Medium-Term Outcomes of Treatment with a VIABAHN VBX Covered Stent for Aortoiliac Occlusive Lesions in Patients with Peripheral Artery Disease.

BACKGROUND: Endovascular treatment (EVT) for aortoiliac (AI) occlusive lesions is now conducted worldwide, but there are challenges in EVT for complex AI lesions. The VIABAHN VBX (W.L. Gore & Associates, Flagstaff, AZ) is a next-generation balloon-expandable covered stent designed for use with complex AI lesions. The purpose of this study is to evaluate the medium-term outcomes of VIABAHN VBX for such lesions. METHODS: Symptomatic patients who underwent EVT with VIABAHN VBX for an AI lesion from 2018 to 2020 at 7 Japanese centers were reviewed retrospectively. The primary endpoints were primary patency and freedom from target lesion revascularization (TLR). RESULTS: A total of 95 EVT procedures with VIABAHN VBX for AI occlusive lesions were performed in 71 patients. The patients had high rates of dyslipidemia (53%) and chronic kidney disease (61%), and 22% had chronic limb-threatening ischemia (CLTI). The Transatlantic Inter-Society Consensus (TASC Ⅱ) class was A in 12 patients (17%), B in 12 (17%), C in 10 (14%), and D in 37 (52%). Severe calcification (360°) of the treated lesion was present in 31 patients (33%). The median procedure time was 84 (49-158) min, with a technical success rate of 100%. The median follow-up period was 36 (32-43) months. The 3-year primary and secondary patency of VIABAHN VBX were 91% and 99%, the 3-year freedom from TLR was 92%, and the 3-year freedom from major adverse limb event (MALE) was 98%. No limbs required major amputation. Lesion severity (TASC Ⅱ C or D) and severe calcification did not affect the primary patency or freedom from TLR. CONCLUSIONS: Medium-term outcomes after EVT with VIABAHN VBX for AI lesions were acceptable regardless of lesion severity and calcification. These results suggest that VIABAHN VBX may be suitable for AI occlusive lesions with severe anatomical complexity and/or severe calcification.

Clinical Outcomes of Common Femoral Thromboendarterectomy with Bovine Pericardium Patch Angioplasty.

BACKGROUND: The purpose of the study is to evaluate the efficacy of thromboendarterectomy (TEA) for common femoral occlusive disease using bovine pericardium patch angioplasty. METHODS: The subjects were patients who underwent TEA for common femoral occlusive disease with bovine pericardium patch angioplasty from October 2020 to August 2021. The study had a prospective, multicenter, and observational design. The primary end point was primary patency (freedom from restenosis). The secondary end points were secondary patency, amputation-free survival (AFS), postoperative wound complication, hospital death within 30 days, and major adverse cardiovascular events (MACE) within 30 days. RESULTS: Forty-seven TEA procedures with a bovine patch were performed in 42 patients (34 males; median age, 78 years; diabetes mellitus, 57%; end-stage renal disease with hemodialysis, 19%). Clinical presentations were intermittent claudication (68%) and critical limb-threatening ischemia (32%). Sixteen (34%) limbs underwent TEA alone and 31 (66%) underwent a combined procedure. Surgical site infection (SSI) occurred in 4 limbs (9%) and lymphatic fistulas in 3 limbs (6%). One limb with SSI required surgical debridement 19 days after the procedure, and 1 limb (2%) without postoperative wound complications required additional treatment due to acute bleeding. Hospital death within 30 days occurred in 1 case due to panperitonitis. There was no MACE within 30 days. Claudication was improved in all cases. Postoperative ABI of 0.92 [0.72-1.00] was significantly higher than the preoperative value (P < 0.001). The median follow-up period was 10 months [9-13 months]. One limb (2%) required additional endovascular therapy due to stenosis at the endarterectomy site at 5 months postoperatively. Primary and secondary patencies were 98% and 100% at 12 months, respectively, and the AFS rate was 90% at 12 months. CONCLUSIONS: Common femoral TEA with bovine pericardium patch angioplasty has satisfactory clinical outcomes.

