-smoker: 153 (62.4%) and smoker: 92 (37.6%)] were enrolled. The %LAA in the upper lung field was higher than that in the lower lung field (p < 0.001). The %LAA in smokers was significantly higher than that in non-/light-smokers (p = 0.021). The %LAA showed significant but weak correlation with age in all subjects (r = 0.141, p = 0.028). Divided by genotype, the %LAA of the upper lung field was significantly correlated with age in smokers with genotype GG (wild type) (r = 0.333, p = 0.022), but was not significantly correlated with age in smokers with genotype AG/AA. These correlations were not observed in non-/light smokers. CONCLUSION: A polymorphism rs6726395 in Nrf2 can contribute to the development of emphysema-associated aging in smokers. The Nrf2 SNP may be a predictive factor for smoking-induced emphysema, and genotyping of Nrf2 SNP may serve as biomarker for emphysema prevention.

Excellent results with high-dose mizoribine combined with cyclosporine, corticosteroid, and basiliximab in renal transplant recipients: multicenter study in Japan.

We performed a multicenter study in Japan to assess the efficacy and safety of immunosuppressive therapy with high-dose mizoribine (MZR; 6 mg/kg) combined with basiliximab (Bas), cyclosporine (CyA), and a corticosteroid in 90 patients. MZR was adjusted to maintain a target trough level of 1 to 2 µg/mL. CyA was started at 7 mg/kg to maintain blood levels in the target therapeutic range of 200 ng/mL (trough [C0]), 1200 ng/mL (2-hour post-dose [C2]), and 6000 ng·h/mL (area under the curve(0-9)). Bas (20 mg/body weight) was administered on the day of transplantation and on postoperative day 4. Rejection was diagnosed by episode and protocol biopsies. Cytomegalovirus (CMV) antigenemia (direct immunological staining of leukocytes using peroxidase-labeled monoclonal antibody [C7-HRP]) levels were measured every 2 weeks for 6 months. At 12 months, all patients and grafts were surviving except for one death from infection: the 1-year patient and graft survival rate was 98.9%. The acute rejection rate was 21.1%. The mean serum creatinine level at 1 year was 1.51 ± 0.61 mg/dL. The incidence of CMV disease was 0% with 28.9%, CMV antigenemia and 5.6%, ganoyclovir treatment. The incidence of BK virus disease was 2.2%. The mean serum uric acid level was 7.15 ± 1.79 mg/dL at 1 month and 7.06 ± 1.78 mg/dL at 3 months. We observed that a high-dose MZR regimen in combination with CyA, Bas, and corticosteroid was safe and effective to reduce the frequency of CMV and BK virus-related events in renal transplant recipients.

Histologic studies of islets of Langerhans in transplanted pancreata from marginal donors in Japan.

The serious shortage of brain-dead donors leads to the use of pancreata from marginal donors, including cardiac death in Japan. We studied the islet histology of pancreas graft biopsies to investigate the adequacy of using pancreata from marginal donors. Pancreas allograft biopsy was performed originally to diagnose acute rejection (Drachenberg grade I-III) at a mean of 6 months after transplantation. The percentage of beta cells showing oxidative DNA changes, replication, and apoptosis was investigated in 7 recipients of simultaneous pancreas-kidney transplantations with good graft function from marginal donors. Their causes of death were cerebrovascular with donor ages >44 years (n = 3), cardiac (n = 2), and cerebrovascular (n = 2). The percentage of beta cells per islet in the transplanted pancreas (71.9 +/- 3.3%) did not correlate with glycemic control or insulin secretion, but did correlated inversely with donor age (r = -0.81; P < .05). Oxidative DNA changes as revealed by 8-hydroxy-2'-deoxyguanosine (8-OHdG) staining were diffusely present in islet cells as well as in the exocrine cells of the transplanted pancreas. The percentage of 8-OHdG-positive cells per pancreas (71.8 +/- 4.5%) did not correlate with glycemic levels, insulin secretion, donor age, or ischemic time. There were no Ki67-positive replicating cells or terminal deoxynucleotide transferase-mediated dUTP nick-end labeling-positive apoptotic islet cells. Transplanted pancreata from marginal donors showed preserved beta cells and function despite diffuse oxidative changes.

