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1.
Oncology ; 102(7): 556-564, 2024.
Article in English | MEDLINE | ID: mdl-38142688

ABSTRACT

INTRODUCTION: The inflammatory burden index (IBI) serves as a prognostic marker for several cancers. Here, we evaluated the predictive value of preoperative IBI associated with the surgical and oncological outcomes of patients with esophageal cancer (EC). METHODS: The IBI was formulated as C-reactive protein × neutrophil/lymphocyte. We retrospectively analyzed preoperative IBI of 147 EC patients receiving esophagectomy between 2008 and 2018. Cox proportional hazards models and multivariable logistic regression were employed to identify independent risk factors of surgical site infection and prognosis. RESULTS: Increased preoperative IBI significantly correlated with higher tumor stage. Patients with high IBI experienced shorter overall survival (p = 0.0002) and disease-free survival (p = 0.002) compared with those with low IBI. In the adjusted Cox proportional hazards regression models, increased IBI served as an independent prognostic factor for overall survival (hazard ratio, 3.56; 95% confidence interval, 1.79-7.34; p = 0.0003) and disease-free survival (hazard ratio, 3.03; 95% confidence interval, 1.60-5.92; p = 0.007). Multivariable analysis identified preoperative high IBI which served as an independent risk factor for overall surgical site infection (odds ratio, 2.53; 95% confidence interval, 1.00-6.38; p = 0.049). CONCLUSION: Preoperative IBI may serve as a useful predictor of prognosis and surgical site infection of patients with EC after esophagectomy.


Subject(s)
C-Reactive Protein , Esophageal Neoplasms , Esophagectomy , Inflammation , Neutrophils , Humans , Esophageal Neoplasms/surgery , Esophageal Neoplasms/pathology , Esophageal Neoplasms/mortality , Male , Female , Middle Aged , Aged , Retrospective Studies , C-Reactive Protein/analysis , C-Reactive Protein/metabolism , Neutrophils/pathology , Prognosis , Risk Factors , Disease-Free Survival , Proportional Hazards Models , Preoperative Period , Surgical Wound Infection/etiology , Lymphocytes/pathology , Neoplasm Staging , Clinical Relevance
2.
Surg Today ; 54(4): 347-355, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37610628

ABSTRACT

PURPOSE: To determine the methylation level of the miR-124 promoter in non-neoplastic rectal mucosa of patients with pediatric-onset ulcerative colitis (UC) to predict UC-associated colorectal cancer (UC-CRC). METHODS: Between 2005 and 2017, non-neoplastic rectal tissue specimens were collected from 86 patients with UC, including 13 patients with UC-CRC; cancer tissues were obtained from the latter group. The methylation status of the miR-124 promoter was quantified using bisulfite pyrosequencing and compared between pediatric- and adult-onset UC patients. RESULTS: Patients with pediatric-onset UC experienced a significantly shorter disease duration than those with adult-onset UC. The levels of miR-124 promoter methylation in non-neoplastic rectal mucosa were positively correlated with the age at the diagnosis and duration of UC. The rate of increase in miR-124 methylation was accelerated in patients with pediatric-onset UC compared to those with adult-onset UC. Furthermore, the miR-124 methylation levels in non-neoplastic rectal mucosa were significantly higher in patients with UC-CRC than in those with UC alone (P = 0.02). A receiver operating characteristic analysis revealed that miR-124 methylation in non-neoplastic tissue discriminated between patients with pediatric-onset UC with or without CRC. CONCLUSION: miR-124 methylation in non-neoplastic rectal mucosa may be a useful biomarker for identifying patients with pediatric-onset UC who face the highest risk of developing UC-CRC.


