Clinical and biological significance of circulating miRNAs in chronic pancreatitis patients undergoing total pancreatectomy with islet autotransplantation.

BACKGROUND: Specific microRNAs (miRNAs) were elevated in chronic pancreatitis (CP) patients during islet infusion after total pancreatectomy (TPIAT). We aimed to identify circulating miRNA signatures of pancreatic damage, predict miRNA-mRNA networks to identify potential links to CP pathogenesis and identify islet isolation and transplantation functional outcomes. METHODS: Small RNA sequencing was performed to identify distinct circulating miRNA signatures in CP. Plasma miRNAs were measured using miRCURY LNA SYBR green quantitative real-time polymerase chain reaction assays. Correlation analyses were performed using R software. The miRNA target and disease interactions were determined using miRNet and the miRNA enrichment and annotation tool. RESULTS: Alterations were found in circulating miRNAs in CP patients compared to healthy controls. Further studies were conducted on 12 circulating miRNAs enriched in the pancreas, other tissues and other diseases including cancer and fibrosis. Approximately 2888 mRNAs in the pancreas were their targets, demonstrating interactions with 76 small molecules. Three miRNAs exhibited interactions with morphine and five exhibited interactions with glucose. The miRNA panel targeted 22 genes associated with pancreatitis. The islet-specific, acinar cell-specific and liver-specific miRNAs were elevated at 6 h after islet infusion and returned to baseline levels 3 months after TPIAT. Circulating levels of miRNAs returned to pre-transplant levels 1-year post-transplant. Circulating miRNAs measured before and 6 h after islet infusion were directly or inversely associated with metabolic outcomes at 3 and 6 months post-transplant. CONCLUSIONS: miRNAs may contribute to CP pathogenesis, and elevated circulating levels may be specific to pancreatic inflammation and fibrosis, warranting further investigation.

Diffuse calcification of pancreas impairs endocrine function and predicts poor outcome in total pancreatectomy with islet autotransplantation.

In patients with chronic pancreatitis, pancreatic calcification is a risk factor for diabetes development, poor islet yield, and metabolic outcomes after total pancreatectomy with islet autotransplantation (TPIAT). We investigated whether calcification pattern based on computed tomography is associated with outcomes using our database of 200 consecutive TPIAT procedures. Three groups were compared: noncalcification (NC); focal calcification, limited to the pancreas head, body, or tail; and diffuse calcification (DC), with calcification in >2 sections. Maximum changes in outcomes were seen in the DC vs focal calcification group. In the DC group, preoperative hemoglobin A1c levels were higher (P < .01), and stimulated C-peptide levels were lower (P < .01) than in the NC group. Islet isolation from the DC pancreas resulted in the lowest islet equivalent (IEQ) yield and IEQ/kg among the 3 groups (P < .0001), with no insulin independence 12 months posttransplant (P < .05 vs NC group). Notably, at 12 months, the DC group was 91.7% narcotic-free, significantly higher than the NC group (P < .05). Although DC is a sign of diabetes risk after TPIAT, the DC group showed exceptional pain relief. These findings suggest that TPIAT can be beneficial for patients with chronic pancreatitis with severe calcification.

Surgical Strategies to Approaching the Splenic Artery in Robotic Distal Pancreatectomy.

