Risk factors of "loss of independence" in elderly patients who received gastrectomy for gastric cancer.

OBJECTIVE: The aim of this study was to clarify the risk of loss of independence (LOI) following gastrectomy in elderly patients with gastric cancer (GC). METHODS: In this prospective study, frailty was assessed preoperatively by a frailty index (FI) in 243 patients aged ≥ 65 years who underwent gastrectomy for GC between August 2016 and December 2020. Patients were assigned into two groups (high FI vs. low FI) to investigate frailty and the risk of LOI after gastrectomy for GC. RESULTS: Overall and minor (Clavien-Dindo classification [CD] 1, 2) complication rates were significantly higher in the high FI group, but the two groups had similar rates of major (CD ≥ 3) complications. The frequency of pneumonia was significantly higher in the high FI group. In univariate and multivariate analyses for LOI after surgery, high FI, older age (≥ 75 years), and major (CD ≥ 3) complications were independent risk factors. A risk score assigning 1 point for each of these variables was useful in predicting postoperative LOI (LOI: score 0, 7.4%; score 1, 18.2%; score 2, 43.9%; score 3, 100%; area under the curve [AUC] = 0.765.) CONCLUSIONS: LOI after gastrectomy was independently associated with high FI, older age (≥ 75 years), and major (CD ≥ 3) complications. A simple risk score assigning points for these factors was an accurate predictor of postoperative LOI. We propose that frailty screening should be applied for all elderly GC patients before surgery.

The Cancer Cachexia Index Can Be Used to Prognostically Predict Patients with Gastric Cancer Undergoing Gastrectomy.

INTRODUCTION: Cancer cachexia occurs in cancer patients more frequently as the cancer progresses, with a negative impact on treatment outcomes. In this study, we sought to clarify the clinical impact of a cancer cachexia index (CXI) in patients with gastric cancer (GC) undergoing gastrectomy. METHODS: Between January 2013 and December 2018, we reviewed data from 556 patients treated for GC at our hospital. CXI was calculated using skeletal muscle index (SMI), serum albumin, and neutrophil-lymphocyte ratios (NLR). Patients were divided into high (n = 414) or low CXI (n = 142) groups. We investigated the clinical impact of CXI in patients with GC undergoing gastrectomy. RESULTS: Multivariate analyses of 5-year overall survival (OS) and cancer-specific survival (CSS) rates indicated that a low CXI was independently associated with unfavorable outcomes for patients with GC. In multivariate analyses, SMI was independent predictor of OS but not CSS. NLR was not an independent predictor of either OS or CSS. Complication incidences (≥ Clavien Dindo 3) were non-significantly higher in the low (vs. high) CXI group. CONCLUSION: CXI was a more valuable prognostic biomarker when compared with SMI or NLR in GC patients undergoing gastrectomy. We suggest that patients with low CXI values should be given more comprehensive treatment, including exercise and nutritional therapy to improve clinical outcomes.

[Surgical Technique for Mesorectal Division in the Robotic Anterior Resection for Rectal Cancer].

Since April 2018, robot-assisted rectal resection has been approved as an insurance medical treatment, and robot- assisted rectal resection is rapidly becoming widespread. Even in robot-assisted laparoscopic surgery, mesorectal division is difficult in a narrow pelvic cavity. At the beginning of the operation, Vessel Sealer ExtendTM(price 89,250 yen)was used, but as the procedure became stable, the mesorectal division was started with bipolar forceps and monopolar scissors. The purpose of this study was to investigate the mesorectal division time and postoperative complications associated with changes in the procedure. 36 patients who underwent robot-assisted anterior resection for rectal cancer by the same surgeon from January 2019 to December 2021. We compared mesorectal division time and postoperative complication. Median operation time were 267 minutes, median console time were 132 minutes. There were no complications such as intestinal obstruction or anastomotic leakage. There was no difference in mesorectal division time time between Vessel Sealer groups and Scissors groups(14 min 55 sec vs 16 min 5 sec). The mesorectal division with bipolar forceps and monopolar scissors could be performed without extending the operation time, and could be performed with cost-benefit and safely.

[Impact of Sarcopenia on Patients with Advanced Gastric Cancer Who Underwent Surgery].

