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PubMed2002

Thymoglobulin for induction or rejection therapy in pancreas allograft recipients: a single centre experience.

PURPOSE: To review the safety and efficacy of thymoglobulin in pancreas transplant patients receiving tacrolimus and mycophenolate mofetil. METHODS: Retrospective, single centre analysis of 45 patients transplanted between 1995 and 2000 who received 54 courses of thymoglobulin, including 36 courses in 29 solitary pancreas transplant recipients (16 pancreas alone, 13 pancreas after kidney transplants) and 18 courses in 16 simultaneous kidney-pancreas transplant patients. Thirty-two patients (71%) were primary pancreas transplants, 10 (22%) were second transplants and three (7%) were third transplants. Of the 54 treatment courses, 19 (35%) were for induction, 27 (50%) were for primary rejection and eight (15%) were rescue therapy for rejection. All rejection episodes were biopsy-proven in at least one organ. RESULTS: The median thymoglobulin dose was 1.5 mg/kg/d with a mean of six doses (range 3-10). Dose reduction or interruption was required in 28 courses (52%), most often due to leukopenia (n = 24), fever (n = 2) and thrombocytopenia (n = 2). Thymoglobulin was resumed in all but three patients, two with persistent fever and one with infection. Infectious complications (n = 25) occurred in 17 patients (38%) within 30 days and included bacterial (n = 16), cytomegalovirus (n = 4), polyoma (n = 1), fungal (Candida albicans, n = 1), toxoplasmosis (n = 1) and ehrlichiosis (n = 2). Post-transplant lymphoproliferative disease occurred in two patients (4%) at a mean of 70 d post-thymoglobulin treatment. In the 19 patients that received thymoglobulin induction, one simultaneous kidney-pancreas transplant, two pancreas alone and four pancreas after kidney transplant recipients developed rejection (37% incidence), while all remaining patients followed by surveillance protocol biopsies were rejection-free. In the 35 patients that received thymoglobulin for rejection, reversal occurred in 26 of the patients (74%). Rejection recurred within 30 d in five patients and post-treatment biopsies revealed persistent rejection in three of 20 pancreas and two of eight renal biopsies. After a mean follow-up of 6 months, the actual patient and pancreas graft survival rates were 93% and 71%, respectively. CONCLUSION: Thymoglobulin was effective as induction therapy in high-risk pancreas transplant recipients, and resulted in initial reversal of rejection in 74% of patients. Dose adjustments were required in over half the cases and were usually due to leukopenia. Infections occurring subsequent to thymoglobulin were not uncommon and reflected the immunosuppressive burden of the patient population.

Adult↗
PubMed1991

Pancreas retransplants compared with primary transplants.

The improved results with pancreas transplantation in general, and the emerging evidence that the procedure favorably influences the course of secondary diabetic complications, given an impetus to retransplant patients whose initial graft has failed. In order to determine whether a pancreas retransplant policy is justified, we analyzed the results at our own institution. From 1978 through 1989, 327 pancreas transplants were performed in 261 patients, including 259 primary (79%) and 68 retransplants (21%) after a previous one failed (including 2 primary transplants performed elsewhere), with 48 second (15%), 18 third (5%), and 2 fourth (1%) transplants. The surgical techniques used in the 261 primary PxTxs were open-duct free drainage into the peritoneal cavity in 15 recipients, of whom 3 (20%) were retransplanted: duct occlusion in 34, of whom 9 (26%) were retransplanted intestinal drainage in 78, of whom 23 (29%) were retransplanted; and bladder drainage in 134, of whom 13 (10%) were retransplanted. The surgical techniques used for the 68 pancreas retransplants were duct occlusion in 11 (10 second, 1 third), intestinal drainage in 12 (9 second, 3 third), and bladder drainage in 45 (29 second, 14 third, and 2 forth); bladder drainage has been used nearly exclusively for the most recent pancreas retransplants. The recipient categories in the 261 primary transplants were pancreas alone in 115, of whom 29 (25%) were retransplanted, pancreas after kidney in 81, of whom 17 (21%) were retransplanted, and simultaneous pancreas and kidney transplants in 63, of whom 2 (3%) were retransplanted. Of the 68 pancreas retransplants, 32 (47%) were pancreas alone (26 second, 6 third), 24 (35%) were pancreas after kidney (17 second, 6 third, 1 fourth), and 12 (18%) were simultaneous pancreas and kidney (5 second, 6 third, 1 fourth). Overall patient survival rates were similar (P = 0.48), at 1 month (actual [98% after primary and 94% after retransplantation]) and at 1 year (actuarial [91% vs. 89%]). Overall graft functional rates were also similar, at 1 month (actual [76% for all primary and 79% for all retransplants - P = 0.9]), and at 1 year (actuarial [46% vs. 43% - P = 0.9]). Causes of graft losses at 1 months were similar for primary (18% were technical failures, 6% were rejected) and retransplant (16% were technical failures, 3% were rejected) cases.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1992

Differential effects of preexisting uremia and a synchronous kidney graft on pancreas allograft functional survival in rats.

