Cholangiocarcinoma is a highly malignant cancer. Many patients need systemic chemotherapy to prevent tumor development and recurrence; however, their prognosis is poor due to the lack of effective ...therapy. Therefore, a new treatment option is urgently required. We recently identified glypican-1 (GPC1) as a novel cancer antigen of esophageal squamous cell carcinoma. We also demonstrated the efficacy and safety of GPC1-targeted ADC (GPC1-ADC) conjugating anti-GPC1 mAb possessing high internalization activity with monomethyl auristatin F (MMAF), which is a potent tubulin polymerizing inhibitor. In this study, we confirmed that GPC1 was highly expressed in cholangiocarcinoma cells and tissues. IHC analysis of 49 extrahepatic cholangiocarcinoma patient tumor specimens revealed high expression of GPC1 in 47% of patients. These patients demonstrated significantly poorer prognosis compared with the low-expression group in terms of disease-free survival and overall survival (
< 0.05). GPC1 was also expressed in tumor vessels of cholangiocarcinoma, but not on the vessels of nontumor tissues. MMAF-conjugated GPC1-ADC showed potent tumor growth inhibition against GPC1-positive cholangiocarcinoma cells
and
In a GPC1 knockout xenograft model, GPC1-ADC partially inhibited tumor growth. Vascular endothelial cells in tumor tissues of GPC1-negative xenograft mice expressed GPC1 and were arrested in the G
-M phase of cell cycle by GPC1-ADC. GPC1-ADC exhibits direct as well as indirect antitumor effects via inhibition of tumor angiogenesis. Our preclinical data highlight GPC1-ADC as a promising therapy for GPC1-positive cholangiocarcinoma.
Purpose
Postoperative pancreatic fistula is a serious complication of distal pancreatectomy. Although many studies have described the incidence and risk factors associated with postoperative ...pancreatic fistula (POPF), few have focused on the healing time. This study investigated the healing time and potential factors associated with the healing time of POPF after distal pancreatectomy (DP).
Methods
Among 114 patients that underwent DP in our hospital from January 2010 to December 2020, we included 88 that developed POPF. The healing time for a postoperative pancreatic fistula was defined as the interval between the completion of DP and the removal of all drains related to the treatment for POPF. Based on the definition, three cases who required additional treatment after removal of all drains were excluded from this study. Clinical factors associated with the fistula healing times were investigated in the 85 patients.
Results
The average POPF healing time was 11 ± 10 days (median: 6 days, range: 3‐57). We found that the neutrophil‐to‐lymphocyte ratio, a marker of inflammatory and nutritional status, was the only factor independently associated with the POPF healing time; the mean healing time was significantly shorter in patients with neutrophil‐to‐lymphocyte ratio ≤2.1 (8 ± 6 days) than in those with neutrophil‐to‐lymphocyte ratio >2.1 (13 ± 12 days; P = .0139).
Conclusion
We demonstrated that the neutrophil‐to‐lymphocyte ratio could independently predict the POPF healing time after DP. These findings suggested that improving the neutrophil‐to‐lymphocyte ratio might shorten the healing times for POPF after DP.
The healing time of postoperative pancreatic fistula after distal pancreatectomy was associated significantly with the neutrophil‐to‐lymphocyte ratio. This result suggested that improving patients' inflammatory and nutritional status might shorten that healing time.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Background
The change impact of body composition during neoadjuvant therapy on clinical outcomes in patients with pancreatic ductal adenocarcinoma (PDAC) remains unclear. The aim of this study was to ...investigate the association between changes in body composition during neoadjuvant chemoradiotherapy (NACRT) and postoperative outcomes in patients with PDAC undergoing pancreatectomy, using three-dimensional images.
Methods
We reviewed 66 consecutive patients with resectable/borderline resectable PDAC receiving gemcitabine and S-1 with radiotherapy between April 2010 and June 2016. Body compositions were evaluated pre- and post-NACRT. All patients were hospitalized and supplied with regulated diet during NACRT treatment.