BACKGROUND/AIM: Understanding different surgical approaches and anatomical landmarks adjacent to the splenic artery (SpA) is important for safe robotic distal pancreatectomy (RDP). Herein, we propose our standardized RDP techniques, focusing on these issues. PATIENTS AND METHODS: Between April 2021 and April 2022, 19 patients who underwent RDP at our Institution were reviewed. Anatomical patterns of the SpA were classified into three types: Type 1, no pancreatic parenchyma on the root of the SpA; type 2, any pancreatic parenchyma on the root of the SpA; and type 3, dorsal pancreatic artery around the bifurcation of the common hepatic artery and SpA. Next, the surgical strategy for approaching the SPA was determined according to the location of the pancreatic transection line: On the superior mesenteric vein (SMV) or on the left side of the root of the SpA. RESULTS: There were seven cases of type 1, nine cases of type 2, and three cases of type 3. When transecting the pancreas on the SMV, the SpA-first ligation technique was used for type 1 SpA anatomy, and the pancreas-first division technique was applied for types 2 and 3. In patients in whom the pancreas was transected at the left side of the root of the SpA, the SpA-first ligation technique was used. CONCLUSION: Our standardized surgical strategy based on anatomical landmarks and focusing on the approach to the SpA in RDP is demonstrated. Our strategy should help trainees approach the SpA and perform RDP safely.

Spleen-preserving total pancreatectomy and islet autotransplantation with complete preservation of the splenic arterial and venous supply does not impact islet yield and function.

BACKGROUND: Standard total pancreatectomy and islet autotransplantation (TPIAT) for chronic pancreatitis includes splenectomy, but TPIAT can be performed without splenectomy by full preservation of the blood supply to the spleen. METHODS: We compared the metabolic and clinical outcomes of patients who underwent TPIAT at our center between 2015 and 2021 with or without splenectomy. A total of 89 patients were included in the study, and 17 of them underwent spleen-preserving total pancreatectomy (SPTP). RESULTS: The two study groups had similar demographic and metabolic parameters. Short-term morbidity and long-term outcomes were similar. The operative time was significantly shorter with splenectomy: a median of 9.91 h (interquartile range [IQR] 8.89-10.83) compared to 10.78 h (IQR 10.2-11.6) for SPTP (P = 0.021). There was no difference between the groups in postoperative morbidity. Metabolic outcomes at 1 year were better in the SPTP group compared to the splenectomy group, with a median daily insulin requirement of 7 units (IQR 4-12) vs 15 units (IQR 7-26; P = 0.049) and a median C-peptide at 1 year of 0.65 (IQR 0.40-1.26) vs 1.00 (IQR 0.80-1.90; P = 0.63). The reduction in morphine milligram equivalents per day over time was significantly better in the SPTP group (P < 0.001), as was the decrease in pain score (P < 0.001). CONCLUSION: TPIAT with full arterial and venous preservation of the spleen had no adverse impact on islet yield or function. TPIAT can be safely and effectively performed with preservation of the spleen and the entire splenic artery and vein. The spleen should be preserved when feasible in every TPIAT surgery.

Favorable control of hepatocellular carcinoma with peritoneal dissemination by surgical resection using indocyanine green fluorescence imaging: a case report and review of the literature.

BACKGROUND: The optimal management for peritoneal dissemination in patients with hepatocellular carcinoma remains unclear. Although several reports have described the usefulness of surgical resection, the indications should be carefully considered. Herein, we report the case of a patient with hepatocellular carcinoma with peritoneal recurrence who underwent surgical resection using an indocyanine green fluorescence navigation system and achieved favorable disease control. CASE PRESENTATION: A 45-year-old Asian woman underwent left hemihepatectomy for a ruptured hepatocellular carcinoma. Seventeen months after the initial surgery, a single nodule near the cut surface of the liver was detected on computed tomography, along with elevation of tumor markers. The patient was diagnosed with peritoneal metastasis and underwent a surgical resection. Twelve months later, a single nodule on the dorsal side of the right hepatic lobe was detected on computed tomography, and we performed surgical resection. Indocyanine green (0.5 mg/kg) was intravenously administered 3 days before surgery, and the indocyanine green fluorescence imaging system revealed clear green fluorescence in the tumor, which helped us perform complete resection. Indocyanine green fluorescence enabled the detection of additional lesions that could not be identified by preoperative imaging, especially in the second metastasectomy. There was no further recurrence at 3 months postoperatively. CONCLUSION: When considering surgical intervention for peritoneal recurrence in patients with hepatocellular carcinoma, complete resection is mandatory. Given that disseminated nodules are sometimes too small to be detected by preoperative imaging studies, intraoperative indocyanine green fluorescence may be an essential tool for determining the indications for surgical resection.

