Factors Associated With Morbidity Following Total Pancreatectomy and Islet Autotransplantation: A NSQIP Analysis

BackgroundTotal pancreatectomy with islet autotransplantation is a therapeutic surgical option for patients with chronic pancreatitis leading to significant reduction in pain, improvement in quality of life, and potential for preservation of partial to full endocrine function. Data on the factors associated with short-term morbidities are limited.MethodsWe queried the American College of Surgeons National Surgery Quality Improvement Project for patients undergoing total pancreatectomy with islet autotransplantation from 2005 to 2015. We determined 30-day morbidity and mortality and performed univariate and multivariate analysis to determine the preoperative and intraoperative factors associated with development of postoperative infectious complications.ResultsThe rate of 30-day postoperative morbidity in 384 patients undergoing total pancreatectomy with islet autotransplantation was 36% with an overall mortality of 1%. Postoperative infectious complications developed in 29% of patients and were associated with increased operative time (P = .016),and higher postoperative wound class (P = .045). After risk adjustment, only increased operative time was independently associated with increased rates of infectious complications (OR=1.1, 95% CI = 1.01-1.13, P = .02).ConclusionsTotal operative time is independently associated with increased postoperative infectious complications in total pancreatectomy with islet autotransplantation. Future interventions aimed at optimizing islet isolation, surgical approach, and refinement of patient selection criteria present opportunities for reducing operative time and potentially reducing the morbidity of this surgical procedure.     

Islet Autotransplantation in Diabetic Patients

IntroductionPainful chronic pancreatitis (CP) is the main indication for analgesic pancreatectomy with simultaneous islet autotransplantation to prevent postoperative diabetes mellitus (DM). However, advanced CP may lead to insulin secretion disorders and DM. There are doubts as to whether islet autotransplantation in such cases is an appropriate procedure. The aim of this study was to analyze the results of islet autotransplantation in patients with CP with already diagnosed with DM.MethodBetween 2008 and 2015, at the Department of General and Transplantation Surgery, patients with CP and unsatisfying pain treatment with positive fasting C-peptide ( > 0.3 ng/mL) level were qualified for simultaneous pancreatectomy and islet autotransplantation. Eight procedures were performed. In 5 cases patients had DM diagnosed prior to the procedure (DM group n = 5). Three patients without DM diagnosed prior to surgery were the control group (n = 3).ResultThere were no cases of procedure-related deaths in either group. Pain relief without analgesics was reported by all patients. Good islet function was observed in 80% (4/5) of the DM group vs 100% (3/3) in the control group (P = ns). Brittle diabetes was diagnosed in 1 patient in the DM group as a result of islet primary non-function.ConclusionPatients with CP-related severe pain and DM patients with positive C-peptides should be considered for pancreatectomy and islet autotransplantation.     

Islet damage during isolation as assessed by miRNAs and the correlation of miRNA levels with posttransplantation outcome in islet autotransplantation

High‐quality pancreatic islets are essential for better posttransplantation endocrine function in total pancreatectomy with islet autotransplantation (TPIAT), yet stress during the isolation process affects quality and yield. We analyzed islet‐enriched microRNAs (miRNAs) ‐375 and ‐200c released during isolation to assess damage and correlated the data with posttransplantation endocrine function. The absolute concentration of miR‐375, miR‐200c, and C‐peptide was measured in various islet isolation steps, including digestion, dilution, recombination, purification, and bagging, in 12 cases of TPIAT. Posttransplantation glycemic control was monitored through C‐peptide, hemoglobin A_1c, insulin requirement, and SUITO index. The amount of miR‐375 released was significantly higher during enzymatic digestion followed by the islet bagging (P < .001). Mir‐200c mirrored these changes, albeit at lower concentrations. In contrast, the C‐peptide amount was significantly higher in the purification and bagging steps (P < .001). Lower amounts of miR‐375 were associated with a lower 6‐month insulin requirement (P = .01) and lower hemoglobin A_1c (P = .04). Measurement of the absolute quantity of miRNA‐375 and ‐200c released during islet isolation is a useful tool to assess islet damage. The quantity of released miRNA is indicative of posttransplantation endocrine function in TPIAT patients.     

