Publications by authors named "Mototsugu Shimokawa"

202 Publications

Clinical significance of part-solid lung cancer in the eighth edition TNM staging system.

Interact Cardiovasc Thorac Surg 2021 Sep 25. Epub 2021 Sep 25.

Department of Thoracic and Breast Surgery, Oita University Faculty of Medicine, Oita, Japan.

Objectives: The ground-glass component of part-solid tumour (PST) was eliminated as a clinical T (cT) descriptor in the eighth edition of the tumour, node and metastasis (TNM) staging system. We aimed to validate the new cT descriptor and investigate the prognostic impact of PST in the new staging system.

Methods: Non-small-cell lung cancer (NSCLC) patients (n = 1061) who underwent lung resection and were available for the assessment of thin-section computed tomography images were retrospectively reviewed. Tumours with a solid component (SC) size-to-whole tumour size (STR) ratio of 0, those with 0 < STR < 1 and those with an STR of 1 were defined as pure ground-glass tumours, PSTs and solid tumours (STs), respectively.

Results: Tumours with an SC diameter of >30 mm were less frequently observed among PSTs than among STs (4.83% vs 32.6%, P < 0.001). The postoperative 5-year survival of NSCLC patients with ground-glass tumour, PST and ST was 97.6%, 89.0% and 76.3%, respectively. In the survival analysis of patients with an SC diameter ≤30 mm, significant differences were observed among PST and ST (5-year survival, 90.7% vs 74.6%, P < 0.001). The multivariable analysis showed that age <70 years old, female sex, procedures with a lobectomy or more, SC size, pN0 disease and PST were independent predictors of a better survival among all PST and ST patients.

Conclusions: Among patients with cT1 tumours, those with PST showed a significantly better survival than did those with ST. Small-sized PST tumours may not be suitable for the new cT descriptor.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/icvts/ivab255DOI Listing
September 2021

Clinical outcomes of surgical resection for recurrent lesion after curative esophagectomy for esophageal squamous cell carcinoma: a nationwide, large-scale retrospective study.

Esophagus 2021 Sep 12. Epub 2021 Sep 12.

Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.

Background: Several studies have reported the efficacy of resection for recurrent lesions. However, they involved a limited number of subjects. This study aimed to identify a subset of patients who benefit from surgical resection of recurrent lesions after curative esophagectomy for esophageal squamous cell carcinoma.

Methods: Clinicopathological features of 186 patients with esophageal squamous cell carcinoma who underwent surgical treatment for postoperative recurrent lesions at 37 accredited institutions of the Japanese Esophageal Society were evaluated.

Results: The most common recurrence site was the lymph node (106 cases; 58.6%), followed by the lung (40 cases; 22.1%). Univariate analyses revealed that pN 0-1 at esophagectomy (P = 0.0348), recurrence-free interval of ≥ 550 days (P = 0.0306), R0 resection (P < 0.0001), and absence of severe complications after resection for recurrent lesions (Clavien-Dindo grade < IIIa) (P = 0.0472) were associated with better overall survival after surgical resection. According to multivariate analyses, pN 0-1 (P = 0.0146), lung metastasis (P = 0.0274), recurrence-free interval after curative esophagectomy of ≥ 550 days (P = 0.0266), R0 resection (P = 0.0009), and absence of severe complications after resection for recurrent lesions (Clavien-Dindo grade < IIIa) (P = 0.0420) were independent predictive factors for better overall survival.

Conclusions: Surgical resection of recurrent esophageal squamous cell carcinoma lesions is a useful option, especially for cases involving lower pN stage, lung metastasis, long recurrence-free intervals after esophagectomy, and technically resectable lesions. Surgical risks should be minimized as much as possible.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10388-021-00878-2DOI Listing
September 2021

Re: COVID-19 in patients with neuroendocrine neoplasms: Preliminary results of a worldwide survey (The INTENSIVE study).

Eur J Cancer 2021 Aug 26. Epub 2021 Aug 26.

Department of Biostatistics, Yamaguchi University Graduate School of Medicine, 1-1-1 Minamikogushi, Ube, Yamaguchi, 755-8505, Japan.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejca.2021.07.046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8387225PMC
August 2021

Comments on 'The Impact of Beta Blockers on Survival Outcomes in Patients With Non-small-cell Lung Cancer Treated With Immune Checkpoint Inhibitors'.

Clin Lung Cancer 2021 Aug 10. Epub 2021 Aug 10.

Department of Biostatistics, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cllc.2021.08.004DOI Listing
August 2021

Prognostic value of postoperative decrease in serum albumin on surgically resected early-stage non-small cell lung carcinoma: A multicenter retrospective study.

PLoS One 2021 2;16(9):e0256894. Epub 2021 Sep 2.

Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Background: Preoperative nutritional status is an important host-related prognostic factor for non-small cell lung carcinoma (NSCLC); however, the significance of postoperative changes in nutritional status remains unclear. This study aimed to elucidate the significance of postoperative decreases in serum albumin (ΔAlb) on the outcomes of early-stage NSCLC.

Methods: We analyzed 443 training cohort (TC) and 642 validation cohort (VC) patients with pStage IA NSCLC who underwent surgery and did not recur within 1 year. We measured preoperative serum albumin levels (preAlb) and postoperative levels 1 year after surgery (postAlb), and calculated ΔAlb as (preAlb - postAlb)/preAlb × 100%. A cutoff value of 11% for ΔAlb was defined on the basis of the receiver operating characteristic curve for the TC.

Results: Patients were divided into ΔAlb-Decreased and ΔAlb-Stable groups, including 100 (22.6%) and 343 (77.4%) in the TC, and 58 (9.0%) and 584 (90.1%) in the VC. ΔAlb-Decreased was associated with male sex (p = 0.0490), smoking (p = 0.0156), and non-adenocarcinoma (p<0.0001) in the TC, and pT1b (p = 0.0169) and non-adenocarcinoma (p = 0.0251) in the VC. Multivariable analysis identified ΔAlb as an independent prognostic factor for disease-free survival (DFS) and overall survival (OS) in both cohorts (VC: DFS, HR = 1.9, 95%CI: 1.10-3.15, p = 0.0197; OS, HR = 2.0, 95%CI: 1.13-3.45, p = 0.0173). Moreover, subgroup analysis demonstrated that the prognostic value of ΔAlb was consistent for age, sex, smoking history, surgical procedure, and histological type.