Adenomatoid mesothelioma arising from the diaphragm: a case report and review of the literature.

BACKGROUND: Adenomatoid mesothelioma is a rare subtype of malignant mesothelioma that can be confused with adenomatoid tumors, which are classified as benign. The clinical features and optimal management of adenomatoid mesothelioma have not been elucidated in the literature. In this report, we present an extremely rare case of adenomatoid mesothelioma that developed on the peritoneal surface of the diaphragm as well as a literature review of adenomatoid mesothelioma in the abdominal cavity. CASE PRESENTATION: The patient was a 61-year-old Japanese woman who had undergone resection of a malignant peripheral nerve sheath tumor of the hand 18 years prior. She was diagnosed with clinical stage I lung adenocarcinoma on follow-up chest radiography. Simultaneously, a 20-mm enhancing nodule with slow growth on the right diaphragm was detected on contrast-enhanced computed tomography. She presented no specific clinical symptoms. At this point, the lesion was suspected to be a hypervascular tumor of borderline malignancy, such as a solitary fibrous tumor. After a left upper lobectomy for lung adenocarcinoma, she was referred to our department, and laparoscopic tumor resection was performed. Adenomatoid tumors were also considered based on the histopathological and immunohistochemical analyses, but we made the final diagnosis of adenomatoid mesothelioma using the results of the genetic profile. The patient remains alive, with no recurrence noted 6 months after surgery. CONCLUSION: We encountered a valuable case of adenomatoid mesothelioma of peritoneal origin. There are some previously reported cases of adenomatoid mesothelioma and adenomatoid tumors that may need to be recategorized according to the current classification. It is important to accumulate and share new findings to clarify the clinicopathological characteristics and genetic status of adenomatoid mesothelioma.

Feasibility of local therapy for recurrent pancreatic cancer.

BACKGROUND: Despite advances in perioperative management, recurrence after curative pancreatectomy is a critical issue in the treatment of pancreatic ductal adenocarcinoma (PDAC). The significance of local therapy for recurrent PDAC remains unclear. METHODS: We reviewed the medical records of patients with PDAC who underwent curative resection at our institution between January 2009 and December 2019. We examined the patterns of relapse and assessed the clinical outcomes of patients with recurrence who underwent local therapy, including surgical resection, radiotherapy, and radiofrequency ablation. RESULTS: A total of 246 patients with PDAC who underwent R0 or R1 resection were included in this study. The 3-year overall survival (OS) rate was 39.8%, and the 1-year recurrence-free survival rate was 51.2% for the entire population. Recurrence was observed in 172/246 (69.9%) patients, including multiple site recurrences in 50, liver metastasis in 41, locoregional recurrence in 34, and peritoneal dissemination in 27. Of the 172 patients, treatment was administered in 137 (79.7%), and 16 received local therapy, including surgical resection (n = 13), radiotherapy (n = 5), and RFA (n = 1). PS-matched analysis revealed that patients with recurrence who were treated with chemotherapy combined with local therapy showed better post-recurrence survival rates than those treated with chemotherapy alone (P = 0.016). Detailed clinical courses of these patients are presented in the main manuscript. CONCLUSIONS: Our results suggest that a multimodal approach may improve the clinical outcomes of patients with recurrent PDAC.

Prognostic Value of the Regional Lymph Node Station in Pancreatic Neuroendocrine Tumor.