Pain Control and Quality of Life After Pancreatectomy with Islet Autotransplantation for Chronic Pancreatitis

Introduction  

In selected patients with chronic pancreatitis, total pancreatectomy with islet autotransplantation can be effective for the treatment of intractable pain while ameliorating postoperative diabetes. Improved quality of life scores and decreased daily narcotic use, as indicators of successful pain relief, are expected after total pancreatectomy. These outcomes and their relationship have not been well examined in this patient group.     

Effect of intraoperative fluid type on postoperative systemic inflammatory response and end organ dysfunction following total pancreatectomy with islet autotransplantation in children

PurposeTo evaluate the effect of intraoperative fluid type [half normal saline (0.45NS) or lactated Ringer's solution (LR)] on the risk of systemic inflammatory response syndrome (SIRS) and acute kidney injury after total pancreatectomy with islet autotransplantation in children.MethodsRetrospective review where demographics, operative details, systemic inflammatory response, and evaluation for end organ dysfunction over the first 5 postoperative days was obtained. Mixed effects Poisson regression compared risk of SIRS and acute kidney injury by intraoperative fluid type.ResultsForty three patients were included with no difference in demographic characteristics between groups. SIRS was observed in 95, 77, and 71% over post operative days 1, 3, and 5. Intraoperative fluid type was found to not be associated with postoperative SIRS (RR: 0.91, p = 0.23). However, female sex (RR: 1.30, p < 0.01), increased BMI (RR: 1.08, p < 0.01), and longer operative time (RR: 1.07, p < 0.01) were found to be factors that are associated with increased risk of postoperative SIRS. Intraoperative 0.45NS use was associated with increased acute kidney injury compared to LR on postoperative day 1 (52% vs 0%, p < 0.01), but not on postoperative days 3 or 5.ConclusionIntraoperative fluid type (0.45NS vs LR) does not increase the risk of postoperative SIRS in children after TPIAT. Predictive factors that are associated with an increased risk of eliciting postoperative SIRS includes female sex, increased BMI, and longer operative times.Level of evidenceIII     

Targeting CXCR1/2 in the first multicenter,double-blinded,randomized trial in autologous islet transplant recipients

Several cytokines and chemokines are elevated after islet infusion in patients undergoing total pancreatectomy with islet autotransplantation (TPIAT), including CXCL8 (also known as interleukin-8), leading to islet loss. We investigated whether use of reparixin for blockade of the CXCL8 pathway would improve islet engraftment and insulin independence after TPIAT. Adults without diabetes scheduled for TPIAT at nine academic centers were randomized to a continuous infusion of reparixin or placebo (double-blinded) for 7 days in the peri-transplant period. Efficacy measures included insulin independence (primary), insulin dose, hemoglobin A_1c (HbA_1c), and mixed meal tolerance testing. The intent-to-treat population included 102 participants (age 39.5 ± 12.2 years, 69% female), n = 50 reparixin-treated, n = 52 placebo-treated. The proportion insulin-independent at Day 365 was similar in reparixin and placebo: 20% vs. 21% (p = .542). Twenty-seven of 42 (64.3%) in the reparixin group and 28/45 (62.2%) in the placebo group maintained HbA_1c ≤6.5% (p = .842, Day 365). Area under the curve C-peptide from mixed meal testing was similar between groups, as were adverse events. In conclusion, reparixin infusion did not improve diabetes outcomes. CXCL8 inhibition alone may be insufficient to prevent islet damage from innate inflammation in islet autotransplantation. This first multicenter clinical trial in TPIAT highlights the potential for future multicenter collaborations.     