Postoperative nonalcoholic fatty liver disease is correlated with malnutrition leading to an unpreferable clinical course for pancreatic cancer patients undergoing pancreaticoduodenectomy.

PURPOSES: This study aimed to clarify the impact of postoperative nonalcoholic fatty liver disease (NAFLD) on the clinical course of patients with pancreatic ductal adenocarcinoma (PDAC). METHODS: One hundred and eight patients with pancreatic cancer undergoing pancreaticoduodenectomy (PD) with curative intent in between 2005 and 2016 were enrolled in this study. Post-PD NAFLD was assessed by computed tomography (CT), which was routinely performed at 3 months, 6 months, and 1 year after surgery. The clinical impact of post-PD NAFLD was examined from an oncological perspective. RESULTS: There were 50 (46.2%) post-PD NAFLD patients. The NAFLD group showed significantly lower CT values at 3 months, 6 months, and 1 year after surgery than those without NAFLD. Patients with NAFLD showed significant body weight loss and a decrease in serum albumin level after surgery compared with those without NAFLD. Consequently, the 70% completion rate of adjuvant chemotherapy with gemcitabine, but not S1, was significantly lower in the NAFLD group than in the non-NAFLD group. The 5-year overall survival and disease-free survival rates were comparable between the two groups. CONCLUSION: Post-PD NAFLD was associated with malnutrition in patients with PDAC, reducing their tolerance to gemcitabine-based adjuvant chemotherapy. Post-PD NAFLD needs to be emphasized and requires special nutritional intervention in patients with PDAC.

Preoperative High Maximum Standardized Uptake Value in Association with Glucose Transporter 1 Predicts Poor Prognosis in Pancreatic Cancer.

BACKGROUND: The diagnosis of malignant diseases worldwide has been determined using 18F-fluorodeoxyglucose positron emission tomography (FDG-PET). Glucose transporter type 1 (Glut-1) is a key protein associated with the accumulation of FDG in cancer cells. This study evaluated the relationship between Glut-1 expression and FDG accumulation to determine the usefulness of FDG-PET for prediction of long-term outcomes of pancreatic cancer. METHODS: The expression of Glut-1 was immunohistochemically examined in 138 surgically resected pancreatic cancer specimens. The Glut-1-positive and Glut-1-negative groups were analyzed with respect to their clinicopathologic characteristics and prognosis. Before surgery, 93 patients underwent FDG-PET and measurement of the corrected maximum standardized uptake value (cSUVmax). The relationship between Glut-1 expression and cSUVmax were examined, and prognostic factors were identified using uni- and multivariate analyses. RESULTS: Glut-1 was positive in 69 patients (50%). The median relapse-free and overall survival times were significantly shorter in the Glut-1-positive group (11 vs. 22 months, respectively) than in the Glut-1-negative group (23 vs. 42 months, respectively). The cSUVmax was significantly associated with long-term survival. The relapse-free and overall survival rates were significantly poorer in the high-cSUVmax group than in the low-cSUVmax group. Glut-1 expression was associated with cSUVmax accumulation. In the multivariate Cox regression analysis using forward stepwise selection, male gender, positive lymph node metastases, high CA19-9, and high cSUVmax were identified as independent prognostic factors for pancreatic cancer. CONCLUSION: A significant relationship exists between high preoperative cSUVmax and Glut-1 expression. High cSUVmax is one of the prognostic factors for overall survival after resection of pancreatic cancer.

Unused sterile instruments for closure prevent wound surgical site infection after pancreatic surgery.