Subject(s)
Colitis, Ulcerative , Colitis-Associated Neoplasms , Colorectal Neoplasms , MicroRNAs , Adult , Humans , Child , DNA Methylation , MicroRNAs/genetics , Colitis, Ulcerative/complications , Colitis, Ulcerative/genetics , Biomarkers , Mucous Membrane , Colorectal Neoplasms/genetics , Intestinal Mucosa
3.
Gan To Kagaku Ryoho ; 50(3): 363-365, 2023 Mar.
Article in Japanese | MEDLINE | ID: mdl-36927910

ABSTRACT

A 78-year-old man presenting with a chief complaint of discomfort was found to have advanced gastric cancer invading pancreatic body, and with the metastasis of paraaortic lymph node(No. 16). After 3 courses of the S-1 plus oxaliplatin regimen, CT scan showed the disappearance of invasion to pancreatic body, and the No. 16 lymph node. Then total gastrectomy(D2+No. 19+No. 16a1+No. 16a2), Roux-en-Y reconstruction and cholecystectomy were undergoing. Histological assessment for treatment response showed Grade 1a, and we finally diagnosed gastric cancer: MU, Post, type 2, 30×20 mm, tub1>por1, ypT3, ypN1, ycM0, ypStage ⅡB. The postoperative course was uneventful, and the patient was discharged from the hospital on postoperative day 19. S-1 as adjuvant chemotherapy was performed for 12 months, and no recurrence was recognized for 5 years and 9 months after operation.


Subject(s)
Stomach Neoplasms , Male , Humans , Aged , Stomach Neoplasms/drug therapy , Stomach Neoplasms/surgery , Stomach Neoplasms/pathology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Lymph Nodes/pathology , Lymph Node Excision , Chemotherapy, Adjuvant , Gastrectomy
4.
Gan To Kagaku Ryoho ; 50(13): 1866-1868, 2023 Dec.
Article in Japanese | MEDLINE | ID: mdl-38303234

ABSTRACT

In our department, total neoadjuvant therapy(TNT), which is a combination of preoperative chemotherapy and preoperative chemoradiotherapy(nCRT), has been introduced for the purpose of local and systemic disease control for lower rectal cancer. For patients in whom a clinical complete response(cCR)was obtained by TNT, we avoid the surgery and preserve organs, and follow-up strictly under the informed consent(watch and wait). In addition, for patients with remarkably reduced primary lesions(near cCR)without lymphadenopathy after TNT, the option of omitting total mesorectal excision (TME)and performing organ preservation by local excision can be introduced. Here, we report a case in which near cCR was obtained by TNT and organ preservation was performed by local excision. A 67-year-old man with lower rectal cancer(AV 5 cm, 15 mm, type 2, cT2N0M0, cStage Ⅰ)was referred to our department with a desire to preserve the anus. TNT with nCRT→CAPOX was performed, and near cCR was obtained. After that, full thickness local excision of the residual disease was performed by transanal minimally invasive surgery(TAMIS). The final pathological diagnosis was Rb, 0.7 mm, por2, ypT1a, ypPM0, ypDM0, ypRM0. No recurrence is recognized for 3 years and 10 months after the operation.


Subject(s)
Neoadjuvant Therapy , Rectal Neoplasms , Male , Humans , Aged , Treatment Outcome , Organ Preservation , Retrospective Studies , Neoplasm Recurrence, Local/drug therapy , Watchful Waiting , Rectal Neoplasms/drug therapy , Rectal Neoplasms/surgery , Chemoradiotherapy
5.
Br J Cancer ; 126(2): 228-237, 2022 02.
Article in English | MEDLINE | ID: mdl-34675398

ABSTRACT

BACKGROUND: While emerging evidence indicates that N6-methyladenosine (m6A) regulators play crucial roles in cancer progression, their clinical significance in gastric cancer (GC) has thus far not been elucidated. METHODS: We investigated the expression of the m6A regulator genes and their prognostic potential in a large clinical cohort of 173 GC patients using qRT-PCR assays. In addition, we undertook a series of in-vitro and in-vivo functional studies to investigate the oncogenic role of FTO. RESULTS: GC patients with low expression of METTL3, METTL14, ALKBH5, WTAP and YTHDF1 demonstrated significantly poor OS, while patients with high FTO expression exhibited markedly worse OS. Furthermore, the cumulative risk-score derived from these gene panel also significantly associated with poor OS, with a corresponding hazard ratio of 5.47 (95% CI: 3.18-9.41, p < 0.0001). We observed that FTO expression was frequently upregulated in GC cell lines, with epithelial-mesenchymal-transition (EMT) features. FTO knockdown in HGC27 and AGS cells inhibited cell proliferation and migratory potential, while its overexpression in MKN28 cells resulted in enhanced proliferation and migration. Finally, confirming our in-vitro findings, FTO suppression led to significant tumour growth inhibition in a HGC27 xenograft model. CONCLUSIONS: We demonstrate that m6A regulators may serve as promising prognostic biomarkers in GC. Our functional studies reveal that FTO is an important oncogene and may be a promising therapeutic target associated with EMT-alterations in gastric cancer.


