Preoperative level of serum transthyretin as a novel biomarker predicting survival in resected pancreatic ductal adenocarcinoma with neoadjuvant therapy.

BACKGROUND: Systemic inflammation and altered metabolism are essential hallmarks of cancer. We hypothesized that the rapid turnover protein transthyretin (TTR) (half-life: 2-3 days), compared with the conventional marker albumin (21 days), better reflects the inflammatory/metabolic dynamics of pancreatic ductal adenocarcinoma (PDAC) after neoadjuvant therapy (NAT) and is a useful prognostic marker. METHODS: Serum TTR and albumin levels were measured in 104 consecutive post-NAT PDAC patients before curative resection. The associations of preoperative TTR and albumin levels with overall survival (OS) after pancreatectomy were retrospectively analyzed. RESULTS: The mean (SD) TTR and albumin levels were 21.6 (6.4) mg/dL (normal range: ≥22.0 mg/dL) and 3.9 (0.55) g/dL. A low (<22.0 mg/dL) post-NAT TTR level was associated with an advanced tumor stage and higher CEA and CRP levels. Patients with low TTR levels showed significantly worse OS compared with normal levels (3-year OS 39 % vs. 54 %, P = 0.037), although albumin levels did not. We modified prognostic biomarkers of systemic inflammation/metabolism, such as GPS, PNI, and CONUT scores, using the serum TTR instead of albumin level and successfully showed that modified scores were better associated with OS compared with original scores using serum albumin level. CONCLUSIONS: Our data suggest that the TTR level is a promising prognostic biomarker for PDAC patients after NAT.

Optimal cutoff values of drain amylase for predicting pancreatic fistula are different between open and laparoscopic distal pancreatectomy.

BACKGROUND: Drainage fluid amylase (DFA) is useful for predicting clinically relevant postoperative pancreatic fistula (CR-POPF) after distal pancreatectomy (DP). However, difference in optimal cutoff value of DFA for predicting CR-POPF between open DP (ODP) and laparoscopic DP (LDP) has not been investigated. This study aimed to identify the optimal cutoff values of DFA for predicting CR-POPF after ODP and LDP. METHODS: Data for 294 patients (ODP, n = 127; LDP, n = 167) undergoing DP at Kobe University Hospital between 2010 and 2021 were reviewed. Propensity score matching was performed to minimize treatment selection bias. Receiver operating characteristic (ROC) analysis was performed to determine the optimal cutoff values of DFA for predicting CR-POPF for ODP and LDP. Logistic regression analysis for CR-POPF was performed to investigate the diagnostic value of DFA on postoperative day (POD) three with identified cutoff value. RESULTS: In the matched cohort, CR-POPF rates were 24.7% and 7.9% after ODP and LDP, respectively. DFA on POD one was significantly lower after ODP than after LDP (2263 U/L vs 4243 U/L, p < 0.001), while the difference was not significant on POD three (543 U/L vs 1221 U/L, p = 0.171). ROC analysis revealed that the optimal cutoff value of DFA on POD one and three for predicting CR-POPF were different between ODP and LDP (ODP, 3697 U/L on POD one, 1114 U/L on POD three; LDP, 10564 U/L on POD one, 6020 U/L on POD three). Multivariate analysis showed that DFA on POD three with identified cutoff value was the independent predictor for CR-POPF both for ODP and LDP. CONCLUSIONS: DFA on POD three is an independent predictor for CR-POPF after both ODP and LDP. However, the optimal cutoff value for it is significantly higher after LDP than after ODP. Optimal threshold of DFA for drain removal may be different between ODP and LDP.

Comparison of laparoscopic liver resection for the ventral versus the dorsal areas of segment 8.

