Efficacy of chemotherapy for comorbid cancer in patients with simultaneous double cancers: a multicenter study.

PURPOSE: Anticancer drugs for double cancers are selected based on their therapeutic effects on the target cancer, but there are insufficient data on the effects of anticancer drugs on comorbid cancer. We investigated the effect of chemotherapy on comorbid cancer in patients with simultaneous double cancers. METHODS: The subjects of this retrospective study were 51 patients with simultaneous double cancers at the time of receiving systemic chemotherapy. We evaluated the types of anticancer drugs used for double cancers, the therapeutic effects on targeted and comorbid cancers, and prognoses. RESULTS: Disease control was achieved for 90.9% of the target cancers and 90.7% of the comorbid cancers. The prognosis was significantly better when the disease was controlled, not only in the target cancer but also in the comorbid cancer. CONCLUSION: Physicians treating double cancers should develop treatment strategies focusing not only on the treatment for advanced cancer, but also on the course of comorbidities and the therapeutic effects of anticancer drugs. This study is important because it presents new possibilities to expand the indications for anticancer drugs, while allowing unnecessary clinical research to be avoided.

[Usefulness of an Epidural Catheter with a Subcutaneous Port for Locally Advanced Rectal Cancer Pain Which Was Difficult to Manage with Opioids-A Case Report].

A 56-year-old woman was diagnosed with advanced rectal cancer, with tumor invasion to the sacrum and levator muscle of the anus and multiple lymph node metastasis. After construction of an artificial anus, chemotherapy was started. However, tumor invasion and the cancer pain progressed. Finally, she was hospitalized for pain control; an anesthesiologist planned to insert an epidural catheter. The epidural catheter was placed at the L5-S1 interspace, and continuous administration of 0.2% ropivacaine was started. Cancer pain in the buttocks improved quickly. Therefore, an epidural catheter with a subcutaneous port was placed to prevent catheter-related infection after a long period. The postoperative course was uneventful, and she was discharged from the hospital on the 10th day postoperatively. She could receive home medical care and pain control treatment in an outpatient clinic. Finally, she died due to progression of the rectal cancer, 3 months after placement of the epidural catheter with the subcutaneous port. Some patients with advanced rectal cancer develop cancer pain even though they are sufficiently treated with opioids or palliative radiation therapy. Here, we describe the case of a patient with locally advanced rectal cancer, treated with an epidural catheter with a subcutaneous port for cancer pain that was difficult to manage with opioids alone.

Changes in the Gustave Roussy Immune Score as a Powerful Prognostic Marker of the Therapeutic Sensitivity of Nivolumab in Advanced Gastric Cancer: A Multicenter, Retrospective Study.

BACKGROUND: Identification of positive biomarkers for the effects of nivolumab on patients with advanced gastric cancer (AGC) is significant. The Gustave Roussy Immune Score (GRIm-s) is associated with therapeutic resistance of immune checkpoint inhibitors (ICIs) in other cancers. This multicenter, retrospective study was designed to analyze the association of GRIm-s with therapeutic sensitivity of nivolumab in patients with AGC. METHODS: We reviewed 58 patients with AGC treated with nivolumab from October 2017 to November 2018 at five participating institutions. We performed blood tests before the start of nivolumab and after administration of two courses. We evaluated the correlation between the best overall response and GRIm-s. Additionally, we focused on the changes in GRIm-s before the start of nivolumab and after administration of two courses. RESULTS: Of the 58 patients, 21 (36.2%) were classified into the disease control (DC) group and 37 (63.8%) into the progressive disease (PD) group. GRIm-s before nivolumab treatment did not correlate with the best therapeutic response (p = 0.086). However, GRIm-s after two courses of nivolumab showed that significantly more PD cases were in the high-risk group (p < 0.0001). After two courses of nivolumab, overall survival was significantly worse in the high-risk group (p < 0.0001). For progression-free survival, the high-risk group had a significantly worse prognosis both before (p = 0.04) and after two courses of nivolumab treatment (p < 0.0001). CONCLUSIONS: GRIm-s after two courses of nivolumab and its changes compared to pretreatment values proved beneficial in predicting nivolumab sensitivity.

