[Effect of Upfront Dose Reduction in the First Cycle of Chemotherapy for Unresectable/Recurrent Gastric Cancers in Patients Aged Over 80 Years].

Chemotherapy for elderly patients requires ingenuity in treatment to mitigate its high risk. Therefore, we investigated an upfront dose reduction in the first cycle of chemotherapy for unresectable/recurrent gastric cancers in patients over 80 years old. We examined 6 patients over 80 years old, who underwent S-1 plus L-OHP therapy(SOX)for unresectable/recurrent gastric cancer in our department between January 2020 and January 2021. There were no adverse events over Grade 3 in the upfront dose reduction group(U group), while 1 case(50.0%)in the normal dose group(N group)experienced an adverse event over Grade 3. Moreover, only the U group continued treatment for 4 or more courses, whereas none from the N group did. Partial response(PR)was achieved as a therapeutic effect in 3 patients of the U group. Only 2 cases of the U group advanced to the second-line regimen and both were able to transition to the third-line regimen. However, none were able to even transition to the second-line regimen in the N group. Therefore, it was suggested that by reducing the dose of chemotherapy from the first cycle for elderly patients over 80 years old, the incidence of adverse events can be kept low, which makes it possible to continue long-term chemotherapy.

Prognostic impacts of tumoral expression and serum levels of PD-L1 and CTLA-4 in colorectal cancer patients.

BACKGROUND: Programmed cell death ligand-1 (PD-L1) and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) play a pivotal role in cancer immunotherapy. Each of these molecules has a membrane-bound receptor form (mPD-L1/mCTLA-4) and a soluble form (sPD-L1/sCTLA-4). However, these prognostic impacts in colorectal cancer (CRC) remain unclear. METHODS: We immunohistochemically scored tumoral mPD-L1/mCTLA-4 expression and quantified preoperative circulating sPD-L1/sCTLA-4 levels using matched serum specimens from 131 patients with pStage I-III CRC. We also examined the association between these statuses and tumor infiltrating lymphocytes (TILs) in these patients. RESULTS: Elevated levels of mPD-L1, mCTLA-4, sPD-L1 and sCTLA-4 were significantly correlated with poor overall survival (OS) and disease-free survival (DFS). Co-high expression of tumoral mPD-L1 and mCTLA-4 or co-elevated levels of serum sPD-L1 and sCTLA-4 were strongly correlated with poor OS and DFS. Multivariate analysis revealed that both statuses were negative independent prognostic factors for OS [hazard ratio (HR) 3.86, 95% confidence interval (95% CI) 1.71-8.51, p = 0.001; HR 5.72, 95% CI 1.87-14.54, p = 0.004, respectively] and DFS (HR 2.53, 95% CI 1.23-4.95, p = 0.01; HR 6.88, 95% CI 2.42-17.13, p = 0.0008, respectively). Although low expression of tumoral mCTLA-4 was significantly correlated with increased CD8(+) TILs, there was no correlation in any other combination. CONCLUSIONS: We verified the prognostic impacts of mPD-L1, mCTLA-4, sPD-L1 and sCTLA-4 in pStage I-III CRC patients. Dual evaluation of immune checkpoint molecules in primary tissues or preoperative serum could identify a patient population with poor prognosis in these patients.

Crohn's-Like Lymphoid Reaction is Associated with Oncological Prognosis and Nutritional Status in Patients with Pathological Stage II/III Gastric Cancer.

BACKGROUND: Peritumoral lymphoid aggregates, termed Crohn's-like lymphoid reaction (CLR), are markers of an antitumor immune response, which is an important predictor of patient outcome. In this study, we investigated the prognostic utility of CLR and its relationship with nutritional status in patients with gastric cancer (GC). METHODS: The study included 170 patients who underwent curative surgery for pathological stage (pStage) II/III GC. The maximum diameters of peritumoral and normal mucosal CLR aggregates were measured, and the median peritumoral diameter (0.57 mm) was used to stratify patients into two groups (large-CLR and small-CLR). The relationships between CLR size and preoperative nutritional status (body mass index, body composition status, Onodera's prognostic nutritional index), tumor-infiltrating CD8+ T-lymphocyte count, and survival were evaluated. RESULTS: Peritumoral CLR aggregates were significantly larger than aggregates in the normal mucosa. Clinicopathological variables were not significantly different between the two patient groups; however, the large-CLR group had better cancer-specific survival (p = 0.018) and recurrence-free survival (p = 0.03) than the small-CLR group. Multivariate analysis revealed that CLR size was an independent prognostic factor for cancer-specific survival [hazard ratio (HR) 2.13, 95% confidence interval (CI) 1.3-3.56, p = 0.002] and recurrence-free survival (HR 1.96, 95% CI 1.22-3.19, p = 0.005). Nutritional status markers were significantly poorer for the small-CLR group than the large-CLR group. CD8+ T-cell tumor infiltration was positively correlated with CLR size but not with patient survival. CONCLUSIONS: CLR size correlated with patient nutritional status and prognosis and may be helpful in identifying high-risk populations of pStage II/III GC patients.