A case of recurrent type 1 diabetes mellitus with insulitis of transplanted pancreas in simultaneous pancreas-kidney transplantation from cardiac death donor.

AIMS/HYPOTHESIS: A 41-year-old woman undergoing simultaneous pancreas-kidney transplantation from an HLA-mismatched cardiac death donor abruptly developed overt hyperglycaemia under standard immunosuppressive therapy at 48 months after transplantation. Unexpectedly, we found insulitis in the transplanted pancreas and characterised the insulitis. METHODS: Pancreas graft biopsies were performed 3 years before and after the development of hyperglycaemia and the specimens were examined histologically. RESULTS: Insulitis was absent in the first biopsy, although oxidative DNA changes revealed by 8-hydroxy-2'-deoxyguanosine (8-OHdG) staining were diffusely present both in islet cells and exocrine cells. No Ki67-positive proliferating cells were seen in the islets. Anti-glutamic acid decarboxylase antibody was undetectable 6 months earlier but increased to 6.3 U/l at the development of hyperglycaemia. The level of anti-insulinoma-associated protein 2 antibody was 18.5 U/l. Insulin secretion was severely suppressed and insulin therapy was resumed. In the second biopsy, although acute allograft rejection was minimal, insulin-positive beta cells were markedly reduced, and glucagon-positive alpha cells predominated. CD3-positive T lymphocytes, CD8-positive cytotoxic T lymphocytes and CD68-positive macrophages infiltrated around and into islets. The infiltrating cells expressed Fas ligand as well as granzyme B. More than 80% of islets were affected by insulitis. 8-OHdG-positive cells were also present in islets and exocrine tissue. The percentage of Ki67-positive cells in total islet cells was 1.5%. There were no TUNEL-positive apoptotic cells in the islet cells. CONCLUSIONS/INTERPRETATION: The histological features of insulitis in transplanted pancreas were consistent with common type 1 diabetes mellitus, but the clinical course of the recurrence appeared to be more rapid.

Availability of pancreatic allograft biopsies via a laparotomy.

OBJECTIVE: The aim of this study was to evaluate the availability of a pancreatic allograft biopsy via a laparotpmy. PATIENTS AND METHODS: From September 2004 to November 2007, 17 pancreas transplantations were performed: 15 simultaneous pancreas and kidney transplantations (SPK), 1 pancreas transplant alone (PTA), and one pancreas after kidney transplantation (PAK). Thirteen pancreatic allograft biopsies were obtained via an open laparotomy. This study evaluated the complications associated with this procedure, the rate of obtaining an adequate sample, and the relationship between biopsy-proven rejections and laboratory markers. In SPK cases we evaluated the synchronization between pancreas and kidney rejection. The pancreatic samples were diagnosed according to the Drachenberg classification. RESULTS: No complications resulted from the procedure. The rate of obtaining adequate samples was 84.6%. Pancreas rejection correlated with elevation of the laboratory markers in 71.4%. Simultaneous pancreas and kidney rejection occurred in 62.5%, only kidney in 25%, and only pancreas in 12.5%. CONCLUSION: A pancreas graft biopsy was absolutely imperative to improve the outcome in PTA, and even in SPK cases. A pancreatic allograft biopsy via a laparotomy was a safe, necessary and easy procedure to obtain an accurate diagnosis of rejection among pancreas transplantation patients.

Present status of pancreas transplantation in Japan--donation predominantly from marginal donors and modified surgical technique: report of Japan pancreas transplantation registry.