Pancreas transplant results have been better in uremic recipients of a simultaneous kidney than in nonuremic recipients of a pancreas alone. We studied the relative effect of uremia versus a double transplant on functional survival by performing bladder-drained pancreas transplants alone (PTA), kidney transplants alone (KTA), and simultaneous pancreas/kidney (SPK) transplants from Buffalo donors to diabetic Lewis rat recipients that were or were not made uremic 2-3 weeks before by 1 4/5 native nephrectomy. Pancreas graft exocrine function was monitored by urinary amylase (UA). In the PTA and SPK recipients made diabetic by streptozotocin, endocrine function was monitored by measuring nonfasting plasma glucose (PG) levels. Kidney graft function was monitored by plasma creatinine (Cr). Rejection of the endocrine pancreas was defined as an increase of PG to greater than 200 mg/dl; of the exocrine pancreas, as a decline in UA to less than 6000 U/L or to less than 100 U/24 hr; and of the kidney, as an elevation of Cr to greater than 3 mg/dl. The mean functional survival times (MST) of both the endocrine (12.0 +/- 2.1 versus 10.1 +/- 1.1 days, P = 0.036) and exocrine (8.0 +/- 2.1 versus 6.3 +/- 1.3 days, P = 0.016) components of the pancreas grafts were significantly longer in SPK than in PTA recipients. The MST of kidney allografts, however, was not significantly longer in nonuremic SPK than nonuremic KTA recipients (6.7 +/- 1.4 versus 5.7 +/- 0.7 days, P = 0.13). In parallel experiments in recipients immunosuppressed with cyclosporine, the graft survival times were longer, but the relative differences between the PTA, SPK, and KTA groups persisted. Histologically, lymphocyte infiltration began in the two organs almost simultaneously, but the severity of the rejection was more vigorous in the kidney than in the pancreas in doubly grafted rats, and destruction of pancreas grafts progressed more slowly in SPK than in PTA recipients. Preexisting uremia delayed pancreas rejection in both SPK (exocrine 10.6 +/- 2.3, P = 0.032, and endocrine 14.8 +/- 3.4 days, P = 0.065, versus nonuremics) and PTA (exocrine 8.5 +/- 1.7, P = 0.007, and endocrine 12.6 +/- 2.5, P = 0.026, versus nonuremics) nonimmunosuppressed recipients. The MST of kidney grafts was not significantly longer in uremic (8.9 +/- 2.8 days) than in nonuremic (6.7 +/- 1.4 days) SPK recipients (P = 0.081). A synchronous kidney transplant and uremia independently down-modulate the rejection response to a pancreas graft, and a simultaneous pancreas graft has no detrimental effect on the survival of a kidney graft.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1998

Diagnosis of pancreas rejection: cystoscopic transduodenal versus percutaneous computed tomography scan-guided biopsy.

BACKGROUND: The most common cause of graft failure after technically successful pancreas transplants is rejection. Laboratory parameters for detecting pancreas graft rejection are not consistently reliable and can lead to unnecessary antirejection treatment. Histopathologic evaluation is the gold standard in the differential diagnosis of pancreas graft dysfunction. Four biopsy techniques have been described: cystoscopic transduodenal (CB), percutaneous computed tomography scan-guided (PB), open, and laparoscopic biopsy. METHODS: We studied the two most common techniques, CB and PB, in pancreas transplant recipients with presumed rejection. Group 1 comprised 103 attempts at CB in 82 recipients (53 men, 29 women) with bladder-drained (BD) pancreas transplants, at 1 to 80 (median, 14) months after transplant. Group 2 comprised 93 attempts at PB in 68 recipients (41 men, 27 women), at 0.5 to 64 (median, 14) months after transplant. RESULTS: In group 1, of 103 attempts at CB, adequate tissue was obtained in 90 (87%): pancreas alone in 23 (22%), pancreas + duodenum in 35 (34%), duodenum alone in 32 (31%). Of the 58 pancreas biopsies, 23 (40%) showed acute rejection. Of the 67 duodenal biopsies, 16 (24%) showed acute rejection. Complications of CB included macrohematuria in 4 recipients (4%) and microhematuria in 32 (31%). We noted no biopsy-related pancreatitis. The mean cost of CB was $2561+/-246. In group 2, of 93 attempts at PB, adequate tissue (all pancreas) was obtained in 67 (72%); of these, 29 (43%) showed acute rejection. Of 23 inaccessible pancreases, 9 (39%) underwent CB; pancreatic tissue was obtained in four (45%), and results were consistent with rejection in all four. Complications of PB included biopsy-related pancreatitis (serum amylase > or = 25%) in five (7%) recipients, macrohematuria in one (1%), and abdominal hemorrhage in two (3%). The mean cost of PB was $1038+/-78. (1) CB and PB prevented unnecessary antirejection treatment in 44% of our recipients with successful biopsies; (2) CB had a higher success rate for obtaining tissue (including duodenal specimens) and a lower rate of major complications; (3) PB was easier and cheaper, did not require general anesthesia, and was performed as an outpatient procedure. CONCLUSIONS: We conclude that PB should become the biopsy technique of choice in recipients with presumed pancreas graft rejection. If PB fails, recipients with bladder-drained pancreas transplants should undergo CB. If CB fails, or in recipients with enteric-drained or duct-injected pancreas transplants, a laparoscopic or open biopsy should be considered.

Adolescent↗
PubMed1994

The ontogeny of insulin-like growth factor (IGF) and IGF-binding protein gene expression in the rat pancreas.