Clinical significance of advanced lung cancer inflammation index, a nutritional and inflammation index, in gastric cancer patients after surgical resection: A propensity score matching analysis.

BACKGROUND: The advanced lung cancer inflammation index (ALI) has recently been shown as a prognostic marker for several cancers. However, its predictive value for surgical and oncological outcomes in gastric cancer (GC) remains unclear. METHODS: We retrospectively reviewed the preoperative ALI in 620 GC patients receiving gastrectomy to elucidate the prognostic value for overall survival (OS) and disease-free survival (DFS) and to clarify its predictive value for perioperative risk of surgical site infection (SSI) in GC patients. Propensity score matching (PSM) analysis was also conducted to certify these potentials of preoperative ALI. RESULTS: Preoperative low ALI was significantly correlated with advanced tumor-node-metastasis stage classification. Patients with low ALI showed poorer OS (p < 0.0001) and DFS (p < 0.0001) compared to those with high ALI, and multivariate analysis showed that decreased ALI was an independent prognostic factor for OS [hazard ratios of 1.59; 95% confidence interval (CI) of 1.15-2.19, p = 0.006]. Meanwhile, preoperative low ALI was also an independent risk factor for overall SSI [odds ratio (OR) of 2.04, 95% CI of 1.24-3.35, p = 0.005] or organ-space SSI (OR of 2.69, 95% CI of 1.40-5.23, p = 0.003). We further conducted PSM analysis and verified all of these findings in the PSM cohort. CONCLUSION: Quantification of preoperative ALI can identify patients with high risk of adverse perioperative and oncological outcomes in GC patients.

Prognostic Potential of Lymphocyte-C-Reactive Protein Ratio in Patients with Rectal Cancer Receiving Preoperative Chemoradiotherapy.

PURPOSE: The systemic inflammatory response is attracting increasing attention as a predictive biomarker for oncological outcome in patients with colorectal cancer. This study is aimed at verifying if the lymphocyte-C-reactive protein (CRP) ratio (LCR) could be used as a predictor of oncological outcome in patients with rectal cancer (RC) receiving preoperative chemoradiotherapy (CRT). METHODS: We analyzed data for 86 patients with RC who received preoperative CRT followed by total mesorectal excision at our institution. A ratio of 6000 was used as the cut-off value for LCR for further analysis. RESULTS: The post-CRT LCR was significantly lower than the pre-CRT LCR in patients with RC. Although post-CRT LCR status was not significantly correlated with overall survival (OS), low pre-CRT LCR was significantly associated with shorter recurrence-free survival (RFS: p = 0.02) and OS (p = 0.017) in this population and was an independent prognostic factor for both RFS and OS (hazard ratio (HR) 3.19, 95% confidence interval (CI) 1.33-7.66, p = 0.009; HR 2.83, 95%CI 1.14-7.01, p = 0.025, respectively). Furthermore, low pre-CRT LCR was a stronger indicator of early recurrence (p = 0.001) and poor prognosis (p = 0.025) in RC patients without pathological lymph node metastasis compared with patients with pathological lymph node metastasis, and prognostic potential of pre-CRT LCR was clearly revealed especially RC patients receiving long-course CRT. CONCLUSIONS: Assessment of pretreatment LCR status might aid decision-making regarding postoperative treatment strategies in patients with RC receiving CRT followed by potentially curative resection.

Modified intramuscular adipose tissue content as a feasible surrogate marker for malnutrition in gastrointestinal cancer.