In Japan, organ donation has been still limited because of the strict donor criteria. The aim of this study was to show the effectiveness of pancreas transplantation (PTx) by analyzing the outcomes even under poor donor conditions. Thirty-six cases of PTx (32 simultaneous pancreas and kidney transplantations [SPK], 4 pancreas after kidney transplantations) performed during the last 8 years were examined especially for donor characteristics. Mean donor age of 41.4 +/- 11.9 years was considerably older compared with that in the United States and Europe; donors aged over 40 years comprised 67% of the total. According to the criteria described by Kapur, 29 cases (81%) in our series would be considered marginal. Thus, to increase blood supply into the pancreatic head, the gastroduodenal artery (GDA) was anastomosed using donor artery to common hepatic artery or iliac Y graft. These procedures were performed in 16 of the 24 cases in which there was liver procurement. Eventually, 34 cases (94%) preserved GDA continuity. Mean total cold ischemic time of pancreatic grafts was 12 hours 15 minutes. Of 214 registrants, 17 patients on the waiting list for SPK died of diabetic complications. To date, patient survival remains 100% with a mean follow-up period of 33 months. Pancreas graft survivals at 1, 3, and 5 years posttransplantation were 92%, 80%, and 80%, respectively. In contrast, kidney survivals were 91%, 91%, and 91%, respectively. The integrity of the pancreas head and duodenum by preservation of the GDA continuity might have decreased the risk associated with the marginal donors.

The combined use of prostaglandin I2 analogue (OP-2507) and thromboxane A2 synthetase inhibitor (OKY-046) strongly inhibits atherosclerosis of aortic allografts in rats.

BACKGROUND: Atherosclerosis is the main lesion in allografts undergoing chronic rejection. We investigated the effect of OP-2507 (prostaglandin I2 analogue) and OKY-046 (thromboxane A2 synthetase inhibitor) on graft atherosclerosis morphologically and the production of eicosanoids in grafts in a rat aortic allograft model. METHODS: Abdominal aortic allografts of Lewis (RT-1(l)) rats were transplanted orthotopically into fully major histocompatibility complex mismatched Wistar King A/Qdj (RT-1(u)) rats that were subcutaneously administered OP-2507 (0.1 mg/kg/d) or OKY-046 (125 mg/kg/d), or both, with an osmotic pump. Four, 8, or 12 weeks later, the grafts were harvested and examined histologically, and the concentration of eicosanoids in the grafts were analyzed. RESULTS: Lewis aortic allografts in Wistar King A recipients with no treatment displayed atherosclerosis, which involved gradual intimal thickening and medial thinning with continuous inflammation in adventitia. Neither OP-2507 nor OKY-046 treatment affected the intensity of adventitial inflammation. Although inhibition of medial thinning or a decrease in medial nuclear density was not observed, OKY-046 administration alone significantly inhibited an increase in intimal thickness. OP-2507 administration alone significantly inhibited a decrease in medial nuclear density and intimal thickening. Combined treatment with OP-2507 and OKY-046 further decreased the alteration of media and intima. The ratio of thromboxane B2 and 6-keto-prostaglandin F(1alpha) in the grafts was significantly reduced by OKY-046 but not by OP-2507 alone. CONCLUSIONS: We have demonstrated that atherosclerosis in aortic allografts is inhibited by the continuous administration of either OP-2507 or OKY-046, and a combination of both agents strongly increases this inhibitory effect. Amelioration of balance in eicosanoid production in the grafts by the use of thromboxane A2 synthetase inhibitor and the simultaneous usage of stable prostaglandin I2 analogue may be a strategy for preventing atherosclerosis that results from chronic rejection.

Intraductal papillary-mucinous tumor of the pancreas: assessing the grade of malignancy from natural history.

Intraductal papillary-mucinous tumor of the pancreas is a spectrum of conditions ranging from benign to malignant, and very few papers have referred to the natural history of this disease. In this communication the indicators of malignancy were examined from a viewpoint of natural history. Follow-up computed tomographies (CTs) more than 6 months after the diagnosis were reviewed in 17 Japanese patients with intraductal papillary-mucinous tumor of the pancreas. They were divided into two groups by the presence or absence of morphological progressive changes by the follow-up CTs, and the clinicopathological features were compared between the two groups to examine possible malignant indicators. The 17 patients consisted of seven patients in the no-change group and ten in the progressive group. The distribution of the patients was not different with regard to age; gender; or presence or absence of pancreatitis, diabetes mellitus, or unique findings of the ampulla of Vater between the two groups. The dilatation of the main pancreatic duct (> or = 3 mm) was more frequent in the progressive group: (eight of ten patients; 80%) than in the no-change group (two of seven patients; 29%) (P = 0.03). Six (86%) of the seven tumors in the no-change group were located in the branch duct, whereas five (50%) of the ten in the progressive group were situated in the main pancreatic duct. Histopathologic diagnoses of the resected specimens of the four in the no-change group examined were intraductal papillary-mucinous adenoma in three and adenoma with moderate dysplasia in one, whereas the diagnoses in the six in the progressive group examined were adenoma in two, adenoma with moderate dysplasia in two, and carcinoma (invasive) in two. The patients with intraductal papillary-mucinous tumor of the pancreas with a dilatation of the main pancreatic duct at the time of diagnosis should be followed up more carefully than those without dilatation. Once progressive morphological changes are detected by the follow-up CTs surgical resection should be considered because of possible malignancy.