Conclusion: We demonstrated a negative impact of postoperative decrease of the serum albumin on the prognosis of patients with early-stage NSCLC. Postoperative changes in nutritional status might be important in NSCLC outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0256894PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8412276PMC
September 2021

Phase III study of adjuvant gemcitabine compared with adjuvant uracil-tegafur in patients with completely resected pathological stage IB-IIIA non-small cell lung cancer (WJTOG0101).

Int J Clin Oncol 2021 Aug 31. Epub 2021 Aug 31.

Research Institute for Diseases of the Chest, Kyushu University, Fukuoka City, Fukuoka, Japan.

Background: Adjuvant oral uracil-tegafur (UFT) has led to significantly longer postoperative survival among patients with non-small-cell lung cancer (NSCLC). Gemcitabine (GEM) monotherapy is also reportedly effective for NSCLC and has minor adverse events (AEs). This study compared the efficacy of GEM- versus UFT-based adjuvant regimens in patients with completely resected pathological stage (p-stage) IB-IIIA NSCLC.

Patients And Methods: Patients with completely resected p-stage IB-IIIA NSCLC were randomly assigned to GEM or UFT. The primary endpoint was overall survival (OS); secondary endpoints were disease-free survival (DFS), and AEs.

Results: We assigned 305 patients to the GEM group and 303 to the UFT group. Baseline factors were balanced between the arms. Of the 608 patients, 293 (48.1%) had p-stage IB disease, 195 (32.0%) had p-stage II disease and 121 (19.9%) had p-stage IIIA disease. AEs were generally mild in both groups, and only one death occurred, in the GEM group. After a median follow-up of 6.8 years, the two groups did not significantly differ in survival: 5 year OS rates were GEM: 70.0%, UFT: 68.8% (hazard ratio 0.948; 95% confidence interval 0.73-1.23; P = 0.69).

Conclusion: Although GEM-based adjuvant therapy for patients with completely resected stage IB-IIIA NSCLC was associated with acceptable toxicity, it did not provide longer OS than did UFT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10147-021-02012-9DOI Listing
August 2021

Comparison of laparoscopic surgery with open standard surgery for advanced gastric carcinoma in a single institute: a propensity score matching analysis.

Surg Endosc 2021 Aug 23. Epub 2021 Aug 23.

Department of Gastroenterological Surgery, National Kyushu Cancer Center, 3-1-1 Notame, Minami-ku, Fukuoka, 811-1395, Japan.

Background: Compared with open standard gastrectomy (OG), laparoscopic gastrectomy (LG) did not result in inferior disease-free survival for early-stage and locally advanced gastric cancer (AGC). However, whether LG for AGC in elderly patients is more beneficial than OG is unclear.

Methods: This study examined 458 patients with AGC. The mortality, morbidity, and prognosis were compared by age, gender, T and N factors, and pathological stage in the LG and OG groups using propensity score matching analysis. For the final analysis, 151 pairs of patients were selected from at each group.

Results: The results showed that no significant difference in mortality and morbidity existed between the two groups. The 5-year relapse-free survival (RFS) rates were 70% and 62% in the LG and OG groups, respectively (p = 0.104). The 5-year RFS rates in patients with pathological stages I, II, and III who had undergone LG were 84%, 80%, and 55%, respectively, and 78%, 70%, and 45%, respectively, in those who had undergone OG (p < 0.005). The 5-year RFS rates in nonelderly patients who underwent LG or OG were 75% and 68%, respectively, and 58% and 40%, respectively, in elderly patients who underwent LG or OG (p < 0.005).

Conclusion: The 5-year RFS rates in patients with AGC at each stage did not significantly differ between LG and OG. However, the benefits at 5-year RFS in patients who underwent LG compared with OG were larger in elderly patients than those in nonelderly patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00464-021-08652-2DOI Listing
August 2021

Neoadjuvant pemetrexed plus cisplatin followed by pleurectomy for malignant pleural mesothelioma.

J Thorac Cardiovasc Surg 2021 Jul 17. Epub 2021 Jul 17.

Otemae Hospital, Osaka, Japan.

Purpose: Despite becoming the preferred surgical technique for malignant pleural mesothelioma, pleurectomy/decortication has received few prospective clinical trials. Therefore, the Japan Mesothelioma Interest Group conducted a prospective multi-institutional study to evaluate the feasibility of neoadjuvant chemotherapy followed by pleurectomy/decortication.

Methods: Patients with histologically confirmed, resectable malignant pleural mesothelioma underwent neoadjuvant chemotherapy comprising pemetrexed 500 mg/m plus cisplatin 75 mg/m for 3 cycles, followed by pleurectomy/decortication. The primary end point was macroscopic complete resection rate regardless of the surgical technique used.

Results: Among the 24 patients enrolled, 20 received neoadjuvant chemotherapy and 18 proceeded to surgery, all of whom achieved macroscopic complete resection. Pleurectomy/decortication was performed in 15 patients. The trial satisfied the primary end point, with a macroscopic complete resection rate of 90% (18/20, 95% confidence interval, 68.3-98.8). No treatment-related 30- and 90-day mortality occurred. The overall survival after 1 and 2 years and median overall survival after registration were 95.0% (95% confidence interval, 69.5-99.3), 70.0% (95% confidence interval, 45.1-85.3), and 3.45 years (95% confidence interval, 1.64 to not available), respectively. The cumulative incidence of progression after 1 and 2 years and median time to progression were 33.3% (95% confidence interval, 17.3-64.1), 61.1% (95% confidence interval, 42.3-88.3), and 1.71 years (95% confidence interval, 1.00-2.99), respectively. The best postoperative value for forced expiratory volume was 78.0% of preoperative values.

Conclusions: Neoadjuvant chemotherapy followed by pleurectomy/decortication was feasible with acceptable survival and mortality/morbidity. Postoperative pulmonary function was approximately 80% of the preoperative pulmonary function.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jtcvs.2021.07.017DOI Listing
July 2021

Risk factors for disease progression in Japanese patients with COVID-19 with no or mild symptoms on admission.

BMC Infect Dis 2021 Aug 21;21(1):850. Epub 2021 Aug 21.

Kitakyushu City Hospital Organization, 1-35 Furusenbamachi, Kokurakita-ku, Kitakyushu, 802-0082, Japan.

Background: Although the risk factors for coronavirus disease 2019 (COVID-19) mortality have been identified, there is limited information about the risk factors for disease progression after hospitalization among Japanese patients with COVID-19 exhibiting no or mild symptoms.

