Purpose
To investigate the usefulness of clinicopathological systemic inflammatory response and nutritional biomarkers for predicting the efficacy of nivolumab in patients with advanced gastric ...cancer.
Methods
The subjects of this study were 29 patients who received nivolumab treatment for advanced gastric cancer at the Kochi Medical School between 2017 and 2019. Clinicopathological information, including systemic inflammatory response data, were obtained to investigate the associations between baseline cancer-related prognostic variables and survival outcomes.
Results
Immune-related adverse events (irAEs) of any grade were identified in 34.5% (10/29) of the patients. The median progression-free survival of patients with irAEs was significantly greater than that of patients without irAEs (5.8 months vs. 1.2 months, respectively;
P
= 0.028). The neutrophil to lymphocyte ratio (NLR) after 4 weeks of treatment in the complete response (CR) or partial response (PR) group was significantly lower than that in the stable disease (SD) or progression disease (PD) group (2.2 vs. 2.9, respectively;
P
= 0.044). The prognostic nutrition index (PNI) before treatment in the CR or PR group was significantly higher than that in the SD or PD group (37.1 vs. 32.1, respectively;
P
= 0.011). The PNI 8 weeks after treatment and the Glasgow prognostic score (GPS) before treatment were significantly associated with a poor outcome.
Conclusion
The irAE, NLR, PNI, and GPS may be useful predictive markers for nivolumab efficacy in patients with advanced gastric cancer.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background
Postoperative anastomotic leakage is a severe complication after gastric tube reconstruction during esophagectomy. The aim of this study was to evaluate the usefulness of postoperative ...endoscopic assessment of anastomosis and its correlation with intraoperative indocyanine green (ICG) fluorescence assessment of the gastric tube.
Methods
We retrospectively reviewed 72 consecutive patients who underwent gastric tube reconstruction using the ICG fluorescence method during esophagectomy. Forty-six patients underwent the ICG line-marking method (LMM group; ICG before gastric tube creation). The other 26 underwent the conventional procedure and comprised the control group (ICG after gastric tube creation). Postoperative endoscopic assessment (PEA) of anastomosis was performed 7 days after surgery and results were classified as follows: grade 1 (normal or partial white coat), grade 2 (ulcer comprising less than half the circumference), and grade 3 (ulcer comprising more than half the circumference).
Results
Anastomotic leakage occurred in 7 of 72 patients (9.7%). The incidence of anastomotic leakage in the LMM group was tended to be lower than those in the control group (6.5% vs. 15.4%;
P
= 0.244). Of the 40 patients who underwent PEA, 3 (7.5%) had leakage. PEA grading was significantly associated with anastomotic leakage (
P
< 0.001). Better intraoperative ICG assessment was significantly associated with better endoscopic assessment grade (
P
= 0.041).
Conclusion
Intraoperative ICG assessment of the gastric tube was associated with PEA grading on anastomosis during esophagectomy.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Purpose
Zinc is an essential dietary component for humans and the second most prevalent trace element; however, serum zinc levels after gastrectomy have not been fully elucidated. This study aimed to ...evaluate the correlation between clinicopathologic features and serum zinc levels in patients who underwent gastrectomy for gastric cancer.
Methods
The study enrolled 617 patients who underwent gastrectomy for gastric cancer at the Kochi Medical School. Clinical data were obtained to investigate associations between clinicopathological features, including nutritional indicators and serum zinc levels. Serum zinc deficiency was defined as serum zinc level < 80 μg/dL.
Results
The median zinc level of the 617 patients was 73 μg/dL (range, 31–144 μg/dL), and serum zinc deficiency was present in 68.6% of patients. Median age was significantly higher in the zinc low level group than in the normal group (69 vs. 66 years,
P
< 0.001). Albumin was significantly lower in the zinc low level group than in the normal group (3.9 vs. 4.2 g/dL,
P
< 0.001). C-reactive protein level was significantly higher in the zinc low level group than in the normal group (0.12 vs. 0.10 mg/dL,
P
= 0.014). The median serum zinc level was significantly lower in the patients who received chemotherapy after gastrectomy than in those who were not received chemotherapy (72 vs. 76 μg/dL,
P
< 0.001). Serum zinc levels showed a significant positive correlation with serum albumin (
r
= 0.505,
P
= 0.044). Multivariate analysis showed that serum albumin level was significantly associated with serum zinc level (
β
= 0.489,
P
< 0.001).
Conclusions
Serum zinc deficiency was found in 68.6% of postoperative patients who underwent gastrectomy for gastric cancer, which was highly correlated with serum albumin.