Effect of FR167653 on pancreatic ischemia-reperfusion injury in dogs.

BACKGROUND: The role of inflammatory cytokines is still unclear in ischemia-reperfusion injury of the pancreas. We investigated the effect of FR167653 (FR), a newly developed compound that is a potent suppressor of interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha on ischemia-reperfusion injury of the isolated pancreatic tail in dogs. METHODS: The tail of the pancreas was subjected to ischemia for 90 minutes. During occlusion of the vascular inflow, the head of the pancreas was removed. A control group (n = 14) and an FR treatment group (n = 11) were evaluated for survival rate, tissue blood flow, arterial oxygen pressure (Pao(2)), serum amylase and lipase levels, glucose and insulin, liver enzymes, creatinine, IL-1beta mRNA in the peripheral blood, and histopathology. RESULTS: Six of the 14 control animals and 2 of the 11 FR-treated animals died. The FR treatment group showed lower amylase (P=.037) and lipase (P =.030) levels, lower IL-1beta mRNA expression (P =.033), and less pancreatic tissue damage (P =.041) than did the control group, but there was no remarkable change in endocrine function (P =.422). Pao(2) during the acute phase in the FR treatment group was maintained (P=.009), but pulmonary tissue was damaged. Results of biochemical and histologic examinations of the liver and kidneys were unremarkable. CONCLUSIONS: FR ameliorates ischemia-reperfusion injury of the pancreas and reduces the production of inflammatory cytokines that may contribute to secondary damage to distant organs.

Role of surgery for gallbladder carcinoma with special reference to lymph node metastasis and stage using western and Japanese classification systems.

The role of radical resection in the treatment of gallbladder carcinoma was examined with special reference to lymph node metastasis using two classifications: one proposed by the American Joint Committee on Cancer (AJCC) and the other by the Japanese Society of Biliary Surgery (JSBS). Histologic evaluations for the depth of tumor invasion (T), lymph node metastasis (N), stage, and follow-up for a mean period of 38 months (range 4-185 months) were completed in 52 patients with gallbladder carcinoma who underwent surgical resection from 1982 to 1997. The definition of T was similar in the two classifications. The extent of nodal involvement (N, AJCC; n, JSBS), stage, and survival were examined. In the absence of lymph node metastasis, the 5-year survival rate reached 71%. The 5-year survival rate in patients with involved nodes confined to the hepatoduodenal ligament, posterosuperior pancreaticoduodenal region, or along the common hepatic artery (N1 and part of N2 by AJCC; nl and n2 by JSBS) approximated 28%. In contrast, postoperative survival was poor in the presence of more extensive nodal involvement (rest of N2 by AJCC; n3 and n4 by JSBS), with no 2-year survivors. The definition of stage I was the same in both classifications, and all patients in this stage are alive. The 5-year survival rates in stages II and III by the AJCC were 70.7% and 22.4%, respectively, and those by JSBS 61.9% and 23.1%, respectively. Thus the survival rates in stages I to III were essentially similar irrespective of the staging system. Stage IV showed significantly worse survival than stage III by the JSBS classification. In contrast, the differentiation of stage IV from III by the AJCC was not significant because of the better survival in stage IV that contained any T with nodal involvement in the posterosuperior pancreaticoduodenal region and along the common hepatic artery. Radical resection should be considered for patients with stage I to III disease defined by either classification and applied to the tumor invasion up to T3 with nodal involvement confined to the hepatoduodenal ligament, posterosuperior pancreaticoduodenal region, and along the common hepatic artery. The role of radical surgery seems to be limited in patients with more extensive tumor invasion or lymph node metastasis.