Insulin is important for optimal fetal and neonatal growth and development. Its continued availability is due, in part, to ongoing islet cell growth within the pancreas. IGFs and IGF-binding proteins (IGFBPs) have been implicated as paracrine regulators of islet cell growth within the developing pancreas. The purpose of this study was to determine whether the intact rat pancreas expresses mRNAs for IGF-I, IGF-II and IGFBPs, and how these might change with development. Liver was studied as a control tissue. Pancreas and liver were taken from fetal rats at 20-22 days of gestation, from postnatal rats at 1-21 days and from adult animals, and mRNAs for IGFs-I and -II and IGFBPs-1 to -6 were detected by Northern blot hybridization. The amount of IGF-II mRNA was greatest in the liver and pancreas of the fetal rat, and declined in both tissues during the neonatal period. Conversely, IGF-I mRNA levels were low but detectable in fetal life, and rose to adult levels within 2 weeks of birth. Both IGFBP-1 and IGFBP-2 mRNAs were present in fetal rat liver, increasing in amount over the first week of life, and declining in the adult. However, within the pancreas, IGFBP-1 mRNA was undetectable and IGFBP-2 mRNA was very low in the fetus and neonate. Both IGFBP-1 and IGFBP-2 mRNAs transiently appeared in the pancreas between postnatal weeks 2 and 3 and declined in the adult. IGFBP-3 and IGFBP-4 mRNAs were detected in both the liver and pancreas throughout the developmental period studied. IGFBP-3 mRNA increased in amount immediately following birth, while the quantity of IGFBP-4 mRNA increased sharply in liver from postnatal day 21, but declined in the pancreas. mRNA for IGFBP-5 or -6 was undetectable in either tissue. The reslts show that both IGF-I and IGF-II are expressed by rat pancreas from at least 20 days of gestation, the latter being predominant in fetal life and the former during postnatal development. In addition, at least four IGFBP mRNAs (IGFBPs-1, -2, -3 and -4) were expressed within the pancreas with distinct developmental patterns. IGFBP-3 and -4 were predominant in the fetal and neonatal periods, while increased expression of IGFBPs-1 and -2 occurred 2-3 weeks after birth. The ontogeny of IGFBP mRNA expression in pancreas differed from that in liver.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2002

Impact of simultaneous pancreas and kidney transplantation on progression of coronary atherosclerosis in patients with end-stage renal failure due to type 1 diabetes.

OBJECTIVE: Mortality in type 1 diabetic patients with end-stage renal failure is high and dominated by coronary atherosclerotic events. With regard to prognosis, simultaneous transplantation of pancreas and kidney (SPK) may be superior to kidney transplantation alone (KTA) in type 1 diabetic patients, because normalization of blood glucose levels may reduce progression of coronary atherosclerosis and because it is well known that progression of coronary atherosclerosis is one of the major factors that determines clinical prognosis. However, no data are available on progression of coronary atherosclerosis after SPK. RESEARCH DESIGN AND METHODS: We performed an observational angiographic study comparing progression of coronary atherosclerosis, analyzed with quantitative coronary angiography, in patients with (n = 26) and those without (n = 6) a functioning pancreas graft after SPK, to test the hypothesis that normalization of blood glucose levels by SPK may indeed reduce progression of coronary atherosclerosis in type 1 diabetic patients and thereby improve prognosis. RESULTS: Mean follow-up was 3.9 years. Average glucose control was significantly worse for the patients without a pancreas graft than for patients with a functioning pancreas graft: 11.3 (SD 3.5) vs. 5.9 mmol/l (SD 1.1) (P = 0.03). Mean segment diameter loss (progression of diffuse coronary atherosclerosis) was 0.024 mm/year (SD 0.067) in patients with a functioning pancreas graft, compared with 0.044 mm/year (SD 0.038) in patients in whom the pancreas graft was lost. Minimum obstruction diameter loss (progression of focal coronary atherosclerosis) was 0.037 mm/year (SD 0.086) in patients with a functioning pancreas graft compared with 0.061 mm/year (SD 0.038) in patients in whom the pancreas graft was lost. Regression of atherosclerosis occurred in 38% of patients with a functioning pancreas graft compared with 0% of patients of whom the pancreas graft was lost (P = 0.035). CONCLUSIONS: Our study provides, for the first time, evidence that in patients who have undergone SPK, progression of coronary atherosclerosis in patients with a functioning pancreas graft is reduced compared with patients with pancreas graft failure. Our observation is an important part of the explanation for the observed improved mortality rates reported in type 1 diabetic patients with end-stage renal failure after SPK compared with KTA. In light of these findings described above, SPK must to be carefully considered for all diabetic transplant candidates.

Adult↗
PubMed1991

A single institution's experience with solitary pancreas transplantation: a multivariate analysis of factors leading to improved outcome.