Clinical features as potential prognostic factors in patients treated with nivolumab for highly pretreated metastatic gastric cancer: a multicenter retrospective study.

BACKGROUND: Although nivolumab (anti-programmed cell death-1 antibody) is a promising approach for advanced gastric cancer (AGC), the response rate remains limited. The aim of this multicenter retrospective study was to determine if clinical features could serve as prognostic factors of the efficacy of nivolumab in patients with AGC. METHODS: Fifty-eight patients with AGC who were treated with nivolumab as a third or later line from October 2017 to December 2018 at any of five clinical sites were enrolled in the study. The correlation between the best overall response and clinical features was investigated. Overall survival and progression-free survival after initiation of nivolumab were calculated and clinical features that could be predictors of the prognosis were sought. RESULTS: The disease control rate (DCR) for nivolumab was 36.2% and was significantly correlated with performance status (p = 0.021), metastasis to one organ (p = 0.006), and grade 2 or higher immune-related adverse events (p = 0.027). There was also a significant association between response to nivolumab and ability to receive subsequent chemotherapy (p = 0.022). In the analysis of overall survival, the following variables were identified as being significantly associated with a poor outcome: Eastern Cooperative Oncology Group performance status ≥1, prior treatment with trastuzumab, no immune-related adverse events, lack of a response to nivolumab, and inability to receive subsequent chemotherapy. CONCLUSION: The findings of this study suggest that nivolumab may be ineffective for AGC in patients with poor performance status and those with a history of treatment with trastuzumab.

Role of PD-L1 Expression during the Progression of Submucosal Gastric Cancer.

INTRODUCTION: Programmed death-ligand 1 (PD-L1) expression is a prognostic marker for gastric cancer that correlates with tumor diameter and depth of penetration. But the role of PD-L1 and mechanism(s) employed in the initial phase of invasion in early gastric cancer is yet to be understood. OBJECTIVE: This study aims to elucidate the role of PD-L1 during the progression of gastric cancer, specifically invading the submucosa beyond the lamina muscularis mucosa. METHODS: Using 107 patients with pathological submucosal gastric cancer, we determined the expression of PD-L1 based on the staining of the cell membrane or cytoplasm of tumor cells in the central and invasive front of the tumor. Samples were categorized into 3 groups based on the intensity of PD-L1 expression. CD8+ lymphocytes expressing PD-1 and CD163+ macrophages were used to determine the number of cell nuclei at the invasive front, similar to PD-L1. CMTM6 levels were determined and used to stratify samples into 3 groups. RESULTS: PD-L1 expression was higher in the invasive front (26.2%) than in the central portion of the tumors (7.4%; p < 0.001). Moreover, lymphatic and vascular invasion were more frequently observed in samples with high levels of PD-L1 (lymphatic invasion: 60.7 vs. 35.4%, p = 0.0026, and vascular invasion: 39.3 vs. 16.5%, p = 0.0018). There was no correlation between PD-L1 expression and the levels of PD-1, CD8, CD163, and CMTM6. CONCLUSIONS: PD-L1-expressing cancer cells at the invasive front of gastric cancer influence the initial stages of tumor invasion and lymphovascular permeation in early-stage gastric cancers. Immune checkpoint signaling may be the driving force in the invasive front during the invasion of the submucosa beyond the lamina muscularis mucosa.

Migrating contractions of the afferent and Roux limbs show peristaltic movement independently of each other in conscious dogs after Roux-en-Y reconstruction after distal gastrectomy.

PURPOSE: The Roux-en-Y (RY) procedure is used frequently for surgical reconstruction after gastrectomy. However, a minority of patients suffer a serious motility disorder of the Roux and afferent limb postoperatively. We conducted this study to clarify the association between the motility and peristaltic direction of two limbs in conscious dogs. METHODS: We performed distal gastrectomy on five dogs and implanted seven force transducers on the serosal surfaces of the remnant gastric body and afferent and Roux limbs. We then analyzed the electric signals from these force transducers. RESULTS: Migrating contractions were observed in the two limbs, but not in the gastric remnant body. Migrating contractions in the forward direction propagated independently from the most proximal side in each limb. There was no propagation of contraction across the jejunojejunostomy between the two limbs. CONCLUSIONS: Each proximal part of the Roux and afferent limbs has an independent motility pacemaker in conscious dogs after gastrectomy with RY reconstruction.