Subject(s)
Adenosine/analogs & derivatives , Alpha-Ketoglutarate-Dependent Dioxygenase FTO/metabolism , Biomarkers/metabolism , DNA Methylation , Gene Expression Regulation, Neoplastic , Stomach Neoplasms/pathology , Adenosine/metabolism , Adult , Aged , Aged, 80 and over , Alpha-Ketoglutarate-Dependent Dioxygenase FTO/genetics , Animals , Cell Movement , Cell Proliferation , Female , Humans , Male , Mice , Mice, Nude , Middle Aged , Prognosis , ROC Curve , Stomach Neoplasms/genetics , Stomach Neoplasms/metabolism , Survival Rate , Xenograft Model Antitumor Assays , Young Adult
6.
Cancer Immunol Immunother ; 71(11): 2743-2755, 2022 Nov.
Article in English | MEDLINE | ID: mdl-35429246

ABSTRACT

The aim of this study was to determine the efficacy and the biomarkers of the CHP-NY-ESO-1 vaccine complexed with full-length NY-ESO-1 protein and a cholesteryl pullulan (CHP) in patients with esophageal squamous cell carcinoma (ESCC) after surgery. We conducted a randomized phase II trial. Fifty-four patients with NY-ESO-1-expressing ESCC who underwent radical surgery following cisplatin/5-fluorouracil-based neoadjuvant chemotherapy were assigned to receive either CHP-NY-ESO-1 vaccination or observation as control. Six doses of CHP-NY-ESO-1 were administered subcutaneously once every two weeks, followed by nine more doses once every four weeks. The endpoints were disease-free survival (DFS) and safety. Exploratory analysis of tumor tissues using gene-expression profiles was also performed to seek the biomarker. As there were no serious adverse events in 27 vaccinated patients, we verified the safety of the vaccine. DFS in 2 years were 56.0% and 58.3% in the vaccine arm and in the control, respectively. Twenty-four of 25 patients showed NY-ESO-1-specific IgG responses after vaccination. Analysis of intra-cohort correlations among vaccinated patients revealed that 5% or greater expression of NY-ESO-1 was a favorable factor. Comprehensive analysis of gene expression profiles revealed that the expression of the gene encoding polymeric immunoglobulin receptor (PIGR) in tumors had a significantly favorable impact on outcomes in the vaccinated cohort. The high PIGR-expressing tumors that had higher NY-ESO-1-specific IgA response tended to have favorable prognosis. These results suggest that PIGR would play a major role in tumor immunity in an antigen-specific manner during NY-ESO-1 vaccinations. The IgA response may be relevant.


Subject(s)
Cancer Vaccines , Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Receptors, Polymeric Immunoglobulin , Antibodies, Neoplasm , Antigens, Neoplasm , Cisplatin , Esophageal Squamous Cell Carcinoma/drug therapy , Fluorouracil , Glucans , Humans , Immunoglobulin A , Immunoglobulin G , Membrane Proteins , Prognosis
7.
Gan To Kagaku Ryoho ; 49(3): 297-299, 2022 Mar.
Article in Japanese | MEDLINE | ID: mdl-35299186

ABSTRACT

The watch and wait strategy(W&W)is optional non-operative management for lower advanced rectal cancer patients who have achieved clinical complete response(cCR)following neoadjuvant treatment. However, the clinical implication of surgical intervention for the primary lesion is not well elucidated when distant metastasis appears with complete remission of the primary lesion. We report a case of a 47-year-old-woman with lower rectal cancer presenting inguinal lymph node metastasis after total neoadjuvant therapy(TNT)and managed through W&W after achieving cCR following chemotherapy. TNT was performed as a preoperative treatment for lower advanced rectal cancer, cT3N2aM0, cStage Ⅲb. Although the primary lesion and mesenteric lymph node metastasis completely disappeared, bilateral inguinal lymph node metastasis appeared immediately after TNT. The patient was treated with FOLFOX plus panitumumab for rectal cancer with RAS and BRAF wild-type. Four months after chemotherapy, the inguinal lymph node metastasis disappeared, and W&W was used for the management. She stayed alive without recurrence 1 year and 9 months after chemotherapy.


