Effects of postoperative oral elemental nutritional supplement on skeletal muscle loss after gastrectomy for gastric cancer.

BACKGROUND: We previously showed that daily nutritional intervention with an oral elemental diet (ED) at 300 kcal/day for 6-8 weeks postoperatively decreased the percentage of body weight loss (%BWL), and that the effect was maintained for 1 year. This post hoc analysis aimed to determine whether this intervention decreased skeletal muscle mass loss 1-year post-gastrectomy. METHODS: Data from consecutive, untreated patients with histopathologically confirmed stage I-III gastric adenocarcinoma who planned to undergo total gastrectomy (TG) or distal gastrectomy (DG) and were enrolled in a previously published randomized trial were used. The primary endpoint was the percentage of skeletal muscle mass index (%SMI) loss from baseline at 1 year postoperatively, based on abdominal computed tomography images obtained preoperatively and at 1 year postoperatively. RESULTS: The overall median %SMI loss was lower in the ED versus control group, but the difference was not significant. The difference in %SMI loss in the ED and control groups was greater in patients with TG (10.1 vs. 13.0; P = 0.12) than in those with DG (5.5 vs. 6.8; P = 0.69). A correlation was observed between %BWL and %SMI loss in both groups (ED group, coefficient 0.591; control group, coefficient 0.644; P < 0.001 for both). Type of gastrectomy (coefficient 7.38; P = 0.001) and disease stage (coefficient - 6.43; P = 0.04) were independent predictors of postoperative skeletal muscle mass loss. CONCLUSION: ED administration for 6-8 weeks following gastrectomy had no inhibitory effect on skeletal muscle loss at 1 year postoperatively. CLINICAL TRIAL REGISTRATION: UMIN000023455.

The cachexia index is a prognostic factor for patients with recurrent pancreatic cancer.

PURPOSE: Cancer cachexia leads to poor outcomes, especially for patients with advanced stage disease. The cachexia index (CXI), a novel biomarker for cancer cachexia, has been identified as a prognostic indicator for several malignancies. The present study aimed to clarify the prognostic significance of the CXI for patients with recurrent pancreatic cancer. METHODS: This retrospective study enrolled 113 patients diagnosed with recurrence following pancreatectomy for pancreatic cancer, to analyze the association between the CXI and prognostic survival. RESULTS: The 2-year overall survival rate and median survival of all patients were 28.5% and 12.6 months, respectively. The 2-year overall survival curve in the high CXI group was significantly better than that in the low CXI group (p < 0.001). The rate of chemotherapy after recurrence was significantly lower in the low CXI group than in the high CXI group (p = 0.002). Multivariate analysis identified the CXI as an independent prognostic factor for patients with recurrent pancreatic cancer (p = 0.011). CONCLUSIONS: The CXI proved useful for predicting the post-recurrence prognosis of patients with recurrent pancreatic cancer. Patients with a low CXI at the time of recurrence have poorer prognostic outcomes than those with a high CXI.

Preoperative low skeletal muscle volume can result in insufficient administration of S-1 adjuvant chemotherapy in older patients with stage II/III gastric cancer.

BACKGROUND AND PURPOSE: Older patients are more likely to encounter difficulties receiving chemotherapy, but the factors involved in the continuation of chemotherapy in these patients remain unclear. We investigated the importance of muscle mass as a factor involved in delivering a sufficient dose of postoperative S-1 adjuvant chemotherapy (ACT) to older patients with gastric cancer. METHODS: The subjects of this study were 79 patients aged ≥ 65 years with stage II/III gastric adenocarcinoma, who underwent curative gastrectomy and received S-1 ACT. RESULTS: The overall median relative dose intensity (RDI) was 75.0% (18.8-93.5%). Patients were divided into two groups for receiver operating characteristic analysis according to the cutoff value. Significantly more patients in the high skeletal muscle index (SMI) group achieved > 62% RDI of S-1 ACT (p = 0.03). Conversely, more patients in the low SMI group suffered from S-1-induced nausea (p = 0.03) and discontinued chemotherapy because of adverse events (p = 0.02). Multivariate analysis identified low SMI as an independent factor for insufficient S-1 dose delivery (p = 0.03, hazard ratio = 2.87). CONCLUSION: Preoperative SMI is an indicator of the low-dose intensity of S-1 ACT in older patients following curative gastrectomy.