CT texture analysis as a predictor of favorable response to anti-PD1 monoclonal antibodies in metastatic skin melanoma

PurposeThe purpose of this study was to determine whether texture analysis features on pretreatment contrast-enhanced computed tomography (CT) images and their evolution can predict treatment response of metastatic skin melanoma (SM) treated with anti-PD1 monoclonal antibodies.Materials and methodsSixty patients (29 men, 31 women; median age, 56 years; age range: 27–91 years) with metastatic SM treated with pembrolizumab (43/60; 72%) or nivolumab (17/60; 28%) were included. Texture analysis of SM metastases was performed on baseline and first post-treatment evaluation CT examinations. Mean gray-level, entropy, kurtosis, skewness, and standard deviation values were derived from the pixel distribution histogram before and after spatial filtration at different anatomic scales, ranging from fine to coarse. Lasso penalized Cox regression analyses were performed to identify independent variables associated with favorable response to treatment.ResultsA total of 127 metastases were analyzed, with a median of two metastases per patient. Skewness at fine texture scale (spatial scale filtration [SSF] = 2; Hazard ratio [HR]: 3.51; 95% CI: 2.08–8.57; P = 0.010), skewness at medium texture scale (SSF = 3; HR: 0.56; 95% CI: 0.11–1.59; P = 0.014), variation of entropy at fine texture scale (SSF = 2; HR: 37.76; 95% CI: 3.48–496.22; P = 0.008) and LDH above the threshold of 248 UI/L (HR: 3.56; 95% CI: 1.78–21.35; P = 0.032] were independent predictors of response to treatment.ConclusionPretreatment CT texture analysis-derived tumor skewness and variation of entropy between baseline and first control CT examination may be used as predictors of favorable response to anti-PD1 monoclonal antibodies in patients with metastatic SM.     

Pancreatic surgery in infants with Beckwith–Wiedemann Syndrome and Hyperinsulinism

PurposeTo present our experience in the care of infants with Beckwith–Wiedemann syndrome (BWS) who required pancreatectomy for the management of severe Congenital Hyperinsulinism (HI).MethodsWe did a retrospective chart review of patients with BWS who underwent pancreatectomy between 2009 and 2012.ResultsFour patients with BWS and severe HI underwent pancreatectomy, 3 females and one male. Eight other BWS patients with HI could be managed medically. The diagnosis of BWS was established by the presence of mosaic 11p15 loss of heterozygosity and uniparental disomy in peripheral blood and/or pancreatic tissue. All patients had hypoglycemia since birth that did not respond to medical management with diazoxide or octreotide, and required glucose infusion rates of up to 30 mg/kg/min. Preoperative 18-F-DOPA PET/CT scans showed diffuse uptake of the radiotracer throughout an enlarged pancreas in three patients and a normal sized pancreas with a large area of focal uptake in the pancreatic body in one patient. None of the patients had mutations in the ABCC8 or KCNJ1 genes that are typically associated with diazoxide-resistant HI. Age at surgery was 1, 2, 4, and 12 months and the procedures were 85%, 95%, 90%, and 75% pancreatectomy, respectively, with the pancreatectomy extent tailored to HI severity. Pathologic analysis revealed marked diffuse endocrine proliferation throughout the pancreas that occupied up to 80% of the parenchyma with scattered islet cell nucleomegaly. One patient had a small pancreatoblastoma in the pancreatectomy specimen. The HI improved in all cases after the pancreatectomy, with patients being able to fast safely for more than 8 h. All patients are under close surveillance for embryonal tumors. One patient developed a hepatoblastoma at age 2.ConclusionThe pathophysiology of HI in BWS patients is likely multifactorial and is associated with a dramatic increase in pancreatic endocrine tissue. Severe cases of HI that do not respond to medical therapy improve when the mass of endocrine tissue is reduced by subtotal or near-total pancreatectomy.     

Combination of pancreas volume and HbA1c level predicts islet yield in patients undergoing total pancreatectomy and islet autotransplantation

Islet yield is an important predictor of acceptable glucose control after total pancreatectomy with islet autotransplantation (TP-IAT). We assessed if pancreas volume calculated with preoperative MRI could assess islet yield and postoperative outcomes. We reviewed dynamic MRI studies from 154 adult TP-IAT patients (2009-2016), and associations between calculated volumes and digest islet equivalents (IEQs) were tested. In multivariate regression analysis, pancreas volume (P < .001) and preoperative HbA1c levels (P = .009) were independently associated with digest IEQs. The IEQ prediction formula was calculated according to each preoperative HbA1c level, (a) pancreas volume × 5800 for HbA1c ≥ 6.5, (b) pancreas volume × 10 000 for HbA1c ≥5.7/<6.5 and (iii) pancreas volume × 11 400 for HbA1c < 5.7. The formula was internally validated with 28 TP-IAT patients between 2017 and 2018 (r² = .657 and r² = .710 when restricted to 24 patients without prior pancreatectomy). An estimated IEQs/Body Weight (kg) ≥3700 predicted HbA1c ≤6.5 and insulin independence at 1 year after TP-IAT with 77% and 88% sensitivity and 55% and 43% specificity, respectively. The combination of pancreas volume and preoperative HbA1c levels may be useful to estimate islet yield. Estimated IEQs were reasonably sensitive to predict acceptable glucose control at 1 year.     