Subject(s)
Neoadjuvant Therapy , Rectal Neoplasms , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Female , Humans , Lymph Nodes/pathology , Lymphatic Metastasis , Middle Aged , Rectal Neoplasms/drug therapy , Rectal Neoplasms/surgery
8.
Jpn J Clin Oncol ; 51(2): 305-309, 2021 Feb 08.
Article in English | MEDLINE | ID: mdl-33017014

ABSTRACT

This prospective multicenter non-randomized phase III study aims to evaluate the long-term outcome of sentinel node navigation surgery for early gastric cancer compared with conventional distal or total gastrectomy. Clinically diagnosed primary T1N0M0 gastric cancer patients with a single lesion (≤40 mm) and without previous endoscopic treatment will be enrolled in this study. Sentinel nodes are identified by dye and radioisotope tracers and are subjected to intraoperative rapid pathology. For patients with negative sentinel node metastasis, individualized surgery consisting of limited stomach resection and sentinel node basin dissection is performed, while standard gastrectomy with D2 lymph node dissection is employed for the positive sentinel node patients. A total of 225 patients will be accrued from 13 hospitals that have experience in sentinel node mapping. The primary endpoint is 5-year relapse-free survival. The secondary endpoints are overall survival, sentinel node detection rate, diagnostic accuracy for sentinel node, distribution of sentinel nodes and metastatic sentinel node/non-sentinel node, and postoperative quality of life.


Subject(s)
Sentinel Lymph Node Biopsy , Sentinel Lymph Node/surgery , Stomach Neoplasms/surgery , Endpoint Determination , Female , Follow-Up Studies , Humans , Lymph Node Excision , Male , Neoplasm Recurrence, Local/pathology , Prospective Studies , Quality of Life , Sentinel Lymph Node/pathology , Stomach Neoplasms/pathology
9.
Int J Clin Oncol ; 26(4): 708-716, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33415573

ABSTRACT

PURPOSE: The clinical significance of the platelet count × C-reactive protein level multiplier (P-CRP) in patients with locally advanced rectal cancer (LARC) undergoing neoadjuvant chemoradiotherapy followed by curative surgery has not been fully evaluated. METHODS: In this retrospective study, the correlation between the P-CRP and prognosis was evaluated in 135 patients with LARC. We also performed a subgroup analysis limited to patients with pathological TNM stage III [ypN(+)] LARC. RESULTS: The cut-off value of the P-CRP for prognosis was set at 4.11. The high and low P-CRP groups comprised 39 (28.89%) and 96 (71.11%) patients, respectively. Among the investigated clinicopathological factors, the serum carcinoembryonic antigen level and presence of recurrence were significantly associated with the P-CRP value. In the Kaplan-Meier analysis, both overall survival (OS) and disease-free survival (DFS) were shorter in the high P-CRP group (p < 0.0001 and p = 0.0002, respectively; log-rank test). Multivariate analysis using a Cox proportional hazards model showed that a high P-CRP was an independent prognostic factor for OS [hazard ratio (HR) 29.20; 95% confidence interval (CI), 3.42-294.44; p = 0.0024] and DFS (HR 5.89; 95%CI 1.31-22.69; p = 0.023) in patients with LARC. In addition, a high P-CRP predicted poor OS and DFS in patients with pathological TNM stage III [ypN(+)] LARC (p = 0.0001 and p = 0.0012, respectively; log-rank test). CONCLUSIONS: The P-CRP is a promising predictor of survival and recurrence in patients with LARC treated by neoadjuvant chemoradiotherapy followed by curative surgery.