Methods: All 302 consecutive patients who were admitted to our institutions and diagnosed with COVID-19 between March and December 2020 were retrospectively assessed. Ultimately, 210 adult patients exhibiting no or mild symptoms on admission were included in the analysis. They were categorized into the stable (no oxygen needed) and worsened (oxygen needed) groups, and their characteristics and laboratory data were compared.

Results: Among 210 patients, 49 progressed to a severe disease stage, whereas 161 did not. The mean patient age was 52.14 years, and 126 (60.0%) patients were male. The mean body mass index (BMI) was 23.0 kg/m, and 71 patients were overweight (BMI ≥ 25 kg/m). Multivariate logistic analysis showed that old age, overweight, diabetes mellitus (DM), and high serum ferritin levels were independent risk factors for disease progression.

Conclusions: Clinicians should closely observe patients with COVID-19, especially those with risk factors such as old age, overweight, DM, and high serum ferritin levels, regardless of whether they have no or mild symptoms.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12879-021-06574-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8379599PMC
August 2021

Phase II study of S-1 and oxaliplatin as neoadjuvant chemotherapy for locally advanced adenocarcinoma of the gastric or esophagogastric junction: KSCC1601.

Gastric Cancer 2021 Aug 11. Epub 2021 Aug 11.

Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.

Background: Perioperative chemotherapy is the standard of care for locally advanced gastric cancer (LAGC). This phase II study investigated the efficacy and safety of S-1 and oxaliplatin (SOX) as neoadjuvant chemotherapy (NAC) for LAGC and esophagogastric junction cancer (EGJC).

Methods: Patients completed up to three cycles of SOX (oxaliplatin 130 mg/m on day 1, oral S-1 40-60 mg twice daily for 2 weeks every 3 weeks), followed by gastrectomy and D2 lymphadenectomy. The primary endpoint was the pathological response rate (pRR). The anastomosis leakage rate was the secondary endpoint in patients with EGJC, and other secondary endpoints were the R0 resection, overall survival (OS), and relapse-free survival (RFS) rates.

Results: Between April 2016 and July 2017, 47 patients (24 EGJC, 23 LAGC) were enrolled in this study. Forty-two patients (89.4%, 95% confidence interval [CI] = 76.9-96.5) underwent surgery, and R0 resection was achieved in 41 patients. The pRR was 59.5% (90% CI = 45.7-72.3). The major grade 3 or 4 toxicities were appetite loss in six patients (12.8%), thrombocytopenia in five patients (10.6%), and neutropenia and diarrhea in three patients (6.4%) each. The rate of severe anastomotic leakage (Clavien-Dindo classification grade III or higher) in 20 EGJC was 25.0% (90% CI = 10.4-45.6). The 3-year OS and RFS rate were 62.9% (95% CI = 47.2-75.1) and 53.2% (95% CI = 38.1-66.2), respectively.

Conclusion: SOX demonstrated substantial benefit for LAGC and EGJC. However, special attention should be paid to anastomotic leakage during surgery for EGJC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10120-021-01218-0DOI Listing
August 2021

Re: Predictive ability of a drug-based score in patients with advanced non-small-cell lung cancer receiving first-line immunotherapy.

Eur J Cancer 2021 Sep 6;155:313-314. Epub 2021 Aug 6.

Department of Biostatistics, Yamaguchi University Graduate School of Medicine, 1-1-1 Minamikogushi, Ube, Yamaguchi 755-8505, Japan.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejca.2021.06.057DOI Listing
September 2021

Gemcitabine Plus Nab-Paclitaxel Versus FOLFIRINOX in Locally Advanced, Unresectable Pancreatic Cancer: A Multicenter Observational Study (NAPOLEON Study).

Pancreas 2021 Aug 3. Epub 2021 Aug 3.

From the Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima Clinical Research Institute, National Kyushu Cancer Center, Fukuoka Department of Biostatistics, Yamaguchi University Graduate School of Medicine, Yamaguchi Department of Hepato-biliary-pancreatic Medicine, Saga-ken Medical Center Koseikan, Saga Department of Hematology and Oncology, Japanese Red Cross Kumamoto Hospital, Kumamoto Department of Gastroenterology and Hepatology, Kagoshima City Hospital, Kagoshima Department of Medical Oncology and Hematology, Oita University Faculty of Medicine, Oita Department of Medicine, Division of Gastroenterology, Kurume University Hospital Department of Hematology/Oncology, Japan Community Healthcare Organization Kyushu Hospital, Fukuoka Cancer Center, Gifu University Hospital, Gifu Department of Gastroenterology, Saiseikai Sendai Hospital Department of Gastroenterology, Izumi General Medical Center, Kagoshima Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki Department of Gastroenterology, Imari Arita Kyoritsu Hospital, Saga Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Chiba Department of Medical Oncology, Hamanomachi Hospital, Fukuoka Department of Medical Oncology, Sasebo Kyosai Hospital, Nagasaki Department of Internal Medicine, Karatsu Red Cross Hospital Department of Medical Oncology, Saga-ken Medical Center Koseikan, Saga Department of Medical Oncology, Kimitsu Chuo Hospital, Chiba Department of Internal Medicine, Fujikawa Hospital, Saga Department of Medical Oncology, Fukuoka Wajiro Hospital, Fukuoka Karatsu Higashi-Matsuura Medical Association Center, Saga Department of Internal Medicine, Minato Medical Clinic, Fukuoka, Japan.

Objectives: FOLFIRINOX (FFX, a combination of oxaliplatin, irinotecan, fluorouracil, and leucovorin) and gemcitabine plus nab-paclitaxel (GnP) have been used as standard, first-line treatments for advanced pancreatic cancer. However, no study has compared the efficacy of the 2 regimens. This study retrospectively compared the efficacy and safety of the 2 regimens in patients with locally advanced pancreatic cancer.

Methods: We reviewed the records of patients with locally advanced pancreatic cancer who started FFX or GnP as first-line chemotherapy as part of a multicenter retrospective study in patients with unresectable pancreatic cancer treated with FFX or GnP (NAPOLEON study).

Results: Sixteen of the 63 patients were treated with FFX, and the other 47 patients were treated with GnP between December 2013 and March 2017. There were no significant differences in median overall survival rate between the GnP (15.5 months) and FFX (14.3 months, P = 0.60) groups or median progression-free survival rate between the GnP (8.8 months) and FFX (8.1 months, P = 0.51) groups. Both treatments were generally well tolerated, although anorexia was more severe in the FFX group than in the GnP group.