Pancreatic islet autotransplantation with total pancreatectomy for chronic pancreatitis

Achieving pain relief and improving the quality of life are the main targets of treatment for patients with chronic pancreatitis. The use of total pancreatectomy to treat chronic pancreatitis is a radical and in some ways ideal strategy. However, total pancreatectomy is associated with severe diabetic control problems. Total pancreatectomy with islet autotransplantation can relieve severe pain and prevent the development of postsurgical diabetes. With islet autotransplantation, patients with chronic pancreatitis receive their own islet cells and therefore do not require immunosuppressive therapy. In the future, total pancreatectomy with islet autotransplantation may be considered a treatment option for chronic pancreatitis patients.     

Ultrasound changes within the liver after total pancreatectomy and intrahepatic islet cell autotransplantation

OBJECTIVE: Intrahepatic infusion is the most common method of islet autotransplantation. Structural and functional changes within the liver may result from a number of factors, including embolization of the terminal branches of the portal vein, the effects of high insulin concentration on surrounding hepatocytes or responses to the death of admixed exocrine tissue. Awareness of the potential changes in the appearance of the liver on ultrasonography (USS), together with an assessment of liver function, is important in the postoperative surveillance of these patients. METHODS: We retrospectively reviewed 83 patients who underwent total pancreatectomy between 1993 and 2006. Thirty-three patients had total pancreatectomy alone (control group) and 50 patients underwent total pancreatectomy and islet autotransplantation (islet group). The islets were infused into the left lobe of the liver through the middle colic or recannalated umbilical vein. All patients underwent USS as part of their hepaticojejunostomy surveillance (initially every 6 months and then yearly). RESULTS: "Echogenic nodularity" of the liver was observed in 25% of the islet group of patients and in none of the control group patients (P=0.03). These USS changes occurred from 6 to 12 months after islet autotransplantation and were not associated with any significant loss of liver function or increase in insulin requirements. The islet group had significantly less insulin requirement compared with the control group (P<0.01). CONCLUSION: Echogenicity with a nodular appearance is a common ultrasonographic finding in the liver after intrahepatic islet autotransplantation. These changes do not seem to adversely affect liver function or insulin requirement. Appreciating these changes is important to avoid misinterpretation or over-interpretation of postoperative USS images.     

Metabolic measures before surgery and long-term diabetes outcomes in recipients of total pancreatectomy and islet autotransplantation

In this single-center, retrospective cohort study, we aimed to elucidate simple metabolic markers or surrogate indices of β-cell function that best predict long-term insulin independence and goal glycemic HbA1c control (HbA1c ≤ 6.5%) after total pancreatectomy with islet autotransplantation (TP-IAT). Patients who underwent TP-IAT (n = 371) were reviewed for metabolic measures before TP-IAT and for insulin independence and glycemic control at 1, 3, and 5 years after TP-IAT. Insulin independence and goal glycemic control were achieved in 33% and 68% at 1 year, respectively. Although the groups who were insulin independent and dependent overlap substantially on baseline measures, an individual who has abnormal glycemia (prediabetes HbA1c or fasting glucose) or estimated IEQs/kg < 2500 has a very high likelihood of remaining insulin dependent after surgery. In multivariate logistic regression modelling, metabolic measures correctly predicted insulin independence in about 70% of patients at 1, 3, and 5 years after TP-IAT. In conclusion, metabolic testing measures before surgery are highly associated with diabetes outcomes after TP-IAT at a population level and correctly predict outcomes in approximately two out of three patients. These findings may aid in prognostic counseling for chronic pancreatitis patients who are likely to eventually need TP-IAT.     