The role of percutaneous transhepatic abscess drainage for liver abscess.

To evaluate the efficacy of percutaneous transhepatic abscess drainage (PTAD) as an initial choice of treatment for liver abscess, the medical records of 28 patients with liver abscess were retrospectively analyzed. The patients were predominantly men (23 of 28) with a mean age of 59 years (range, 19-86 years). Their chief complaints were fever (86%), right hypochondralgia (32%), and jaundice (11%). Fifteen of the 28 patients (54%) had hepatobiliary and pancreatic carcinoma, and 31% had postoperative liver abscess. PTAD was performed in 23 patients and surgical drainage in 5. The overall success rate for PTAD was 83%. The success rate for PTAD for patients with multiple abscesses was 83% (5 of 6), compared with a success rate of 82% (14 of 17) for patients with solitary abscess. The prognostic factors for survival were cancer and sepsis and the mortality rate for patients with cancer was 40% (6 of 15) while the mortality rate for patients with sepsis was 56% (5 of 9). As a complication of drainage, 1 patient (4%) in the PTAD group had pleural abscess due to the transpleural puncture. Our findings support the use of PTAD as the primary treatment for liver abscess, as it is safe and effective irrespective of the number of abscesses and the patient's condition.

Pancreatic carcinoma: < or = 2 cm versus > 2 cm in size.

BACKGROUND: Despite recent progress in diagnosis and therapy, the clinical course of patients with pancreatic carcinoma remains dismal. There have been several approaches to improve the clinical course of patients with pancreatic carcinoma, namely: (i) detection of small pancreatic carcinoma; (ii) radical resection with retroperitoneal clearance and portal vein resection; (iii) multidisciplinary therapy including chemoradiation; and so forth. METHODS: In this series, eight Japanese patients with small pancreatic carcinoma measuring less than 2 cm in diameter (including two with non-invasive carcinoma and one with minimally invasive carcinoma) and 53 with larger pancreatic carcinoma were reviewed to find the diagnostic and therapeutic clues to improve the clinical course of patients with pancreatic carcinoma. RESULTS: Lymphatic (ly) and perineural (pn) permeation was significantly more frequent and extensive in the 53 patients with large pancreatic carcinoma than in the eight with small pancreatic carcinoma (ly 0/1/2/3:3/24/18/8 versus 5/2/1/0, P = 0.0284; pn 011/2/3:4/29/14/6 versus 3/2/3/0, P = 0.0491). The surgical margin was affected by malignant cells in 18 (34%) of the 53 patients with large carcinoma but none (0%) of the eight with small carcinoma (P = 0.0004). The comprehensive stage was significantly earlier in the eight with small carcinoma than in the 53 with large carcinoma (comprehensive stage I/II/II/IV:4/0/3/1 versus 0/3/26/24, P < 0.0001). Comprehensive curability of the eight small carcinoma cases was significantly higher than that of the 53 large carcinoma cases (comprehensive curability A/B/C:5/3/0 versus 9/5/39; P = 0.0003). 1-year and 3-year cumulative survival rates of the eight patients with small carcinoma were 100% and 82%, whereas those of the 53 with large carcinoma were 51% and 17%, respectively (P = 0.0207). However, the eight small carcinoma cases already showed frequent invasion to the vascular (v), lymphatic (ly) and perineural (pn) structure [v(+): 3/8, ly(+): 5/8, pn(+):5 /8] and lymph node metastasis (n) [n(+): 3/8]. Out of the eight small pancreatic carcinomas, one minimally invasive carcinoma and two non-invasive carcinomas showed no vascular, lymphatic or perineural invasion or lymph node metastasis. All the three patients have been doing well 19, 32 and 44 months after the operation. The diagnostic clues in the three patients were dilatation of the main pancreatic duct in one and of the branch duct in the other two. CONCLUSIONS: These findings suggest that surgical resection frequently cures patients with small pancreatic carcinoma but more effective adjuvant therapy should be developed to control lymphatic permeation, venous invasion or perineural infiltration in surgical resection of large pancreatic carcinoma. The supreme goal is to detect non-invasive or minimally invasive pancreatic carcinoma with a dilatation of the main or branch pancreatic duct as a diagnostic aid.

