Decreased Intestinal Microbiota Diversity Is Associated With Increased Gastrointestinal Symptoms in Patients With Chronic Pancreatitis.

OBJECTIVES: Chronic pancreatitis (CP) is characterized by abdominal pain, recurrent hospitalizations, frequent exposure to antibiotics, nutritional deficiencies, and chronic opioid use. Data describing the gut microbial community structure of patients with CP is limited. We aimed to compare gut microbiota of a group of patients with severe CP being considered for total pancreatectomy with islet autotransplantation (TPIAT) with those of healthy controls and to associate these differences with severity of clinical symptoms. METHODS: We collected stool from healthy donors (n = 14) and patients with CP (n = 20) undergoing workup for TPIAT, in addition to clinical metadata and a validated abdominal symptoms severity survey. RESULTS: Patients with CP had significantly lower alpha diversity than healthy controls ( P < 0.001). There was a significantly increased mean relative abundance of Faecalibacterium in healthy controls compared with patients with CP ( P = 0.02). Among participants with CP, those with lower alpha diversity reported worse functional abdominal symptoms ( P = 0.006). CONCLUSIONS: These findings indicate that changes in gut microbial community structure may contribute to gastrointestinal symptoms and provide basis for future studies on whether enrichment of healthy commensal bacteria such as Faecalibacterium could provide clinically meaningful improvements in outcomes for CP patients undergoing TPIAT.

Reduced bone mineral density in the first year after total pancreatectomy with islet autotransplantation (TPIAT).

BACKGROUND/OBJECTIVES: The effect of total pancreatectomy with islet autotransplantation (TPIAT) on bone mineral density (BMD) in patients with CP is unknown. We aimed to assess bone health in patients with CP after TPIAT. METHODS: We measured BMD, BMD Z-score, and bone mineral content (BMC) for total body, lumbar spine, right and left hip in 78 patients before and after TPIAT using dual-energy X-ray absorptiometry (DXA, n = 78 pre-TPIAT, n = 65 paired pre- and 12 months post-TPIAT, n = 33 paired 12 and 18 months post-TPIAT), and tested for association with clinical history including age, smoking status, and medications using paired and two-sample t-tests, linear regression, and Fisher's exact test. Laboratory measures related to bone health were also assessed. RESULTS: In the patients with pre-TPIAT DXA, 12% had low BMD (Z-score ≤ -2). BMD, BMD Z-score, and BMC all decreased from pre-to 12 months post-TPIAT. BMD declined by 1.7%-4.1% with the greatest change at the hips. Adjusted for change in lean and fat body mass, DXA changes remained significant for total body and hip. Serum carboxy-terminal collagen crosslinks telopeptide and alkaline phosphatase increased at 12 months post-TPIAT, suggesting possible increased bone remodeling. BMD, BMD Z-score, and BMC did not change between 12 months and 18 months in any of the four regions (p > 0.6). CONCLUSIONS: TPIAT is associated with decreases in BMD in the body, lumbar, and hip regions of patients with CP in the first year after TPIAT but these appear to stabilize between 12 and 18 months after TPIAT.

Atypical Hepatic Steatosis Patterns on MRI After Total Pancreatectomy With Islet Autotransplant.

OBJECTIVE. The purpose of this retrospective study was to investigate the prevalence and patterns of hepatic steatosis after total pancreatectomy with islet autotransplant (TPIAT) and to determine if the unique patterns of steatosis seen in this study correlated with islet graft function. MATERIALS AND METHODS. Fifty-two subjects who had undergone MRI after TPIAT were reviewed for the presence of hepatic steatosis. Patterns of steatosis were categorized into three groups: normal (no steatosis), homogeneous, and atypical. Demographics and outcomes were compared between the groups. Islet graft function 1 year after surgery was classified as full graft function, partial graft function, and graft failure. Statistical analysis was performed using ANOVA, Kruskal-Wallis, and Fisher exact tests. RESULTS. Sixty-three percent of patients had steatosis present on MRI after TPIAT (33 subjects of 52 total), and 48% (25/52) exhibited an atypical pattern. Twenty-four percent of the 37 patients who had MRI examinations before TPIAT showed steatosis preoperatively, yet none of these showed an atypical steatosis pattern. Islet graft function was not statistically different between the groups. The only statistically significant variable difference between the groups was body mass index (p = .02). CONCLUSION. Steatosis is a common finding after TPIAT, and atypical steatosis patterns frequently develop after the procedure, implying that the procedure itself is the causal factor. There was no correlation between islet graft function and the presence or pattern of steatosis. An atypical pattern of hepatic steatosis can therefore be considered an incidental finding after TPIAT and does not require additional workup or treatment.

Surgical microwave ablation for multifocal non-resectable liver metastases: a single institution experience treating five or more liver lesions.