The results of cadaveric donor pancreas transplantation at a single institution using the bladder drainage technique have been analyzed according to several factors that may impinge on outcome. Both multivariate and univariate statistical methods were used, with emphasis on solitary (pancreas after kidney and pancreas transplant alone) as opposed to simultaneous pancreas/kidney transplants. Of the 444 pancreas transplants performed at our institution from December 1966 through December 1991, we analyzed 249 bladder-drained cadaver donor pancreas transplants from November 1984 through August 1991. The factors that had a significant impact on outcome in the Cox multivariate analysis included retransplantation, age, preservation time, and degree of HLA mismatching. The results of solitary pancreas transplants improved with time as the factors that have an impact on graft survival rates were deliberately manipulated. During the 1988 to 1991 era, pancreas graft functional survival (insulin-independent) rates were not significantly different among the 3 recipient categories. Solitary pancreas transplant recipients less than 45 years old receiving primary grafts had a 1-year function rate of 61% in the pancreas transplant alone group (n = 32) and 74% in the pancreas after kidney group (n = 24). By placing emphasis on minimizing HLA mismatches, by giving adequate immunosuppression, and by detecting and treating rejection episodes early based on a decline in urine amylase, the results with solitary pancreas transplantation can be as good as those with simultaneous pancreas kidney transplantation. There are limitations to the interpretations that can be given to retrospective studies using inhomogeneous factors, as is the case in the analyses presented here. We cannot identify risk factors with certainty because the protocols changed over time, eg, immunosuppressive regimens, policies on HLA matching, and choice of duct-management techniques. Thus, in the analysis of all cases, not only was there a higher proportion by the bladder-drainage techniques in the later period, but the proportion of cases with good HLA matches was also higher: yet the earlier cases (more poorly matched, performed by the other techniques, and with worse results), were in the model. Retransplantation is also a problem for the analysis. The number performed was proportionately greater in the later period, and the possibility of retransplantation differed according to the patient's age. Over such a long time, we cannot evaluate our gain in experience statistically.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1987

Pancreas transplantation with pancreaticocystostomy and quadruple immunosuppression.

Forty-three whole-pancreas transplantations with pancreaticocystostomy were performed. Eighteen patients received pancreas transplants after previously receiving living-related kidney transplants, 18 patients received simultaneous kidney and pancreas transplants, and seven patients received pancreas transplants after previously receiving cadaver kidney transplants. All patients were immunosuppressed with quadruple immunosuppression including antilymphocyte globulin, prednisone, cyclosporine, and azathioprine. Overall graft survival for pancreas transplants is 73.1%. In the group with pancreas after living-related kidney, 1-year graft survival was 50% for the pancreas and 95.4% for the kidney. In the pancreas after cadaver kidney group, pancreas and kidney survival rates were 100% at 1 year, and in the simultaneous pancreas and kidney group, pancreas 1-year graft survival was 87.5% and kidney transplant survival was 93.8%. Overall patient survival at 1-year is 95.6%. Technical complications occurred in 21 patients. These included wound infections, intra-abdominal abscess formation, bleeding, and disruption of the pancreaticocystostomy. We believe that pancreas transplantation can now be performed with acceptable graft and patient survival.

Adult↗
PubMed1993

Quantification of human cytoplasmic islet-cell antibodies which cross-react with mouse pancreas: a follow-up study in type 1 (insulin-dependent) diabetic patients and in first-degree relatives.

We studied the heterogeneity of cytoplasmic islet-cell antibodies for cross-reaction with mouse pancreas in 31 recent-onset Type 1 (insulin-dependent) diabetic patients and 31 first-degree relatives with islet-cell autoantibodies detected on human pancreas. Only six Type 1 diabetic patients displayed islet-cell antibodies binding to human pancreas but not to mouse pancreas. Among 15 first-degree relatives displaying such antibodies which did not react with mouse pancreas, including one identical twin and one subject with polyglandular autoimmunity, none developed diabetes or even lost acute insulin response to intravenous glucose after 5 years of follow-up. By contrast, 14 of 20 (70%) of the Type 1 diabetic patients with islet-cell antibodies detected on human pancreas, and five first-degree relatives who progressed to a loss of acute insulin response to glucose and then to either Type 1 diabetes or glucose intolerance, also displayed antibodies reactive with mouse islets. Surprisingly, islet-cell antibodies were detectable on mouse pancreas but not on human pancreas in four Type 1 diabetic patients and in one relative who progressed to diabetes. In the five relatives who progressed to metabolic abnormalities, islet-cell antibody titres on mouse pancreas, quantified by the fluorescence intensity per islet at each serum dilution, progressively increased concomitantly with the loss of acute insulin response to glucose, whereas islet-cell antibody titres on human pancreas remained stable. The usefulness of such quantification was also validated by the fact that antibody titres on mouse pancreas were decreased after 3 months (p < 0.01) in recent-onset Type 1 diabetic patients, while titres on human pancreas were not.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1998

Immunosuppression in pancreas transplantation: progress, problems and perspective.