Conclusions: The effects of FFX and GnP were similar but resulted in different toxicities, which could guide agent choice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MPA.0000000000001859DOI Listing
August 2021

Comments on "Lobe-specific Lymph Node Dissection in Clinical Stage IA Solid-dominant Non-small-cell Lung Cancer: A Propensity Score Matching Study".

Clin Lung Cancer 2021 Jul 7. Epub 2021 Jul 7.

Department of Thoracic Oncology, National Hospital Organization Kyushu Cancer Center, Minami-ku, Fukuoka, Japan.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cllc.2021.06.014DOI Listing
July 2021

Preoperative iron status is a prognosis factor for stage II and III colorectal cancer.

Int J Clin Oncol 2021 Jul 23. Epub 2021 Jul 23.

Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan.

Background: Iron deficiency anemia is represented in colorectal cancer (CRC) patients. Iron surplus load to increase non-transferrin bound iron (NTBI), and NTBI promotes cancer progression and influences microbiota. This study investigated whether preoperative serum iron status was associated with prognosis after CRC resection.

Methods: We evaluated preoperative iron and transferrin saturation (TSAT), which was calculated as iron divided by total iron-binding capacity, in 327 patients who underwent surgery for Stage II-III CRC. Fe < 60 μg/dl and TSAT > 40% were defined as low and high iron, respectively. The associations between iron status and overall survival (OS) were evaluated in univariate and multivariate Cox proportional hazards analysis.

Results: Of the 327 patients, 179 (54.7%), 124 (37.9%) and 24 (7.3%) had low, normal and high iron, respectively. In univariate analysis, low iron was associated with shorter OS (hazard ratio [HR] 2.821, 95% confidence interval [CI] 1.451-5.485, P = 0.002). High iron was also associated with shorter OS (HR 3.396, 95% CI 1.359-8.489, P = 0.009). In multivariate analysis, high age (P = 0.002), depth of invasion pT4 (P = 0.012), lymph-node metastasis presence (P = 0.035), low albumin (P = 0.011), low iron (HR 2.282, 95% CI 1.163-4.478, P = 0.016) and high iron (HR 3.757, 95% CI 1.486-9.494 P = 0.005) were independently associated with shorter OS. High iron was associated with the amount of intratumoral Fusobacterium nucleatum compared with normal iron.

Conclusion: Both low and high preoperative iron in Stage II-III CRC patients were associated with unfavorable OS in univariate and multivariate analyses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10147-021-01995-9DOI Listing
July 2021

Gemcitabine Plus Nanoparticle Albumin-bound Paclitaxel FOLFIRINOX for Recurrent Pancreatic Cancer After Resection.

Anticancer Res 2021 Jul;41(7):3573-3582

Department of Medical Oncology, Fukuoka Wajiro Hospital, Fukuoka, Japan.

Background/aim: The aim of the study was to evaluate gemcitabine plus nanoparticle albumin-bound paclitaxel (GnP) and FOLFIRINOX for recurrent pancreatic cancer (rPC) after resection.

Patients And Methods: Forty-four patients with rPC and 211 with de novo metastatic pancreatic cancer (mPC) who received GnP or FOLFIRINOX as first-line chemotherapy were retrospectively analyzed.

Results: On crude analysis, the median overall survival (OS) was significantly longer in the rPC group than in the mPC group (14.0 vs. 10.6 months, respectively; p=0.02). However, the difference was not significant on adjusted analysis using the Cox proportional hazards model (adjusted p=0.90). Patients receiving FOLFIRINOX (n=10) and GnP (n=34) in the rPC group had comparable OS (medians, 12.2 vs. 14.4 months, respectively; p=0.82) even after adjusting for covariates using the Cox model (adjusted p=0.18).

Conclusion: The outcomes of patients in the rPC and mPC groups were comparable following chemotherapy. Both FOLFIRINOX and GnP may be reasonable options for treating rPC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21873/anticanres.15145DOI Listing
July 2021

A 10-Item Frailty Index Based on a Comprehensive Geriatric Assessment (FI-CGA-10) in Older Adults with Cancer: Development and Construct Validation.

Oncologist 2021 Jul 3. Epub 2021 Jul 3.

Department of Medicine, Division of Oncology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.

Background: A frailty index (FI) based on domain-level deficits identified through a comprehensive geriatric assessment (CGA) has been previously developed and validated in general geriatric patients. Our objectives were to construct an FI-CGA and to assess its construct validity in the geriatric oncology setting.

Methods: Five hundred forty consecutive Japanese patients with cancer who underwent a CGA on a geriatric oncology service were included (median age 80 years, range 66-96 years). We developed a 10-item frailty index based on deficits in 10 domains (FI-CGA-10): cognition, mood, communication, mobility, balance, nutrition, basic and instrumental activities of daily living, social support, and comorbidity. Deficits in each domain were scored as 0 (no problem), 0.5 (minor problem), and 1.0 (major problem). Scores were calculated by dividing the sum of the scores for each domain by 10 and then categorized as fit (<0.2), pre-frail (0.2-0.35), and frail (>0.35). Construct validity was tested by correlating the FI-CGA-10 with other established frailty measures.

Results: FI-CGA-10 was well approximated by the gamma distribution. Overall, 20% of patients were fit, 41% were pre-frail, and 39% were frail. FI-CGA-10 was correlated with Canadian Study of Health and Aging (CSHA) Clinical Frailty Scale (r = 0.83), CSHA rules-based frailty definition (r = 0.67), and CSHA Function Score (r = 0.77). Increasing levels of frailty were significantly associated with functional and cognitive impairments, high comorbidity burden, poor self-rated health, and low estimated survival probabilities.

Conclusion: The FI-CGA-10 is a user-friendly and construct-validated measure for quantifying frailty from a CGA.

Implications For Practice: This article describes the construction of a user-friendly 10-item frailty index based on a comprehensive geriatric assessment (FI-CGA-10) for older adults with cancer: cognition, mood, communication, mobility, balance, nutrition, basic and instrumental activities of daily living, social support, and comorbidity. The FI-CGA-10 simplifies the original FI-CGA used in the general geriatric setting while maintaining its content validity. The index's construct validity was demonstrated in a cohort of older adults with various cancer types. The advantage of the FI-CGA-10 is that a frailty score can be calculated more readily and interpreted in a more clinically sensible manner than the original FI-CGA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/onco.13894DOI Listing
July 2021

Gemcitabine plus nab-paclitaxel in older patients with metastatic pancreatic cancer: A post-hoc analysis of the real-world data of a multicenter study (the NAPOLEON study).