Subject(s)
Neoadjuvant Therapy , Rectal Neoplasms , C-Reactive Protein , Chemoradiotherapy , Disease-Free Survival , Humans , Neoplasm Recurrence, Local , Neoplasm Staging , Prognosis , Rectal Neoplasms/drug therapy , Rectal Neoplasms/pathology , Retrospective Studies
10.
World J Surg Oncol ; 19(1): 34, 2021 Jan 30.
Article in English | MEDLINE | ID: mdl-33516219

ABSTRACT

AIM: The clinical significance of the geriatric nutritional risk index (GNRI) in locally advanced rectal cancer (LARC) patients undergoing preoperative chemoradiotherapy (CRT) followed by curative surgery has not been comprehensively evaluated. METHODS: This retrospective study enrolled 93 LARC patients diagnosed with clinical lymph node metastasis. The GNRI formula was as follows: 1.489 × albumin (g/l) + 41.7 × current weight/ideal weight. Patients were categorized as GNRI low (GNRI < 104.25) or high (GNRI > 104.25) according to the receiver operating characteristic (ROC) curve for survival analysis. The impact of GNRI status on the prognostic outcomes of curative surgery for LARC was examined. RESULTS: There were 55 (59.14%) and 38 (40.86%) patients in the GNRI high and low groups, respectively. Of the investigated demographic factors, age, pathological tumor invasion, and presence of recurrence were significantly associated with the GNRI value. In Kaplan-Meier analysis, overall survival (OS) and disease-free survival (DFS) were significantly shorter in the GNRI low group (OS: p = 0.00020, DFS: p = 0.0044, log-rank test). Multivariate analysis using a Cox proportional hazards model showed that a low GNRI was an independent risk factor for poor OS (hazard ratio (HR) = 3.22; 95% confidence interval (CI), 1.37-8.23; p = 0.0068) and DFS (HR = 2.32; 95%CI = 1.15-4.79; p = 0.018). Although use of adjuvant therapy has no impact on prognosis (OS: p = 0.26, DFS: p = 0.29), low GNRI showed shorter OS and DFS in patients with pathological lymph node metastasis [ypN(+)] (OS: p = 0.033, DFS: p = 0.032, log-rank test). CONCLUSIONS: GNRI is a useful marker for LARC patients diagnosed with clinical lymph node metastasis and treated by preoperative CRT followed by curative surgery. GNRI is a useful tool to identify high risk of recurrence for improving the survival in LARC patients.


Subject(s)
Neoplasm Recurrence, Local , Rectal Neoplasms , Aged , Chemoradiotherapy , Humans , Neoplasm Recurrence, Local/therapy , Prognosis , Rectal Neoplasms/drug therapy , Retrospective Studies
11.
Surg Today ; 51(12): 1906-1917, 2021 Dec.
Article in English | MEDLINE | ID: mdl-33954875

ABSTRACT

PURPOSE: Systemic inflammatory response influences cancer development and perioperative surgical stress can affect the survival of patients with colorectal cancer (CRC). We developed a system to cumulatively assess perioperative inflammatory response and compare the prognostic value of various cumulative inflammatory and nutritional markers in patients with CRC. METHODS: We assessed perioperative cumulative markers using the trapezoidal area method in 307 patients who underwent surgery for CRC and analyzed the results statistically. RESULTS: The cumulative lymphocyte to C-reactive protein (CRP) ratio (LCR) predicted survival more accurately than other well-established markers (sensitivity: 80.0%, specificity: 69.3%; area under the curve (AUC): 0.779; P < 0.001). A low cumulative LCR was correlated with factors associated with disease development, including undifferentiated histology, advanced T stage, lymph node metastasis, distant metastasis, and advanced TNM stage classification. A decreased cumulative LCR was an independent prognostic factor for both overall survival (OS) (Hazard Ratio (HR):5.21, 95% confidence interval [CI] 2.42-11.2; P < 0.0001) and disease-free survival (DFS) (HR: 1.88, 95% CI 1.07-3.31; P = 0.02), and its prognostic significance was verified in a different clinical setting. The cumulative LCR was correlated negatively with the intraoperative bleeding volume (P < 0.0001, R = -0.4). Combined analysis of cumulative and preoperative LCR could help stratify risk for the oncological outcomes of CRC patients. CONCLUSIONS: The findings of this study demonstrate the value of the cumulative LCR in the postoperative management of patients with CRC.