Prognostic significance of the cachexia index in patients with unresectable advanced gastric cancer receiving palliative chemotherapy: a retrospective single-center study.

PURPOSE: To investigate the prognostic utility of the cachexia index (CXI) in unresectable advanced gastric cancer (UAGC). METHODS: The relationship between CXI and the outcomes was evaluated in 102 patients with UAGC who had received first-line palliative 5-fluorouracil-based chemotherapy between January 2012 and December 2021. RESULTS: The median survival time (MST) from first-line chemotherapy initiation was 16.2 months, and the cohort included 60 and 42 patients with high and low CXIs, respectively, based on the optimal CXI cutoff. The rates of patients with a performance status score of 0, recurrence, third-line chemotherapy, and all grade 3-4 side effects, including febrile neutropenia (FN), were significantly higher in the CXIhigh group than in the CXIlow group. The prognosis based on MST was significantly better in the CXIhigh group than in the CXIlow group (22.5 vs. 11.6 months, p < 0.001). According to a multivariate analysis, a low CXI and performance status score of 1-2 were poor prognostic factors. CONCLUSIONS: Patients with UAGC and a low CXI had poorer prognoses and more frequent grade 3-4 side effects, including FN, than those with a high CXI. Patients with UAGC and a low CXI should be carefully managed to control for side effects to receive subsequent treatment.

Using the geriatric nutritional risk index to predict outcomes in older patients with remnant gastric cancer after gastrectomy: a retrospective multicenter study in Japan.

PURPOSE: This study investigated the prognostic value of the geriatric nutritional risk index (GNRI) in patients undergoing curative gastrectomy for remnant gastric cancer (RGC). METHODS: This multicenter retrospective study included 105 patients with RGC of ≥ 65 years of age who underwent curative gastrectomy at 10 institutions in Japan between January 2000 and December 2016. Postoperative complications, overall survival (OS), and disease-specific survival (DSS) were analyzed. RESULTS: Receiver operating curve analyses indicated that the optimal cutoff value of the GNRI for OS was 95.4. Patients were categorized into high and low GNRI groups based on the optimal GNRI cutoff value. The GNRI was significantly correlated with body mass index (p < 0.001), amount of bleeding (p = 0.021), Clavien-Dindo grade 5 postoperative complications (p = 0.040), death caused by primary disease (p = 0.010), and death caused by other diseases (p = 0.002). The OS and DSS were significantly worse in the low GNRI group. A low GNRI and T3 or deeper tumor invasion were independent prognostic factors for OS and DSS. CONCLUSIONS: The GNRI is a promising predictor of both short- and long-term outcomes in older patients with RGC.

Inhibition of the bone morphogenetic protein pathway suppresses tumor growth through downregulation of epidermal growth factor receptor in MEK/ERK-dependent colorectal cancer.

The bone morphogenetic protein (BMP) pathway promotes differentiation and induces apoptosis in normal colorectal epithelial cells. However, its role in colorectal cancer (CRC) is controversial, where it can act as context-dependent tumor promoter or tumor suppressor. Here we have found that CRC cells reside in a BMP-rich environment based on curation of two publicly available RNA-sequencing databases. Suppression of BMP using a specific BMP inhibitor, LDN193189, suppresses the growth of select CRC organoids. Colorectal cancer organoids treated with LDN193189 showed a decrease in epidermal growth factor receptor, which was mediated by protein degradation induced by leucine-rich repeats and immunoglobulin-like domains protein 1 (LRIG1) expression. Among 18 molecularly characterized CRC organoids, suppression of growth by BMP inhibition correlated with induction of LRIG1 gene expression. Notably, knockdown of LRIG1 in organoids diminished the growth-suppressive effect of LDN193189. Furthermore, in CRC organoids, which are susceptible to growth suppression by LDN193189, simultaneous treatment with LDN193189 and trametinib, an FDA-approved MEK inhibitor, resulted in cooperative growth inhibition both in vitro and in vivo. Taken together, the simultaneous inhibition of BMP and MEK could be a novel treatment option in CRC cases, and evaluating in vitro growth suppression and LRIG1 induction by BMP inhibition using patient-derived organoids could offer functional biomarkers for predicting potential responders to this regimen.

Impact of Frailty and Sarcopenia on Short- and Long-Term Outcomes in Elderly Patients Undergoing Radical Gastrectomy for Gastric Cancer.

