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1.
Surg Endosc ; 38(5): 2699-2708, 2024 May.
Article in English | MEDLINE | ID: mdl-38528262

ABSTRACT

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.


Subject(s)
Amylases , Drainage , Laparoscopy , Pancreatectomy , Pancreatic Fistula , Postoperative Complications , Humans , Pancreatic Fistula/etiology , Pancreatic Fistula/diagnosis , Pancreatectomy/methods , Male , Female , Amylases/analysis , Amylases/metabolism , Drainage/methods , Middle Aged , Laparoscopy/methods , Aged , Retrospective Studies , Postoperative Complications/diagnosis , Postoperative Complications/etiology , Predictive Value of Tests , Propensity Score , Adult , ROC Curve
2.
Ann Surg Oncol ; 30(1): 381-382, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36284055

ABSTRACT

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.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Middle Aged , Carcinoma, Hepatocellular/surgery , Liver Neoplasms/surgery
3.
Ann Surg Oncol ; 30(6): 3493-3500, 2023 Jun.
Article in English | MEDLINE | ID: mdl-36795254

ABSTRACT

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.


Subject(s)
Neuroendocrine Tumors , Pancreatic Neoplasms , Humans , Neuroendocrine Tumors/pathology , Retrospective Studies , Pancreatic Neoplasms/pathology , Risk Assessment , Pancreatic Elastase
4.
Ann Surg Oncol ; 30(9): 5776-5787, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37191859

ABSTRACT

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.


Subject(s)
CD8-Positive T-Lymphocytes , Carcinoma, Pancreatic Ductal , Lymphocytes, Tumor-Infiltrating , Muscle, Skeletal , Pancreatic Neoplasms , Sarcopenia , Sarcopenia/diagnostic imaging , Sarcopenia/etiology , Prognosis , Carcinoma, Pancreatic Ductal/complications , Carcinoma, Pancreatic Ductal/diagnosis , Carcinoma, Pancreatic Ductal/immunology , Pancreatic Neoplasms/complications , Pancreatic Neoplasms/diagnosis , Pancreatic Neoplasms/immunology , Lymphocytes, Tumor-Infiltrating/immunology , CD8-Positive T-Lymphocytes/immunology , Neoplasm Staging , Humans , Male , Female , Adult , Middle Aged , Aged , Aged, 80 and over , Muscle, Skeletal/diagnostic imaging , Muscle, Skeletal/pathology
5.
World J Surg ; 47(10): 2499-2506, 2023 10.
Article in English | MEDLINE | ID: mdl-37442827

ABSTRACT

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.


Subject(s)
Cholangitis , Pancreaticoduodenectomy , Humans , Pancreaticoduodenectomy/adverse effects , Retrospective Studies , Quality of Life , Cholangitis/epidemiology , Cholangitis/etiology , Risk Factors , Stents/adverse effects , Constipation/etiology , Postoperative Complications/epidemiology , Postoperative Complications/etiology
6.
Surg Today ; 53(1): 153-157, 2023 Jan.
Article in English | MEDLINE | ID: mdl-35879473

ABSTRACT

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.


Subject(s)
Laparoscopy , Pancreatectomy , Humans , Pancreatectomy/methods , Surgical Stapling/methods , Pancreas/surgery , Pancreatic Fistula/etiology , Pancreatic Fistula/prevention & control , Laparoscopy/methods , Postoperative Complications/prevention & control
7.
Surg Today ; 53(12): 1396-1400, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37355500

ABSTRACT

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.


Subject(s)
Carcinoma, Hepatocellular , Chemoembolization, Therapeutic , Liver Neoplasms , Neuroendocrine Tumors , Pancreatic Neoplasms , Humans , Chemoembolization, Therapeutic/methods , Liver Neoplasms/therapy , Liver Neoplasms/secondary , Neuroendocrine Tumors/therapy , Neuroendocrine Tumors/pathology , Pancreatic Neoplasms/therapy , Pancreatic Neoplasms/pathology , Retrospective Studies , Treatment Outcome
8.
Gan To Kagaku Ryoho ; 50(13): 1534-1536, 2023 Dec.
Article in Japanese | MEDLINE | ID: mdl-38303332

ABSTRACT

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.


Subject(s)
Ampulla of Vater , Arterial Occlusive Diseases , Aged , Humans , Male , Ampulla of Vater/surgery , Arterial Occlusive Diseases/surgery , Celiac Artery/surgery , Constriction, Pathologic/surgery , Pancreaticoduodenectomy
9.
Surg Endosc ; 36(11): 8600-8606, 2022 11.
Article in English | MEDLINE | ID: mdl-36123546

ABSTRACT

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.


Subject(s)
Angiomyolipoma , Carcinoma, Hepatocellular , Laparoscopy , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/diagnostic imaging , Carcinoma, Hepatocellular/surgery , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/surgery , Liver Neoplasms/pathology , Angiomyolipoma/surgery , Hepatectomy/methods , Laparoscopy/methods , Reference Standards
10.
Dig Surg ; 39(2-3): 65-74, 2022.
Article in English | MEDLINE | ID: mdl-35051946

ABSTRACT

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.


Subject(s)
Bile Duct Neoplasms , Cholangiocarcinoma , Bile Duct Neoplasms/pathology , Bile Duct Neoplasms/surgery , Bile Ducts, Intrahepatic/pathology , Cholangiocarcinoma/pathology , Cholangiocarcinoma/surgery , Humans , Inflammation , Prognosis , Retrospective Studies
11.
Am J Transplant ; 21(10): 3411-3420, 2021 10.
Article in English | MEDLINE | ID: mdl-33754431

ABSTRACT

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.