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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
The development of a closed‐loop artificial pancreas (AP) in the Western countries and Japan is different. In Western countries, wearable AP with a closed‐loop glycemic control system has been ...developed as a treatment for patients with type 1 and type 2 diabetes. On the contrary, in Japan, bedside closed‐loop AP explored by a Japanese company (Nikkiso, Tokyo, Japan) has developed as perioperative glycemic control device in surgical patients and acute care patients with emergency. In this article, we reviewed the scientific evidence in the past and present and future prospects of perioperative glycemic control using bedside AP with a closed‐loop system in Japan. Conventional perioperative strict glycemic controls have three major problems: hyperglycemia, hypoglycemia, and variability in blood glucose concentrations. In Japan, perioperative strict glycemic control using the current bedside AP STG‐55 (Nikkiso, Tokyo, Japan) has been developed since 2010. This novel glycemic control method achieved not only stable glycemic control without hyperglycemia, hypoglycemia, and less variability of blood glucose concentrations but also reduced postoperative infectious complications in patients undergoing major surgeries. Among the rapidly increasing number of surgical or emergency patients with diabetes, frailty, and sarcopenia of intrinsic glucose intolerance, more sophisticated and smaller AP available easily in operating rooms and intensive care units will be warranted to promote improved therapeutic outcomes in such critically ill patients.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Pancreatic ductal adenocarcinoma (PDAC) is a stroma-rich cancer. Extracellular matrix proteins produced by cancer-associated fibroblasts (CAFs) found in tumor stroma that impedes effective delivery ...of chemotherapeutic agents results in poor response in patients with PDAC. Previously, our group reported that glypican-1 (GPC1) was overexpressed in human PDAC and negatively correlated with patient survival. Immunohistochemical analysis of 25 patients with PDAC tumor specimens revealed elevated expression of GPC1 in stromal cells and pancreatic cancer cells in 80% of patients. Interestingly, GPC1 was expressed on CAFs in PDAC. We generated a GPC1 antibody-drug conjugate conjugated with monomethyl auristatin E GPC1-ADC(MMAE) and evaluated its preclinical antitumor activity by targeting GPC1-positive CAF and cancer cells in PDAC. GPC1-ADC(MMAE) inhibited the growth of GPC1-positive PDAC cell lines
Furthermore, GPC1-ADC(MMAE) showed a potent antitumor effect in the PDAC patient-derived tumor xenograft (PDX) model against GPC1-positive CAF and heterogeneous GPC1-expressing cancer cells. Notably, GPC1-ADC(MMAE) showed robust preclinical efficacy against GPC1 in a stroma-positive/cancer-negative PDAC PDX model. GPC1-ADC(MMAE) was delivered and internalized to CAFs. Although apoptosis was not observed in CAFs, the released MMAE from CAFs via MDR-1 induced apoptosis of cancer cells neighboring CAFs and efficiently inhibited PDAC tumor growth. GPC1-ADC(MMAE) exhibited potent and unique antitumor activity in GPC1-positive PDAC PDX models, which suggests that GPC1 is a novel therapeutic target in PDAC and other stromal GPC1-positive solid tumors. These findings show that targeting GPC1 on CAF using GPC1-ADC(MMAE) is a useful approach in case of stroma-rich tumors such as PDAC.
Purpose
Patients with unresectable advanced metastatic gastric cancer have a poor prognosis. This study examined the incidence and prognostic impact of cachexia during systemic drug treatment in such ...patients.
Methods
We enrolled patients with unresectable advanced gastric cancer who were treated with chemotherapy at Kochi Medical School from 2007 to 2020. Cancer cachexia was defined as > 5% weight loss or > 2% weight loss with a body mass index of < 20 kg/m
2
within the past 6 months. Associations between clinicopathological parameters, cancer cachexia, and the overall survival were analyzed.
Results
Cancer cachexia occurred in 55.2% of 134 enrolled patients 6 months after chemotherapy. The incidence of cancer cachexia in initial unresectable gastric cancer was significantly higher than that in patients with recurrent cancer after curative resection. The median overall survival was significantly lower in the patients with cancer cachexia than in those without cancer cachexia at 6 months after starting systemic chemotherapy (13.7 months vs. 21.6 months,
P
= 0.032). Cancer cachexia at 6 months of starting treatment and CRP > 0.14 were identified as significantly associated with poor outcomes in a multivariate analysis (hazard ratio HR 1.339, 95% confidence interval CI 1.160–2.085,
P
= 0.019; HR 1.885, 95% CI 1.124–3.161,
P
= 0.016); respectively).