BACKGROUND: The impact of frailty and sarcopenia in patients with gastric cancer is unclear. This study aimed to comprehensively examine the impact of frailty and sarcopenia on the short- and long-term outcomes in elderly patients undergoing radical gastrectomy for gastric cancer. METHODS: We retrospectively assessed 246 patients aged ≥ 65 years who underwent radical gastrectomy. Frailty and sarcopenia were assessed using the modified frailty index (mFI) and psoas muscle mass index (PMI), respectively. RESULTS: There were 30 (12.2%) and 60 (24.4%) patients with High-mFI and Low-PMI, respectively. As the age increased, both sexes showed significant correlations with PMI and mFI (r = - 0.238, 0.322, P = 0.003 and 0.002, respectively). High-mFI and Low-PMI did not affect the short-term outcomes. However, High-mFI was an independent risk factor for non-home discharge (P = 0.004) and was a significant predictor of 3- and 5-year overall survival (OS) (HR = 2.76 and 2.26; P = 0.002 and 0.005, respectively) and 1-, 3- and 5-year non-cancer-specific survival (non-CSS) (HR = 4.88, 8.05, and 4.01; P = 0.017, < 0.001, < 0.001, respectively). Low-PMI was a significant predictor of only 5-year OS (HR = 2.03, P = 0.003) and non-CSS (HR = 2.10, P = 0.020). CONCLUSIONS: Frailty is significant predictor of non-home discharge and 1-, 3-, 5-year OS and 3- and 5-year non-CSS. Sarcopenia is a significant predictor of 5-year OS and non-CSS. Preoperative assessment of both frailty and sarcopenia can help surgeons to select adequate treatment strategies for the elderly population.

Evaluation of perioperative D-dimer concentration for predicting postoperative deep vein thrombosis following hepatobiliary-pancreatic surgery.

PURPOSE: This study was performed to investigate the predictive value of the perioperative D-dimer concentration for the development of postoperative deep vein thrombosis (DVT) after hepatobiliary-pancreatic (HBP) surgery. METHODS: The subjects of this retrospective study were 178 patients who underwent HBP surgery in our hospital between January, 2017 and December, 2021. The D-dimer concentration was measured preoperatively and on postoperative days (POD) 1, 3, and 5. Postoperative DVT was diagnosed based on compression ultrasonography in both lower limbs on POD 6 or 7. RESULTS: Postoperative DVT developed in 21 (11.8%) of the 178 patients. The D-dimer concentration was significantly higher in the patients with than in those without postoperative DVT before surgery and on PODs 1, 3, and 5. The highest area under the curve of the D-dimer concentration for predicting DVT was 0.762 on POD 3. Multivariate analysis revealed that the D-dimer concentration on POD 3 was an independent predictive risk factor for postoperative DVT, along with the preoperative estimated glomerular filtration rate. Preoperative albumin and D-dimer concentrations were also identified as independent predictive factors of an increase in D-dimer concentration on POD 3. CONCLUSIONS: The D-dimer concentration on POD 3 is a useful predictor of DVT after HBP surgery.

Impact of gastrectomy on body composition within 1 month in patients with gastric cancer.

PURPOSE: The present study examined the changes in and risk factors for body composition (BC) during the first postoperative month when dynamic biological reactions occur. METHODS: We retrospectively assessed 202 patients who underwent gastrectomy. The BC was assessed using a bioelectrical impedance analysis and evaluated within 1 month preoperatively, 1 week postoperatively, and 1 month postoperatively. Multiple regression analyses were performed to identify predictive factors for BC change. RESULTS: The mean reduction rate in BC at 1 month postoperatively was - 6.0, - 10.5, - 5.6, - 1.1, - 10.1, and + 1.2% for body weight, body fat, skeletal muscle, bone mineral, extracellular water/total body water, and the whole-body phase angle, respectively. A multiple regression analysis revealed that independent risk factors for weight loss were complications, operative time, and type of gastrectomy (P = 0.004, 0.011, 0.015, respectively), and those for skeletal muscle loss were complications and gastrectomy type (P = 0.002, 0.010, respectively). A segmental lean mass analysis revealed that the lower limbs were markedly reduced at 1 week postoperatively (- 8.0%), and these independent risk factors were the female sex and Stage II/III disease (P = 0.008, 0.036, respectively). CONCLUSION: Detailed analyses of BC might help elucidate the mechanisms underlying postoperative physical changes, which might be useful for perioperative management.