PURPOSE: The technical difficulties of laparoscopic liver resection (LLR) are greatly associated with the location of liver tumors. Since segment 8 (S8) contains a wide area, the difficulty of LLR for S8 tumors may vary depending on the location within the segment, such as the ventral (S8v) and dorsal (S8d) area, but the difference is unclear. METHODS: We retrospectively investigated 30 patients who underwent primary laparoscopic partial liver resection for liver tumors in S8 at Kobe University Hospital between January 2018 and June 2023. RESULTS: Thirteen and 17 patients underwent LLR for S8v and S8d, respectively. The operation time was significantly longer (S8v 203[135-259] vs. S8d 261[186-415] min, P = 0.002) and the amount of blood loss was significantly higher (10[10-150] vs. 10[10-200] mL, P = 0.034) in the S8d group than in the S8v group. No significant differences were observed in postoperative complications or postoperative length of hospital stay. Additionally, intraoperative findings revealed that the rate at which the case performed partial liver mobilization in the S8d group was higher (2[15.4%] vs. 8[47.1%], P = 0.060) and the median parenchymal transection time of the S8d group was longer (102[27-148] vs. 129[37-175] min, P = 0.097) than those in the S8v group, but there were no significant differences. CONCLUSION: The safety of LLR for the S8d was comparable to that of LLR for S8v, although LLR for S8d resulted in longer operative time and more blood loss. THE TRIAL REGISTRATION NUMBER: B230165 (approved at December 26, 2023).

Impact of bile leak on the prognosis of patients with hepatocellular carcinoma who have undergone liver resection.

PURPOSE: The impact of postoperative bile leak on the prognosis of patients with hepatocellular carcinoma who underwent liver resection is controversial. This study aimed to investigate the prognostic impact of bile leak for patients with hepatocellular carcinoma who underwent liver resection. METHODS: Patients with hepatocellular carcinoma who underwent liver resection between 2009 and 2019 at Kobe University Hospital and Hyogo Cancer Center were included. After propensity score matching between the bile leak and no bile leak groups, differences in 5-year recurrence-free and overall survival rates were evaluated using the Kaplan-Meier method. RESULTS: A total of 781 patients, including 43 with postoperative bile leak, were analyzed. In the matched cohort, 40 patients were included in each group. The 5-year recurrence-free survival rates after liver resection were 35% and 32% for the bile leak and no bile leak groups, respectively (P = 0.857). The 5-year overall survival rates were 44% and 54% for the bile leak and no bile leak groups, respectively (P = 0.216). CONCLUSION: Overall, bile leak may not have a profound negative impact on the prognosis of patients with hepatocellular carcinoma who have undergone liver resection.

Laparoscopic Medial-to-Lateral Approach for the Resection of Hepatocellular Carcinoma Located at the Spiegel Lobe of the Liver.

BACKGROUND: Laparoscopic caudate lobe resection is a challenging procedure. Several researchers have reported the safety of laparoscopic liver resections;1.Transl Gastroenterol Hepatol. 1:56;2.Asian J Endosc Surg. 12:232-236;3.Ann Surg Oncol. 26:2980; however, a standardized procedure has not yet been established. Herein, we present a video showing laparoscopic Spiegel lobectomy in a patient with 6-cm hepatocellular carcinoma (HCC) using a novel approach. PATIENT AND METHODS: A 63-year-old man with a caudate lobe HCC was referred to our hospital. Computed tomography showed a 5 × 6 cm2 HCC located in the Spiegel lobe, which profoundly displaced the inferior vena cava (IVC) to the lower right side, and mobilization of the Spiegel lobe was considered difficult. To perform the dissection between the Siegel lobe and IVC safely, we performed parenchymal transection along the ventral side of the IVC initially. The Spiegel lobe was then dislocated to the left side of the IVC. We dissected the left lateral side of the IVC, including the proper hepatic vein draining the caudate lobe and the left IVC ligament with a safe operative field, and successfully removed the Spiegel lobe with large HCC. RESULTS: The operation time was 383 min. The blood loss was 10 mL. The patient was discharged on the seventh postoperative day without any complications. Histopathological examination revealed well-differentiated HCC with a negative surgical margin. CONCLUSIONS: Laparoscopic medial-to-lateral approach with initial parenchymal transection at the medial side of the Spiegel lobe followed by dissection of the left lateral side of the IVC is considered as a safe and effective procedure for large tumors in the Spiegel lobe.

Reappraisal of Malignant Risk Assessment for Small (≤20 mm) Non-functioning Pancreatic Neuroendocrine Tumors.

