Surgical Outcomes of Pancreaticoduodenectomy for Pancreatic Cancer with Proximal Dorsal Jejunal Vein Involvement

Background/Purpose

The proximal jejunal vein which branches from the dorsal side of the superior mesenteric vein (SMV) usually drains the inferior pancreatoduodenal veins (IPDVs) and contacts the uncinate process of the pancreas. We focused on this vein, termed the proximal dorsal jejunal vein (PDJV), and evaluated the anatomical classification of the PDJV and surgical outcomes in patients with pancreatic ductal adenocarcinoma (PDAC) with PDJV involvement (PDJVI).

Methods

The jejunal veins that branch from the dorsal side of the SMV above the inferior border of the duodenum are defined as PDJVs. We investigated 121 patients who underwent upfront pancreaticoduodenectomy for PDAC between 2011 and 2017; PDJVs were resected in all patients. The anatomical classification of PDJV was evaluated using multidetector computed tomography. Surgical and prognostic outcomes of pancreticoduodenectomy for PDAC with PDJVI were evaluated.

Results

The PDJVs were classified into seven types depending on the position of the first and second jejunal veins relative to the superior mesenteric artery. In all patients, the morbidity and mortality rates were 15.7 and 0.8%, respectively. The rates for parameters including SMV resection, presence of pathological T3–4, R0 resection, and 3-year survival were 46.2, 92.3, 92.3, and 61.1%, respectively, when there was PDJVI (n?=?13). When there was no PDJVI (n?=?108), the rates were 60.2, 93.5, 86.1, and 58.3%, respectively. Overall, there were no significant differences.

Conclusions

Pancreaticoduodenectomy with PDJV resection is feasible for PDAC with PDJVI and satisfactory overall survival rates are achievable. It may be necessary to reconsider the resectability of PDAC with PDJVI.

     

Successful treatment with steroid and cyclosporine A in a patient with immunoglobulin A–proliferative glomerulonephritis with monoclonal immunoglobulin deposits

We report a case of glomerulonephritis with monoclonal immunoglobulin (Ig) A deposits as a form of monoclonal gammopathy of renal significance (MGRS) caused by monoclonal immunoglobulins without blood disorders in a 41‐year‐old woman. She developed lower leg oedema and was hospitalized because of nephrotic syndrome. Serum and urine were negative for M protein, and the free light chain κ/λ ratio was within the normal range. Renal histopathological findings included mesangial proliferation, endocapillary cell proliferation, and a double‐contour appearance of the capillary walls. Immunofluorescent staining indicated IgA and C3 deposits on the mesangium and capillary walls. Only λ chain and IgA1 deposits were noted. Fine granular sub‐endothelial deposits with no specific structure were observed under electron microscopy. The patient was diagnosed with IgA–proliferative glomerulonephritis with monoclonal immunoglobulin deposits (IgA‐PGNMID). The patient had decreased urine protein and sediment erythrocytes after she underwent two rounds of steroid pulse therapy and oral steroid therapy, but proteinuria and haematuria still remained. Four months later, the patient was administered 50 mg/day cyclosporine (CsA), and proteinuria and haematuria dramatically decreased. Only a few case reports have been published on IgA‐PGNMID. This case is rare in that the patient achieved successful treatment using a combination of steroids and CsA.     

Clinicopathological analysis of biopsy-proven diabetic nephropathy based on the Japanese classification of diabetic nephropathy

Background

The Japanese classification of diabetic nephropathy reflects the risks of mortality, cardiovascular events and kidney prognosis and is clinically useful. Furthermore, pathological findings of diabetic nephropathy are useful for predicting prognoses. In this study, we evaluated the characteristics of pathological findings in relation to the Japanese classification of diabetic nephropathy and their ability to predict prognosis.

Methods

The clinical data of 600 biopsy-confirmed diabetic nephropathy patients were collected retrospectively from 13 centers across Japan. Composite kidney events, kidney death, cardiovascular events, all-cause mortality, and decreasing rate of estimated GFR (eGFR) were evaluated based on the Japanese classification of diabetic nephropathy.

Results

The median observation period was 70.4 (IQR 20.9–101.0) months. Each stage had specific characteristic pathological findings. Diffuse lesions, interstitial fibrosis and/or tubular atrophy (IFTA), interstitial cell infiltration, arteriolar hyalinosis, and intimal thickening were detected in more than half the cases, even in Stage 1. An analysis of the impacts on outcomes in all data showed that hazard ratios of diffuse lesions, widening of the subendothelial space, exudative lesions, mesangiolysis, IFTA, and interstitial cell infiltration were 2.7, 2.8, 2.7, 2.6, 3.5, and 3.7, respectively. Median declining speed of eGFR in all cases was 5.61 mL/min/1.73 m²/year, and the median rate of declining kidney function within 2 years after kidney biopsy was 24.0%.