BACKGROUND: The incidence of incisional surgical site infection (SSI) after pancreatic surgery remains high. The aim of this study was to assess the effectiveness of the unused sterile instruments that were not used throughout the course of surgery and were opened exactly at the moment of wound closure to prevent incisional SSI after open pancreatic surgery. MATERIALS AND METHODS: We retrospectively evaluated the incidence of incisional SSI and the clinical course in 203 patients who underwent pancreatic resection in our institution between April 2012 and October 2015. RESULTS: Twenty-one patients were excluded because they underwent laparoscopic pancreatic surgery; therefore, data from 182 patients were analyzed. Of these, 93 underwent abdominal closure with unused sterile forceps and drape, and 89 did not. The intervention group included 53 pancreaticoduodenectomies, 20 distal pancreatectomies, and 20 underwent other procedures. The control group included 55 pancreaticoduodenectomies, 26 distal pancreatectomies, and eight underwent other procedures. The incidence of incisional SSI in the intervention group (two cases, 2/93, 2.2%) was significantly lower (P = 0.017) compared with that of the control group (11 cases, 11/89, 12.4%). All incisional SSIs in the control group occurred after pancreaticoduodenectomy (11 cases, 11/89, 20.0%). However, none of the pancreaticoduodenectomy patients in the intervention group experienced incisional SSI (P = 0.002). CONCLUSIONS: Unused sterile forceps and drapes during abdominal closure reduced the incidence of incisional SSI after pancreatic surgery, especially pancreaticoduodenectomy.

The diagnostic role of the neutrophil-to-lymphocyte ratio in predicting pancreatic ductal adenocarcinoma in patients with pancreatic diseases.

BACKGROUND: Accurately diagnosing pancreatic ductal adenocarcinomas (PDACs) is challenging because of the loss of vascularity and poor imaging. The neutrophil-to-lymphocyte ratio (NLR) has been reported to predict poor prognosis in several types of malignancy including PDAC; however, the diagnostic role of NLR in PDAC has never been addressed. METHODS: This study retrospectively assessed 297 patients who underwent curative pancreatic resection for pancreatic tumors from 1995-2015, including 140 with PDACs, 58 with pancreatic neuroendocrine tumors (PNETs), 76 with intraductal papillary mucinous neoplasms (IPMNs), 13 with mucinous/serous cyst neoplasms, 7 with solid pseudopapillary neoplasms, and 3 with tumor-forming pancreatitis. The role of preoperative NLR in predicting PDACs was investigated. RESULTS: Preoperative NLR was significantly higher in patients with PDACs (2.52 ± 1.34) than in patients with PNETs (1.93 ± 0.68, P = 0.0004) and IPMNs (2.17 ± 0.79, P = 0.0253). Only eight patients with PDACs (5.7 %) had NLR >5; of these, three had normal carcinoembyronic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) levels. Multivariate analysis revealed that abnormal CA19-9 levels, abnormal CEA levels, age >67 years, and NLR >5 were independent predictors of PDACs. Both the specificity and the positive predictive value of NLR >5 for predicting PDACs were 100 %; however, the sensitivity was 4.6 % and the negative predictive value was 43.8 %. CONCLUSIONS: NLR >5 could independently predict the occurrence of PDACs in pancreatic neoplastic disease irrespective of other tumor markers, CEA and CA19-9, in pancreatic disease.

Intraoperative blood loss is not a predictor of prognosis for pancreatic cancer.

PURPOSE: The relationship between intraoperative blood loss (IBL) and prognosis has been reported for some types of cancer, but not for pancreatic cancer, which has one of the highest mortality rates of any cancer. We conducted this study to analyze the relationship between IBL and clinical outcome for patients undergoing radical surgery for pancreatic cancer. METHODS: The subjects of this study were 144 patients who underwent curative pancreatectomy for invasive pancreatic cancer between 2002 and 2014. Clinicopathological characteristics were recorded and prognostic factors were identified by univariate and multivariate analyses. RESULTS: Large IBL was significantly associated with advanced tumor stage, a long operation time, a large tumor, portal vein resection, and blood transfusion. According to univariate analysis, IBL was also significantly associated with overall survival (OS) and relapse-free survival (RFS); however, it was not an independent prognostic factor for OS and RFS in multivariate analysis. According to multivariate analysis, lymph node metastasis and R-status were independent prognostic factors for OS and RFS. A subgroup analysis of patients who received no blood transfusion showed similar results. CONCLUSION: Minimizing IBL is very important; however, the present study found that positive lymph node metastasis and R-status were stronger independent prognostic factors for pancreatic cancer.