BACKGROUND: Optimal management of non-functioning pancreatic neuroendocrine tumors (PanNETs) ≤20 mm is controversial. The biological heterogeneity of these tumors poses challenges when deciding between resection and observation. METHODS: In this multicenter, retrospective cohort study, we analyzed all patients (n = 78) who underwent resection of non-functioning PanNETs ≤20 mm at three tertiary medical centers from 2004 to 2020 to assess the utility of preoperatively available radiological features and serological biomarkers of non-functioning PanNETs in choosing an optimal surgical indication. The radiological features included non-hyper-attenuation pattern on enhancement computed tomography (CT; hetero/hypo-attenuation) and main pancreatic duct (MPD) involvement, and serological biomarkers included elevation of serum elastase 1 and plasma chromogranin A (CgA) levels. RESULTS: Of all small non-functioning PanNETs, 5/78 (6%) had lymph node metastasis, 11/76 (14%) were WHO grade II, and 9/66 (14%) had microvascular invasion; 20/78 (26%) had at least one of these high-risk pathological factors. In the preoperative assessment, hetero/hypo-attenuation and MPD involvement were observed in 25/69 (36%) and 8/76 (11%), respectively. Elevated serum elastase 1 and plasma CgA levels were observed in 1/33 (3%) and 0/11 (0%) patients, respectively. On multivariate logistic regression analysis, hetero/hypo-attenuation (odds ratio [OR] 6.1, 95% confidence interval [CI] 1.7-22.2) and MPD involvement (OR 16.8, 95% CI 1.6-174.3) were significantly associated with the high-risk pathological factors. The combination of the two radiological worrisome features correctly predicted non-functioning PanNETs with high-risk pathological factors, with about 75% sensitivity, 79% specificity, and 78% accuracy. CONCLUSIONS: This combination of radiological worrisome features can accurately predict non-functioning PanNETs that may require resection.

Association of Sarcopenia with a Poor Prognosis and Decreased Tumor-Infiltrating CD8-Positive T Cells in Pancreatic Ductal Adenocarcinoma: A Retrospective Analysis.

BACKGROUND: Sarcopenia, defined as a loss of skeletal muscle mass and quality, is found in 30-65% of patients with pancreatic ductal adenocarcinoma (PDAC) at diagnosis, and is a poor prognostic factor. However, it is yet to be evaluated why sarcopenia is associated with poor prognosis. Therefore, this study elucidated the tumor characteristics of PDAC with sarcopenia, including driver gene alterations and tumor microenvironment. PATIENTS AND METHODS: We retrospectively analyzed 162 patients with PDAC who underwent pancreatic surgery between 2008 and 2017. We defined sarcopenia by measuring the skeletal muscle mass at the L3 level using preoperative computed tomography images and evaluated driver gene alteration (KRAS, TP53, CDKN2A/p16, and SMAD4) and tumor immune (CD4+, CD8+, and FOXP3+) and fibrosis status (stromal collagen). RESULTS: In localized-stage PDAC (stage ≤ IIa), overall survival (OS) and recurrence-free survival were significantly shorter in the sarcopenia group than in the non-sarcopenia group (2-year OS 89.7% versus 59.1%, P = 0.03; 2-year RFS 74.9% versus 50.0%, P = 0.02). Multivariate analysis revealed that sarcopenia was an independent poor prognostic factor in localized-stage PDAC. Additionally, tumor-infiltrating CD8+ T cells in the sarcopenia group were significantly less than in the non-sarcopenia group (P = 0.02). However, no difference was observed in driver gene alteration and fib.rotic status. These findings were not observed in advanced-stage PDAC (stage ≥ IIb). CONCLUSIONS: Sarcopenia was associated with a worse prognosis and decreased tumor-infiltrating CD8+ T cells in localized-stage PDAC. Sarcopenia may worsen a patient's prognosis by suppressing local tumor immunity.

Risk Factors for Recurrence of Cholangitis After Pancreaticoduodenectomy and Comparison of Stents in Hepaticojejunostomy.

