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
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
A higher incidence of apalutamide-related skin rash has been observed in Japanese patients with prostate cancer (PC).
This integrated analysis of data of Japanese patients from 2 global Phase 3 ...studies, SPARTAN ( NCT01946204 ; patients with non-metastatic castration-resistant PC nmCRPC) and TITAN ( NCT02489318 ; patients with metastatic castration-sensitive PC mCSPC), and the Phase 1 study 56021927PCR1008 ( NCT02162836 ; patients with metastatic CRPC mCRPC), assessed clinical risk factors of apalutamide-related skin rash as well as the potential correlation with plasma exposure to apalutamide. Kaplan-Meier method was used for time-to-event analyses. Clinical risk factors for skin rash were assessed using odds ratio.
Data from 68 patients (SPARTAN: n = 34, TITAN: n = 28, 56021927PCR1008: n = 6) receiving apalutamide 240 mg orally once-daily were analyzed. Rash (13 19.1%) and maculo-papular rash (11 16.2%) were the most frequently reported skin rash. All Grade and Grade 3 skin rash occurred in 35 (51.5%) and 10 (14.7%) patients, respectively. Most (85.7%) skin rash occurred within 4 months of apalutamide initiation and resolved in a median time of 1 month following the use of antihistamines, topical or systemic corticosteroids, with/without apalutamide dose interruptions/reductions. Median time-to-remission of first incidence of rash and maximum grade incidence of rash were 1.0 month (IQR: 0.36-1.81) and 1.0 month (IQR: 0.30-2.43), respectively. No significant clinical risk factors for the incidence of skin rash were observed. Areas under the curve (0-24 h) (AUC
) at steady-state of plasma apalutamide concentration were numerically slightly higher in patients with skin rash than those without.
No clinical risk factors for rash could be detected. There is a potential correlation between incidence of skin rash and plasma exposure to apalutamide. In general, apalutamide-related skin rash is easily managed, with appropriate treatment with or without dose adjustment.
Retrospective pooled analysis of NCT01946204 , NCT02489318 , and NCT02162836 .
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
Despite the widespread use of laparoscopic surgery, intracorporeal anastomosis remains a complicated procedure that often prolongs the operation time. This study aimed to investigate the efficacy of ...a novel staple line reinforcement (SLR) during laparoscopic gastrectomy for gastric cancer.
The study included 30 patients who underwent laparoscopic gastrectomy for gastric cancer at the Kochi Medical School between November 2021 and May 2022. A review of these patients was conducted, and perioperative outcomes were compared according to the use of SLR.
The reconstruction time using SLR was significantly shorter compared to when SLR was not used (20.5 min vs. 32.0 min, p=0.048). The incidence of hemostasis during anastomosis was significantly lower in the SLR group than in the non-SLR group (0 vs. 3 times, p=0.041). There were no significant differences in the operating time and estimated blood loss after surgery between the two groups. Furthermore, there were no significant differences in postoperative complications or nutritional status between the two groups.
The usefulness of SLR in reducing the time for intracorporeal reconstruction and archiving the best interaction between device and tissue during laparoscopic gastrectomy for gastric cancer, was herein demonstrated.
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
This study evaluated the prognostic value of C-reactive protein–to–albumin (CAR) and neutrophil-to-lymphocyte ratios (NLR) in conjunction with host-related factors in patients with ...unresectable advanced or recurrent gastric cancer.
Methods
A total of 411 patients with unresectable advanced gastric cancer were treated at Kochi Medical School between 2007 and 2019. Associations between clinicopathological parameters and systemic inflammatory and nutritional markers, including CAR and NLR, with overall survival were analyzed retrospectively.
Results
The optimal cut-off values of predicted median survival time were 0.096 (sensitivity, 74.9%; specificity, 42.5%) for CAR and 3.47 (sensitivity, 64.1%; specificity, 57.5%) for NLR, based on the results of receiver operating characteristic analysis. A weak significant positive correlation was identified between CAR and NLR (
r
= 0.388,
P
< 0.001). The median survival time was significantly higher in patients with intestinal-type than those with diffuse-type histology (18.3 months vs. 9.5 months;
P
= 0.001), CAR < 0.096 than those with CAR ≥ 0.096 (14.8 months vs. 9.9 months;
P
< 0.029), and those with NLR < 3.47 than NLR ≥ 3.47 (14.7 months vs. 8.8 months;
P
< 0.001). Multivariate survival analysis revealed that diffuse-type histology (hazard ratio (HR) 1.865; 95% confidence interval (CI) 1.397–2.490;
P
< 0.001)), 1 or more performance status (HR 11.510; 95% CI 7.941–16.683;
P
< 0.001), and NLR ≥ 3.47 (HR 1.341; 95% CI 1.174–1.769;
P
= 0.023) were significantly associated with independent predictors of worse prognosis.
Conclusions
High CAR and NLR are associated with poor survival in patients with unresectable and recurrent gastric cancer.
Full text
Available for:
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
Abiraterone acetate has been approved in >70 countries for chemotherapy-naïve metastatic castration-resistant prostate cancer patients. Efficacy and safety of abiraterone acetate (1000 mg/once daily) ...with prednisolone (5 mg/twice daily) in chemotherapy-naïve Japanese patients with metastatic castration-resistant prostate cancer was evaluated.
Men, ≥20 years, with prostate-specific antigen levels of ≥5 ng/ml and evidence of progression were enrolled in this Phase 2, multicenter, open-label study. Primary efficacy endpoint was proportion of patients achieving a prostate-specific antigen decline of ≥50% from baseline (prostate-specific antigen response) after 12 week of treatment. Secondary efficacy endpoints and safety were assessed.