Through 1997, over 10,000 pancreas transplants have been performed world-wide, with 88% being simultaneous kidney-pancreas transplants (SKPTs). Current 1-year patient survival exceeds 90% and pancreas graft survival (complete insulin independence) exceeds 80% for SKPT, 70% for sequential pancreas after kidney transplant (PAKT), and 65% for pancreas transplant alone (PTA). According to Registry data, rejection accounts for 32% of graft failures in the first year after pancreas transplantation. However, improving outcomes are expected to continue with the evolution of treatment protocols. Most pancreas transplant centres employ quadruple drug immunosuppression with anti-lymphocyte induction, using either a monoclonal or polyclonal antibody agent. In recent years, there has been an overall decline in the use of antibody-induction therapy from 90% during 1987-93, to 83% of pancreas transplants performed during 1994-97. Maintenance immunosuppression is triple therapy consisting of a calcineurin inhibitor (cyclosporine or tacrolimus), corticosteroids, and an anti-metabolite such as azathioprine (AZA) or mycophenolate mofetil (MMF). Prior to 1995, nearly all pancreas transplant recipients were managed with Sandimmune. Since 1986, tacrolimus-based therapy has been used in approximately 20% of cases, and a new microemulsion formulation of cyclosporine (Neoral) has replaced Sandimmune in contemporary post-transplant immunosuppression. In addition, MMF is replacing AZA as part of the standard immunosuppressive regimen following pancreas transplantation. At present, a number of centres are conducting various trials with new drug combinations including either Neoral or tacrolimus in combination with steroids and MMF, with or without antibody-induction therapy. From 1994 to 1997, the 1-year rates of immunologic graft loss have decreased to 2% after SKPT, 9% after PAKT, and 16% after PTA. The current array of new immunosuppressive agents are providing more effective control of rejection and permitting solitary pancreas transplantation to become an accepted treatment option in diabetic patients without advanced complications. The apparent potency of new drug combinations has also resulted in a resurgence of interest in steroid withdrawal. Immunosuppressive strategies will continue to evolve to achieve effective control of rejection while minimizing injury to the allograft and risk to the patient. In addition, new regimens must not only address the issue of specific drug toxicities, but also long-term economic, metabolic, and quality of life outcomes. Pancreas transplantation will remain an important alternative in the treatment of diabetic patients until other strategies are developed that can provide equal glycaemic control with less immunosuppression and overall morbidity.

Humans↗
PubMed1994

Cigarette smoking and pancreas cancer: a case-control study based on direct interviews.

BACKGROUND: Cigarette smoking is the most consistently reported risk factor for pancreas cancer, yet the dose-response relationship in many pancreas cancer studies is weak. Because of the poor prognosis for pancreas cancer, many case-control studies have been based largely on interviews with proxy respondents, who are known to report less reliable information on detailed smoking habits than original subjects. PURPOSE: Our purpose was to evaluate cigarette smoking as a risk factor for pancreas cancer based on data obtained only from direct interviews and to estimate the effects of quitting smoking and of switching from nonfiltered to filtered cigarettes on risk. Our objective also was to estimate the contribution of cigarette smoking toward explaining the higher pancreas cancer incidence experienced by black Americans compared with white Americans. METHODS: A population-based, case-control study of pancreas cancer was conducted during 1986-1989 in Atlanta, Ga., Detroit, Mich., and 10 counties in New Jersey. Direct interviews were successfully completed with 526 case patients and 2153 control subjects aged 30-79 years, making this the largest population-based, case-control study of pancreas cancer to date based only on direct interviews. RESULTS: Cigarette smokers had a significant, 70% increased risk of pancreas cancer compared with the risk in nonsmokers. A significant, positive trend in risk with increasing duration smoked was apparent (P < .0001), with long-term (> or = 40 years) smokers experiencing a modest 2.1-fold risk. We also observed a negative trend in risk with increasing years quit smoking. Smokers who quit for more than 10 years experienced about a 30% reduction in risk relative to current smokers; quitters of 10 years or less experienced no risk reduction. Switching from nonfiltered to filtered cigarettes did not appear to decrease risk. Compared with nonsmokers, subjects who smoked only filtered cigarettes had a 50% elevated risk and those who smoked only nonfiltered cigarettes had a 40% elevated risk. The proportion of pancreas cancer attributable to cigarette smoking was 29% in blacks and 26% in whites. CONCLUSIONS: The relationship between cigarette smoking and pancreas cancer risk is likely to be causal, despite the weakness of the dose-response data. Long-term smoking cessation clearly reduces risk, whereas switching from nonfiltered to filtered cigarettes may not be beneficial. Cigarette smoking appears to explain little of the excess pancreas cancer risk experienced by blacks. IMPLICATIONS: Elimination of cigarette smoking would eventually prevent approximately 27% of pancreas cancer, saving 6750 lives in the United States annually.

Adult↗
PubMed2000

Prognosis and surgical treatment of gastric cancer invading the pancreas.

The clinicopathologic characteristics of gastric cancer invading the pancreas have not been determined. Gastrectomy was performed in 282 patients with gastric cancer invading adjacent organs at the Department of Surgery II, Kyushu University Hospital, between 1970 and 1987, and patient data were retrospectively analyzed using univariate and multivariate analyses. Of these patients, 150 (53.2%) had tumors invading the pancreas and 132 had tumors invading adjacent organs other than the pancreas. In both groups, the undifferentiated tissue type with infiltrative growth, lymphatic involvement and lymph node metastasis was common. In cases of pancreas invasion, the extent of lymph node metastasis was more severe, vascular involvement was more frequent and the rate of concomitant liver metastasis was higher. The survival time of the patients with pancreas invasion was shorter compared to patients with cancer invading other organs, and pancreas involvement was one of the independent factors predicting a poor prognosis. With respect to surgical treatment of gastric cancer invading the pancreas, the prognosis was better for cases treated with curative surgery and pancreas resection. Of 39 patients treated with partial resection of the pancreas, the tumor had invaded only the capsule of the pancreas in 18 and the pancreas in the other 21. Pancreas-invasive gastric cancer cells are likely to advance via lymphatic and vascular routes and survival time is shorter, but curative resection can improve the survival rate, and perioperative treatment should be appropriately designed.