High RAD18 Expression is Associated with Disease Progression and Poor Prognosis in Patients with Gastric Cancer.

BACKGROUND: RAD18 plays an important role in DNA damage repair by inducing monoubiquitinated PCNA (mUB-PCNA) in both cancer and normal tissues. Previous studies have not determined the significance of RAD18 expression in clinical gastric cancer (GC) samples. Thus, this study aimed to clarify the expression and functional significance of RAD18 in GC. METHODS: Overall, 96 resected GC samples were subjected to an immunohistochemical analysis of RAD18. GC cell lines were also subjected to functional RNA interference analyses of RAD18. RESULTS: RAD18 expression was predominantly nuclear and was observed at higher levels in GC tissues than in normal tissues. In GC tissues, strong RAD18 expression was associated with progression of lymph node metastasis (p = 0.0001), lymphatic invasion (p = 0.0255), venous invasion (p < 0.0001), recurrence (p = 0.028), and disease stage (p = 0.0253). Moreover, GC patients with high tumor RAD18 expression had shorter overall survival (p = 0.0061) and recurrence-free survival durations (p = 0.035) than those with low tumor RAD18 expression. RAD18 knockdown inhibited GC proliferation and invasiveness and increased chemosensitivity by suppressing mUB-PCNA. CONCLUSIONS: RAD18 expression may be a useful marker of progression and poor prognosis of GC. Moreover, therapeutic strategies that target RAD18 might be a novel chemosensitizer to eradicate the refractory GC.

High Stromal TGFBI in Lung Cancer and Intratumoral CD8-Positive T Cells were Associated with Poor Prognosis and Therapeutic Resistance to Immune Checkpoint Inhibitors.

BACKGROUND: We investigated whether the expression of transforming growth factor-beta-induced protein (TGFBI) and intratumoral immune cells including CD8- and Forkhead box protein P3 (Foxp3)-positive T cells in clinical lung cancer patients could predict the therapeutic response to nivolumab. METHODS: Thirty-three patients who were treated with nivolumab were enrolled in this study. Immunohistochemical analyses of TGFBI, PD-L1, CD8, Foxp3, and vimentin expression were conducted. Serum concentrations of TGFBI and transforming growth factor-beta1 (TGF-ß1) were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: Cancer TGFBI was not associated with prognosis and therapeutic response to nivolumab, but cancer stromal TGFBI and intratumoral CD8-positive T cells were associated with them. Therefore, we evaluated cancer stromal TGFBI and intratumoral CD8-positive T cells. The high-TGFBI-expression group had poorer clinical responses than did the low-TGFBI-expression group (p < 0.0001). The number of times nivolumab was administered in the high-CD8-expression group was significantly higher than that in the low-CD8-expression group (p = 0.0046). The high-CD8-expression group had better clinical responses than did the low-CD8-expression group (p = 0.0013). Interestingly, all patients in the high-TGFBI/low-CD8-expression group had progressive disease (PD). In contrast, all patients in the low-TGFBI/high-CD8-expression group had PR + SD (partial response + stable disease) by the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). CONCLUSIONS: The dual evaluation of stromal TGFBI and intratumoral CD8-positive T cells could be a useful predictive marker for nivolumab.

Long-Term Imatinib Treatment for Patients with Unresectable or Recurrent Gastrointestinal Stromal Tumors.