BACKGROUND: Postoperative cholangitis is a common complication of pancreaticoduodenectomy. Frequent cholangitis impairs patients' quality of life after pancreaticoduodenectomy. However, the risk factors for recurrence of cholangitis remain unclear. Hence, this retrospective study aimed to identify risk factors for recurrence of cholangitis after pancreaticoduodenectomy. METHODS: The medical records of patients who underwent pancreaticoduodenectomy between 2015 and 2019 in our institution were retrospectively reviewed. At least two episodes of cholangitis a year after pancreaticoduodenectomy were defined as 'recurrence of cholangitis' in the present study. Univariate and multivariate analyses were performed. RESULTS: The recurrence of cholangitis occurred in 40 of 207 patients (19.3%). Multivariate analysis revealed that internal stent (external, RR: 2.16, P = 0.026; none, RR: 4.76, P = 0.011), firm pancreas (RR: 2.61, P = 0.021), constipation (RR: 3.49, P = 0.008), and postoperative total bilirubin>1.7 mg/dL (RR: 2.94, P = 0.006) were risk factors of recurrence of cholangitis. Among patients with internal stents (n = 54), those with remnant stents beyond 5 months had more frequent recurrence of cholangitis (≥5 months, 75%; <5 months, 30%). CONCLUSIONS: Internal stents, firm pancreas, constipation, and postoperative high bilirubin levels are risk factors for cholangitis recurrence after pancreaticoduodenectomy. In addition, the long-term implantation of internal stents may trigger cholangitis recurrence.

Use of a short cartridge stapler is beneficial in pancreatic transection at the neck during laparoscopic distal pancreatectomy.

Stapling is the standard method for pancreatic transection during laparoscopic distal pancreatectomy. Although most surgeons use a 60 mm cartridge stapler, space limitations created by laparoscopic surgery make the instrument difficult to handle, especially during pancreatic transection at the neck. Therefore, we currently use a 45 mm cartridge stapler for laparoscopic pancreatic transection at the neck. Between October 2019 and December 2020, we performed pancreatic transection using a 45 mm cartridge stapler in 27 patients. Fifteen patients experienced biochemical leakage, but no patients developed clinically relevant pancreatic fistula. The compactness of the 45 mm cartridge has several benefits: (1) less space is required for flexing, opening, and closing the device; (2) it enables easy insertion of the lower jaw behind the pancreas, even if the dissected space behind the pancreas is narrow; (3) less obstruction of the surgeons' view prevents accidental injury to the surrounding tissues and vessels. These benefits may enable safe pancreatic transection.

Transarterial chemoembolization for liver metastases of a pancreatic neuroendocrine neoplasm: a single-center experience.

Transarterial chemoembolization (TACE) is performed for pancreatic neuroendocrine tumor (PanNEN) liver metastases; however, the safety and efficacy of TACE procedures, especially for patients who have undergone previous pancreatic surgery, have not been established. We reviewed 48 TACE procedures (1-6 procedures/patient) performed on 11 patients with PanNEN liver metastases, including 16 TACE procedures (4-6 procedures/patient) for 3 patients with a history of biliary-enteric anastomosis. The overall tumor objective response rate was 94%. The incidence of Clavien‒Dindo grade ≥ 2 complications was 1/16 (6%) and 1/32 (3%), and the median time to untreatable progression was 31 (14-41) and 27 (2-60) months among patients with and without a history of biliary-enteric anastomosis, respectively. Although validation is needed in future studies, our experiences have shown that TACE treatment is a viable treatment option for PanNEN liver metastases, even after biliary-enteric anastomosis with experienced teams and careful patient follow-up.

[A Case of Ampullary Carcinoma with Celiac Axis Stenosis That Underwent Pancreaticoduodenectomy and Arterial Reconstruction].

A 72-year-old male patient presented with obstructive jaundice and was diagnosed with ampullary carcinoma. Contrast- enhanced computed tomography(CT)showed stenosis of the common hepatic artery and dilatation of the pancreaticoduodenal arcade(PDA)due to celiac axis stenosis(CAS)at the origin, suggesting that hepatic artery blood flow was supplied from the superior mesenteric artery via the PDA. Since calcification of the arterial wall was observed at the origin of the celiac artery(CA), the cause of the CAS was diagnosed as atherosclerotic. An intraoperative gastroduodenal artery(GDA) clamp test showed no obvious decrease in hepatic arterial blood flow. However, because of concerns about the postoperative patency of the CA, an inferior pancreaticoduodenal artery-GDA bypass using the left great saphenous vein and subtotal stomach-preserving pancreaticoduodenectomy were performed. The postoperative course was uneventful. When pancreaticoduodenectomy is performed in patients with atherosclerotic CAS, this arterial reconstruction method can be considered as an option.

Standardization of laparoscopic anatomic liver resection of segment 2 by the Glissonean approach.