BACKGROUND/AIM: Little is known regarding the impact of lymph node dissection on survival benefit after curative resection for pancreatic neuroendocrine tumor (PNET). This study aimed to evaluate the efficacy of lymph node dissection based on tumor location of PNET. PATIENTS AND METHODS: A retrospective study, including 50 patients with surgical resection for PNET between 2004 and 2020, was performed. The efficacy index (EI) was calculated by multiplication of the incidence of lymph node metastasis (LNM) at the station and the 5-year survival rate of patients with LNM at the station. RESULTS: In the pancreatic head tumors, the peri-pancreatic head and superior mesenteric artery lymph node stations had high EI of 13.3 and 25, respectively. In contrast, other stations, including stations 8 and 12, had zero EI. In the pancreatic body and tail tumors, only the splenic artery lymph node station had a survival benefit from lymph node dissection with an EI of 6.7. CONCLUSION: The extent of lymph node dissection for PNET should be decided based on the efficacy of lymph node dissection in accordance with tumor location. Our findings may be helpful in determining the extent of lymph node dissection required.

Prognostic Value of the Regional Lymph Node Station in Pancreatoduodenectomy for Ampullary Carcinoma.

BACKGROUND/AIM: The optimal extent of lymph node dissection for ampullary carcinoma is controversial. The aim of this study was to investigate the efficacy of lymph node dissection for ampullary carcinoma. PATIENTS AND METHODS: Between 2000 and 2020, a total of 75 patients undergoing radical resection for ampullary carcinoma were included. The efficacy index (EI) was calculated by multiplication of the frequency of lymph node metastasis (LNM) at the station and the 5-year survival rate of patients with metastasis at the station. RESULTS: Out of 75 patients, 14 had LNM. The EI for the peri-pancreatic head (station 13 and 17) and superior mesenteric artery (station 14) lymph node were 4.4 and 3.5, respectively. Whereas the peri-gastric (station 5 and 6), common hepatic artery (station 8), and liver hilum (station 12) lymph node stations had zero EI. Although the number of patients with the station 16 dissected was small (9%), the para-aortic (station 16) lymph nodes had the highest EI of 14.3 despite being distant lymph nodes. CONCLUSION: We identified the distribution of LNM and survival benefit of lymph node dissection for ampullary carcinoma. Our results suggest that the optimal extent of lymph node dissection for ampullary carcinoma could be reconsidered.

Surgical resection of mixed neuroendocrine-non-neuroendocrine neoplasm in the biliary system: a report of two cases.

BACKGROUND: Mixed neuroendocrine-non-neuroendocrine neoplasm (MINEN) is a rare disease and there is scarce literature on its diagnosis, treatment, and prognosis. We encountered two unusual cases of MINEN in the biliary tract, one in the ampulla of Vater and the other in the distal bile duct. In this report, we describe the clinical course of these two cases in detail. CASE PRESENTATION: Case 1: A 69-year-old woman presented with a chief complaint of epigastric pain. When endoscopic sphincterotomy and retrograde biliary drainage were performed for gallstone pancreatitis, an ulcerated lesion was found in the ampulla of the Vater. Based on the biopsy results, the lesion was diagnosed as the ampulla of Vater carcinoma and subtotal stomach-preserving pancreatoduodenectomy (SSPPD) was performed. Postoperative histopathological examination revealed the coexistence of adenocarcinoma and neuroendocrine carcinoma components, consistent with the diagnosis of MINEN. In addition, lymph node metastasis was found on the dorsal side of the pancreas and the metastatic component was adenocarcinoma. Adjuvant chemotherapy with etoposide and cisplatin was administered for 6 months, and presently the patient is alive without recurrence 64 months after surgery. Case 2: A 79-year-old man presented with a chief complaint of anorexia. Cholangiography showed severe stenosis of the distal bile duct. A biopsy was conducted from the stenotic lesion and it revealed the lesion to be adenocarcinoma. A diagnosis of distal bile duct carcinoma was made, and SSPPD was performed. Histopathological examination revealed the coexistence of adenocarcinoma and neuroendocrine carcinoma components, and the tumor was confirmed as MINEN of the distal bile duct. No adjuvant chemotherapy was administered due to the poor performance status. 7 months later, the patient was found to have a liver metastasis. CONCLUSION: We experienced two valuable cases of biliary MINEN. To identify better treatments, it is important to consider the diversity of individual cases and to continue sharing a variety of cases with different presentations.