Results
Psoas major muscle volume index (PMI), abdominal fat volume index, and visceral fat volume index decreased significantly after NACRT (
P
< 0.0001,
P
< 0.0001,
P
< 0.0001, respectively). The post-NACRT CA19-9 level decreased significantly in the small-PMI-decrease group compared with the large-PMI-decrease group (
P
= 0.046). Recurrence-free survival (RFS) and overall survival (OS) of the large-PMI-decrease group were significantly poorer than those of the small-PMI-decrease group (
P
= 0.002,
P
= 0.006, respectively). On the other hand, there were no significant differences in RFS and OS between groups with high and low PMI, at the point of either pre-NACRT (
P
= 0.117,
P
= 0.123, respectively) or post-NACRT (
P
= 0.065,
P
= 0.064, respectively). Multivariate analysis identified a large percentage decrease in PMI as an independent risk factor for recurrence and death (
P
= 0.003,
P
= 0.002, respectively).
Conclusions
Loss of skeletal muscle mass during NACRT was an independent risk factor for survival in patients with PDAC.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Purpose
Pancreaticoduodenectomy (PD) for pancreatic cancer carries a high risk of massive intraoperative blood loss. The artery first approach (AFA) prevents blood loss during PD, but the optimal ...approach is unclear. The first jejunal vein (FJV) often comprises multiple veins and broadly supports venous drainage of the proximal jejunum. Its ligation carries a risk of proximal jejunum congestion
.
Here we investigated the anatomical characteristics of PD-associated vessels and AFA approach selection based on FJV anatomy.
Methods
This study included 148 Japanese living donors for liver transplantation. We reviewed their computed tomography images and assessed the anatomical pattern of PD-associated vessels in terms of FJV anatomy.
Results
The FJV traveled posterior to the superior mesenteric artery in 128 patients (86.5%, dorsal group) and anterior in 20 (13.5%, ventral group). The predominant draining vein of the inferior pancreaticoduodenal vein was the superior mesenteric vein in the ventral group (87.5%) and the FJV in the dorsal group (97.9%). Compared with the dorsal group, the ventral group had a significantly greater percentage with the superior mesenteric vein ventral to the superior mesenteric artery (30.0% versus 10.9%) and a significantly larger posterior superior pancreaticoduodenal vein diameter (3.2 ± 0.9 versus 2.7 ± 0.6 mm,
p
= 0.0029). These results were validated in patients with pancreatic head cancer.
Conclusions
The anatomical characteristics of PD-associated vessels differed significantly between groups defined by FJV anatomy. Understanding the venous anatomy, especially the FJV, could support selection of the best approach in AFA for PD.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Islet transplantation is an effective replacement therapy for type 1 diabetes (T1D) patients. However, shortage of donor organ for allograft is obstacle for further development of the treatment. ...Subcutaneous transplantation with stem cell-derived β-cells might overcome this, but poor vascularity in the site is burden for success in the transplantation. We investigated the effect of subcutaneous transplantation of vascularized β-cell spheroid tissue constructed 3-dimensionally using a layer-by-layer (LbL) cell-coating technique in a T1D model mouse.
We used MIN6 cells to determine optimal conditions for the coculture of β-cell spheroids, normal human dermal fibroblasts, and human umbilical vein endothelial cells, and then, under those conditions, we constructed vascularized spheroid tissue using human induced pluripotent stem cell-derived β-cells (hiPS β cells). The function of insulin secretion of the vascularized hiPS β-cell spheroid tissue was evaluated in vitro. Furthermore, the function was investigated in T1D model NOD/SCID mice subcutaneously transplanted with the tissue.
In vitro, the vascularized hiPS β-cell spheroid tissue exhibited enhanced insulin secretion. The vascularized hiPS β-cell spheroid tissue also significantly decreased blood glucose levels in diabetic immunodeficient mice when transplanted subcutaneously. Furthermore, host mouse vessels were observed in the explanted vascularized hiPS β-cell spheroid tissue.
Vascularized hiPS β-cell spheroid tissue decreased blood glucose levels in the diabetic mice. This therapeutic effect was suggested due to host angiogenesis in the graft. This method could lead to a promising regenerative treatment for T1D patients.
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