This study aimed to investigate the short- and long-term outcomes in patients with sarcopenia who underwent surgery for advanced gastric cancer. We included 76 patients with pStage Ⅱ or Ⅲ gastric cancer who underwent gastrectomy between January 2017 and June 2021. Patients with pT3N0 cancer were excluded. Using the Asian Working Group for Sarcopenia( AWGS)2019 criteria, the patients were divided into the sarcopenia group(S group)and the non-sarcopenia group (NS group). The surgical outcomes, effects on postoperative adjuvant chemotherapy, and prognosis of the 2 groups were evaluated and compared. No significant differences were observed in the operative time, blood loss, postoperative hospital stays, or incidence of postoperative complications with a grade higher than Clavien-Dindo Grade Ⅱ. The number of patients who received postoperative adjuvant chemotherapy was 5(26.3%)in the S group and 38(66.7%)in the NS group which was significantly lower in the S group(p=0.003). The 3-year overall survival rate was 45.7% in the S group and 71.0% in the NS group(p=0.302). There was no significant difference but survival rate was lower in the S group. The results suggest that postoperative adjuvant chemotherapy is not always available for patients with advanced gastric cancer, and that may worsen the prognosis.

[A Case of Robotic Surgery for Local and Peritoneal Recurrence of Colorectal Cancer].

A 35-year-old women with sigmoid cancer(pT4aN1aM0, pStage Ⅲb)underwent laparoscopic sigmoidectomy. She had 8 courses of CapeOX for adjuvant chemotherapy, but follow up CT scan 1 year after the operation detected intraabdominal nodules in anastomotic site and in left lower quadrant of abdomen. After 10 courses of IRIS plus bevacizumab, the both intraabdominal nodules decreased in size. Robot assisted laparoscopic lower anterior resection and laparoscopic disseminated nodule resection were performed. The patient had no postoperative complications and the postoperative course was good. She remains alive without recurrence at 6 months after the second operation.

[A Case of pStage IB Gastric Cancer Relapsed on Both Pleura and Peritoneum Eight Year after Radical Gastrectomy].

An 86-year-old man presented with upper abdominal pain and was diagnosed with type 0-Ⅲ gastric cancer located at the posterior wall of the upper stomach by upper gastrointestinal endoscopy. Laparoscopic total gastrectomy(D1+)was performed for gastric cancer of cStage Ⅰ. As final pathological diagnosis was pT2N0(0/27)M0H0P0CY0, pStage ⅠB, adjuvant chemotherapy was not administrated. The patient has been alive with no recurrence for 5 years after surgery. 8 years and 1 month after procedure, he visited our hospital with chief complaint of abdominal distention and anorexia. Chest and abdominal CT showed pleural fluid and ascites, but PET-CT could not detect any sites of recurrence. Cytopathology and cell blocks by immunohistochemical staining of ascites proved recurrence of previous gastric cancer. Any treatment was rejected, and the patient died 3 months after recurrence and 8 years and 4 months after gastrectomy. Late recurrence on both pleura and peritoneum of gastric cancer is very rare. We report a case of pStage ⅠB gastric cancer relapsed on both pleura and peritoneum 8 year after radical gastrectomy.

[A Case of Recurrent Gastric Cancer of Multiple Organ Metastasis with Long-Term Survival Due to Multimodal Treatment].

A 67-year-old man was introduced to examine for abnormal findings in physical examination. Upper gastrointestinal endoscopy detected the 3 lesions and diagnosed multiple gastric cancers with biopsy. Laparoscopic total gastrectomy was performed and final pathological diagnosis was pT2N1M0, pStage ⅡA with HER2 positive(3+). Adjuvant chemotherapy was not administrated. CT findings 6 months after procedure showed 2 liver metastases(S6, S7)and laparoscopic partial liver resection was performed. Pathological findings proved the metastasis of previous gastric cancer. Although adjuvant chemotherapy of S-1 was started 2 months after hepatectomy, CT findings showed second recurrences in liver and right adrenal gland. Chemotherapy was changed to S-1 plus cisplatin(SP)plus trastuzumab. AS these recurrence sites and ascites could not be detected by CT after 6 courses, therapeutic effect was judged as clinical CR(cCR)and SP plus trastuzumab was stopped due to side effect. Since then, regular follow-up CT showed preservation of status of cCR without chemotherapy and he has been alive without recurrence for 8 years and 9 months after gastrectomy. We report a case of recurrent gastric cancer of multiple organ metastasis with long-term survival due to multimodal treatment.