Conclusions
Cancer cachexia was frequently observed in unresectable advanced gastric cancer patients who received chemotherapy and was useful as a prognostic factor for the overall survival.
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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
Background/Purpose
The day of the week can impact medical treatment outcomes; however, few large‐scale, disease‐specific studies have focused on the association between the day of the week and ...mortality in patients after pancreatoduodenectomy for pancreatic head cancer.
Methods
Data were obtained from the National Clinical Database. Twenty‐two clinical variables were adopted for hierarchal logistic regression modeling to determine adjusted odds ratios (ORs) for surgical mortality after elective pancreatoduodenectomy.
Results
The 30‐day mortality and surgical mortality rates were 1.0% and 1.7%, respectively (n = 29 720). Surgeries were performed the least on Fridays (13.4%) compared with other weekdays. Crude rates of severe postoperative complications (mean, 14.1%; range, 13.5%‐14.8%) and pancreatic fistulas (mean, 10.0%; range, 9.6%‐10.3%) remained stable throughout the week. Unadjusted/adjusted ORs did not significantly differ between Friday and Monday (0.868, 95% CI: 0.636‐1.173, P = .365, and 0.928, 95% CI: 0.668‐1.287, P = .653, respectively), and results were similar for the remaining weekdays. Nineteen independent factors were associated with surgical mortality.
Conclusions
The rate of perioperative mortality for elective pancreatoduodenectomy is low in Japan, with no evidence of disparities in surgical mortality rates between weekdays.
Uemura and colleagues investigated the association between day of the week and surgical mortality after elective pancreatoduodenectomy for pancreatic head cancer. Analysis of 29,270 patients from the Japanese National Clinical Database demonstrated low rates of perioperative mortality for elective pancreatoduodenectomy, showing no disparities in surgical mortality rates from Monday to Friday.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Background
This study evaluated the prognostic value of alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) together with host-related factors in patients with unresectable advanced gastric ...cancer.
Methods
The study enrolled 262 patients who received chemotherapy for unresectable advanced gastric cancer at Kochi Medical School from 2007 to 2015. Clinicopathological information and systemic inflammatory response data were analyzed for associations between baseline cancer-related prognostic variables and survival outcomes.
Results
The median survival time was significantly lower for patients with high ALP, high LDH, high total bilirubin, high aspartate aminotransferase, high alanine transaminase, high gamma-glutamyltransferase, high creatinine, a Glasgow prognostic score (GPS) of 1 or 2 score compared to GPS 0, higher compared to lower neutrophil to lymphocyte ratio (NLR) 3.9, lower compared to higher prognostic nutrition index 36.1, T3–4 compared to T1–2 tumor and diffuse-type compared to intestinal-type histology. Multivariate survival analysis identified high ALP 322 (HR 1.808; 95% CI 1.015–3.220;
P
= 0.044), T2–3 (HR 2.622; 95% CI 1.224–5.618;
P
= 0.013), and diffuse-type gastric cancer (HR 2.325; 95% CI 1.341–4.032;
P
= 0.003) as significant independent predictors of worse prognosis in the studied group of cancer patients.
Conclusions
High level of ALP is an independent, worse prognosis factor for patients receiving chemotherapy for unresectable and recurrent gastric cancer.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Purpose
To evaluate the correlation between blood supply speed in the gastric tube (GT), assessed by the intraoperative indocyanine green (ICG) fluorescence method, and postoperative endoscopic ...assessment (PEA) of the anastomosis or anastomotic leakage (AL).
Methods
The subjects of this retrospective analysis were 66 consecutive patients who underwent GT reconstruction using ICG fluorescence during esophageal surgery. We measured the ICG visualization time, from ICG injection to visualization at the top of the GT. We performed PEA on 54 patients and classified ulcer formation as involving less than or more than half of the circumference.
Results
PEA revealed that nine patients (16.7%) had an anastomotic ulcer involving more than half of the circumference and ten (15.4%) had AL. The ICG visualization time in these patients was significantly delayed compared with that in those with less than half of the circumference involved by ulcer formation (37 s vs. 27 s;
P
= 0.015) and without AL (36 s vs. 28 s;
P
= 0.045). Multivariate analysis revealed that delay in the ICG visualization time (> 36 s) of the pulled-up GT (odds ratio, 6.098; 95% confidence interval, 1.125–33.024;
P
= 0.036) was an independent risk factor associated with AL.
Conclusion
Delay in the ICG visualization time of pulled-up GT was associated with ulcer formation on the anastomosis and AL after esophageal surgery.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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