BACKGROUND: Thermal ablation is an effective treatment for patients with metastatic colon and rectal cancer and allows surgeons to offer curative intent therapy to patients who are otherwise not candidates for resection. We aimed to report outcomes of a single institution experience using microwave ablation (MWA) with or without resection to treat five or more liver metastases. METHODS: In this retrospective cohort study, the University of Minnesota Division of Surgical Oncology liver surgery database was queried to identify all patients who underwent thermal ablation of five or more colorectal liver metastases (CRLM) between 2012-2018. We reviewed patient, disease, and tumor characteristics and measured local, intrahepatic, and extrahepatic recurrence (EHR) rates. We also calculated median overall survival (OS) and disease-free survival (DFS). RESULTS: Ten patients identified had five or more (range, 5-18) tumors ablated with or without combined liver and bowel resection. Median age was 50, and most patients were male (70%) and Caucasian (90%). Four patients received ablation alone (5-12 lesions), while six had combined resection and ablation (5-18 lesions). Ablation was performed laparoscopically in six patients, and four had ablations without resection. All patients received pre- and post-operative chemotherapy. A median of 7 tumors were ablated per patient. Median follow-up was 2.3 years. Among 75 tumors ablated, ablation site recurrence (ASR) (within 1 cm of ablation site) was seen in three with a per-lesion recurrence rate of 4%. Intrahepatic recurrence (IHR) occurred in 6 (60%) patients and EHR in 1 (10%). Five patients underwent retreatment of IHR during follow-up. Median OS was 3 years and DFS was 7.1 months. At the time of last follow up, 6 patients were disease-free. CONCLUSIONS: Thermal ablation can provide acceptable DFS and OS, even with high volume metastatic colorectal cancers. Future efforts should be focused on defining selection criteria for those most likely to benefit from this aggressive approach.

Performance of modified Igls criteria to evaluate islet autograft function after total pancreatectomy with islet autotransplantation - a retrospective study.

The Igls criteria assess islet function after islet allotransplant, based on C-peptide, insulin use, hemoglobin A1c, and severe hypoglycemia. However, these criteria as currently defined cannot be applied to total pancreatectomy islet autotransplant (TPIAT) patients. We tested modified criteria for assessing islet function in a large cohort of TPIAT patients (n = 379). Metabolic outcomes were assessed. We assigned Auto-Igls class to each patient as able and evaluated the utility, validity, and perioperative risk factors of Auto-Igls at 1-year post-IAT. We tested the association of Auto-Igls with independent measures of islet graft function, specifically continuous glucose monitoring (CGM) data or acute C-peptide response to glucose (ACRglu) from intravenous glucose tolerance tests. An Auto-Igls class was assigned to 264 patients (69%). Among patients who could not be classified, most were missing exact insulin dose. Seventy-three percent of TPIAT recipients were classified as optimal or good at 1 year. The only significant predictor of Auto-Igls class was islet mass transplanted (P < 0.0001). Auto-Igls class was associated with percent time in range (70-140 mg/dl) on CGM (P = 0.02) and ACRglu (P < 0.0001). Modified Igls classification for IAT permits simple, comprehensive assessment of metabolic outcomes after TPIAT and is associated with other islet functional measures.

Early use of continuous glucose monitoring in children and adolescents after total pancreatectomy with islet autotransplantation.

BACKGROUND: Children undergoing total pancreatectomy with islet autotransplantation (TPIAT) for chronic pancreatitis require intensive insulin therapy early after TPIAT with narrow glycemic targets, which can a present significant care burden. Outpatient use of continuous glucose monitoring (CGM) systems by children and caregivers early after TPIAT is inadequately studied. METHODS: In this open-label study, we randomized 14 children and adolescents (mean age 15.4 years) after hospital discharge for TPIAT to Dexcom G6 CGM (n = 7) or standard care with a glucometer (n = 7) to assess acceptability and glycemic control with use of CGM versus usual care (glucometer). Participants in the control arm also wore a blinded CGM for 1 week. RESULT: Children randomized to real-time CGM had lower mean sensor glucose values compared with controls (p = 0.002), and high overall satisfaction with CGM. CONCLUSIONS: Our data indicate that CGM is a useful adjunct to diabetes management for children who have recently undergone TPIAT.

Surgical microwave ablation of otherwise non-resectable colorectal cancer liver metastases: Expanding opportunities for long term survival.

BACKGROUND: Colorectal liver metastases (CRLM) are the most common extra-lymphatic metastases in colorectal cancers, however, only 15-20% of these patients are candidates for resection. We reviewed our institutional experience with 135 surgical ablations for unresectable CRLM. METHODS: Retrospective review of surgically ablated CRLM from 2009 to 2018. Patient-specific variables were obtained from the medical record. Kaplan-Meier modeling was performed for survival analyses. RESULTS: We ablated 135 CRLM in 36 patients over 40 procedures. Median age was 52 years and 58% of patients were male. All patients received systemic chemotherapy. The ablation procedure was completed laparoscopically in 68% of procedures. Median number of ablated lesions per patient was 2 (range 1-15). Median maximum diameter of ablated lesions was 1.9 cm (range 0.5-12.2). Median follow up of the study was 28 months. In this time, median disease-free survival was not reached. Of the 135 lesions ablated, the per-lesion recurrence rate was 6/135 (4.4%). Median overall survival was 81 months. CONCLUSIONS: Surgical ablation of CRLM can provide excellent local control and long-term survival outcomes in patients who may otherwise not be candidates for other liver-directed therapies.