Estimation of the physiologic ability and surgical stress scoring system as a useful predictor of postoperative recurrence in patients with stage II colorectal cancer: a multicenter study.

PURPOSE: We determined the usefulness of the estimation of physiologic ability and surgical stress (E-PASS), initially reported as a predictive factor for postoperative morbidity and mortality, as a prognostic indicator in stage II colorectal cancer (CRC). METHODS: Overall, 739 patients who underwent proctocolectomy for CRC at Tottori University Hospital and affiliated hospitals and histologically diagnosed with stage II CRC were included in the current study. RESULTS: A receiver operating characteristic (ROC) analysis of the five-year recurrence-free survival indicated that the comprehensive risk score (CRS) of E-PASS predicted postoperative recurrence. A multivariate analysis revealed that the presence of preoperative perforation, T4, v ≥ 2, and CRSHigh (≥ 0.2267) were independent predictors of postoperative recurrence. Patients were assigned a score using these factors, as follows: the presence of perforation = 1, the absence of preoperative perforation = 0, T4 = 1, T3 = 0, v2/3 = 1, v0/1 = 0, CRSHigh = 1, and CRSLow = 0 (total score: 0-4). Accordingly, the respective 5-year relapse-free survival rates were 91.0%, 83.6%, 70.3%, and 52.0% among those with scores of 0, 1, 2, and both 3 and 4 (P < 0.001). CONCLUSIONS: The CRS predicts postoperative recurrence in patients with stage II CRC.

The prognostic impact of the lymphocyte-to-C-reactive protein ratio in patients with unresectable or recurrent advanced gastric cancer treated with first- and second-line treatment.

PURPOSE: The goal of this study was to determine which markers are the most useful as first- and second-line pre-treatment markers in patients with unresectable or recurrent gastric cancer (URGC). METHODS: This study included 101 URGC patients who were treated with first- and second-line chemotherapy. Several prognostic scores based on nutrition and inflammation were analyzed using a receiver operating characteristic (ROC) analysis to determine the most useful prognostic marker. RESULTS: The lymphocyte-to-C-reactive protein ratio (LCR) had the highest area under the curve for both first- and second-line chemotherapy, according to an ROC analysis. An ROC analysis was used to determine the optimal LCR cut-off for the median survival time before first- and second-line chemotherapy, and patients were divided into high- and low-LCR groups. Patients with a high LCR had a significantly longer survival than those with a low LCR before first- and second-line chemotherapy (p = 0.004, p < 0.001, respectively). A low LCR before both first- and second-line chemotherapy was an independent poor prognostic factor in a multivariate analysis. CONCLUSIONS: URGC patients with a low LCR before both first- and second-line chemotherapy had a significantly worse prognosis than those with a high LCR in this study. Nutritional intervention during chemotherapy induction may lead to a better prognosis.

A low cumulative perioperative prognostic nutritional index predicts poor long-term outcomes in patients with gastric cancer: A single-center retrospective study in Japan.

PURPOSE: Perioperative surgical stress and systemic inflammation resulting from complex interactions between cancer and the host play an important role in cancer progression. This retrospective study compared the prognostic impact of various perioperative cumulative inflammation- and nutrition-based markers in patients with gastric cancer (GC). METHODS: This study included 301 patients with a histopathological diagnosis of gastric adenocarcinoma who underwent curative surgery. Perioperative cumulative markers were calculated using the newly developed trapezoidal area method. RESULTS: The cumulative prognostic nutritional index (cum-PNI) had the highest area under the receiver operating characteristic (ROC) curve for predicting the overall survival (OS) as well as the relapse-free survival (RFS). The cum-PNI was significantly correlated with tumor-related factors, including tumor size, depth of invasion, lymph node metastasis, lymphatic involvement, vascular involvement, and TNM stage classification. The cum-PNI was also significantly correlated with surgical factors, including surgical approach, gastrectomy, lymphadenectomy, intraoperative blood loss, and postoperative complications. Furthermore, the OS and RFS were poorer in patients with a low cum-PNI (< 236.3) than in those with a high cum-PNI (> 236.3). A multivariate analysis indicated that a low cum-PNI was an independent prognostic indicator in patients with GC. CONCLUSIONS: The cum-PNI might be useful for predicting the prognosis and guiding the perioperative management of patients with GC.

Impact of the hospital volume and setting on postoperative complications of surgery for gastroenterological cancers in a regional area of Western Japan.