Treatment of celiac artery rupture with a hybrid procedure involving aortic stent grafting and open surgery in a patient with neurofibromatosis type 1.

Neurofibromatosis type 1 is associated with vascular fragility, and vascular disease is the second leading cause of death in these patients. A 42-year-old woman with neurofibromatosis type 1 was transferred to our hospital owing to shock. A computed tomography scan revealed a ruptured celiac artery aneurysm, which had expanded from 14 to 26 mm in 1 day. The survival rate of patients with celiac artery rupture is extremely low, and there is no consensus on treatment. Here, we successfully performed a hybrid procedure with emergent implantation of aortic stent grafts for life-saving treatment and subsequent laparotomy for complete hemostasis.

Successful Aortic Remodeling Through the Candy-Plug Technique for Chronic Type B Aortic Dissection.

PURPOSE: To describe the efficiency of the candy-plug technique using an Excluder aortic extender and obtain optimal aortic remodeling. CASE: A 46-year-old male patient had a history of acute type B aortic dissection and progressive dilation of the descending aorta (53 mm diameter) with a patent false lumen. He was treated with the candy-plug technique, using an Excluder aortic extender of 32-45 mm was placed and a 16-mm Amplatzer Vascular Plug II. No technical complications were observed in the patient. Good aortic remodeling was observed after 6 months, CT showed complete thrombosis of the false lumen and reduction of the maximum perpendicular diameter of the descending aorta from 53 to 47 mm. The diameter of the other proximal zones of the descending aorta was 45-47 mm, and the Excluder aortic extender changed into an elliptical shape. This is the first report of good aortic remodeling with an elliptical shape by performing the candy-plug technique. DISCUSSION: The candy-plug technique using an Excluder aortic extender is an improved method for occluding the false lumen as it provides improved aortic remodeling. The 2 indications for this surgery are limited. A large entry point in the descending abdominal aorta that is more peripheral than the candy-plug position must be visible on contrast-enhanced CT and the false lumen is not too large. We consider candy-plug placement in the true lumen central to the TEVAR to avoid occluding the artery of Adamkiewicz, since we have to avoid the thrombosis of the peripheral false lumen where a candy-plug was placed. Since it is unclear whether long-term results are satisfactory, we must continue to study chronic aortic type B dissection.

Strong exercise stress exacerbates dermatitis in atopic model mice, NC/Nga mice, while proper exercise reduces it.

Atopic dermatitis is well known to exacerbate by stress. How the influence of exercise stress on the skin symptoms in patients with atopic dermatitis has not been clarified. The purpose of our research is to investigate how different strength of exercise stress acts on atopic dermatitis. Specific pathogen-free (SPF) and conventional NC/Nga male mice were used for the experiments. Conventional mice but not SPF group spontaneously develop dermal symptom similar to that of patients with atopic dermatitis at their age of 7 weeks. They were given two types of stress, mild (20 m/min for 60 min) or strong exercise (25 m/min for 90 min), using a treadmill four times per day. The dermal symptom of the conventional group was strongly exacerbated by strong exercise but ameliorated by mild exercise. Under the standard experimental conditions, plasma concentrations of α-melanocyte-stimulating hormone (α-MSH), transforming growth factor-ß (TGF-ß) and substance P in conventional mice increased markedly with concomitant exacerbation of the symptom. The plasma concentrations of these proteins elevated after strong exercise but decreased after mild exercise. Under the conventional conditions, plasma levels of ß-endorphin increased with time by some mechanisms enhanced by the mild exercise. These observations suggested that exercise-induced stress significantly affect the symptom of atopic dermatitis in a pivotal manner depending on the plasma levels of TGF-ß, α-MSH, substance P and ß-endorphin.