J Geriatr Oncol 2021 Jun 29. Epub 2021 Jun 29.

Department of Medical Oncology, Hamanomachi Hospital, 3-3-1 Nagahama, Chuo-ku, Fukuoka-shi, Fukuoka, 810-8539, Japan.

Objectives: This study aimed to examine the efficacy and safety of gemcitabine plus nab-paclitaxel (GnP) in older patients with metastatic pancreatic cancer (MPC), especially those ≥75 years old.

Materials And Methods: This study retrospectively enrolled 153 patients with MPC who received GnP as first-line chemotherapy. Patients ≥75 years old were allocated to the older group, and those <75 years old were assigned to the non-older group. We compared safety, antitumor efficacy, and survival between the two groups. In the older group, prognostic indicators of survival were also assessed.

Results: The pretreatment characteristics of the two groups were not significantly different excluding age, history of malignancy, and C-reactive protein levels. The initial dose and relative dose intensities of GnP were significantly lower in the older group. There were no significant differences in the adverse event and antitumor response rates between the two groups. Median progression-free survival and overall survival were 5.5 and 12.0 months, respectively, in the older group, versus 6.0 and 11.1 months, respectively, in the non-older group. In the older group, a Geriatric Nutrition Risk Index (GNRI) of less than 86 was associated with poor prognosis.

Conclusion: GnP exhibited acceptable efficacy and safety in patients ≥75 years old with MPC. GNRI might be helpful for identifying older individuals at higher risk of unfavorable outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jgo.2021.06.011DOI Listing
June 2021

Identification of SLC38A7 as a Prognostic Marker and Potential Therapeutic Target of Lung Squamous Cell Carcinoma.

Ann Surg 2021 09;274(3):500-507

Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Background: No effective molecular targeted therapy has been established for SCC. We conducted a comprehensive study of SCC patients using RNA-sequencing and TCGA dataset to clarify the driver oncogene of SCC.

Method: Forty-six samples of 23 patients were totally analyzed with RNA-sequencing. We then searched for candidate-oncogenes of SCC using the TCGA database. To identify candidate oncogenes, we used the following 2 criteria: (1) the genes of interest were overexpressed in tumor tissues of SCC patients in comparison to normal tissues; and (2) using an integrated mRNA expression and DNA copy number profiling analysis using the TCGA dataset, the DNA copy number of the genes was positively correlated with the mRNA expression.

Result: We identified 188 candidate-oncogenes. Among those, the high expression of SLC38A7 was a strong prognostic marker that was significantly associated with a poor prognosis in terms of both overall survival (OS) and recurrence-free survival in the TCGA dataset (P < 0.05). Additionally, 202 resected SCC specimens were also subjected to an immunohistochemical analysis. Patients with the high expression of SLC38A7 (alternative name is sodium-coupled amino acid transporters 7) protein showed significantly shorter OS in comparison to those with the low expression of SLC38A7 protein [median OS 3.9 years (95% confidence interval, 2.4-6.4 years) vs 2.2 years (95% confidence interval, 1.9-4.1 years); log rank test: P = 0.0021].

Conclusion: SLC38A7, which is the primary lysosomal glutamine transporter required for the extracellular protein-dependent growth of cancer cells, was identified as a candidate therapeutic target of SCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/SLA.0000000000005001DOI Listing
September 2021

The effects of ARID1A mutations on colorectal cancer and associations with PD-L1 expression by stromal cells.

Cancer Rep (Hoboken) 2021 May 27:e1420. Epub 2021 May 27.

Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Background: ARID1A is a component of the SWI/SNF complex, which controls the accessibility of proteins to DNA. ARID1A mutations are frequently observed in colorectal cancers (CRCs) and have been reported to be associated with high mutational burden and tumor PD-L1 expression in vitro.

Aim: To clarify the role of ARID1A mutation in CRC.

Method And Results: We used next generation sequencing (NGS) and immunohistochemistry on clinically obtained samples. A total of 201 CRC tissues from Niigata University and Niigata Center Hospital were processed by NGS using the CANCERPLEX panel. Immunohistochemistry for ARID1A, PD-L1, MLH1, and MSH2 was performed on 66 propensity-matched (33 microsatellite instability-high [MSI-H] and 33 microsatellite-stable [MSS]) cases among 499 cases from Kyushu University. TCGA data were downloaded from cBioPortal. NGS showed significantly more mutations in ARID1A mutated CRCs (p = 0.01), and the trend was stronger for right-sided CRCs than left-sided. TCGA data confirmed these findings (p < 0.01). BRAF V600E and ATM mutations were also found at higher frequencies. Immunohistochemistry showed that 30% of MSI-H CRCs had ARID1A loss, while this was true in only 6% of MSS CRCs. In both MSI-H and MSS, PD-L1 expression by stromal cells was enhanced in the ARID1A-mutant groups (90% vs 39% in MSI-H, 100% vs 26% in MSS).

Conclusion: We found a higher mutational burden in ARID1A-mutant CRCs, and IHC study showed that ARID1A loss was correlated with high PD-L1 expression in stromal cells regardless of MSI status. These data support the idea that mutant ARID1A is a potential biomarker for CRCs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cnr2.1420DOI Listing
May 2021

Phase II Study of Neoadjuvant Concurrent Chemo-immuno-radiation Therapy Followed by Surgery and Adjuvant Immunotherapy for Resectable Stage IIIA-B (Discrete N2) Non-small-cell Lung Cancer: SQUAT trial (WJOG 12119L).

Clin Lung Cancer 2021 Apr 27. Epub 2021 Apr 27.

Division of Thoracic Surgery, Department of Surgery, Kindai University Faculty of Medicine, Osaka-Sayama, Japan. Electronic address:

Introduction: We describe our ongoing multicenter, prospective, single-arm, phase II trial of neoadjuvant concurrent chemo-immuno-radiation therapy followed by surgical resection and adjuvant immunotherapy for resectable stage IIIA-B (discrete N2) non-small-cell lung cancer (NSCLC) (registered at the Japan Pharmaceutical Information Center, Clinical Trials Information-195069).