Technique of vessel-skeletonized parenchyma-sparing hepatectomy for the oncological treatment of bilobar colorectal liver metastases.

BACKGROUND: To aid in the oncological management of multiple bilobar colorectal liver metastases (CRLMs), we describe a new surgical procedure, VEssel-Skeletonized PArenchyma-sparing Hepatectomy (VESPAH). STUDY DESIGN: Of 152 patients with CRLMs treated with hepatectomy, 33 patients had multiple bilobar liver metastases (≥8 liver metastases); their surgical procedures and clinical outcomes were retrospectively summarized and compared between those who underwent VESPAH and those who underwent major hepatectomy (Major Hx). RESULTS: Of the 33 patients, 20 patients were resected by VESPAH (the VESPAH group) and 13 patients by major hepatectomy (Major Hx group). The median number of CRLMs was 13 (range, 8-53) in the VESPAH group and 10 (range, 8-41) in the Major Hx group (P=0.511). No operative mortality nor severe morbidity was observed in either group. The VESPAH group showed earlier recovery of remnant liver function after surgery than the Major Hx group; the incidence of grade B/C post hepatectomy liver failure was 5% in the VESPAH group and 38% in the Major Hx group, P=0.048). Intrahepatic tumor recurrence was confirmed in 14 (70%) and 7 (54%) patients in the VESPAH and Major Hx groups, respectively (P=0.416). There was no significant difference in median overall survival (OS) after hepatectomy between the two groups; the median OS was 47 months in the VESPAH group and 33 months in the Major Hx group (P=0.481). The VESPAH group showed the higher induction rate of adjuvant chemotherapy within 2 months after surgery (P=0.002) and total number of repeat hepatectomy for intrahepatic recurrence (P=0.060) than the Major Hx group. CONCLUSIONS: VESPAH enables us to clear surgical navigation by hepatic vessel skeletonization and may enhance patient tolerability of not only adjuvant chemotherapy but also repeat hepatectomies during the patients' lifetimes.

Usefulness of Middle Colic Artery Transposition Technique for Hepatic Arterial Reconstruction in Conversion Surgery for an Initially Unresectable, Locally Advanced Pancreatic Cancer.

The outcomes of pancreatectomy with resection and reconstruction of the involved arteries for locally advanced pancreatic cancer following chemotherapy have improved in recent years. In pancreatic head cancers in which there is contact with the common and proper hepatic arteries, margin-negative resection requires pancreati-coduodenectomy, with the resection of these arteries and the restoration of hepatic arterial flow. Here, we describe a middle colic artery transposition technique in hepatic arterial reconstruction during pancreatoduo-denectomy for an initially unresectable locally advanced pancreatic cancer. This technique was effective and may provide a new option for hepatic artery reconstruction in such cases.

Role of Exosomes in Islet Transplantation.

Exosomes are known for their ability to transport nucleic acid, lipid, and protein molecules, which allows for communication between cells and tissues. The cargo of the exosomes can have a variety of effects on a wide range of targets to mediate biological function. Pancreatic islet transplantation is a minimally invasive cell replacement therapy to prevent or reverse diabetes mellitus and is currently performed in patients with uncontrolled type 1 diabetes or chronic pancreatitis. Exosomes have become a focus in the field of islet transplantation for the study of diagnostic markers of islet cell viability and function. A growing list of miRNAs identified from exosomes collected during the process of isolating islets can be used as diagnostic biomarkers of islet stress and damage, leading to a better understanding of critical steps of the isolation procedure that can be improved to increase islet yield and quality. Exosomes have also been implicated as a possible contributor to islet graft rejection following transplantation, as they carry donor major histocompatibility complex molecules, which are then processed by recipient antigen-presenting cells and sensed by the recipient immune cells. Exosomes may find their way into the therapeutic realm of islet transplantation, as exosomes isolated from mesenchymal stem cells have shown promising results in early studies that have seen increased viability and functionality of isolated and grafted islets in vitro as well as in vivo. With the study of exosomes still in its infancy, continued research on the role of exosomes in islet transplantation will be paramount to understanding beta cell regeneration and improving long-term graft function.