BACKGROUND: Anatomic liver resection (ALR) has been established to eliminate the tumor-bearing hepatic region with preservation of the remnant liver volume for liver malignancies. Recently, laparoscopic ALR has been widely applied; however, there are few reports on laparoscopic segmentectomy 2. This study aimed to present the standardization of laparoscopic segmentectomy 2 with surgical outcomes. METHODS: This study included seven patients who underwent pure laparoscopic segmentectomy 2 by the Glissonean approach from January 2020 to December 2021. Four of them had hepatocellular carcinoma, two had colorectal liver metastasis, and one had hepatic angiomyolipoma, which was preoperatively diagnosed with hepatocellular carcinoma. In all patients, preoperative three-dimensional (3D) simulation images from dynamic CT were reconstructed using a 3D workstation. The layer between the hepatic parenchyma and the Glissonean pedicle of segment 2 (G2) was dissected to encircle the root of G2. After clamping or ligation of the G2, 2.5 mg of indocyanine green was injected intravenously to identify the boundaries between segments 2 and 3 with a negative staining method under near-infrared light. Parenchymal transection was performed from the caudal side to the cranial side according to the demarcation on the liver surface, and the left hepatic vein was exposed on the cut surface if possible. RESULTS: The mean operative time for all patients was 281 min. The mean blood loss was 37 mL, and no transfusion was necessary. Estimated liver resection volumes significantly correlated with actual liver resection volumes (r = 0.61, P = 0.035). After the operation, one patient presented with asymptomatic deep venous and pulmonary thrombosis, which was treated with anticoagulant therapy. The mean length of hospital stay was 8.9 days. CONCLUSION: Laparoscopic segmentectomy 2 by the Glissonean approach is a feasible and safe procedure with the preservation of the nontumor-bearing segment 3 for liver tumors in segment 2.

Prognostic Impact of Inflammation-Based Scores for Extrahepatic Cholangiocarcinoma.

INTRODUCTION: Although the relationship between systemic inflammatory responses and prognosis has been known in various cancers, it remains unclear which scores are most valuable for determining the prognosis of extrahepatic cholangiocarcinoma. We aimed to verify the usefulness of various inflammation-based scores as prognostic factors in patients with resected extrahepatic cholangiocarcinoma. METHODS: We analyzed consecutive patients undergoing surgical resection for extrahepatic cholangiocarcinoma at our institution between January 2000 and December 2019. The usefulness of the following inflammation-based scores as prognostic factor was investigated: glasgow prognostic score (GPS), modified GPS, neutrophil-to-lymphocyte ratio, platelet to lymphocyte ratio, lymphocyte-to-monocyte ratio, prognostic nutrition index, C-reactive protein to albumin ratio (CAR), controlling nutritional status (CONUT), and prognostic index. RESULTS: A total of 169 patients were enrolled in this study. Of the nine scores, CAR and CONUT indicated prognostic value. Furthermore, multivariate analysis for overall survival revealed that high CAR (>0.23) was an independent prognostic factor (hazard ratio: 1.816, 95% confidence interval: 1.135-2.906, p = 0.0129), along with lymph node metastasis and curability. There was no difference in tumor staging and short-term outcomes between the low CAR (≤0.23) and high CAR groups. CONCLUSIONS: CAR was the most valuable prognostic score in patients with resected extrahepatic cholangiocarcinoma.

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 ß-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.

Immunohistochemically Detected Expression of ATRX, TSC2, and PTEN Predicts Clinical Outcomes in Patients With Grade 1 and 2 Pancreatic Neuroendocrine Tumors.

OBJECTIVE: The goal of this retrospective study was to clarify the clinical implications of immunohistochemically detected protein expression for genes that are frequently mutated in pancreatic neuroendocrine tumors (PNETs). BACKGROUND: The clinical management of PNETs is hindered by their heterogenous biological behavior. Whole-exome sequencing recently showed that 5 genes (DAXX/ATRX, MEN1, TSC2, and PTEN) are frequently mutated in PNETs. However, the clinical implications of the associated alterations in protein expression remain unclear. METHODS: We collected Grade 1 and 2 (World Health Organization 2017 Classification) primary PNETs samples from 100 patients who underwent surgical resection. ATRX, DAXX, MEN1, TSC2, and PTEN expression were determined immunohistochemically to clarify their relationships with prognosis and clinicopathological findings. RESULTS: Kaplan-Meier analysis indicated that loss of TSC2 (n = 58) or PTEN (n = 37) was associated with significantly shorter overall survival, and that loss of TSC2 or ATRX (n = 41) was associated with significantly shorter recurrence-free survival. Additionally, loss of ATRX or TSC2 was significantly associated with nodal metastasis. In a multivariate analysis, combined loss of TSC2 and ATRX (n = 31) was an independent prognostic factor for shorter recurrence-free survival (hazard ratio 10.1, 95% confidence interval 2.1-66.9, P = 0.003) in G2 PNETs. CONCLUSIONS: Loss of ATRX, TSC2, and PTEN expression might be useful as a method of clarifying the behavior and clinical outcomes of Grade 1 and 2 PNETs in routine clinical practice. Combined loss of TSC2 and ATRX had an especially strong, independent association with shorter recurrence-free survival in patients with G2 PNETs. Loss of pairs in ATRX, TSC2, or PTEN would be useful for selecting the candidate for postoperative adjuvant therapy.