A confirmed prostate-specific antigen response was observed in 29/48 (60.4%) patients by week 12; lower limit of two-sided 90% confidence interval was >35% (threshold response rate), demonstrating efficacy of abiraterone acetate. Secondary efficacy endpoints: prostate-specific antigen response rate during treatment period: 62.5%; objective radiographic response, partial response: 4/18 (22.2%) patients; complete response: none; stable disease: 11/18 (61.1%) patients; median percent change in prostate-specific antigen level from baseline at Week 12: -66.62%. Median prostate-specific antigen response duration and progression-free survival were not reached, and median radiographic progression-free survival was 253 days. Of 31/48 (64.6%) patients experienced adverse events of special interest; most common was hepatic function abnormality (37.5%, Grade 3: 10.4%). One Grade 3 hypertension was the only mineralocorticoid adverse event >Grade 1/2.
Efficacy of abiraterone acetate plus prednisolone was demonstrated by decline in prostate-specific antigen levels with evidence of antitumor activity by radiography in Japanese patients with chemotherapy-naïve metastatic castration-resistant prostate cancer. Abiraterone acetate plus prednisolone had an acceptable safety profile.
NCT01756638.
•The authors developed a humanized anti-glypican-1 (GPC1) monoclonal antibody (clone T2) and produced an antibody-drug conjugate (ADC) linked to monomethyl auristatin E (MMAE). The ADC potently ...inhibited the growth of GPC1-positive pancreatic ductal adenocarcinoma and esophageal squamous cell carcinoma in vitro and in vivo, and exhibited bystander killing activity. Humanized GPC1-ADC(MMAE) was effective against BxPC-3-Luc#2 pancreatic cancer liver metastases in mice. Humanized GPC1-ADC(MMAE) may provide a promising therapeutic strategy for GPC1-positive tumors.
An antibody-drug conjugate (ADC) is a promising therapeutic modality because selective and effective delivery of an anti-cancer drug is achieved by drug-conjugated antibody-targeting cancer antigen. Glypican 1 (GPC1) is highly expressed in malignant tumors, including pancreatic ductal adenocarcinoma (PDAC) and esophageal squamous cell carcinoma (ESCC). Herein, we describe the usefulness of GPC1-targeting ADC. Humanized anti-GPC1 antibody (clone T2) was developed and conjugated with monomethyl auristatin E (MMAE) via maleimidocaproyl-valine-citrulline-p-aminobenzyloxycarbonyl (mc-vc-PABC) linkers (humanized GPC1-ADCMMAE). Humanized GPC1-ADC(MMAE) inhibited the growth of GPC1-positive PDAC and ESCC cell lines via inducing cycle arrest in the G2/M phase and apoptosis in vitro. The binding activity of humanized GPC1-ADC(MMAE) with GPC1 was comparable with that of the unconjugated anti-GPC1 antibody. The humanized GPC1-ADC(MMAE) was effective in GPC1-positive BxPC-3 subcutaneously xenografted mice but not in GPC1-negative BxPC-3-GPC1-KO xenografted mice. To assess the bystander killing activity of the humanized GPC1-ADC(MMAE), a mixture of GPC1-positive BxPC-3 and GPC1-negative BxPC-3-GPC1-KO-Luc cells were subcutaneously inoculated, and a heterogenous GPC1-expressing tumor model was developed. The humanized GPC1-ADC(MMAE) inhibited the tumor growth and decreased the luciferase signal, measured with an in vivo imaging system (IVIS), which suggests that the suppression of the BxPC-3-GPC1-KO-Luc population. The humanized GPC1-ADC(MMAE) also inhibited the established liver metastases of BxPC-3 cells and significantly improved the overall survival of the mice. It exhibited a potent antitumor effect on the GPC1-positive PDAC and ESCC patient-derived xenograft (PDX) models. Our preclinical data demonstrate that GPC1 is a promising therapeutic target for ADC.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
This study aimed to investigate the efficacy of enteral supplementation of vitamin B12 for vitamin B12 deficiency in patients who underwent total gastrectomy for gastric cancer.
The study enrolled ...133 patients who underwent total gastrectomy for gastric cancer at Kochi Medical School. Clinical data were obtained to investigate associations between vitamin B12 supplementation and vitamin B12 levels. Vitamin B12 deficiency was defined as serum vitamin B12 less than 200 pg/mL. Baseline characteristics and changes in hematological variables, including vitamin B12 levels, were examined.
Vitamin B12 deficiency was present in 71.4% of the 133 patients. Vitamin B12 levels at 3, 6, and 12 months after enteral supplementation were 306 pg/mL, 294 pg/mL, and 367 pg/mL, respectively, which were all significantly higher than those before supplementation (p < 0.001 for all comparisons). The median red blood cell count at 3, 6, and 12 months after enteral supplementation were 380 × 104/mm3, 394 × 104/mm3, and 395 × 104/mm3, respectively, which were all significantly higher than those before supplementation (p = 0.020, p = 0.001, and p = 0.003, respectively). Vitamin B12 levels at 3, 6, and 12 months after supplementation were significantly higher in patients supplemented enterally than those supplemented parenterally (p < 0.001 for all comparisons).
Vitamin B12 deficiency was found in 71.4% of postoperative patients who underwent total gastrectomy for gastric cancer, and enteral vitamin B12 supplements might be effective to improve anemia in these patients.
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