Dioxotriazine derivatives as a new class of P2X3 receptor antagonists: Identification of a lead and initial SAR studies.

P2X3 receptor is an ATP-gated ion channel, mainly localized on peripheral sensory neurons. Currently, several clinical trials are being conducted with P2X3 receptor antagonists for the treatment of chronic pain or cough. To identify a P2X3 lead compound, we reexamined the HTS evaluation compounds and selected dioxotriazine derivatives from which we identified a hit compound. As a result of the hit-to-lead SAR, we obtained lead compound 1 which had a moderate inhibitory effect on P2X3 receptors (IC50, 128 nM). Further improvement of the potency and PK profiles of this lead compound finally led to the selected compound 74 (P2X3 IC50, 16.1 nM; P2X2/3 IC50, 2931 nM), which demonstrated a strong analgesic effect against allodynia on oral administration in the rat partial sciatic nerve ligation model of neuropathic pain (ED50, 3.1 mg/kg).

Asporin Expression on Stromal Cells and/or Cancer Cells Might Be A Useful Prognostic Marker in Patients with Diffuse-Type Gastric Cancer.

BACKGROUND: Asporin (ASPN), a member of the proteoglycan family, has been shown to have a close correlation with cancer progression. It is not known whether ASPN is an oncogenic driver or a tumor suppressor in human gastric cancer. We sought herein to determine the relationship between ASPN expression and clinicopathological features of gastric cancer. PATIENTS AND METHODS: A total of 296 gastric cancer patients (diffuse type, n = 144; intestinal type, n = 152) were enrolled. The ASPN expression level in each case was analyzed by immunohistochemistry. RESULTS: ASPN was mainly found on stromal cells, especially on fibroblasts in tumor stroma, i.e., cancer-associated fibroblasts. The ASPN expression on either cancer cells or stromal cells was significantly high in macroscopic scirrhous-type tumors (p < 0.001) and histologically abundant stroma-type tumors (p < 0.001). Interestingly, a Kaplan-Meier survival curve of the 144 cases of diffuse-type gastric cancer revealed a significantly poorer prognosis in patients with ASPN-positive expression (p = 0.043; log rank) compared to those with ASPN-negative expression, but the prognoses were not significantly different in these subgroups of the 152 cases of intestinal-type gastric cancer. A multivariate analysis with respect to overall survival showed that ASPN expression on stromal cells and/or cancer cells was significantly correlated with overall survival in patients with diffuse-type gastric cancer (p = 0.041). CONCLUSION: In gastric cancer, ASPN was expressed mainly on stromal cells and partially on cancer cells. ASPN expression on stromal cells and/or cancer cells might be a useful prognostic marker in patients with diffuse-type gastric cancer.

[Two Cases of Advanced and Recurrent Gastric Cancer with Long-Term Survival Due to Successful Chemotherapy].

Case 1: A 73-year-old man underwent total gastrectomy for residual gastric cancer, and final pathological diagnosis was pStage ⅠB. Adjuvant chemotherapy was not performed. CT findings showed multiple liver metastasis 16 months after procedure. S-1 and CDDP were administered for 28 months. Although chemotherapy regimen was changed to S-1, paclitaxel plus ramucirumab, nivolumab, irinotecan and S-1 plus oxaliplatin(SOX)after progression, he died 73 months after operation, and 57 months after recurrence. Case 2: A 72-year-old man was pointed out swelling of gastric lymph nodes in CT imaging. He was diagnosed as advanced gastric cancer with para-aortic lymph node metastasis by followed examination. S- 1 plus CDDP was administrated for 30 months. S-1 and SOX were administered after progressive findings, but he died 48 months after diagnosis. We report 2 cases of recurrent and advanced gastric cancer with long-term survival because of successful chemotherapy.

Pyrrolinone derivatives as a new class of P2X3 receptor antagonists. Part 3: Structure-activity relationships of pyrropyrazolone derivatives.

The P2X3 receptor is an attractive target for the treatment of pain and chronic coughing, and thus P2X3 antagonists have been developed as new therapeutic drugs. We previously reported selective P2X3 receptor antagonists by derivatization of hit compound 1. As a result, we identified hit compound 3, the structure of which was similar to hit compound 1. On the basis of SAR studies of hit compound 1, we modified hit compound 3 and compound 42 was identified as having analgesic efficacy by oral administration.