Aged↗
PubMed2003

[Prospects for standardization of surgical procedures for carcinoma of the pancreas].

Since physicians need to guarantee the efficacy of medical therapy for patients, therapies for patients with cancer should be standardized to some extent. Carcinoma of the pancreas has the highest death rate of all cancers, with a resection rate as low as about 25% to 30% and a 5-year survival rate of around 9%. It is very difficult in such a situation to standardize the surgical strategy for carcinoma of the pancreas. Because pancreatic cancer is a general disease, the treatment strategy should include not only complete surgical resection but also local control methods with intraoperative radiation, prevention of liver metastasis, development of effective anti-cancer drugs, etc. Major progress in therapy for pancreatic carcinoma may be expected in the near future by with the cumulative use of effective therapies. Standard resection and extended resection: For carcinoma of the head of the pancreas, pancreaticoduodenectomy with regional lymph node dissection is performed in Japan, as is extended resection with thorough lymph node dissection of the retroperitoneal and paraaortic region. However, so far the prognosis of patients who undergo extended resection is not better than those who undergo standard resection. A randomized controlled trial of the two types of resection is now being conducted and its results are awaited. For carcinoma of the body and tail of the pancreas, distal pancreatectomy and splenectomy with lymph node dissection is performed if hematogenous or massive lymph node metastasis or direct invasion of the large vessels has not occurred. The Appleby procedure is performed in some cases. Reconstruction and complications of surgical procedures of carcinoma of the pancreas: It appears that a decrease in complications and a lower death rate have been achieved due to pancreaticoduodenectomy rather than due to the extent of lymph node dissection. In particular, progress in anastomosis techniques of the pancreas and intestine and in perioperative control has been marked. For prevention of complications, it is important that absorbable synthetic sutures be used in the pancreaticojejunal anastomosis, that the cut end of the pancreas be sutured and covered by the jejunum without dead space, and that the stent tube be inserted into the main pancreatic duct. The pancreaticojejunal anastomosis should be bordered by the greater omentum. This technique will prevent both the spread of the pancreatic juice into the intraabdominal cavity and rupture of the blood vessels, which can cause fatal postoperative bleeding. Sufficient intraabdominal drains should be in place, especially around the pancreaticojejunal anastomosis. Radiochemotherapy: There are no effective anticancer drugs for the treatment of carcinoma of the pancreas. It was reported that low-dose 5-fluorouracil and cisplatin (5-FU and CDDP) and gemcitabine plus either 5-FU, epirubicin, or CDDP has some effect. The efficacy of intraoperative radiotherapy has not been confirmed. It is not apparent whether radiochemotherapy is superior to surgery. Curable pancreatic carcinoma: Intraductal papillary-mucinous tumors of the pancreas (IPMT) take their name from the histological feature of mucin production and correspond to so-called mucin-producing tumors of the pancreas. This tumor is classified into two types, the main pancreatic duct type and the branch type. About 90% of the main pancreatic duct type and 20% of the branch type are malignant. The branch type of IPMT resembles a bunch of grasps in imaging procedures. Approximately 60% of cases with the branch type of IPMT can be followed up without surgery. Since the prognosis of IPMT is fairly good and the 5-year survival after surgery is about 70% to 80%, limited resection of the pancreas with organ preservation is under investigation. Mucinous cystic tumors of the pancreasin are characterized by development in the body and tail of the pancreas in middle-aged women, with histological ovarian-type stroma in the wall of the tumor, and round cystic lesions with a fibrous capsule containing multiple cystic components of various sizes, which resembles a Chinese citron upon imaging procedures. Surgery should be performed if such a diagnosis is made.

Digestive System Surgical Procedures↗
PubMed1995

Correlation between cystoscopic biopsy results and hypoamylasuria in bladder-drained pancreas transplants.

BACKGROUND: Urinary amylase (UA) remains the most common biochemical parameter to detect rejection in bladder-drained pancreas allografts. With the development of the cystoscopic transduodenal pancreas transplant biopsy technique, tissue samples of the pancreas graft are now frequently obtained. A definitive correlative analysis between UA activity and biopsy results has not been done in the three different pancreas transplant categories (simultaneous pancreas-kidney, pancreas transplant alone, and pancreas after kidney). METHODS: We studied 66 pancreaticoduodenal biopsy specimens obtained for hypoamylasuria. Rejection was defined as a greater than 25% decrease from stable posttransplantation baseline on two consecutive measurements at least 12 hours apart. To perform biopsies we used our newly developed 14- and 16-gauge core-cut needles (50 cm long). Biopsy specimens were considered positive if either pancreatic or duodenal rejection was found. To assess the quality of UA activity we studied 13 biopsy specimens from patients with stable UA levels; these 13 specimens were negative for rejection. RESULTS: Acute rejection was diagnosed in 36 biopsy specimens (55%). The mean decrease in UA levels was 67% +/- 8% (range, 28% to 99%) for the positive biopsy results, and 57% +/- 16% (range, 22% to 92%) for the negative biopsy results (p = 0.147). Within 1 month, UA levels returned to baseline in 19% of our patients with positive biopsy results versus 97% with negative results; postbiopsy 1-year graft survival was 64% versus 97% (p < or = 0.05). In assessing the test quality of our biopsy specimens (including 13 obtained for reasons other than hypoamylasuria), we found a sensitivity of 100% (stable UA levels mean no rejection) and a specificity of 30%. The predictive value of a positive test was 53%; of a negative test it was 100%. By performing biopsies we avoided antirejection treatment in 47% of the patients studied. We found no biopsy-related complications. CONCLUSIONS: Stable UA levels reliably rule out rejection; a decrease is a marker for acute rejection but is unspecific. Performing biopsy is currently the only way to reliably diagnose rejection in solitary pancreas recipients (pancreas transplant alone and pancreas after kidney) and in simultaneous pancreas-kidney recipients with isolated hypoamylasuria. The procedure is safe and should always be attempted to avoid unnecessary rejection treatment.