Subject(s)
C-Reactive Protein , Colorectal Neoplasms/diagnosis , Lymphocyte Count , Adult , Aged , Aged, 80 and over , Biomarkers/blood , Colorectal Neoplasms/mortality , Colorectal Neoplasms/pathology , Female , Humans , Male , Middle Aged , Neoplasm Staging , Perioperative Period , Predictive Value of Tests , Prognosis , Risk , Survival Rate
12.
Surg Today ; 51(5): 745-755, 2021 May.
Article in English | MEDLINE | ID: mdl-33130991

ABSTRACT

PURPOSE: We recently revealed the preoperative lymphocyte C-reactive protein ratio (LCR) to be a new marker for predicting various outcomes in malignancies. The aim of our present study was to clarify the potential utility of the preoperative LCR for predicting the perioperative risk and oncological outcome in esophageal cancer patients. METHODS: We analyzed the preoperative LCR from 153 esophageal cancer patients to clarify its clinical relevance. RESULTS: The preoperative LCR was significantly decreased in a stage-dependent manner, and a decreased preoperative LCR was significantly associated with the occurrence of postoperative surgical site infection. Esophageal cancer patients with a low LCR showed a poor outcome in both the overall survival and disease-free survival compared with those who had a high LCR. Multivariate analyses showed that a decreased LCR was an independent prognostic factor for both a poor overall survival and disease-free survival. A decreased preoperative LCR was an independent predictive factor for postoperative surgical site infection and significantly correlated with nutritional and inflammatory indicators. In addition, the LCR was useful for identifying esophageal cancer patients likely to have a poor outcome among patients with and without neoadjuvant chemotherapy. CONCLUSIONS: Assessing the preoperative LCR might help physicians identify populations at high risk for perioperative complication and oncological outcomes, and determine individualized perioperative therapeutic strategies.


Subject(s)
C-Reactive Protein/metabolism , Esophageal Neoplasms/diagnosis , Esophageal Neoplasms/surgery , Biomarkers/blood , Disease-Free Survival , Esophageal Neoplasms/mortality , Female , Humans , Inflammation , Lymphocytes/metabolism , Male , Nutritional Status , Postoperative Complications/diagnosis , Predictive Value of Tests , Preoperative Period , Risk , Surgical Wound Infection/diagnosis , Treatment Outcome
13.
Esophagus ; 18(2): 228-238, 2021 04.
Article in English | MEDLINE | ID: mdl-32743739

ABSTRACT

BACKGROUND: Recurrent laryngeal nerve paralysis (RLNP) after thoracoscopic esophagectomy for esophageal cancer (EC) is known to be a major complication leading to poor quality of life. RLNP is mainly associated with surgical procedures performed near the RLN. Therefore, with focus on the region of the RLN, we used preoperative computed tomography to investigate the risk factors of RLNP in patients with EC undergoing thoracoscopic esophagectomy. METHODS: We retrospectively examined 77 EC patients who underwent thoracoscopic esophagectomy in the prone position at our department between January 2010 and December 2018. Bilateral cross-sectional areas (mm2) of the fatty tissue around the RLN at the level of the lower pole of the thyroid gland were measured on preoperative axial computed tomography (CT) images. Univariate and multivariate logistic regression analysis was used to evaluate the association between the incidence of RLNP and patient clinical factors, including the cross-sectional areas. RESULTS: RLNP occurred in 24 of 77 patients (31.2%). The incidence of RLNP was significantly more frequent on the left side than on the right. (26% vs. 5.2%, respectively). Univariate analysis identified the following left RLNP risk factors: intrathoracic operative time (> 235 min), and area around the RLN (> 174.3 mm2). Multivariate analysis found that the area around the RLN was an independent risk factor of left RLNP. CONCLUSION: An increased area around the RLN measured on an axial CT view at the level of the lower pole of the thyroid gland was a risk factor of RLNP in EC patients undergoing thoracoscopic esophagectomy in the prone position.