Conclusions

This study indicated that pathological findings could categorize the high-risk group as well as the Japanese classification of diabetic nephropathy. Further study using biopsy specimens is required to clarify the pathogenesis of diabetic kidney disease.

     

Cancer stem cells and epithelial–mesenchymal transition in urothelial carcinoma: Possible pathways and potential therapeutic approaches

There is growing evidence of the presence of cancer stem cells in urothelial carcinoma. Cancer stem cells have the ability to self‐renew and to differentiate into all cell types of the original heterogeneous tumor. A panel of diverse cancer stem cell markers might be suitable for simulation studies of urothelial cancer stem cells and for the development of optimized treatment protocols. The present review focuses on the advances in recognizing the markers of urothelial cancer stem cells and possible therapeutic targets. The commonly reported markers and pathways that were evaluated include CD44, CD133, ALDH1, SOX2 & SOX4, BMI1, EZH1, PD‐L1, MAGE‐A3, COX2/PGE2/STAT3, AR, and autophagy. Studies on the epithelial–mesenchymal transition‐related pathways (Shh, Wnt/β‐catenin, Notch, PI3K/Akt, TGF‐β, miRNA) are also reviewed. Most of these markers were recognized through the expression patterns of cancer stem cell‐rich side populations. Their regulative role in the development and differentiation of urothelial cancer stem cells was confirmed in vitro by functional analyses (e.g. cell migration, colony formation, sphere formation), and in vivo in xenograft experiments. Although a small number of these pathways are targeted by currently available drugs or drugs that are the currently being tested in clinical trials, a clear treatment approach has not been developed for most pathways. A greater understanding of the mechanisms that control the proliferation and differentiation of cancer stem cells is expected to lead to improvements in targeted therapy.     

Human CD200 suppresses macrophage-mediated xenogeneic cytotoxicity and phagocytosis

Purpose

Various strategies, such as the generation of alpha-1,3-galactosyltransferase knocked-out pigs and CD55 transgenic pigs, have been investigated to inhibit pig to human xenogeneic rejection. Our aim is to develop strategies to overcome the hurdle of not only hyper acute rejection, but also that of cellular xenogeneic rejection (CXR). Although macrophages have been well known to play a critical role in CXR, monocyte/macrophage-mediated xenogeneic rejection has not been well studied. In this study, we evaluated the effect of CD200 in xenogeneic rejection by macrophages.

Methods

Naïve swine endothelial cells (SEC) and SEC/CD200 were co-cultured with M0 macrophages and the cytotoxicity was measured by a WST-8 assay. The phagocytosis of SEC and SEC/CD200 by macrophages was analyzed by flow cytometry.

Results

While CD200 failed to suppress a significant amount of cytotoxicity against SEC by monocytes, M0 macrophage-mediated cytotoxicity was significantly suppressed by human CD200. The phagocytosis by M0 macrophages was also tested. The phagocytosis assay revealed that human CD200 suppresses M0 macrophage-mediated phagocytosis.

Conclusions

Our findings indicate that human CD200 suppresses the xenogeneic rejection by CD200R⁺ macrophages and that the generation of hCD200 transgenic pigs for use in xenografts is very attractive for preventing the macrophage-mediated rejection.

     

Expression of podoplanin in stromal fibroblasts plays a pivotal role in the prognosis of patients with pancreatic cancer

Purpose

To investigate the role of podoplanin (PDPN) expression in invasive ductal carcinoma of the pancreas (IDCP) in humans.

Methods

Tumor samples were obtained from 95 patients with IDCP. Immunohistochemical staining was done to evaluate the expression of PDPN in cancer tissues.

Results

PDPN was detected predominantly in stromal fibroblasts, stained with α-smooth muscle actin. The cutoff value of PDPN-positive areas was calculated according to a histogram. There was no significant difference in clinicopathologic factors between patients with high vs. those with low PDPN expression. The high PDPN group showed significantly poorer disease-free and disease-specific survival rates than the low PDPN group. Among patients from the high PDPN group, those with lymph node metastases and those with a tumor larger than 20 cm in diameter had significantly poorer prognoses than similar patients from the low PDPN group. Multivariate Cox proportional hazards analysis indicated that a high expression of PDPN was an independent risk factor for disease-specific survival.

Conclusions

PDPN expression in cancer-related fibrotic tissues is associated with a poor prognosis, especially in patients with large tumors or lymph node metastases.

     

The degeneration of adjacent intervertebral discs negatively influence union rate of osteoporotic vertebral fracture: A multicenter cohort study

Background

With the increasing aging population in developed countries, there has been an associated increased prevalence of osteoporotic vertebral fracture (OVF). Many previous reports have attempted to predict the risk of delayed union associated with OVF. However, the role of endplate failure and the degeneration of adjacent intervertebral discs, and their association with delayed union has received little attention. The aim of this study was to evaluate the endplate fracture and disc degeneration rank as risk factors for delayed union.