[A Case of Metastatic Breast Cancer That Recovered from Diffuse Alveolar Damage Associated with Everolims].

A 68-year-old woman was receiving chemotherapy and endocrine therapy for right breast cancer postoperative pulmonary metastasis and local lymph node recurrence. However, she developed interstitial pneumonia 12 weeks after initiating treatment with everolimus and exemestane. Treatment with everolimus and exemestane was discontinued and steroid pulse therapy was initiated; however, she required ventilator management because of the severity of the pneumonia. The patient's condition improved 9 days after ventilator management. Everolimus-induced interstitial pneumonia is often mild, but it can be severe in rare cases. In our case, everolimus-induced diffuse alveoli damage was successfully treated with ventilator management.

Resistivity control by the electrochemical removal of dopant atoms from a nanodot.

Doping impurity atoms into semiconductor materials changes the resistance of the material. Selecting the atomic species of a dopant and the precise control of the number of dopant atoms in a unit volume can control the resistance to a desired value. The number of dopant atoms is usually controlled when the materials are synthesized. It can also be controlled after synthesizing by injecting dopant atoms using an ion implantation technique. This physical method has now enabled atom by atom implantation at the desired position. Here, we propose an additional technique, based on the electrochemical potential of dopant atoms in a material. The technique enables the dynamic control of the number of dopant atoms through the application of bias to the material. We demonstrate the controlled removal of dopant atoms using Ag2+δS and Ag-doped Ta2O5 as model materials. The change in resistance accompanying the removal of dopant atoms is also observed.

Discovery of naldemedine: A potent and orally available opioid receptor antagonist for treatment of opioid-induced adverse effects.

Structure-activity relationship studies of several morphinan derivatives were conducted to obtain dual antagonists for µ- and δ-opioid receptors. We discovered peripherally restricted dual antagonists for µ/δ-opioid receptors as a new chemotype with a morphinan scaffold, which are orally available and do not easily pass the blood-brain barrier. As we expected, some of these compounds inhibit opioid-induced constipation and emesis/vomiting with limited potential to interfere the analgesic effects of morphine. Among them, naldemedine was selected as a potential drug candidate.

[Three Cases of Unresectable Colorectal Cancer Curatively Resected after Effective Chemotherapy].

Case 1: A60-year-old man underwent resection of a brain tumor, which was pathologically diagnosed as adenocarcinoma. As he was diagnosed with unresectable rectal cancer due to pulmonary metastasis, we performed abdominoperineal resection after chemotherapy. Since pulmonary metastasis and local recurrence were detected 1 year after the surgery, he was administered chemotherapy. He died 37 months after the surgery. Case 2: A6 4-year-old man was diagnosed with unresectable rectal cancer due to pulmonary and hepatic metastases, resulting in an examination for melena. We performed laparoscopic low anterior resection and hepatic partial resection after chemotherapy. No relapse has occurred 1 year after the surgery. Case 3: A39 -year-old man was examined for abdominal pain and distension and was diagnosed with unresectable rectal cancer due to invasion of the left ureter and multiple hepatic metastases. We performed anterior resection, hepatic partial resection, and RFAafter chemotherapy. He has remained in relapse-free survival for 15 months after the surgery. These results suggest that curative resection after chemotherapy improves the prognosis of unresectable colorectal cancer.

[Analysis of Renal Toxicity of S-1 plus CDDP Regimen with Short Hydration for Outpatients with Gastric Cancer].

BACKGROUND: Although the S-1 plus CDDP(SP)regimen is the standard treatment for advanced gastric cancer, hydration and admission have been recommended after cisplatin has been administered. In this study, short hydration(SH)method was used and SP was administered in outpatient settings. We evaluated renal toxicity of cisplatin in the SH-SP regimen at our hospital. METHODS: Eleven of 16 patients(5 underwent only 1 course and so were excluded)received the SH-SP regimen between January 2012 and January 2018 to present and were included. Serum creatinine(Cr)and estimated glomerular filtration rate(eGFR)were used to assess renalfunction. RESULTS: Median course was 5. Rate of 5-course accomplishment was 72.7%. Grade 1 Cr elevation was observed in only 3 patients and there was no severe renal disorder. CONCLUSION: The SHSP regimen could be administered in outpatient settings and was considered safe as it did not cause renal toxicity.