Comparison of treatments for hepatolithiasis: hepatic resection versus cholangioscopic lithotomy.

BACKGROUND: Hepatic resection and percutaneous transhepatic cholangioscopic lithotomy (PTCSL) are the two main approaches to the treatment of hepatolithiasis, but comparisons of longterm followup results have not been adequately reported. STUDY DESIGN: Of 86 patients with hepatolithiasis admitted to our institution between 1980 and 1996, we reviewed 54 patients: 26 who underwent hepatic resection and 28 who underwent PTCSL. Five patients who underwent postoperative cholangioscopic lithotomy were included in the former group. The remainder of the hepatolithiasis patients were not treated by hepatic resection or PTCSL and, therefore, were excluded from this study. Hepatic resections were mainly indicated for left-sided localized intrahepatic calculi, atrophic liver, and possible presence of cholangiocellular carcinoma. PTCSL was performed for right-sided, bilateral or recurrent stones at an average of 6 treatments (range 1 to 20 treatments) for each patient. There were no differences between the two groups in terms of gender or age. The recurrence rate of stones and longterm prognosis were analyzed using the Kaplan-Meier method, and other clinical factors listed below were statistically compared. RESULTS: The rate of complete removal of stones was similarly high in each group (96.2% in the hepatic resection group versus 96.4% in the PTCSL group). The complication (38.5% versus 21.4%) and 5-year survival (85.6% versus 100%) rates were comparable. Remaining bile duct stricture (18.2% versus 60.9%, p < 0.01) and 5-year recurrence rates (5.6% versus 31.5%, p < 0.05) were statistically lower in the hepatic resection group than in the PTCSL group. CONCLUSIONS: Hepatic resection, when combined with postoperative cholangioscopic lithotomy, is a preferable treatment for left-sided stones with strictures and bilateral stones.

An early gastric carcinoma treatment strategy based on analysis of lymph node metastasis.

BACKGROUND: Newly developed therapies for early gastric carcinoma attempt to consider patients' quality of life, but the applicability and effectiveness of these treatments remain undetermined. METHODS: Clinicopathologic data of 612 consecutive patients with early gastric carcinoma, all of whom were treated by D1 and D2 gastrectomy, were analyzed. Patients with and without lymph node metastases were compared in relation to age and gender distributions, surgical procedures, histopathology of the tumors, 5-year prognosis, and in reference to the preoperative and intraoperative assessments. RESULTS: The overall incidence of lymph node metastases was 5.7%. Tumor depth and size were related to lymph node metastases judged by univariate and multivariate analyses. Patients with mucosal tumors showed no relation between metastatic rate and tumor size, whereas those with submucosal tumors showed an increasing metastatic rate with tumor size. In all cases but one, lymph node metastases were confined to lymph node stations defined as Group 1 locations. Preoperative endoscopic ultrasonography showed a 55% diagnostic accuracy in determining tumor depth and a 15% sensitivity in diagnosing lymph node metastases. CONCLUSIONS: Patients with early gastric carcinoma may be candidates for endoscopic mucosal resection if their tumor is confined to the mucosa and measures < 1 cm in greatest dimension. Other limited resections including D1 gastrectomy or standard D2 gastrectomy based on tumor depth and size are appropriate. Based on the current study findings, the authors propose a useful algorithm for managing such patients.

Chronic asymptomatic pseudocyst with sludge aggregates masquerading as mucinous cystic neoplasm of the pancreas.