Adult↗
PubMed2000

Simultaneous cadaver pancreas living-donor kidney transplantation: a new approach for the type 1 diabetic uremic patient.

OBJECTIVE: To review the authors' experience with a new approach for type I diabetic uremic patients: simultaneous cadaver-donor pancreas and living-donor kidney transplant (SPLK). SUMMARY BACKGROUND DATA: Simultaneous cadaver kidney and pancreas transplantation (SPK) and living-donor kidney transplantation alone followed by a solitary cadaver-donor pancreas transplant (PAK) have been the transplant options for type I diabetic uremic patients. SPK pancreas graft survival has historically exceeded that of solitary pancreas transplantation. Recent improvement in solitary pancreas transplant survival rates has narrowed the advantage seen with SPK. PAK, however, requires sequential transplant operations. In contrast to PAK and SPK, SPLK is a single operation that offers the potential benefits of living kidney donation: shorter waiting time, expansion of the organ donor pool, and improved short-term and long-term renal graft function. METHODS: Between May 1998 and September 1999, the authors performed 30 SPLK procedures, coordinating the cadaver pancreas transplant with simultaneous transplantation of a laparoscopically removed living-donor kidney. Of the 30 SPLKs, 28 (93%) were portally and enterically drained. During the same period, the authors also performed 19 primary SPK and 17 primary PAK transplants. RESULTS: One-year pancreas, kidney, and patient survival rates were 88%, 95%, and 95% for SPLK recipients. One-year pancreas graft survival rates in SPK and PAK recipients were 84% and 71%. Of 30 SPLK transplants, 29 (97%) had immediate renal graft function, whereas 79% of SPK kidneys had immediate function. Reoperative rates, early readmission to the hospital, and initial length of stay were similar between SPLK and SPK recipients. SPLK recipients had a shorter wait time for transplantation. CONCLUSIONS: Early pancreas, kidney, and patient survival rates after SPLK are similar to those for SPK. Waiting time was significantly shortened. SPLK recipients had lower rates of delayed renal graft function than SPK recipients. Combining cadaver pancreas transplantation with living-donor kidney transplantation does not harm renal graft outcome. Given the advantages of living-donor kidney transplant, SPLK should be considered for all uremic type I diabetic patients with living donors.

Adult↗
PubMed1996

Use of FK 506 in pancreas transplantation.

Until recently, FK 506 was used only for rescue therapy after pancreas transplantation. We report our initial experience with FK 506 for 67 pancreas recipients (treated between 1 May 1993 and 30 April 1995). Of these recipients, 49 (73%) received FK 506 for induction and maintenance therapy, 12 (18%) for rescue or antirejection therapy, and 6 (9%) for reasons other than rescue or antirejection therapy. In our induction and maintenance therapy group, 32 recipients (65%) underwent a simultaneous pancreas-kidney transplant (SPK), 8 (16%) a pancreas transplant alone (PTA), and 9 (19%) a pancreas after previous kidney transplant (PAK). Quadruple immunosuppression was used for induction; the median FK 506 starting dose was 4 mg/day p.o. and target levels were 10-20 ng/ml. The most common side effects were nephrotoxicity (16%) and neurotoxicity (14%); transient episodes of hyperglycemia were also noted (12%), in particular in the presence of concurrent rejection and infection episodes. A matched-pair analysis was done to compare graft outcome with FK 506 versus cyclosporin A (CsA). For SPK recipients, pancreas graft survival at 6 months was 79% with FK 506 versus 65% with CsA (P = 0.04), for PTA, 100% versus 63% (P > 0.35), and for PAK, 88% versus 33% (P > 0.01). Pancreas graft loss due to rejection at 6 months posttransplant was lower with FK 506 versus CsA. Two FK 506 recipients died from B-cell lymphomas (Epstein-Barr virus positive) at 6 and 7 months posttransplant. In our rescue or anti-rejection group, 5 recipients underwent SPK, 3 PTA, and 4 PAK. The mean average FK 506 dose was 10 mg/day p.o. and the mean average FK 506 blood level was 11 ng/ml. The most common side effects were nephrotoxicity (33%) and neurotoxicity (16%). Two recipients developed hyperglycemic episodes, of whom 1 has remained on insulin with good exocrine pancreas graft function. Graft survival at 6 months after conversion was 75% for SPK, 67% for PTA, and 50% for PAK. Only one graft was lost due to chronic rejection. Our single-center experience shows that FK 506 after pancreas transplantation is associated with: (1) a low rate of graft loss due to rejection when used for induction, in particular for solitary pancreas transplants, (2) a high rate of graft salvage when used for rescue, (3) a 1% rate of new-onset insulin-dependent diabetes mellitus, and (4) a 3% rate of posttransplant lymphoma. Further studies are necessary to analyze the long-term impact of FK 506 on pancreas transplant outcome.