Short and long-term outcomes of minimally invasive central pancreatectomy: Comparison with minimally invasive spleen-preserving subtotal distal pancreatectomy

BackgroundCentral pancreatectomy(CP) is more complex surgery and higher complication rate than distal pancreatectomy(DP). However, with the development of minimally invasive surgery, CP has become a safer surgery technique. In this study, we compare minimally invasive CP(MI-CP) and Minimally invasive spleen-preserving subtotal DP(MI-SpSTDP) to figure out the short-term and long-term outcomes of MI-CP.MethodsFrom March 2007 to June 2020, 36 cases of MI-SpSTDP and 23 cases of MI-CP were performed for benign and borderline malignant pancreatic tumors in Severance hospital. The occurrence of postoperative pancreatic fistula(POPF) and Clavian-Dindo classification grade 3 or more in the two group was investigated, and the Controlling nutritional status scores(CONUT score) before and 1-year after surgery were compared to determine the long-term outcomes of exocrine function.ResultsThere was no difference in postoperative complications including POPF between the two groups(17.4% vs 5.1%, p = 0.294). And there were no statistical differences in either the MI-CP group (0.74 ± 0.75 vs. 0.78 ± 0.99, p = 0.803) or the MI-SpSTDP group (0.86 ± 0.83 to 0.61 ± 0.59, p = 0.071).ConclusionsMI-CP had longer operation time and hospital stay and is safe and effective in preserving endocrine and exocrine functions in treatment of benign or borderline tumors located at the neck or proximal body of the pancreas.     

Utility of arginine stimulation testing in preoperative assessment of children undergoing total pancreatectomy with islet autotransplantation

Metabolic outcomes after total pancreatectomy with islet autotransplantation (TPIAT) are influenced by the islet mass transplanted. Preclinical and clinical studies indicate that insulin and C‐peptide levels measured after intravenous administration of the beta cell secretagogue arginine can be used to estimate the available islet mass. We sought to determine if preoperative arginine stimulation test (AST) results predicted transplanted islet mass and metabolic outcomes in pediatric patients undergoing TPIAT. We evaluated the association of preoperative C‐peptide and insulin responses to AST with islet isolation metrics using linear regression, and with postoperative insulin independence using logistic regression. Twenty‐six TPIAT patients underwent preoperative AST from 2015 to 2018. The acute C‐peptide response to arginine (ACRarg) was correlated with isolated islet equivalents (IEQ; r = 0.59, P = 0.002) and islet number (IPN; r = 0.48, P = 0.013). The acute insulin response to arginine (AIRarg) was not significantly correlated with IEQ (r = 0.38, P = 0.095) or IPN (r = 0.41, P = 0.071). Neither ACRarg nor AIRarg was associated with insulin use at 6 months postoperatively. Preoperative C‐peptide response to arginine correlates with islet mass available for transplant in pediatric TPIAT patients. AST represents an additional tool before autotransplant to provide counseling on likely islet mass and to inform quality improvements of islet isolation techniques.     

Optimal extent of initial parathyroid resection in patients with multiple endocrine neoplasia syndrome type 1: A meta-analysis