BACKGROUND: Only limited data are available concerning the long-term outcomes of imatinib treatment among Japanese or Asian patients with advanced or recurrent gastrointestinal stromal tumors (GIST). Our multicenter study, which was conducted in northern Kanto, Japan, aimed to assess the efficacy of imatinib mesylate against advanced or recurrent GIST. SUMMARY: The clinicopathological data of 234 GIST patients who were treated at one of the 11 participating hospitals from 2001 to 2011 were retrospectively reviewed (GREAT study). Imatinib was administered as a first-line therapy in cases involving unresectable disease or postoperative recurrence (41 cases). The patients treated with imatinib (n = 41) exhibited 1-, 3-, and 5-year overall survival (OS) rates of 92.3, 74.9, and 53.8% respectively. In univariate and multivariate analyses, imatinib continuation with dose reduction and achieving a complete or partial response were found to be associated with increased OS. The results of 2 large-scale, long-term trials demonstrate that the risk of tumor progression decreases with increased treatment duration. Furthermore, the interruption of imatinib treatment in responsive and controlled patients results in a high risk of disease progression. Key Messages: Long-term imatinib treatment is recommended for patients with nonprogressive disease. If patients experience significant toxicities, temporary dose reduction and treatment continuation might be useful.

High STMN1 level is associated with chemo-resistance and poor prognosis in gastric cancer patients.

BACKGROUND: Stathmin1 (STMN1) is a cytosolic phosphoprotein that regulates cellular microtubule dynamics and is known to have oncogenic activity. Despite several reports, its roles in gastric cancer (GC) remain unclear owing to a lack of analyses of highly metastatic cases. This study aimed to investigate STMN1 as a prognostic and predictive indicator of response to paclitaxel therapy in patients with GC, including inoperable cases. METHODS: Immunohistochemical analysis of STMN1 was performed on both operable (n=95) and inoperable GC (n=61) samples. The roles of STMN1 in cancer cell proliferation and sensitivity to a microtubule-targeting drug, paclitaxel, were confirmed by knockdown experiments using GC cell lines. RESULTS: Multivariate and Kaplan-Meier analyses demonstrated that high STMN1 was predictive of poor prognosis in both the groups. In the operable cohort, STMN1 expression correlated with cancer curability, recurrence, and resistance to adjuvant therapy. A correlation with paclitaxel resistance was observed in inoperable cases. Knockdown of STMN1 in GC cell lines inhibited proliferation and sensitised the cells to paclitaxel by enhancing apoptosis. CONCLUSIONS: STMN1 is a possible biomarker for paclitaxel sensitivity and poor prognosis in GC and could be a novel therapeutic target in metastatic GC.

Restoration of gastrointestinal motility ameliorates nutritional deficiencies and body weight loss of patients who undergo laparoscopy-assisted proximal gastrectomy.

BACKGROUND: Esophagogastrostomy after proximal gastrectomy (PG) is a simple and safe reconstruction, but it leads to a high incidence of reflux esophagitis and impairs postoperative quality of life. We have already reported gastric tube (GT) reconstruction after PG and performed it on more than 100 patients. No studies have reported long-term outcomes after PG-GT. The aim of this study was to investigate long-term outcomes, including nutrition indices, such as body weight, serum albumin, total protein, hemoglobin, and ferritin after PG, and observe recovery of upper gastrointestinal tract motility. METHODS: We analyzed body weight loss and laboratory findings at our outpatient clinic at 1, 6, 12, 24, 36, 48, and 60 months postoperatively. Manometric recording was carried out at 1, 2, 3, 4, and 5 years after surgery. RESULTS: The percentage change in body weight in the PG-GT group was significantly larger than that in the PG-JI and TG-RY groups at 2.5, 3, 4, and 5 years after surgery. The levels of hemoglobin and ferritin in the PG-GT and PG-JI groups were significantly higher than those in the TG-RY group at all time points except 6 months after surgery. In the fasted state, the phase III originated at the gastric tube was propagated to the duodenum 3 years after surgery. In the fed state, phasic contractions of the duodenum were in harmony with gastric tube contractions 3 years after surgery. CONCLUSIONS: PG-GT is the least invasive procedure, and restoration of gastrointestinal motilities in the gastric tube and duodenum may ameliorate body weight loss and nutritional status, including anemia, in patients after PG.

Nuclear PRMT1 expression is associated with poor prognosis and chemosensitivity in gastric cancer patients.