PURPOSE: A research subgroup was established by the Japanese Society of Gastroenterological Surgery to improve the health care quality in the Chushikoku area of Western Japan. METHODS: The records of four surgical procedures were extracted from the Japanese National Clinical Database and analyzed retrospectively to establish the association between hospital characteristics, defined using a combination of hospital case-volume and patients' hospital travel distance, and the incidences of perioperative complications of ≥ Grade 3 of the Clavien-Dindo classification after gastroenterological surgery. RESULTS: This study analyzed 11,515 cases of distal gastrectomy for gastric cancer, 4,705 cases of total gastrectomy for gastric cancer, 4,996 cases of right hemicolectomy for colon cancer, and 5,243 cases of lower anterior resection for rectal cancer, with composite outcome incidences of 5.6%, 10.2%, 5.5%, and 10.7%, respectively. After adjusting for patient characteristics and surgical procedures, no association was identified between the hospital category and surgical outcomes. CONCLUSION: The findings of our study of the Chushikoku region did not provide positive support for the consolidation and centralization of hospitals, based solely on hospital case volume. Our grouping was unique in that we included patient travel distance in the analysis, but further investigations from other perspectives are needed.

Simultaneous regulation of ferroptosis suppressor protein 1 and glutathione peroxidase 4 as a new therapeutic strategy of ferroptosis for esophageal squamous cell carcinoma.

BACKGROUND: Ferroptosis suppressor protein 1 and glutathione peroxidase 4 have been identified as key molecules in two independent pathways associated with ferroptosis inhibition. This study investigated the prognostic significance and clinical associations of FSP1 and GPX4 expression in esophageal squamous cell carcinoma (ESCC) and assessed the therapeutic potential of regulating these molecules in ESCC cells. METHODS: Immunohistochemical analysis was performed on surgical specimens of 97 patients with ESCC for FSP1 and GPX4 expression. To identify the change in ESCC cell viability, FSP1 and GPX4 inhibitors were administered to three cell lines. In addition, ferroptosis as the cause of reduced cell viability by FSP1 and GPX4 inhibition was confirmed. RESULTS: Prognosis was significantly worse for patients in the group positive for both FSP1 and GPX4 compared with the other groups (p < 0.001). In multivariate analysis, positivity for both FSP1 and GPX4 was an independent poor prognostic factor (p = 0.002). The combination of FSP1 and GPX4 inhibitors induced cell death more potently than each inhibitor did alone. Furthermore, the ferroptosis inhibitor markedly canceled this cell death. CONCLUSIONS: Overexpression of FSP1 and GPX4 is a poor prognostic factor for patients with ESCC. Simultaneous suppression of both FSP1 and GPX4 caused potent cell death, which was markedly abrogated by ferroptosis inhibitors. These findings indicate that simultaneous regulation of FSP1 and GPX4 may be a new therapeutic target in ESCC.

The impact of AMIGO2 on prognosis and hepatic metastasis in gastric cancer patients.

BACKGROUND: Gastric cancer (GC) is one of the most common malignancies, and the liver is the most common site of hematogenous metastasis of GC. AMIGO2 is a type I transmembrane protein that has been implicated in tumour cell adhesion in adenocarcinomas; however, its importance in GC remains undetermined. METHODS: We analyzed AMIGO2 expression by immunohistochemistry using the specific monoclonal antibody for human AMIGO2 in 128 patients who underwent GC surgery to evaluate its relationship between various metastatic and clinical outcomes in GC. RESULTS: Immunohistochemistry revealed that AMIGO2 expression was an independent prognostic factor for overall survival, disease-specific survival, and liver metastasis in GC patients. CONCLUSIONS: This study showed that AMIGO2 is induced in GC tissues and can mediate hepatic metastasis. Determining AMIGO2 expression in GC will help predict patient prognosis and the incidence of liver metastasis.

Combined analysis of preoperative and postoperative lymphocyte-C-reactive protein ratio precisely predicts outcomes of patients with gastric cancer.