Subject(s)
Esophageal Neoplasms , Vocal Cord Paralysis , Esophageal Neoplasms/complications , Esophagectomy/adverse effects , Esophagectomy/methods , Humans , Prone Position , Quality of Life , Recurrent Laryngeal Nerve/surgery , Retrospective Studies , Tomography/adverse effects , Tomography, X-Ray Computed , Vocal Cord Paralysis/epidemiology , Vocal Cord Paralysis/etiology
14.
Ann Surg ; 272(2): 342-351, 2020 08.
Article in English | MEDLINE | ID: mdl-32675548

ABSTRACT

BACKGROUND: Systemic inflammation via host-tumor interactions is currently recognized as a hallmark of cancer. The aim of this study was to evaluate the prognostic value of various combinations of inflammatory factors using preoperative blood, and to assess the clinical significance of our newly developed inflammatory score in colorectal cancer (CRC) patients. METHOD: In total 477 CRC patients from the discovery and validation cohorts were enrolled in this study. We assessed the predictive impact for recurrence using a combination of nine inflammatory markers in the discovery set, and focused on lymphocyte-C-reactive protein ratio (LCR) to elucidate its prognostic and predictive value for peri-operative risk in both cohorts. RESULTS: A combination of lymphocytic count along with C-reactive protein levels demonstrated the highest correlation with recurrence compared with other parameters in CRC patients. Lower levels of preoperative LCR significantly correlated with undifferentiated histology, advanced T stage, presence of lymph node metastasis, distant metastasis, and advanced stage classification. Decreased preoperative LCR (using an optimal cut-off threshold of 6000) was an independent prognostic factor for both disease-free survival and overall survival, and emerged as an independent risk factor for postoperative complications and surgical-site infections in CRC patients. Finally, we assessed the clinical feasibility of LCR in an independent validation cohort, and confirmed that decreased preoperative LCR was an independent prognostic factor for both disease-free survival and overall survival, and was an independent predictor for postoperative complications and surgical-site infections in CRC patients. CONCLUSION: Preoperative LCR is a useful marker for perioperative and postoperative management of CRC patients.


Subject(s)
Biomarkers, Tumor/blood , C-Reactive Protein/metabolism , Colorectal Neoplasms/blood , Colorectal Neoplasms/surgery , Lymphocytes/metabolism , Adult , Aged , Cohort Studies , Colorectal Neoplasms/mortality , Colorectal Neoplasms/pathology , Female , Hospitals, University , Humans , Male , Middle Aged , Neoplasm Invasiveness/pathology , Neoplasm Staging , Predictive Value of Tests , Prognosis , Retrospective Studies , Survival Analysis , Treatment Outcome
15.
Cancer Immunol Immunother ; 69(12): 2533-2546, 2020 Dec.
Article in English | MEDLINE | ID: mdl-32577816

ABSTRACT

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


Subject(s)
B7-H1 Antigen/metabolism , Biomarkers, Tumor/metabolism , CTLA-4 Antigen/metabolism , Colorectal Neoplasms/mortality , Adult , Aged , Aged, 80 and over , B7-H1 Antigen/blood , B7-H1 Antigen/immunology , Biomarkers, Tumor/blood , Biomarkers, Tumor/immunology , CTLA-4 Antigen/blood , CTLA-4 Antigen/immunology , Colon/immunology , Colon/pathology , Colon/surgery , Colorectal Neoplasms/blood , Colorectal Neoplasms/immunology , Colorectal Neoplasms/surgery , Disease-Free Survival , Female , Humans , Kaplan-Meier Estimate , Lymphocytes, Tumor-Infiltrating/immunology , Lymphocytes, Tumor-Infiltrating/metabolism , Male , Middle Aged , Neoplasm Staging , Prognosis , Rectum/immunology , Rectum/pathology , Rectum/surgery , Retrospective Studies
16.
Ann Surg Oncol ; 27(1): 259-267, 2020 Jan.
Article in English | MEDLINE | ID: mdl-31414294

ABSTRACT

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


Subject(s)
Crohn Disease/pathology , Lymphocytes/pathology , Nutritional Status , Stomach Neoplasms/immunology , Stomach Neoplasms/pathology , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/immunology , CD8-Positive T-Lymphocytes , Crohn Disease/immunology , Female , Humans , Lymphocyte Count , Lymphocytes, Tumor-Infiltrating/immunology , Male , Middle Aged , Multivariate Analysis , Neoplasm Recurrence, Local/pathology , Neoplasm Staging , Nutrition Assessment , Prognosis , Stomach Neoplasms/mortality , Survival Rate
17.
Dis Colon Rectum ; 63(9): 1242-1250, 2020 09.
Article in English | MEDLINE | ID: mdl-33216495