Subject(s)
Diabetes Mellitus , Islets of Langerhans Transplantation , Pancreatitis, Chronic , Humans , Pancreatectomy , Pancreatitis, Chronic/surgery , Retrospective Studies , Transplantation, Autologous , Treatment Outcome
12.
Ann Surg ; 274(6): e949-e956, 2021 12 01.
Article in English | MEDLINE | ID: mdl-31599805

ABSTRACT

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.


Subject(s)
Neuroendocrine Tumors/genetics , PTEN Phosphohydrolase/genetics , Pancreatic Neoplasms/genetics , Tuberous Sclerosis Complex 2 Protein/genetics , X-linked Nuclear Protein/genetics , Adult , Aged , Aged, 80 and over , Female , Gene Expression Regulation, Neoplastic , Humans , Japan , Kaplan-Meier Estimate , Male , Middle Aged , Mutation , Neoplasm Grading , Neuroendocrine Tumors/pathology , Neuroendocrine Tumors/surgery , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/surgery , Prognosis , Retrospective Studies
13.
Xenotransplantation ; 27(2): e12567, 2020 03.
Article in English | MEDLINE | ID: mdl-31762117

ABSTRACT

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.


Subject(s)
Antibodies/blood , Antigens, Heterophile/immunology , Graft Rejection/immunology , Heterografts/immunology , Animals , Antibodies/immunology , Disaccharides/immunology , Galactosyltransferases/immunology , Macaca fascicularis , Primates , Transplantation, Heterologous/methods
14.
Clin Transplant ; 34(8): e14008, 2020 08.
Article in English | MEDLINE | ID: mdl-32530540

ABSTRACT

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.


Subject(s)
Islets of Langerhans Transplantation , Pancreatitis, Chronic , Adult , Glycated Hemoglobin , Humans , Pancreas/diagnostic imaging , Pancreas/surgery , Pancreatectomy , Pancreatitis, Chronic/surgery , Transplantation, Autologous , Treatment Outcome
17.
Ann Surg Oncol ; 25(11): 3358-3364, 2018 Oct.
Article in English | MEDLINE | ID: mdl-30054822

ABSTRACT

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.


Subject(s)
Biomarkers, Tumor/blood , Neoplasm Recurrence, Local/blood , Neuroendocrine Tumors/blood , Pancreatic Elastase/blood , Pancreatic Neoplasms/blood , Postoperative Complications , Adult , Aged , Aged, 80 and over , Female , Follow-Up Studies , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/enzymology , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/surgery , Neuroendocrine Tumors/enzymology , Neuroendocrine Tumors/pathology , Neuroendocrine Tumors/surgery , Pancreatic Neoplasms/enzymology , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/surgery , Prognosis , Retrospective Studies , Risk Factors , Survival Rate
18.
Ann Surg Oncol ; 25(3): 638-646, 2018 Mar.
Article in English | MEDLINE | ID: mdl-29264672

ABSTRACT

BACKGROUND: The prognostic impact of pancreatic ductal adenocarcinoma (PDAC) invasion to the splenic vessel is controversial. OBJECTIVE: The aim of this study was to assess the clinical value of pathological and radiological splenic vessel invasion in PDACs of the body and tail. METHODS: Medical records of patients with resectable PDAC of the body and tail who underwent distal pancreatectomy between 2003 and 2016 at the Kobe University Hospital were retrospectively analyzed. RESULTS: Overall, 68 patients (29 female and 39 male patients) were enrolled. Pathologically determined splenic vein invasion (p-SV) and splenic artery invasion (p-SA) were identified in 21 (30.9%) and 5 (7.4%) patients, respectively. The p-SV (but not p-SA) was an independent prognostic factor in multivariate analysis (p = 0.009). On analysis of recurrence patterns, patients with PDAC positive for p-SV were at a higher risk for liver metastasis (p = 0.022); however, the associations were not significant for other recurrence patterns. Liver metastasis occurred earlier in patients who were positive for p-SV (p = 0.015). Preoperative computed tomography effectively diagnosed pathological vessel invasion (SV: sensitivity, 95.2%, specificity, 72.3%; SA: sensitivity, 100%, specificity, 84.1%). Radiological SV invasion remained significant in multivariate analysis regarding postoperative survival (p = 0.007), and was also associated with early liver metastases (p = 0.008). CONCLUSIONS: Pathological/radiological SV invasion were independent adverse prognostic factors associated with early liver metastasis in patients with PDAC of the body/tail. Assessment of these findings may be useful in determining optimal therapeutic options in these patients.


Subject(s)
Adenocarcinoma/surgery , Carcinoma, Pancreatic Ductal/surgery , Liver Neoplasms/secondary , Pancreatectomy/mortality , Pancreatic Neoplasms/surgery , Splenic Vein/diagnostic imaging , Splenic Vein/pathology , Tomography, X-Ray Computed/methods , Adenocarcinoma/pathology , Aged , Carcinoma, Pancreatic Ductal/pathology , Female , Follow-Up Studies , Humans , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/surgery , Male , Neoplasm Invasiveness , Pancreatectomy/adverse effects , Pancreatic Neoplasms/pathology , Prognosis , Retrospective Studies , Survival Rate , Pancreatic Neoplasms
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