BACKGROUND: The systemic inflammatory response resulting from the complex interactions between cancer and the host plays an important role in cancer development. Recently, the lymphocyte-C-reactive protein ratio (LCR), which is a hematological and biochemical marker that reflects the systemic inflammatory response and nutritional status, has been reported to be associated with poor survival. Similar results were observed in patients with certain cancer types. However, these studies focused on the preoperative LCR, and thus far, no studies have reported the relationship between postoperative LCR and prognosis in patients with gastric cancer (GC). METHODS: This study enrolled 455 patients with a histopathological diagnosis of gastric adenocarcinoma who underwent curative surgery at our institution between 2005 and 2018. The relationship between both the preoperative and postoperative LCR and the prognosis of patients with GC was retrospectively investigated. RESULTS: Preoperative LCR showed significant correlations with tumor-related factors, such as tumor size, depth of invasion, and lymph node metastasis. By contrast, no correlation was observed between postoperative LCR and tumor-related factors. The 5 year survival rate was significantly worse in patients with low preoperative LCR than in those with high preoperative LCR (65.4% vs. 83.9%, p < 0.0001). Similarly, the 5 year survival rate was also significantly worse in patients with low postoperative LCR than in those with high postoperative LCR (67.0% vs. 84.1%, p < 0.0001). Furthermore, combination analysis of the pre- and postoperative LCR revealed that the prognosis of patients with both low pre- and postoperative LCR was worse in patients with GC (5 year survival rate was 52.0%). A multivariate analysis indicated that a low pre- and postoperative LCR and age and lymph node metastasis were independent prognostic indicators. CONCLUSIONS: The combination of preoperative and postoperative LCR appears to be useful in predicting the prognosis of patients with GC.

Impact of geriatric nutritional risk index on outcomes after gastrectomy in elderly patients with gastric cancer: a retrospective multicenter study in Japan.

BACKGROUND: Several studies investigated the utility of inflammation and nutritional markers in predicting the prognosis in patients with gastric cancer; however, the markers with the best predictive ability remain unclear. This retrospective study aimed to determine inflammation and nutritional markers that predicted prognosis in elderly patients over 75 years of age undergoing curative gastrectomy for gastric cancer. METHODS: Between January 2005 and December 2015, 497 consecutive elderly gastric cancer patients aged over 75 years underwent curative gastrectomy in 12 institutions. The geriatric nutritional risk index (GNRI), prognostic nutritional index, neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, and C-reactive protein/albumin ratio were examined as prognostic markers for overall survival (OS) and disease-specific survival (DSS) using area under the curve (AUC) using receiver operating characteristic (ROC) curve analysis. RESULTS: The GNRI had the highest AUC and predictive value for both OS (0.637, p < 0.001) and DSS (AUC 0.645, p < 0.001). The study cohort was categorized into the high and low GNRI groups based on the optimal GNRI cut-off values for OS (97.0) and DSS (95.8) determined with the ROC analysis. For both OS and DSS, there was a significant correlation between the GNRI and several clinicopathological factors including age, body mass index, albumin, American Society of Anesthesiologists physical status score, depth of tumor invasion, lymph node metastasis, lymphatic invasion, pathological stage, operation duration, bleeding, procedure, approach, death due to primary disease, and death due to other disease. The GNRI remained a crucial independent prognostic factor for both OS (Hazard ratio [HR] = 1.905, p < 0.001) and DSS in multivariate analysis (HR = 1.780, p = 0.043). CONCLUSIONS: Among a panel of inflammation and nutritional markers, the GNRI exhibited the best performance as a prognostic factor after curative gastrectomy in elderly patients with gastric cancer, indicating its utility as a simple and promising index for predicting OS and DSS in these patients.

CA19-9 in combination with P-CRP as a predictive marker of immune-related adverse events in patients with recurrent or unresectable advanced gastric cancer treated with nivolumab.

BACKGROUND: Immune-check point inhibitors (ICPIs) for treatment of cancer patients sometimes induce potentially life-threatening immune-related adverse events (irAEs), which predict ICPIs treatment efficacy. Prediction of irAEs would be useful for management of irAEs and prediction of ICPIs efficacy. This study aimed to determine predictors of irAEs in patients with recurrent or unresectable advanced gastric cancer (RUGC) treated with nivolumab. METHODS: Seventy-eight RUGC patients treated with nivolumab at nine institutions between January 2017 and April 2020 were included in this study. The usefulness of specific blood test results as predictors of irAEs was evaluated. RESULTS: We observed irAEs in 15 (19.2%) patients. The disease control rate was significantly higher in the patients with irAEs than in those without (86.7% vs. 42.9%; P < 0.001). The median progression-free survival was significantly longer for patients with irAEs than for patients without (4.9 vs. 2.6 months; P = 0.018). The median survival time was longer for patients with irAEs than for those without (9.4 vs. 5.8 months; P = 0.041). The receiver operating characteristic (ROC) curves for irAEs indicated that the area under the curve (AUC) of carbohydrate antigen 19-9 (CA19-9) was highest (0.692; P = 0.022), followed by that for the platelet count × serum C-reactive protein (P-CRP) value (0.680; P = 0.032). The AUC for the CA19-9 + P-CRP combination was 0.782, which was more useful than that for either component and significantly associated with overall survival of nivolumab-treated RUGC patients. CONCLUSIONS: The CA19-9 + P-CRP combination was predictive of irAEs and prognosis in RUGC patients.