BackgroundHyperparathyroidism is an almost universal feature of multiple endocrine neoplasia type 1 syndrome. We present a systematic review and meta-analysis of the postoperative outcomes of patients undergoing initial operative treatment of primary hyperparathyroidism complicating multiple endocrine neoplasia 1.MethodsA comprehensive literature search was performed with a priori defined exclusion criteria for studies comparing total parathyroidectomy, subtotal parathyroidectomy, and less than subtotal parathyroidectomy.ResultsTwenty-one studies incorporating 1,131 patients (272 undergoing total parathyroidectomy, 510 subtotal parathyroidectomy, and 349 less than subtotal parathyroidectomy) were identified. Pooled results revealed increased risk for long-term hypoparathyroidism in total parathyroidectomy patients (relative risk 1.61; 95% confidence interval, 1.12?2.31; P = .009) versus those undergoing subtotal parathyroidectomy. In the less than subtotal parathyroidectomy or subtotal parathyroidectomy comparison group, a greater risk for recurrence of hyperparathyroidism (relative risk 1.37; 95% confidence interval, 1.05?1.79; P = .02), persistence of hyperparathyroidism (relative risk 2.26; 95% confidence interval, 1.49?3.41; P = .0001), and reoperation for hyperparathyroidism (relative risk 2.48; 95% confidence interval, 1.65?3.73; P < .0001) was noted for less than subtotal parathyroidectomy patients, albeit with lesser risk for long-term for hypoparathyroidism (relative risk 0.47; 95% confidence interval, 0.29?0.75; P = .002).ConclusionSubtotal parathyroidectomy compares favorably to total parathyroidectomy, exhibiting similar recurrence and persistence rates with a decreased propensity for long-term postoperative hypoparathyroidism. The benefit of the decreased risk of hypoparathyroidism in less than subtotal parathyroidectomy is negated by the increase in the risk for recurrence, persistence, and reoperation. Future studies evaluating the performance of less than subtotal parathyroidectomy in specific multiple endocrine neoplasia 1 phenotypes should be pursued in an effort to delineate a patient-tailored, operative approach that optimizes long-term outcomes.     

Early versus late tube feeding initiation after PEG tube placement: Does time to feeding matter?

BackgroundVariation exists in the timing of tube feed initiation after percutaneous endoscopic gastrostomy (PEG) tube placement. The aim of our study was to review outcomes of early tube feed (ETF) versus late tube feed (LTF) initiation after PEG tube placement.MethodsWe performed a retrospective review of all trauma patients who underwent PEG tube placement from 1/2014 to 12/2018. ETF was defined as initiation < 24 h and LTF > 24 h after placement. The primary outcome measure was feeding intolerance and secondary outcomes included post-operative complications. All statistical analyses were performed using standard statistical methods (e.g. Pearson's Chi-squared, Fisher's exact and Mann Whitney-U tests).ResultsThere were 295 patients (164 ETF and 131 LTF) that received a PEG tube at our level 1 trauma center. There was no difference with feeding intolerance at 12 h (5% vs. 4%; p = 0.88), 24 h (1% vs. 2%; p = 1.00), and 48 h (4% vs. 4%; p = 1.00). There was no difference when comparing intolerance symptoms such as nausea and vomiting (1% vs. 2%; p = 0.79), abdominal tenderness (2% vs. 3%; p = 0.76), high gastric residuals (2% vs. 2%; p = 1.00) and aspiration (0% vs. 2%; p = 0.39). There was no difference when comparing post-operative complications (4% vs. 8%; p = 0.21).ConclusionsEarly tube feeding after PEG placement is safe and equivalent to late tube feeding in the adult trauma population. Future prospective studies are warranted to establish the optimal timing for initiation of tube feeds after PEG tube placement.     

Total pancreatectomy in the pig for islet transplantation. Technical alternatives

Pigs appear to be a suitable biological and logistical animal donor of islets for xenotransplantation in human diabetic type I recipients. To improve the islet isolation technique in this species, to evaluate the islet function in vivo, and to assess the toxic effects of various immunosuppressive regiments on transplanted islets will necessitate a model of the pancreatectomized pig suitable for islet autotransplantation. We describe three techniques of total pancreatectomy in pigs. The first removed the pancreas in order to study postoperative management and pig survival; no attempt was made to preserve the pancreas for islet isolation. The second consisted of a pancreatectomy in a surviving pig, with careful preservation of the whole pancreas for subsequent islet isolation. The third was rapid en bloc procurement of the pancreas and duodenum, to obtain a pancreas solely for the purpose of islet isolation. We conclude that pigs tolerate and survive a total pancreatectomy--they are suitable animals for islet isolation and possible autotransplantation. The result of islet isolation does not appear related to the pancreas procurement technique; however, the islet yield must be improved before autotransplantation can be functionally successful.     