Withaferin A inhibits lymphocyte proliferation, dendritic cell maturation in vitro and prolongs islet allograft survival.

The immunosuppressive regimen for clinical allogeneic islet transplantation uses beta cell-toxic compounds such as tacrolimus that cause islet graft loss. Previously we reported that the plant-derived steroidal lactone Withaferin A (WA) can protect islet grafts by inhibiting nuclear factor-kappa B (NF-κB). Since the NF-κB signaling pathway is essential for T-cell activation, we hypothesized that long-term WA administration may also provide an immunosuppressive effect. Treatment of BALB/c donor islets and C57BL/6N recipients with WA alone resulted in 80% islet graft long-term survival vs. 40% in low-dose FK506-treated mice. In vitro, WA significantly blocked mouse and human T-cell proliferation by CD3/CD28 bead stimulation and in mixed lymphocyte reaction assay. Treatment of immature dendritic cells with WA prevented their maturation in response to inflammatory stimuli, as seen by decreased expression of CD83 and human leukocyte antigen-DR isotype. Exosomes released by islets treated with WA contained significantly fewer proinflammatory molecules interleukin-6, interleukin-8, monocyte chemoattractant protein-1, interferon-gamma-induced protein-10, inducible nitric oxide synthase, and cyclooxygenase-2. In conclusion, WA treatment not only reduced inflammation but also prolonged allograft survival, possibly through suppression of dendritic cell maturation and T-cell proliferation. WA has the potential to inhibit both the innate and adaptive immune response to prolong allograft survival.

Outcomes of Islet Autotransplantation in Chronic Pancreatitis Patients with Complete Acinar Atrophy.

Total pancreatectomy with islet autotransplantation (TPIAT) is a promising treatment for refractory chronic pancreatitis (CP). Pathological features of CP include progressive fibrosis in pancreas parenchyma, atrophy, and/or ductal occlusion. Complete acinar atrophy (CAA) caused by chronic fibrosis and necroinflammation results in exocrine sufficiency and may influence islet isolation characteristics during TPIAT. In this analysis of patients who underwent TPIAT at our center, we compared transplant outcomes among those with CAA (n = 5) vs non-acinar atrophy (NAA; matching controls, n = 36). Data were analyzed using one-way analysis of variance with Bonferroni post hoc test or Student's t test. Pancreas digestion was longer in CAA than in NAA cases (18.6 vs 14.6 min) despite a lower pancreas weight (55.2 vs 91.2 g). Obtained tissue volume was 1.0 ml in the CAA group and 12.1 ml in the NAA group. Both groups had similar islet viability (96%) and islet dose (CAA, 3,391 IEQ/kg; NAA, 4141.1 IEQ/kg). During islet infusion, serum cytokine (IL-6, IL-8, and MCP-1) levels and plasma hsa-miR-375 levels were lower in the CAA group than in the NAA group, but not significantly. Serum tumor necrosis factor α levels at 3 h after infusion were significantly higher in CAA group than in NAA group. After TPIAT, the metabolic outcomes of the CAA group were comparable with that of the NAA group. Narcotics usage decreased significantly over 24 months in both groups, with the CAA group reporting being pain free at 12 months. Complete atrophy of acinar cells of pancreas did not significantly impact islet yield or endocrine function after TPIAT.