BACKGROUND: Metastatic and refractory gastric cancer (GC) are associated with a poor prognosis; therefore, the identification of prognostic factors and chemosensitivity markers is extremely important. Protein arginine methyltransferase 1 (PRMT1) may play a role in chemosensitivity/apoptosis induction via activation of the tumor suppressor forkhead box O1 (FOXO1). The purpose of this study was to clarify the expression of and relationship between PRMT1 and FOXO1 to evaluate the applicability of PRMT1 as a prognostic marker and a therapeutic tool in GC. METHODS: We investigated the clinical and functional significance of PRMT1 and FOXO1 in 195 clinical GC samples using immunohistochemistry. We performed suppression analysis of PRMT1 using small interfering RNA to determine the biological roles of PRMT1 in chemosensitivity. RESULTS: PRMT1 and FOXO1 in GC samples were predominantly expressed in the nucleus. Patients with lower PRMT1 expression (n = 131) had suppressed nuclear accumulation of FOXO1, higher recurrence after adjuvant chemotherapy, and poorer prognosis than those with higher PRMT1 expression (n = 64). PRMT1 downregulation in GC cells by RNA interference inhibited cisplatin and 5-fluorouracil sensitivity. The expression of phosphorylated FOXO1 and phosphorylated BCL-2 antagonist of cell death was upregulated in PRMT1 small interfering RNA groups. CONCLUSION: Our data suggest that the evaluation of PRMT1 expression in GC is a useful predictor of poor prognosis and recurrence after adjuvant chemotherapy. Moreover, these data suggest that PRMT1 is a promising therapeutic tool for overcoming refractory GC.

Outcomes of patients with early gastric cancer who underwent double endoscopic intraluminal surgery.

BACKGROUND AND AIMS: Endoscopic submucosal dissection (ESD) has been used to treat patients with nonulcerated early gastric cancers of 2  cm or less, because the incidence of lymph node metastasis is negligible. However, the standard ESD procedure is long, complex, and associated with high complication rates. To overcome these limitations, we devised a double endoscopic intraluminal operation (DEILO) and assessed its efficacy and safety for superficial gastric neoplasms in a preliminary prospective study. METHODS: The DEILO procedure was performed on 101 patients with gastric cancers. Two endoscopes were simultaneously inserted into the stomach. One endoscope was used to lift the lesion, and the other was used to excise the lesion. RESULTS: The DEILO technique was performed successfully, and en bloc resection was achieved for 98 (97.0%) of 101 patients. Histologically curative resection was achieved for 85 lesions (84.2%). The mean operating time was 70 min (range 20-178 min). Perforation occurred in four patients (4.0%), all of whom were successfully treated nonsurgically. Three patients developed postoperative hemorrhage, which was controlled endoscopically. CONCLUSION: The DEILO procedure appears to shorten the operating time for ESD, with efficacy and complication rates comparable with the standard procedure.

Outcome of laparoscopic gastrectomy with D1 plus lymph node dissection in gastric cancer patients postoperatively diagnosed with locally advanced disease or lymph node metastasis.

BACKGROUND: Some laparoscopic gastrectomy (LG) patients are postoperatively diagnosed with locally advanced disease or lymph node metastasis. Few reports have reviewed the outcomes or validity of LG in such patients. METHODS: We retrospectively compared the outcomes of LG for gastric cancer patients postoperatively diagnosed with T3 (subserosal invasion) or higher or N1 (metastasis in 1-2 regional lymph nodes), or higher disease (n = 36), with open gastrectomy (OG) for c-stage I gastric cancer patients (n = 62). RESULTS: D1 plus lymph node dissection was performed in all patients in the LG group. Blood loss was significantly lower in the LG group than in the OG group (P < 0.0010). The mean postoperative hospital stay duration was significantly shorter in the LG group than in the OG group (P = 0.0016). In the LG group, lymph node metastasis occurred in 1 patient, peritoneal dissemination in 2 patients, and liver metastasis in 1 patient. The 5-year survival rate did not significantly differ between the LG and OG groups (90.00 vs. 94.52 %; P = 0.6517). CONCLUSIONS: Given the similarity in long-term outcomes between the LG and OG groups, LG is an appropriate indication for gastric cancer patients postoperatively diagnosed with locally advanced disease or lymph node metastasis.