Highly fucosylated N-glycan ligands for mannan-binding protein expressed specifically on CD26 (DPPVI) isolated from a human colorectal carcinoma cell line, SW1116.

The serum mannan-binding protein (MBP) is a host defense C-type lectin specific for mannose, N-acetylglucosamine, and fucose residues, and exhibits growth inhibitory activity toward human colorectal carcinoma cells. The MBP-ligand oligosaccharides (MLO) isolated from a human colorectal carcinoma cell line, SW1116, are large, multiantennary N-glycans with highly fucosylated polylactosamine-type structures having Le(b)-Le(a) or tandem repeats of the Le(a) structure at their nonreducing ends. In this study, we isolated the major MBP-ligand glycoproteins from SW1116 cell lysates with an MBP column and identified them as CD26/dipeptidyl peptidase IV (DPPIV) (110 kDa) and CD98 heavy chain (CD98hc)/4F2hc (82 kDa). Glycosidase digestion revealed that CD26 contained such complex-type N-glycans that appear to mediate the MBP binding. MALDI-MS of the N-glycans released from CD26 by PNGase F demonstrated conclusively that CD26 is the major MLO-carrying protein. More interestingly, a comparison of the N-glycans released from the MBP-binding and non-MBP-binding glycopeptides suggested that complex-type N-glycans carrying a minimum of 4 Le(a)/Le(b) epitopes arranged either as multimeric tandem repeats or terminal epitopes on multiantennary structures are critically important for the high affinity binding to MBP. Analysis of the N-glycan attachment sites demonstrated that the high affinity MLO was expressed preferentially at some N-glycosylation sites, but this site preference was not so stringent. Finally, hypothetical 3D models of tandem repeats of the Le(a) epitope and the MBP-Lewis oligosaccharide complex were presented.

Limited Resection of the Duodenum for Nonampullary Duodenal Tumors, with Review of the Literature.

The surgical management of duodenal pathology is challenging because of its retroperitoneal position and shared blood supply with the pancreas. We present three types of limited resection of the duodenum for the removal of superficial or small nonampullary duodenal (NADL) lesions, and also a review of the English literature regarding management, such as endoscopic resection and limited duodenal resection. Ten cases underwent limited resections of the duodenum for superficial or small NADL lesions from 2011 to 2015. Pancreas-preserving segmental duodenectomy was performed in three cases, local full-thickness resection was performed in three and transduodenal submucosal dissection was performed in four. One patient experienced pancreatic fistula as a postoperative complication. Postoperative pathological diagnosis were adenoma (n = 2), mucosal adenocarcinomas (n = 5), and neuroendocrine tumor (n = 3). Surgical margin was negative in all cases, and no patient has experienced postoperative recurrence or metastasis. Limited resections of the duodenum were feasible and safe procedures for patients with superficial or small NADL lesions. Laparoscopic surgery may be considered in treatment for these tumors. However, the optimal surgical management for superficial or small nonampullary duodenal lesions remains controversial.

Heterogeneity of KRAS Mutations in Pancreatic Ductal Adenocarcinoma.