Grafting Islets to a Dissected Peritoneal Pouch to Improve Transplant Survival and Function.

BACKGROUND: Although the liver is the primary site for clinical islet transplantation, it poses several restrictions, especially limited tissue volume due to portal vein pressure. We evaluated the preperitoneal space as an extrahepatic islet transplant site to deliver high tissue volumes and sustain long-term graft function. METHODS: A peritoneal pouch was formed by dissecting the parietal peritoneum from the transversalis fascia of mice. Syngeneic C57BL/6 donor islets were transplanted into the peritoneal pouch of diabetic mouse recipients. Blood glucose was monitored for islet function, and miR-375 was analyzed for islet damage. Islet graft morphology and vascularization were evaluated by immunohistochemistry. [F] fluoro-D-glucose positron emission tomography/computed tomography was used to image islet grafts. RESULTS: Transplantation of 300 syngeneic islets into the peritoneal pouch of recipients reversed hyperglycemia for >60 days. Serum miR-375 was significantly lower in the peritoneal pouch group than in the peritoneal cavity group. Peritoneal pouch islet grafts showed high neovascularization and sustained insulin and glucagon expression up to 80 days posttransplantation. A peritoneal pouch graft with high tissue volume (1000 islets) could be visualized by positron emission tomography/computed tomography imaging. Human islets transplanted into the peritoneal pouch of diabetic nude mice also reversed hyperglycemia successfully. CONCLUSIONS: Islets transplanted into a dissected peritoneal pouch show high efficiency to reverse diabetes and sustain islet graft function. The preperitoneal site has the advantages of capacity for high tissue volume, enriched revascularization and minimal inflammatory damage. It can also serve as an extrahepatic site for transplanting large volume of islets necessitated in islet autotransplantation.

Impact of microbial contamination of the islet product during total pancreatectomy with islet autotransplantation.

BACKGROUND: The combined use of interleukin-1ß and tumor necrosis factor-α blockers in the peritransplant period has improved outcomes of total pancreatectomy with islet autotransplantation (TPIAT). However, these drugs may suppress the immune system, resulting in severe infection. METHODS: We retrospectively investigated the impact of microbial-contaminated islet product on posttransplant complications and metabolic outcomes of TPIAT patients receiving the IL-1ß and TNF-blockade treatment at our center. RESULTS: Among 108 TPIAT patients, 37 patients (34%) received contaminated products. Preoperative stent treatment and fibrosis score were independent risk factors for the contamination. There were no significant differences between the contaminated and noncontaminated product groups in posttransplant infectious complication rate, length of hospitalization, or readmission rate. However, islet equivalents (P < .0001) and insulin independence rate (P = .036) at 6 months were significantly lower for patients receiving contaminated product. CONCLUSIONS: These results suggest that combined anti-inflammatory drug use is safe and well tolerated in TPIAT patients who receive contaminated islet product and does not increase the rate of infectious complications; however, contaminated islet product is associated with poor metabolic outcomes.

MicroRNA Signatures as Future Biomarkers for Diagnosis of Diabetes States.

Diabetes results from the inability of pancreatic islets to maintain blood glucose concentrations within a normal physiological range. Clinical features are usually not observed until islets begin to fail and irreversible damage has occurred. Diabetes is generally diagnosed based on elevated glucose, which does not distinguish between type 1 and 2 diabetes. Thus, new diagnostic approaches are needed to detect different modes of diabetes before manifestation of disease. During prediabetes (pre-DM), islets undergo stress and release micro (mi) RNAs. Here, we review studies that have measured and tracked miRNAs in the blood for those with recent-onset or longstanding type 1 diabetes, obesity, pre-diabetes, type 2 diabetes, and gestational diabetes. We summarize the findings on miRNA signatures with the potential to stage progression of different modes of diabetes. Advances in identifying selective biomarker signatures may aid in early detection and classification of diabetic conditions and treatments to prevent and reverse diabetes.