Profiling natural serum antibodies of non-human primates with a carbohydrate antigen microarray.

BACKGROUND: Engineering of α-Galactosyltransferase gene-knockout pigs circumvented hyperacute rejection of pig organs after xenotransplantation in non-human primates. Overcoming this hurdle revealed the importance of non-α-Gal carbohydrate antigens in the immunobiology of acute humoral xenograft rejection. METHODS: This study analyzed serum from seven naïve cynomolgus monkeys (blood type O/B/AB = 3/2/2) for the intensity of natural IgM and IgG signals using carbohydrate antigen microarray, which included historically reported α-Gal and non-α-Gal carbohydrate antigens with various modifications. RESULTS: The median (range) of IgM and IgG signals were 12.71 (7.23-16.38) and 9.05 (7.23-15.90), respectively. The highest IgM and IgG signals with narrowest distribution were from mono- and disaccharides, followed by modified structures. Natural anti-α-Gal antibody signals were medium to high in IgM (11.2-15.9) and medium in IgG (8.5-11.6) spectra, and was highest with Lac core structure (Galα1-3Galß1-4Glc, iGb3) and lowest with LacNAc core structure (Galα1-3Galß1-4GlcNAc). Similar signal intensities (up to 15.8 in IgM and up to 11.8 in IgG) were observed for historically detected natural non-α-Gal antigens, which included Tn antigen, T antigen, GM2 glycolipid, and Sda antigen. The hierarchical clustering analysis revealed the presence of clusters of anti-A antibodies and was capable of distinguishing between the blood group B and AB non-human primates. CONCLUSIONS: The results presented here provide the most comprehensive evaluation of natural antibodies present in cynomolgus monkeys.

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.

Serum Elastase 1 Level as a Risk Factor for Postoperative Recurrence in Patients with Well-Differentiated Pancreatic Neuroendocrine Neoplasms.

PURPOSE: This study was designed to assess the potential role of the preoperative serum level of elastase 1 as a risk factor for recurrence in patients with resectable well-differentiated pancreatic neuroendocrine neoplasms (PanNETs). METHODS: Preoperative serum elastase 1 levels were measured in 53 patients with PanNETs who underwent complete tumor resection in two tertiary referral centers between January 2004 and June 2017. The preoperative elastase 1 levels were correlated with clinicopathological characteristics, including tumor recurrence and recurrence-free survival. RESULTS: The median elastase 1 level was 96 ng/dL (range: 21-990 ng/dL). Preoperative serum elastase 1 levels were significantly higher in those with tumors ≥ 20 mm in diameter (vs. < 20 mm, P = 0.018), WHO grade 2 (vs. grade 1, P = 0.035), and microscopic venous invasion (vs. without venous invasion, P = 0.039). The median preoperative serum level of elastase 1 was higher in patients with recurrence than in those without recurrence (251 vs. 80 ng/dL, P = 0.004). Receiver operating characteristic analysis of elastase 1 levels showed that a cutoff level of 250 ng/dL was associated with postoperative recurrence, with 63% sensitivity, 100% specificity, and 94% overall accuracy. Patients with higher elastase 1 levels showed significantly worse recurrence-free survival than that of those with lower levels (2-year recurrence-free survival rate: 25% and 92%, respectively, P < 0.001). CONCLUSIONS: Our data provide the first evidence that high preoperative elastase 1 levels may be a risk factor for postoperative recurrence in patients with resectable PanNETs.