Pseudocyst of the pancreas is sometimes difficult to distinguish from mucinous cystic neoplasm of the pancreas. A 37-year-old asymptomatic Japanese man was diagnosed with hypertension. He had a 20-years history of habitual drinking of alcohol, but no history of pancreatitis or abdominal trauma. During examinations to ascertain the cause of hypertension, ultrasonography and computed tomography incidentally demonstrated a huge cyst in the head of the pancreas. Laboratory data were within normal limits, including serum levels of amylase, carcinoembryonic antigen, and carbohydrate antigen 19-9. Imaging studies showed a huge unilocular cyst, measuring 7 cm, in the head-to-body of the pancreas, and two small unilocular cysts, measuring 1.4 and 1.5 cm, in the tail and head of the pancreas, respectively. A mural nodule was suspected in the largest cyst. Endoscopic retrograde cholangiopancreatography demonstrated communication of the main pancreatic duct with the two small cysts in the head and tail of the pancreas but not with the huge cyst. There were no ductal changes suggesting chronic pancreatitis. Laparotomy was performed under the tentative diagnosis of potentially malignant mucinous cystic neoplasms of the pancreas. However, inflammatory adhesion was dense around the pancreas and the mural nodule suspected preoperatively was found to be sludge aggregates in a pseudocyst. The diagnosis of an intraoperative frozen section of the cyst wall was pseudocyst of the pancreas. Cystojejunostomy was performed. We report this case because the preoperative diagnosis was mucinous cystic neoplasm of the pancreas, but the diagnosis changed with careful intraoperative examinations, to pseudocyst of the pancreas. We discuss the differential diagnosis of the two conditions.

Serum lipase as a marker for pancreatic allograft rejection.

In patients with enteric drainage of pancreas transplants, urinary amylase cannot be used as a marker of rejection. Since most of the patients in our center have enteric drainage, the aim of this study was to evaluate serum lipase as a potential marker for rejection. From July 1994 to March 1997, 100 patients underwent pancreas transplantation with enteric (78) or bladder (22) drainage. Forty-two of the 100 patients had both daily serum lipase (sLip) values and either kidney core or fine needle aspiration biopsies of the pancreas and/or kidney. Thirty-one of the 42 had biopsy proven rejection and were treated on day 0 (D0). From day -7 (D -7) to day +7 (D +7), sLip, serum amylase (sAmy), fasting blood sugar (FBS) and serum creatinine (sCr) were measured daily. Serum lipase values rose from 322 +/- 107 IU/L on D -2 to 634 +/- 247 IU/L on D -1 (p = 0.0203) in 22 of the 31 patients with biopsy proven rejection (sensitivity 71%). The rise in sCr in combined kidney pancreas transplants with biopsy proven rejection was a better marker than sLip (sensitivity 86%). The sensitivity of sAmy and FBS was 50 and 33%, respectively. Other than sCr, sLip appeared to be the best marker for acute rejection in enterically drained pancreas transplants which should be useful as a non-invasive indicator of rejection in solitary pancreas transplants where sCr cannot be used.

Extrinsic intestinal reinnervation after canine small bowel autotransplantation.

BACKGROUND: The process of extrinsic reinnervation after small bowel transplantation is poorly understood. METHODS: Jejunal and ileal specimens, obtained from the dogs that underwent intestinal autotransplantation by an end-to end (E-E) or end-to-side arterial reconstruction, were analyzed at 1 (n = 7), 3 (n = 6), 6 (n = 6), 12 (n = 6), or 24 (n = 2) months and compared with control specimens (n = 7). Tissue catecholamine levels and indirect immunohistochemistry results for extrinsic neuropeptides, calcitonin gene-related peptide, neuropeptide Y, substance P, and tyrosine hydroxylase (TH) were examined. RESULTS: Catecholamine levels in the grafts were undetectable until 6 months but increased significantly after 12 months, particularly in the E-E group. Immunohistochemistry results showed no significant indication of extrinsic reinnervation until 12 months, when TH fibers were observed in five of six dogs. The E-E group revealed some TH fibers extending across the arterial anastomosis toward the graft mesentery. Examination of the intestinal anastomosis at 12 months showed abundant peptidergic and TH extrinsic fibers in the host side, whereas there were few or none on the graft side. CONCLUSIONS: These results suggest that extrinsic reinnervation of the graft intestinal wall does occur but requires a prolonged period, and the major route of extrinsic reinnervation is along the arterial axis of the intestinal graft, not beyond the enteric anastomosis.