Adult↗
PubMed1984

Anatomoclinical and anatomosurgical essay on the lymphatic circulation of the pancreas.

This essay is based on the injection and dissection of 100 cadaver specimens (fetuses, new borns and infants), the study of 34 case reports of pancreatic carcinoma, the injection of the lymphatic system in 14 living dogs and the reconstruction of the dorsal mesentery of an embryo of 30 mm according to Born's method. The results are as follows: the anatomy of the pancreas and of the lymphatic channels show that there are two distinct portions, one is right-sided and corresponds to the primitive ventral bud, the other is situated on the left and corresponds to the primitive dorsal bud. The primitive dorsal mesentery is formed by a double contingent: one right, for the right pancreas, this is the retroportal process (RPP). The other left, for the left pancreas. This is a formation which up until now, has never been described in the literature, the left lateral portal process (LLPP). While the anterior lymphatic drainage of the pancreas does not seem to hold any surprises, the posterior lymphatic drainage, arising from the posterior and anterior surfaces of the pancreas, is very particular. In the right side (anterior and posterior aspects), the drainage runs to the RPP, while in the left side (anterior and posterior aspects) it courses to the LLPP and here, in an exclusive manner. Only a few borderline regions, those situated precisely in the area of inosculation of the two buds, escape this systematisation. The terminal network of the pancreatic lymphatic channels have a short distance to bridge in order to reach the thoracic duct. The study of the distribution of lymph node metastases in carcinoma of the pancreas seems to confirm the anatomical results in the cadaver, but our series is too short to be of statistical value. Very early spread via the thoracic duct probably greatly reduces the value of supra-enlarged operations whose justification is precisely more complete lymph node removal. It might be useful, however, if proof could be provided that tumor reduction in the case of carcinoma of the pancreas is a necessary prelude to complementary therapeutic measures. The anatomy of the pancreas and of the lymphatic channels in mammals seems to confirm the results found in man, i.e. the division of the pancreas into a right and a left pancreas. The precise knowledge of the anatomy of the lymphatic ducts of the pancreas might be the starting point for progress in the experimental studies concerning the modifications of the lymphatic circulation during acute pancreatitis.(ABSTRACT TRUNCATED AT 400 WORDS)

Abdomen↗
PubMed1999

Review of immunosuppressive usage in pancreas transplantation.

Throughout 1997, nearly 10,000 pancreas transplants have been performed worldwide, with 88% being simultaneous kidney transplants (SKPT). The current 1 yr patient survival rate exceeds 90% and pancreas graft survival (complete insulin independence) rate exceeds 80% for SKPT, 70% for sequential pancreas after kidney transplant (PAKT), and 65% for pancreas transplant alone (PTA). According to registry data, rejection accounts for 32% of graft failures in the first year after pancreas transplantation. However, improvements are expected to continue with the evolution of treatment protocols. Most pancreas transplant centers employ quadruple drug immunosuppression with anti-lymphocyte induction with either a monoclonal or polyclonal antibody agent. In recent years, there has been an overall decline in the use of antibody induction therapy from 90% during the period 1987-1993 to 83% of pancreas transplants performed during 1994-1997. Maintenance immunosuppression is triple therapy consisting of a calcineurin inhibitor (cyclosporine or tacrolimus), corticosteroids, and an anti-metabolite (AZA or MMF). Prior to 1995, nearly all pancreas transplant recipients were managed with Sandimmune. In the last 2 yr, tacrolimus-based therapy has been used in approximately 20% of cases and a new microemulsion formulation of cyclosporine (Neoral) has replaced Sandimmune in contemporary post-transplant immunosuppression. In addition, MMF is replacing AZA as part of the standard immunosuppressive regimen after pancreas transplantation. At present, a number of centers are conducting various trials with new drug combinations including either Neoral or tacrolimus in combination with steroids and MMF with or without antibody induction therapy. From 1994 to 1997, the 1 yr rates of immunologic graft loss have decreased to 2% after SKPT, 9% after PAKT, and 16% after PTA. The current array of new immunosuppressive agents are providing more effective control of rejection and permitting solitary pancreas transplantation to become an accepted treatment option in diabetic patients without advanced complications. The apparent potency of new drug combinations has also resulted in a resurgence of interest in steroid withdrawal. Immunosuppressive strategies will continue to evolve in order to achieve effective control of rejection while minimizing injury to the allograft and risk to the patient. In addition, new regimens must not only address the issue of specific drug toxicities but also long-term economic, metabolic, and quality of life outcomes. Pancreas transplantation will remain an important alternative in the treatment of diabetic patients until other strategies are developed that can provide equal glycemic control with less immunosuppression and overall morbidity.

Antilymphocyte Serum↗