Patients And Methods: Key inclusion criteria include (1) clinical T1-3/T4 (tumor size) N2 stage IIIA-B NSCLC, and (2) pathologically confirmed N2 without extranodal invasion (based on diagnostic imaging). Patients will receive concurrent chemoradiotherapy (carboplatin [area under the curve = 2] and paclitaxel [40 mg/m] on days 1, 8, 15, 22, and 29, with involved-field radiation therapy [RT] [dose 50 Gy] on days 1-25) and neoadjuvant immunotherapy (durvalumab [1500 mg] on days 1 and 29). Surgical resection with mediastinal lymph node dissection is performed within 2 to 6 weeks after RT. Consolidation therapy with durvalumab is administered for up to 1 year after surgery. The primary endpoint is major pathologic response (MPR) (≤10% residual viable tumor) according to the central pathological assessment. Secondary endpoints are progression-free survival, overall survival, and safety. The sample size is planned to be 31 patients based on the exact binomial distribution with a 1-sided significance level of 5% and a power of 80%, and assuming a threshold MPR rate of 40% and an expected MPR rate of 65%.

Conclusion: This trial will help establish a novel treatment strategy for resectable N2-positive NSCLC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cllc.2021.04.006DOI Listing
April 2021

Assessment of Intraoperative Microbiological Culture in Patients with Empyema: Comparison with Preoperative Microbiological Culture.

Ann Thorac Cardiovasc Surg 2021 May 8. Epub 2021 May 8.

Department of Surgery, Saiseikai Karatsu Hospital, Karatsu, Saga, Japan.

Purpose: Assessing microbiological culture results is essential in the diagnosis of empyema and appropriate antibiotic selection; however, the guidelines for the management of empyema do not mention assessing microbiological culture intraoperatively. Therefore, we tested the hypothesis that intraoperative microbiological culture may improve the management of empyema.

Methods: We performed a retrospective analysis of 47 patients who underwent surgery for stage II/III empyema from January 2011 to May 2019. We compared the positivity of microbiological culture assessed preoperatively at empyema diagnosis versus intraoperatively. We further investigated the clinical characteristics and postoperative outcomes of patients whose intraoperative microbiological culture results were positive.

Results: The positive rates of preoperative and intraoperative microbiological cultures were 27.7% (13/47) and 36.2% (17/47), respectively. Among 34 patients who were culture-negative preoperatively, eight patients (23.5%) were culture-positive intraoperatively. Intraoperative positive culture was significantly associated with a shorter duration of preoperative antibiotic treatment (p = 0.002). There was no significant difference between intraoperative culture-positive and -negative results regarding postoperative complications.

Conclusions: Intraoperative microbiological culture may help detect bacteria in patients whose microbiological culture results were negative at empyema diagnosis. Assessing microbiological culture should be recommended intraoperatively as well as preoperatively, for the appropriate management of empyema.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5761/atcs.oa.20-00327DOI Listing
May 2021

Clinical and prognostic features of patients with detailed RAS/BRAF-mutant colorectal cancer in Japan.

BMC Cancer 2021 May 7;21(1):518. Epub 2021 May 7.

Cancer Treatment Center, Kansai Medical University Hospital, 2-3-1, Shinmachi, Hirakata, Osaka, 573-1191, Japan.

Background: RAS/BRAF mutations are the most remarkable oncogenic driver mutations in colorectal cancer (CRC) and play an important role in treatment selection. No data are available regarding the clinical and prognostic features of patients with detailed RAS/BRAF-mutant metastatic CRC (mCRC) in Japan.

Methods: A total of 152 chemotherapy-naïve patients with mCRC were included in this study between August 2018 and July 2019. Tumor samples were collected, and RAS/BRAF status was investigated. RAS/BRAF status was examined using a MEBGEN RASKET-B kit and polymerase chain reaction reverse sequence-specific oligonucleotide method.

Results: RAS/BRAF mutations were detected in 54% of cases (KRAS codon 12, 26%; KRAS codon 13, 17%; KRAS non-Exon2, 5%; NRAS, 5%; and BRAF, 7%). BRAF-mutant CRC mainly existed in the right colon, whereas KRAS non-Exon2 and NRAS-mutant CRC was predominantly present in the left colon. KRAS non-Exon2 and NRAS-mutant CRC were associated with shorter survival time than RAS wild-type CRC (hazard ratio [HR], 2.26; 95% confidence interval [CI], 0.64-8.03; p = 0.19; HR, 2.42; 95% CI, 0.68-8.61; p = 0.16) and significantly shorter overall survival than KRAS Exon2-mutant CRC (HR, 3.88; 95% CI, 0.92-16.3; p = 0.04; HR, 4.80; 95% CI, 1.14-20.2; p = 0.02).

Conclusions: In our multicenter study, the findings elucidated the clinical and prognostic features of patients with detailed RAS/BRAF-mutant mCRC in Japan.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12885-021-08271-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105976PMC
May 2021

Preoperative transferrin level is a novel prognostic marker for colorectal cancer.

Ann Gastroenterol Surg 2021 Mar 25;5(2):243-251. Epub 2021 Jan 25.

Department of Gastroenterological Surgery Graduate School of Medical Sciences Kumamoto University Kumamoto Japan.

Aim: This study investigated whether preoperative serum transferrin, a rapid-turnover protein, was associated with prognosis after colorectal cancer (CRC) resection.

Methods: We evaluated preoperative transferrin, which was calculated as iron and unsaturated iron-binding capacity, in 501 patients who underwent surgery for Stage I-III CRC. Transferrin level was directly proportional to total iron-binding capacity (TIBC), and TIBC < 250 μg/dl was defined as low transferrin. The associations between transferrin and prognosis were evaluated in univariate and multivariate Cox proportional hazards analyses.

Results: Fifty-eight of 501 patients (11.5%) had low transferrin. In these patients, low transferrin was significantly associated with high age, female gender, low body mass index (<18.5), high white blood cell count, low total protein, low albumin, high C-reactive protein, low hemoglobin, and low neutrophil/lymphocyte ratio. In the univariate analysis, low transferrin was associated with shorter relapse-free survival (RFS) (hazard ratio [HR] 2.180, 95% confidence interval [CI] 1.417-3.354,  < .001), overall survival (OS) (HR 2.930, 95% CI 1.784-4.811,  < .001), and cancer-specific survival (CSS) (HR 2.122, 95% CI 1.053-4.275,  = .035). In multivariate analysis, high age ( < .001), Glasgow Prognostic Score ( = .009), and low transferrin (HR 2.336, 95% CI 1.173-4.654,  = .011) were independently associated with shorter OS, and depth of invasion pT4 ( = .015), presence of lymph node metastasis ( = .001), low hemoglobin ( = .034), and low transferrin (HR 2.638, 95% CI 1.113-5.043,  = .025) were independently associated with shorter CSS.