Modified geriatric nutritional risk index in patients with pancreatic cancer: a propensity score-matched analysis.

BACKGROUND: The modified nutritional geriatric risk index (mGNRI) was developed as a novel index and provides a more appropriate prognostic index than the original GNRI, which was reported to be a useful index for predicting prognoses for various malignancies. This study investigated the prognostic significance of the mGNRI compared with that of the GNRI in patients with pancreatic cancer and the association with psoas muscle volume (PMV) for survival outcomes. METHODS: This retrospective study included 137 patients who had undergone pancreatectomy for pancreatic cancer. The enrolled patients were grouped as high mGNRI (≥ 85.3) or low mGNRI (< 85.3), and high GNRI (≥ 92) or low GNRI (< 92) for prognostic analysis based on cutoff values. A propensity-matched analysis was performed in this study. RESULTS: The 5-year overall survival of patients in the high mGNRI group or high GNRI group was significantly longer than those in the low mGNRI group or low GNRI group. Statistically significant differences for the 5-year OS were observed in the three groups with respect to the combination of mGNRI and PMV. Patients with low mGNRI/low PMV had a worse 5-year OS rate compared with patients with high GNRI/high PMV or those with high GNRI or high PMV, but not both. The concordance index of the mGNRI to predict the 5-year overall survival was greater than that of the GNRI or the combination of the GNRI and PMV, but lower than that of the combination of the mGNRI and PMV. Multivariate analysis revealed that the mGNRI was an independent prognostic factor for patients with pancreatic cancer (P = 0.005). CONCLUSIONS: The mGNRI might be a more useful prognostic factor than the GNRI for patients with pancreatic cancer, and might predict prognostic outcomes more accurately when combined with PMV.

Risk factors for recurrence in elderly patients with stage II colorectal cancer: a multicenter retrospective study.

BACKGROUND: Adjuvant chemotherapy for stage II colorectal cancer (CRC) is considered appropriate for patients with risk factors for recurrence, rather than for all patients uniformly. However, the risk factors for recurrence remain controversial, and there is limited information, especially for elderly patients. The Geriatric Nutritional Risk Index (GNRI) is widely used as a simple nutritional screening tool in the elderly and is associated with cancer prognosis and recurrence. This study aimed to investigate the risk factors for recurrence in the elderly with stage II CRC, focusing on the GNRI. METHODS: We enrolled 348 elderly patients (≥ 75 years) with stage II CRC who underwent curative resection at the Department of Surgery, Tottori University and our 10 affiliated institutions. The patients were divided into GNRIhigh (≥ 93.465) and GNRIlow (< 93.465) groups. RESULTS: The GNRIlow group showed a significantly worse overall survival (OS), cancer-specific survival (CSS), and relapse-free survival (RFS) (P < 0.001, P < 0.001, and P < 0.001, respectively). In a multivariate analysis, GNRIlow (hazard ratio [HR]: 2.244, P < 0.001), pathologic T4 stage (HR: 1.658, P = 0.014), and moderate to severe lymphatic or venous invasion (HR: 1.460, P = 0.033) were independent factors affecting RFS. By using these three factors to score the risk of recurrence from 0 to 3 points, the prognosis was significantly stratified in terms of OS, CSS, and RFS (P < 0.001, P < 0.001, and P < 0.001, respectively). The recurrence rate for each score was as follows: 0 points, 9.8%; 1 point, 22.0%; 2 points, 37.3%; and 3 points, 61.9%. CONCLUSIONS: GNRIlow, pathologic T4 stage, and moderate to severe lymphatic or venous invasion are high-risk factors for recurrence in the elderly with stage II CRC. The scoring system using these three factors appropriately predicted their recurrence and outcome.