Nesfatin-1 suppresses gastric contractions and inhibits interdigestive migrating contractions in conscious dogs.

BACKGROUND: Nesfatin-1 is a novel 82-amino acid anorectic peptide. Acute injection of nesfatin-1 into the third brain ventricle reduces food consumption during the dark phase in rats. Nesfatin-1 is also expressed in gastric X/A-like cells in the peripheral tissues. Nesfatin-1 has been reported to reduce gastric and duodenal motility and to delay gastric emptying. AIM: In the present study, we investigated the effects of nesfatin-1 on gastrointestinal motility in conscious dogs. METHODS: Force transducers were implanted onto the serosal surfaces of the gastric bodies, gastric antra, duodena, and jejuna of healthy beagle dogs, and gastrointestinal motility was monitored. We evaluated the effects of nesfatin-1 on gastrointestinal motility and on the circulating levels of nesfatin-1 in the fasted and fed states. RESULTS: The intravenous administration of nesfatin-1 reduced gastric contractions and inhibited cyclical interdigestive migrating contractions in the fasted state. In the fasted state, circulating levels of nesfatin-1 tended to increase during late phase I. In addition, the kinetics of the circulating levels of nesfatin-1 were opposite to those of ghrelin during the fasted state. CONCLUSIONS: Nesfatin-1 regulates gastrointestinal motility, and, in particular, it inhibits gastric contractions in the fasted state. Interdigestive migrating contractions may be regulated by interactions between nesfatin-1, ghrelin, and motilin.

A multicenter long-term study of imatinib treatment for Japanese patients with unresectable or recurrent gastrointestinal stromal tumors.

BACKGROUND AND OBJECTIVES: This multicenter study, which was conducted in northern Kanto, Japan, aimed to assess the efficacy of imatinib mesylate against advanced or recurrent gastrointestinal stromal tumors (GIST). METHODS: The clinicopathological data of 234 GIST patients who were treated at one of the 11 participating hospitals from 2001-2011 were retrospectively reviewed. Imatinib was administered as a first-line therapy in cases involving unresectable disease or postoperative recurrence (41 cases). The median follow-up period was 4.0 years. RESULTS: After a median follow-up period of 4.0 years, the patients treated with imatinib (n = 41) exhibited 1-, 3-, and 5-year overall survival (OS) rates of 92.3%, 74.9%, and 53.8%, respectively. In univariate and multivariate analyses, imatinib dose reduction and achieving a complete or partial response were found to be associated with increased OS. CONCLUSIONS: Long-term imatinib treatment is recommended for patients with non-progressive disease. If patients experience significant toxicities, temporary dose reduction might be useful.

Examining the Efficacy of Nivolumab for Gastric Cancer Focusing on Using an Inflammation-based Prognostic Score: A Multicenter Retrospective Study.

BACKGROUND/AIM: To discover the positive therapeutic effects of nivolumab in patients with advanced gastric cancer (AGC), it is necessary to establish a useful biomarker to predict therapeutic efficacy. This multicenter retrospective study sought to evaluate the predictive impact of inflammation-based prognostic score (IBPS) on the therapeutic efficacy of nivolumab in patients with AGC. PATIENTS AND METHODS: In this retrospective study, we evaluated 58 AGC patients treated with nivolumab from October 2017 to November 2018 at five institutes. Patients were categorized follows: progressive disease (PD) or disease control (DC). Blood chemistry tests were performed immediately before and after two courses of nivolumab; the correlation between best overall response and IBPS was investigated. Transition of each blood serum marker was also assessed. RESULTS: Of 58 patients, 37 (63.8%) were in the PD group and 21 (36.2%) in the DC group. No positive correlation was noted between IBPS and therapeutic efficacy of nivolumab both immediately before and after two courses of nivolumab. However, the neutrophil-lymphocyte ratio (NLR) (p=0.045) and prognostic index (PI) (p=0.0042) before nivolumab and NLR (p=0.025), PI (p=0.0030) and Glasgow prognostic score (GPS) (p=0.043) after nivolumab were significantly correlated with treatment sensitivity. Furthermore, a decrease in PNI was an independent prognostic factor to predict nivolumab resistance on univariate analyses (p=0.0051). CONCLUSION: Although no association between IBPS and therapeutic sensitivity was found, it is important to focus on the transition of PNI to predict therapeutic efficacy of nivolumab.