Conclusions: Preoperative serum transferrin in Stage I-III CRC patients was identified as a novel prognostic marker by univariate and multivariate analyses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ags3.12411DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034684PMC
March 2021

Sarcopenia and obesity in long-term survivors of childhood leukemia/lymphoma: a report from a single institution.

Jpn J Clin Oncol 2021 Jul;51(7):1100-1106

Department of Pediatrics, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan.

Background: The incidence and background factors of sarcopenia and obesity in long-term survivors of childhood leukemia/lymphoma were not clear in Japan.

Methods: Between August 2018 and September 2019, we recruited adults aged ≥18 years who had childhood leukemia/lymphoma. Blood sampling, body composition measurement by bioelectrical impedance analysis and grip strength test were performed.

Results: Among 81 adult survivors (34 men and 47 women) with a median age of 25.0 years, 9 (11%) had sarcopenia and 10 (12%) had obesity, of whom, 3 had metabolic syndrome. Sarcopenia was observed in 7 (21%) of 33 survivors with hematopoietic stem cell transplantation (HSCT) and 2 (4%) of 48 survivors without hematopoietic stem cell transplantation (P = 0.012). The incidence of obesity was significantly higher in the cranial radiotherapy (P = 0.021) and non-transplanted cases (P = 0.042). Univariate logistic regression analysis revealed that hematopoietic stem cell transplantation for sarcopenia (odds ratio, 6.19; 95% confidence interval, 1.2-32.0; P = 0.03) and cranial radiotherapy for obesity (odds ratio, 5.6; 95% confidence interval, 1.4-22.4; P = 0.015) were significantly associated. Hypertension was more prevalent among the obese survivors, and higher transaminase levels were found more in both the sarcopenia and obese survivors than in others.

Conclusions: Young adult survivors of childhood leukemia/lymphoma could be at risk of developing sarcopenia after hematopoietic stem cell transplantation and obesity after cranial radiotherapy. Further studies are required to assess the body composition of long-term survivors to find detailed risk factors of sarcopenia and metabolic syndrome.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jjco/hyab046DOI Listing
July 2021

Low-Dose Olanzapine Plus Granisetron and Dexamethasone for Carboplatin-Induced Nausea and Vomiting in Patients with Thoracic Malignancies: A Prospective Multicenter Phase II Trial.

Oncologist 2021 06 4;26(6):e1066-e1072. Epub 2021 May 4.

Department of Cardiology and Respiratory Medicine, Gifu University Graduate School of Medicine, Gifu, Gifu, Japan.

Background: Olanzapine is an inexpensive and durable agent for the treatment of chemotherapy-induced nausea and vomiting and is also superior to neurokinin-1 receptor antagonists in the control of nausea. This study aimed to investigate the efficacy and safety of a low dose of 5 mg olanzapine plus granisetron and dexamethasone for treatment of carboplatin (CBDCA)-induced nausea and vomiting in patients with thoracic malignancies.

Materials And Methods: We conducted a prospective, open-label, single-arm, multicenter, phase II trial in four centers in Japan. Registered patients were scheduled to receive area under the curve (AUC) ≥5 mg/mL per minute of CBDCA and had never received moderately to highly emetogenic chemotherapy. Patients received olanzapine 5 mg/day orally after supper for 4 days, in combination with granisetron and dexamethasone. Primary endpoint was complete response (CR; no emesis and no use of rescue medication) rate during the overall phase (0-120 hours).

Results: Between February 2018 and June 2020, 51 patients were enrolled, and 50 patients were evaluated. The CR rates in the overall (0-120 hours), acute (0-24 hours), and delayed phases (24-120 hours) were 94.0%, 100%, and 94.0%, respectively. No grade 3 or higher adverse effects of olanzapine were observed.

Conclusion: Prophylactic antiemetic therapy with a low dose of 5 mg olanzapine plus granisetron and dexamethasone showed durable efficacy with an acceptable safety profile. This three-drug combination appears to be a reasonable treatment approach in patients with thoracic malignancies receiving an AUC ≥5 mg/mL per minute of CBDCA-based regimen. Clinical trial identification number: UMIN000031267.

Implications For Practice: The results of this phase II trial indicated that the prophylactic administration of low-dose of 5 mg olanzapine combined with granisetron and dexamethasone has promising activity with acceptable safety profile in patients with thoracic malignancy receiving high-dose carboplatin chemotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/onco.13772DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176968PMC
June 2021

Prognostic Impact of Albumin-bilirubin (ALBI) Grade on Non-small Lung Cell Carcinoma: A Propensity-score Matched Analysis.

Anticancer Res 2021 Mar;41(3):1621-1628

Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Background/aim: Albumin-bilirubin (ALBI) grade is an indicator of liver dysfunction and is useful for predicting postoperative prognosis of hepatocellular carcinomas. However, the significance of ALBI grade in non-small cell lung carcinoma (NSCLC) has not been elucidated.

Patients And Methods: We analyzed 947 patients with pStage IA-IIIA NSCLC. We divided patients into ALBI grade 1 and grade 2/3 groups. We then analyzed the association of ABLI grade with clinicopathological characteristics and prognosis in NSCLC by using propensity-score matching.

Results: ALBI grade 2/3 was significantly associated with older age, male sex, advanced pT status, and histological type. Even after propensity-score matching, ALBI grade 2/3 patients had significantly worse cancer-specific survival (CSS) than ALBI grade 1 patients (5-year CSS: 87.3% versus 92.8%; p=0.0247). In multivariate analysis, ALBI grade 2/3 was an independent predictor of CSS (HR=1.9; 95%CI=1.11-3.11; p=0.0177).

Conclusion: ALBI grade was an independent prognostic factor in surgically resected NSCLC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21873/anticanres.14924DOI Listing
March 2021

Monitoring FTD in the peripheral blood mononuclear cells of elderly patients with metastatic colorectal cancer administered FTD plus bevacizumab as first-line treatment.

Cancer Sci 2021 Jun 3;112(6):2436-2441. Epub 2021 May 3.