[A Case of Breast Cancer Liver Metastases with Jaundice Responding to Chemotherapy].

A 50-year-old woman was referred to our hospital due to breast cancer with multiple liver metastasis diagnosed by CT scan. Laboratory findings showed liver dysfunction(T-Bil 7.6mg/dL)with marked elevation of tumor markers(CEA 727.9 ng/mL). Breast tumor biopsy showed an invasive ductal carcinoma(scirrhous type), ER(+), PgR(-), and HER2(3+). Combination therapy with docetaxel, carboplatin and, trastuzumab was administered after the end of 1 course of weekly paclitaxel plus bevacizumab regimen. The patient maintained a good condition without liver dysfunction 8 months after the first visit. Follow-up CT scan showed partial response of breast and hepatic tumors. Our case suggests that careful chemotherapy can improve the prognosis of breast cancer with liver metastasis even if a patient is in an icteric condition.

Significance of the Lysyl Oxidase Members Lysyl Oxidase Like 1, 3, and 4 in Gastric Cancer.

BACKGROUND/AIMS: Lysyl oxidase (LOX) family members play a key role in modifying the primary tumor microenvironment by crosslinking collagens and elastin in the extracellular matrix. The aim of this study was to analyze the LOX-like (LOXL)1, LOXL3, and LOXL4 expressions in gastric cancer tissue by immunohistochemical staining. METHODS: The correlations between the clinicopathological features of 597 primary gastric carcinomas and LOX family members - LOXL1, LOXL3, and LOXL4 - were investigated by immunohistochemical studies. The effect of the transforming growth -factor ß1 (TGFß1) on the expressions of LOXL1, LOXL3, and LOXL4 in gastric cancer was examined using diffuse-type gastric cancer cell lines in vitro. RESULTS: The expressions of LOXL1, LOXL3, and LOXL4 were correlated with T invasion, lymph node metastasis, and lymphatic and venous invasion. LOXL1 expression was associated with histological intestinal-type and expanding growth patterns. The overall survival of patients with LOXL1-, LOXL3-, or LOXL4-positive cancer was poorer than those with negative cancer. LOXL3 and LOXL4 mRNA expressions were significantly high in diffuse-type gastric cancer cells with high invasion ability. TGFß decreased the LOXL1 expression and increased LOXL3 and LOXL4 expression. CONCLUSION: LOXL1, LOXL3, and LOXL4 expressions are associated with distant metastasis of gastric cancer.

[A Case of Apocrine Carcinoma in the Breast That Was Difficult to Distinguish from Axillary Apocrine Adenocarcinoma].

An 86-year-old woman visited our hospital with a tumor on her right axilla. Ultrasonography(US)showed a 4 cm tumor between mammary gland and axilla with swelling of some lymph nodes. No distant metastatic lesions were found. The pathological findings revealed breast apocrine carcinoma; therefore, we performed total mastectomy and axillary lymph node dissection. The postoperative pathological findings revealed breast apocrine carcinoma with pT4N2M0, Stage Ⅲb(ER positive, PgR negative, HER2 positive, Ki-67 6%). We present a case of breast apocrine carcinoma confused with axially apocrine adenocarcinoma during the diagnosis and report the relevant literature.

[A Case of Breast Cancer with Infarcted Necrosis That Was Diagnosed Based on Axillary Lymph Node Metastasis].

A 61-year-old woman with a breast tumor detected by mammography examination was admitted to our hospital. Ultrasonography showed a 15.5×7.2mm sized irregular mass at the left BD area. Vacuum-assisted biopsy did not reveal any malignant cells. After 3 months, ultrasonography reexamination showed that the irregular mass had increased to 24.2×16.5mm in size, and it had spread to multiple axillary lymph nodes. The patient was diagnosed with breast cancer by core needle biopsy of the axillary lymph node. Total mastectomy with axillary lymph node dissection was performed. The pathological diagnosis was solid-tubular carcinoma with infarcted necrosis. The number of metastatic axillary lymph nodes was confirmed to be 23 in total. This case was considered very rare and important because there have been very few reports of breast cancer with infarcted necrosis.