OBJECTIVES: Activating Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations are the most common and frequent changes observed in pancreatic cancer. This study aimed to determine the frequency and extent of intratumoral and metastatic lymph node KRAS mutation heterogeneity of resected pancreatic ductal adenocarcinoma. METHODS: Tumor tissues macrodissected from tumor centers, invasion fronts (n = 97), and lymph nodes (n = 11) were subjected to DNA extraction and mutation analysis of KRAS codons 12 and 13 by pyrosequencing. RESULTS: Activating mutations in codon 12 of KRAS were detected in 90 (92.8%) tumor centers. No mutations were detected in KRAS codon 13 in any patient. After a comparison of tumor centers and invasion fronts, intratumoral heterogeneity of KRAS was observed only in 4 (4.1%) cases. Additional invasion front tumor analysis revealed the same mutation status consistent with each tumor center. No heterogeneity was observed between primary tumors and metastatic lymph nodes. CONCLUSIONS: Intratumoral heterogeneity of the KRAS mutational status is rare in pancreatic ductal adenocarcinoma. In addition, no KRAS heterogeneity between primary tumors and metastatic lymph nodes was detected in this study. This finding is consistent with the hypothesis that oncogenic activation of KRAS is the first driver mutation in pancreatic cancer.

Characterization of oligosaccharide ligands expressed on SW1116 cells recognized by mannan-binding protein. A highly fucosylated polylactosamine type N-glycan.

Mannan-binding protein (MBP) is a C-type serum lectin and activates complement through the lectin pathway when it binds to ligand sugars such as mannose, N-acetylglucosamine, and fucose on microbes. In addition, the vaccinia virus carrying the human MBP gene was shown to exhibit potent growth inhibitory activity toward human colorectal carcinoma, SW1116, cells in nude mice. We have proposed calling this activity MBP-dependent cell-mediated cytotoxicity (MDCC) (Ma, Y., Uemura, K., Oka, S., Kozutsumi, Y., Kawasaki, N., and Kawasaki, T. (1999) Proc. Natl. Acad. Sci. U. S. A. 96, 371-375). In this study, the MBP ligands on the surface of SW1116 cells were characterized. Initial experiments involving plant lectins and anti-Lewis antibodies as inhibitors of MBP binding to SW1116 cells indicated that fucose plays a crucial role in the interaction. Subsequently, Pronase glycopeptides were prepared from whole cell lysates, and oligosaccharides were liberated by hydrazinolysis. After being tagged by pyridylamination, MBP ligand oligosaccharides were isolated with an MBP affinity column, and then their sequences were determined by mass spectrometry and tandem mass spectrometry after permethylation, in combination with endo-beta-galactosidase digestion and chemical defucosylation. The MBP ligands were shown to be large, multiantennary N-glycans carrying a highly fucosylated polylactosamine type structure. At the nonreducing termini, Le(b)/Le(a) or tandem repeats of the Le(a) structure prevail, a substantial proportion of which are attached via internal Le(x) or N-acetyllactosamine units to the trimannosyl core. The structures characterized are unique and distinct from those of other previously reported tumor-specific carbohydrate antigens. It is concluded that MBP requires clusters of tandem repeats of the Le(b)/Le(a) epitope for recognition.

ERK and p38 MAP kinase are involved in arachidonic acid release induced by H(2)O(2) and PDGF in mesangial cells.

Increased prostaglandin production is implicated in the pathogenesis of glomerular disease. With this consideration, we examined the combined effects of reactive oxygen species and platelet-derived growth factor (PDGF), which might initiate glomerular dysfunction, on arachidonic acid release and cytosolic phospholipase A(2) (cPLA(2)) activation in rat mesangial cells. H(2)O(2)-induced release of arachidonic acid was enhanced by PDGF, which by itself had little effect on the release, and the enhancement was completely inhibited by a cPLA(2) inhibitor. The phosphorylation of cPLA(2), extracellular signal-regulated kinase (ERK), and p38 mitogen-activated protein (MAP) kinase was upregulated by H(2)O(2) or PDGF alone and except for ERK was enhanced further by the two in combination. The release of arachidonic acid induced by PDGF together with H(2)O(2) was inhibited partially by an inhibitor of ERK or p38 MAP kinase and completely when the two inhibitors were combined; the inhibitory pattern was similar to that for the phosphorylation of cPLA(2). These results suggest that the ERK and p38 MAP kinase pathways are involved in the increase in cPLA(2) activation and arachidonic acid release induced by PDGF together with H(2)O(2).