Department of Surgery and Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Trifluridine/tipiracil (FTD/TPI) is an orally administrated anticancer drug with efficacy validated for patients with metastatic colorectal cancer (mCRC) or gastric cancer. FTD, a key component of FTD/TPI, exerts antitumor effects via its incorporation into DNA. Using specific antibodies against bromodeoxyuridine, FTD incorporation into DNA is detected in tumors and peripheral blood mononuclear cells (PBMC) of patients with mCRC who are administered FTD/TPI. The proportion of FTD-positive PBMC fluctuates according to the schedule of treatment, although the association between the proportion of FTD-positive PBMC and the clinical outcomes of patients is unknown. To answer this question, here we monitored the FTD-positive PBMC of 39 elderly patients with mCRC enrolled in KSCC1602, a single-arm phase 2 trial of FTD/TPI plus bevacizumab as a first-line treatment, for 1 month, during the first cycle of treatment. The median values and interquartile ranges of the percentage of FTD-positive PBMC on days 8, 15, and 29 were 39.3% (30.7%-52.2%), 66.9% (40.0%-75.3%), and 13.5% (5.7%-26.0%), respectively. Receiver operating characteristic analysis revealed that the percentage of FTD-positive PBMC on day 8 (the end of the first week of treatment) had moderate ability to accurately diagnose the occurrence of severe neutropenia and leukopenia within 1 month (area under the curve = 0.778 [95% confidence interval, 0.554-0.993]). This result suggests that excess FTD incorporation into PBMC at the initial phase of FTD/TPI plus bevacizumab treatment is a risk factor for early onset of severe hematological adverse events.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/cas.14904DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8177777PMC
June 2021

Precision length determination and in silico simulation in PCR of microsatellite repeat sequences.

Electrophoresis 2021 Jul 23;42(12-13):1323-1332. Epub 2021 Apr 23.

Cancer Genetics Laboratory, Clinical Research Institute, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan.

Despite being commonplace, polymerase chain reactions (PCRs) still contain many unknown aspects. One example is microsatellite PCR, which is now widely used for various purposes from ecology to cancer medicine. Since this category of repetitive DNA sequences induces polymerase slippage not only in vivo but also in vitro, microsatellite PCR products comprise a complex combination of DNA fragments with various lengths and have, therefore, been empirically interpreted. The primary obstacle for understanding microsatellite PCR was the intrinsic inaccuracy in sizing of DNA fragments in capillary electrophoresis (CE), which, however, has been overcome by elucidating intrinsic sizing errors in each fragment length range. Secondly, the slippage properties of the thermostable polymerases were first clarified in detail using primer extension assays. Furthermore, using the obtained slippage parameters and our original program, we have first reconstructed microsatellite PCR in silico. The entire processes of complex microsatellite PCR have, thus, been more clearly understood.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/elps.202100021DOI Listing
July 2021

Clinical impact of probiotics on the efficacy of anti-PD-1 monotherapy in patients with nonsmall cell lung cancer: A multicenter retrospective survival analysis study with inverse probability of treatment weighting.

Int J Cancer 2021 07 26;149(2):473-482. Epub 2021 Mar 26.

Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Fukuoka, Japan.

The gastrointestinal microbiota was reported as an important factor for the response to cancer immunotherapy. Probiotics associated with gastrointestinal dysbiosis and bacterial richness may affect the efficacy of cancer immunotherapy drugs. However, the clinical impact of probiotics on the efficacy of cancer immunotherapy in patients with nonsmall cell lung cancer (NSCLC) is poorly understood. The outcomes of 294 patients with advanced or recurrent NSCLC who received antiprogrammed cell death-1 (PD-1) therapy (nivolumab or pembrolizumab monotherapy) at three medical centers in Japan were analyzed in our study. We used inverse probability of treatment weighting (IPTW) to minimize the bias arising from the patients' backgrounds. The IPTW-adjusted Kaplan-Meier curves showed that progression-free survival (nonuse vs use: hazard ratio [HR] [95% confidence interval {CI}] = 1.73 [1.42-2.11], log-rank test P = .0229), but not overall survival (nonuse vs use: HR [95%CI] = 1.40 [1.13-1.74], log-rank test P = .1835), was significantly longer in patients who received probiotics. Moreover, the IPTW-adjusted univariate analyses showed that nonuse or use of probiotics was significantly associated with disease control (nonuse vs use: odds ratio [OR] [95%CI] = 0.51 [0.35-0.74], P = .0004) and overall response (nonuse vs use: OR [95%CI] = 0.43 [0.29-0.63], P < .0001). In this multicenter and retrospective study, probiotics use was associated with favorable clinical outcomes in patients with advanced or recurrent NSCLC who received anti-PD-1 monotherapy. The findings should be validated in a future prospective study.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ijc.33557DOI Listing
July 2021

Preoperative prognostic nutritional index level is associated with tumour-infiltrating lymphocyte status in patients with surgically resected lung squamous cell carcinoma.

Eur J Cardiothorac Surg 2021 07;60(2):393-401

Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Objectives: The prognostic nutritional index (PNI) is an indicator of systemic immune-nutritional condition and is a well-known prognostic biomarker in lung cancer patients. Tumour-infiltrating lymphocytes (TILs) is a specific histological feature of cancers, influencing an individual's immunological tumour responses. However, whether PNI can reflect lung cancer patients' prognosis through local immunity such as TIL is unclear.

Methods: We selected 64 lung squamous cell carcinoma patients who underwent curative operations. We investigated the significance of preoperative PNI level and evaluated the relationship between PNI and immune cells surrounding the lung cancer tissue using immunohistochemical analysis of a cluster of differentiation (CD)3, CD4, CD8 and CD68.

Results: A low-PNI level was significantly associated with a worse postoperative prognosis (P = 0.042). The PNI (hazard ratio 2.768, 95% confidence interval 1.320-5.957; P = 0.007) was an independent prognostic factor. The low-PNI group had a significantly shorter recurrence-free survival and overall survival (P = 0.013 and P = 0.002, log-rank test) compared with the high-PNI group. A significant positive correlation between PNI components including preoperative peripheral blood lymphocyte count and serum albumin concentration, and TILs, was observed. Absolute numbers of TILs in the preoperative high-PNI group were significantly increased compared with those in the preoperative low-PNI group (CD3+ cells; P = 0.002, CD4+ cells; P = 0.049 and CD8+ cells; P = 0.024).

Conclusions: The preoperative PNI level was strongly associated with the postoperative outcome in lung cancer patients. Considering the positive relationship between preoperative PNI level and TIL status, preoperative immune-nutritional condition may influence lung cancer patients' postoperative prognosis through local immunity as well as systemic immune response.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ejcts/ezab046DOI Listing
July 2021
-->