Fat-soluble Vitamin Deficiency is Common in Children With Chronic Pancreatitis Undergoing Total Pancreatectomy With Islet Autotransplantation.

ABSTRACT: The prevalence of fat-soluble vitamin (FSV) deficiency in children undergoing total pancreatectomy with islet autotransplantation (TPIAT) for chronic pancreatitis (CP) is unknown. We quantified FSV deficiency in 100 children (age ≤18) undergoing TPIAT. FSV levels (vitamins A, E, D) and clinical history were abstracted from medical records. Vitamin A was low in 4% before and 7% at 1 year after TPIAT, vitamin E in 17% and 18%, and vitamin D in 22% and 24%, respectively, regardless of pancreatic enzyme or vitamin supplement dosing. Longer duration of CP was associated with pre-TPIAT vitamin D insufficiency (P = 0.0002). This remained significant in a multivariate regression model (adjusted P = 0.01). On multivariate analysis, there were no significant predictors of low FSV levels post-TPIAT. FSV deficiencies are common among children undergoing TPIAT and patients who have had longer disease duration may be at increased risk. All children should be monitored for FSV deficiency after TPIAT.

Alterations in Enteroendocrine Hormones After Total Pancreatectomy With Islet Autotransplantation.

OBJECTIVE: When total pancreatectomy with islet autotransplantation (TPIAT) is performed for chronic pancreatitis, the pancreas and most of the duodenum are removed, with Roux-en-Y reconstruction of the gastrointestinal tract. Enteroendocrine cells in the intestines and pancreas secrete hormones coordinating digestion and motility, but anatomic reconstruction alters transit of nutrients to these cells. We hypothesized that TPIAT leads to changes in enteroendocrine hormones. METHODS: Glucagon-like peptide 1 (GLP-1), peptide YY (PYY), and pancreatic polypeptide (PP) were measured from mixed-meal tolerance tests of 34 clinical trial participants before and 18 months after TPIAT. Area under the curve of GLP-1 and PYY-stimulated responses were calculated by trapezoidal method, and the PP response was measured as the stimulated max minus baseline (ΔPP). RESULTS: Area under the curve of GLP-1 and PYY increased significantly after TPIAT (GLP-1 average +553.1 pg/mL per minute, P = 0.004; PYY average +4647.9 pg/mL per minute, P = 0.02). ΔPP trended toward lower after TPIAT (average, -52.2 pg/mL, P = 0.06). CONCLUSIONS: In this novel study of enteroendocrine hormones in TPIAT patients, stimulated levels of GLP-1 and PYY were significantly higher after versus before TPIAT. ΔPP was lower after TPIAT, but not significantly. These hormone changes have potential clinical implications that warrant further research.

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.

Total pancreatectomy and islet autotransplantion for chronic and recurrent acute pancreatitis.

PURPOSE OF REVIEW: We reviewed the current state of total pancreatectomy with islet autotransplantation (TPIAT) for chronic pancreatitis and recurrent acute pancreatitis (RAP). RECENT FINDINGS: An increasing number of centers in the United States and internationally are performing TPIAT. In selected cases, TPIAT may be performed partially or entirely laparoscopically. Islet isolation is usually performed at the same center as the total pancreatectomy surgery, but new data suggest that diabetes outcomes may be nearly as good when a remote center is used for islet isolation. Ongoing clinical research is focused on patient and disease factors that predict success or failure to respond to TPIAT. Causes of persistent abdominal pain after TPIAT may include gastrointestinal dysmotility and central sensitization to pain. Several clinical trials are underway with anti-inflammatory or other islet protective strategies to better protect islets at the time of infusion and thereby improve the diabetes results of the procedure. SUMMARY: In summary, there is an increasing body of literature emerging from multiple centers highlighting the benefits and persistent challenges of TPIAT for chronic pancreatitis and RAP. Ongoing study will be critical to optimizing the success of this procedure.

Extradural sacrococcygeal subcutaneous ependymoma misdiagnosed as pilonidal disease: case report and review of the literature.

Ependymoma is a type of glial tumor that arises from the ependymal lining of the ventricular system of the central nervous system. These tumors may present as a rare extraspinal variety at the sacrococcygeal region, and may be misdiagnosed as pilonidal disease in the post-sacral area or present with mass-effect symptoms on the bowel or bladder in the pre-sacral region. This is a case of soft tissue swelling at the post-sacral area that, after clinical examination, was diagnosed as pilonidal disease. Surgical excision and pathologic examination revealed a subcutaneous sacrococcygeal ependymoma.