Albumin-derived Neutrophil-to-Lymphocyte Ratio Score as a Marker of Nivolumab Treatment Sensitivity in Gastric Cancer: A Multicenter Study.

BACKGROUND/AIM: Establishment of powerful and easy-to-evaluate biomarkers that can predict immune checkpoint inhibitor sensitivity in patients with gastric cancer (GC) would be highly useful. The albumin-derived neutrophil-to-lymphocyte ratio (Alb-dNLR) score reportedly is an excellent measure of both immunity and nutritional status. However, the association between nivolumab treatment sensitivity and Alb-dNLR in GC has also not been adequately investigated. This multicenter retrospective study was designed to evaluate the association of Alb-dNLR with therapeutic sensitivity of nivolumab in GC patients. PATIENTS AND METHODS: This was a retrospective multicenter study with patients from five sites. The data from 58 patients who received nivolumab for postoperative recurrent or unresectable advanced GC between October 2017 and December 2018 were analyzed. Blood tests had been performed before nivolumab administration. We analyzed the correlation between the Alb-dNLR score and clinicopathological factors, including best overall response. RESULTS: Of the 58 patients, 21 (36.2%) comprised the disease control (DC) group and 37 (63.8%) comprised the progressive disease (PD) group. The nivolumab treatment responses were subjected to receiver operating characteristic analysis. The cutoff value was set to 2.90 g/dl for Alb and to 3.55 for dNLR. All eight patients in the high Alb-dNLR group had PD (p=0.0049). The low Alb-dNLR group had significantly better overall survival (p=0.0023) and progression-free survival rates (p<0.0001). CONCLUSION: The Alb-dNLR score was a very simple and sensitive predictor of nivolumab therapeutic sensitivity and has very good biomarker properties.

Patient with gastric cancer who underwent distal gastrectomy after treatment of COVID-19 infection diagnosed by preoperative PCR screening.

BACKGROUND: Because of the coronavirus disease 2019 (COVID-19) pandemic, preoperative screenings for COVID-19 infection are often performed in many institutions. Some patients are diagnosed with COVID-19 infection by antigen tests or polymerase chain reaction (PCR) testing for COVID-19, even if they have no symptoms, such as fever or respiratory symptoms. We herein describe a patient with gastric cancer who underwent distal gastrectomy 6 weeks after recovering from COVID-19 infection diagnosed by preoperative PCR. CASE PRESENTATION: An 86-year-old man was transferred to our hospital because of hematemesis and melena. A hemorrhagic gastric ulcer was found in the lesser curvature of the antrum by emergency endoscopy. Endoscopic hemostasis was performed, and he was discharged after recovery. A tumor-like lesion in the lesser curvature of the antrum was found on repeat endoscopy and was diagnosed as well-differentiated adenocarcinoma by biopsy. There was no evidence of lymph node metastasis or distant metastasis; therefore, we planned radical surgery. However, he was diagnosed with COVID-19 infection by preoperative PCR screening. Although he had no symptoms, such as fever or respiratory symptoms, he was hospitalized because of his advanced age. He was discharged 10 days after admission, and repeat COVID-19 PCR was negative. We planned radical surgery for the stomach tumor 6 weeks after recovery from the COVID-19 infection. A PCR-negative COVID-19 status was confirmed again before hospitalization. Open distal gastrectomy with Billroth I reconstruction was performed. We avoided ultrasonic scalpels and used a Crystal Vision 450D surgical smoke evacuator (I.C. Medical, Inc., Phoenix, AZ, USA) to reduce intraoperative surgical smoke. The postoperative course was uneventful. CONCLUSION: Because of the COVID-19 pandemic, some patients are diagnosed with COVID-19 infection by preoperative antigen tests or PCR, even if they have no symptoms. If possible, elective surgery should be performed 4 to 6 weeks after recovery from COVID-19 infection to maximize safety. Moreover, surgeons must consider intraoperative surgical smoke.