BACKGROUND & AIMS: Myosteatosis is gathering attention as a feasible indicator for sarcopenia and increased risk of morbidity. However, the prognostic value of intramuscular adipose tissue content (IMAC) as an assessment method for myosteatosis remains controversial. The objectives of this study are to compare the prognostic value of intramuscular adipose tissue content (IMAC) with our newly-developed modified IMAC (mIMAC), and to assess the clinical significance of mIMAC in colorectal cancer (CRC) and gastric cancer (GC). METHODS: We evaluated 892 patients with CRC or GC, and assessed preoperative IMAC and mIMAC to compare their prognostic and predictive values for postoperative infectious complications in both cohorts. RESULTS: Both preoperative IMAC and mIMAC were sex- and disease-dependent, and positively or negatively correlated with age in CRC and GC patients (IMAC: CRC: r = 0.33, P < 0.0001; GC: r = 0.304, P < 0.0001; mIMAC: CRC: r = -0.364, P < 0.0001; GC: r = -0.263, P < 0.0001). In contrast to IMAC, lower preoperative mIMAC was significantly associated with disease-development factors, and was an independent prognostic factor for both overall survival (OS) and disease-free survival (DFS) in both CRC (OS: hazard ratio (HR): 1.95, 95% confidence interval (CI): 1.25-3.03, p = 0.003; DFS: HR: 1.93, 95% CI: 1.22-3.04, p = 0.005) and GC patients (OS: HR: 2.11, 95% CI: 1.22-3.68, P = 0.008; DFS: HR: 2.03, 95% CI: 1.18-3.5, P = 0.011). Patients with postoperative remote infections had a poorer prognosis compared with those without in both cohorts (CRC: HR: 2.67, 95% CI: 1.46-4.89, P = 0.002; GC: HR: 3.01, 95% CI: 1.47-6.19, P = 0.003), and low mIMAC was an independent risk factor for postoperative remote infection in both cancers (CRC: odds ratio (OR): 2.56, 95% CI: 1.06-6.23, P = 0.038; GC: OR: 2.8, 95% CI: 1.03-7.58, P = 0.043). Finally, we assessed the correlation between IMAC or mIMAC and the representative frailty markers body mass index (BMI), serum albumin, and prognostic nutritional index (PNI). We found a positive correlation between preoperative mIMAC and all of these markers in both cohorts (CRC: BMI: r = 0.193, P < 0.0001; serum albumin: r = 0.42, P < 0.0001; PNI: r = 0.39, P < 0.0001; GC: BMI: r = 0.22, P < 0.0001; serum albumin: r = 0.212, P < 0.0001; PNI: r = 0.287, P < 0.0001). CONCLUSIONS: Preoperative mIMAC could be useful for perioperative and postoperative management in CRC and GC.

Continuous intraoperative neuromonitoring for thyroid cancer surgery: A prospective study.

OBJECTIVE: We evaluated the utility of continuous intraoperative neuromonitoring (CIONM) during surgery for thyroid cancer (TC) in an educational university hospital. STUDY DESIGN: Prospective observational study. METHODS: During the period April 2016 to March 2017, 43 patients who underwent standardized surgery with CIONM were prospectively included: 5 men and 38 women, 24-87 years old (median 52 years); 23 lobectomies and 20 total thyroidectomies with node dissection were conducted. Thirty-six operations were performed by a supervising surgeon, and seven were performed by trainees. RESULTS: Temporal vocal cord paresis (VCP) was identified in 9 of 63 nerves at risk (14.3%) by postoperative laryngoscopy. VCP was not related to clinical factors including the surgeon's experience or the severe nerve stress demonstrated by CIONM. A significant relation only between VCP and loss of signal (LOS) was demonstrated (P = .002). The recovery of VCP was rapid (<1 month) in patients with global injury even when LOS was demonstrated, but was prolonged in patients demonstrating obvious segmental nerve injury and LOS. CONCLUSION: The present standard protocol of CIONM was useful to some extent to protect prolonged VCP, but not enough to detect every nerve stress causing VCP during TC surgery. On the other hand, CIONM is a promising method that could contribute surgical education at training hospitals enabling the instant confirmation of the procedure safely. LEVELS OF EVIDENCE: 3b.