The impact of surgical complications on the outcome of total pancreatectomy with islet autotransplantation

Total pancreatectomy with islet autotransplantation is a promising treatment for refractory chronic pancreatitis. We analyzed postoperative complications in 83 TPIAT patients and their impact on islet graft function. We examined patient demographics, preoperative risk factors, intraoperative variables, and 30- and 90-day postoperative morbidity and mortality. Daily insulin requirement, HbA1c, C-peptide levels, and narcotic requirements were analyzed before and after surgery. Adverse events were recorded, with postoperative complications graded according to the Clavien-Dindo classification. There was no mortality in this patient group. Postoperative complications occurred in 38 patients (45.7%). Patients with postoperative complications were readmitted significantly more often within 30 days (p = 0.01) and 90 days posttransplant (p < 0.0003) and had a significantly longer hospital stay (p = 0.004) and intensive care unit stay (p = 0.001). Insulin dependence and graft function assessed by HbA1c, C-Peptide and insulin requirements did not differ significantly by these complications. Postoperative complications after TPIAT are associated with longer hospital and intensive care unit stay and with readmission; however, the surgical complications do not affect islet graft function.     

Total or near total pancreatectomy and islet autotransplantation for treatment of chronic pancreatitis.

Total or near total pancreatectomy is the surest way to relieve the pain of chronic pancreatitis but is rarely applied because the metabolic consequences are so severe. For most patients drainage procedures are applicable, but pancreatectomy may be the only alternative for small duct disease or where procedures to improve duct drainage have failed. Preservation of endocrine function is a major problem in patients who require pancreatectomy. Experiments in pancreatectomized dogs have shown that intrasplenic or intraportal transplantation of unpurified pancreatic islet tissue dispersed by collagenase digestion can prevent diabetes. We have applied this technique to ten patients with chronic pancreatitis, small ducts, and intractable pain. The entire pancreas of > 95% of the pancrease was excised, minced, dispersed by collagenase digestion and infused into the portal vein < 2 1/2 hours after removal. Mean (+/- SD) rise in portal pressure was 17 +/- 8 cm of water. Liver function tests were altered minimally. All patients were relieved of pain. One patient died of a complication not related to the islet autotransplant; viable islets were identified in the liver at autopsy. Of the remaining nine patients, three have been insulin independent for 1, 9, and 38 months. One patient was insulin indpendent for 15 months and now takes 12 units of insulin daily. Three have nonketosis prone diabetes (tested by insulin withdrawal) and take 15--30 units of insulin per day. C-peptide studies in these patients show that functioning islets are present. Two patients are diabetic and require 35 and 60 units of insulin per day. In eight of nine patients tested serum insulin concentrations fell to undetectable levels during the interval between pancreatectomy and islet transplantation. Serum insulin levels during the first few hours after islet transplantation predicted success. In the insulin independent or in the patients with mild diabetes, insulin levels were persistently greater than or equal to 6 microU/ml. In the other two patients, the increase in insulin concentration was not sustained. Islet tissue preparation from a diseased pancreas is difficult. The surgeon and the patient must still be willing to accept diabetes for relief of pain when performing this operation. In some patients, however, islet autotransplantation can prevent or partially ameliorate diabetes after pancreatectomy, and preservation of endocrine function is worthwhile.     

Effects of intrahepatic canine islet autotransplantation on the portal vein pressure and liver function

Currently, the most common method used for human islet transplantation is intrahepatic implantation via the portal vein, which may affect portal vein pressure and liver function. The aim of this study was to investigate the effects of intrahepatic canine islet autotransplantation on portal vein pressure and liver function. After total pancreatectomy was performed in 30 mongrel dogs, islets were isolated and transplanted back into the portal vein of the same dog. In our series, 12 dogs achieved normoglycemia (fasting glucose <200 mg/dL) without exogenous insulin after transplantation. The portal vein pressure increased from 4.6 +/- 1.5 to 7.7 +/- 2.9 cm H(2)O after islet infusion (P < .05). Alanine transferase amino transferase (ALT) levels gradually increased after pancreatectomy with the peak at 4 weeks after islet infusion. But the changes of portal vein pressure and ALT were not significantly different between successful and failed islet transplantation. In summary, elevation of portal vein pressure and liver enzymes were noted after intrahepatic canine islet autotransplantation. However, they did not influence the transplant outcome.