ABSTRACT

BACKGROUND: The advanced lung cancer inflammation index is considered a useful prognostic biomarker of clinical outcomes in patients with malignancies. However, the prognostic value of the advanced lung cancer index in patients with colorectal cancer who underwent surgical resection remains unclear. OBJECTIVE: In this study, we evaluated the prognostic value of the advanced lung cancer index in patients with colorectal cancer. DESIGN: Prospectively obtained data of patients with colorectal cancer were retrospectively evaluated to clarify the clinical relevance of the advanced lung cancer index. SETTINGS: We conducted this study at a single expert center. PATIENTS: We enrolled 298 patients with colorectal cancer who underwent surgical resection in this retrospective study. MAIN OUTCOME MEASURES: The primary outcome was the clinical relevance of the advanced lung cancer index in patients with rectal cancer. RESULTS: Low status of advanced lung cancer index was significantly correlated with undifferentiated histology (p = 0.004), T stage progression (p < 0.001), R1/R2 resection for primary surgery (p = 0.004), and distant metastasis (p < 0.001). Multivariate analysis showed that low advanced lung cancer index status was an independent prognostic factor for both overall survival (HR = 3.21 (95% CI, 1.97-5.19); p < 0.001) and disease-free survival (HR = 2.13 (95% CI, 1.23-3.63); p = 0.008) in patients with colorectal cancer. Furthermore, the clinical burden of the advanced lung cancer index was consistent between sexes, and its prognostic value was verified in patients with clinically relevant stage III colorectal cancer. LIMITATIONS: The present study had several limitations, including retrospective observation and a small sample size of Japanese patients from a single institution. CONCLUSIONS: The advanced lung cancer index could be a useful prognostic indicator of clinical outcomes in patients who underwent surgical resection for colorectal cancer. See Video Abstract at http://links.lww.com/DCR/B267. EL ÍNDICE AVANZADO DE INFLAMACIÓN DEL CÁNCER DE PULMÓN, PREDICE LOS RESULTADOS DE LOS PACIENTES CON CÁNCER COLORRECTAL DESPUÉS DE LA RESECCIÓN QUIRÚRGICA: El índice avanzado de inflamación del cáncer de pulmón, es considerado como un útil biomarcador pronóstico, en los resultados clínicos de pacientes con neoplasias malignas. Sin embargo, aún no está claro el valor pronóstico del índice avanzado de cáncer de pulmón, en pacientes con cáncer colorrectal sometidos a resección quirúrgica.Evaluar el valor pronóstico del índice avanzado del cáncer de pulmón, en pacientes con cáncer colorrectal.Los datos obtenidos prospectivamente de pacientes con cáncer colorrectal, fueron evaluados retrospectivamente, para aclarar la relevancia clínica del índice avanzado del cáncer de pulmónEstudio realizado en un solo centro experto.Estudio retrospectivo, incluyendo 298 pacientes con cáncer colorrectal, sometidos a resección quirúrgica.El resultado primario fue la relevancia clínica del índice avanzado de cáncer de pulmón, en pacientes con cáncer rectal.Un índice avanzado de cáncer de pulmón bajo, se correlacionó significativamente con la histología indiferenciada (p = 0.004), la progresión de la etapa T (p <0.001), la resección R1 / R2 para cirugía primaria (p = 0.004) y la metástasis a distancia (p <0.001). El análisis multivariante mostró que el índice avanzado de cáncer de pulmón bajo, era un factor pronóstico independiente, tanto para la supervivencia general (HR = 3.21 IC 95% 1.97-5.19 p <0.001) como para la supervivencia libre de enfermedad (HR = 2.13, IC 95% 1.23-3.63, p = 0,008), en pacientes con cáncer colorrectal. Además, la carga clínica del índice avanzado de cáncer de pulmón, fue consistente entre los sexos y su valor pronóstico se verificó clínicamente relevante, en pacientes con cáncer colorrectal en estadio III.El presente estudio tuvo varias limitaciones, incluyendo la observación retrospectiva y la pequeña muestra de pacientes japoneses, en una sola institución.El índice avanzado de cáncer de pulmón, podría ser un indicador pronóstico útil, en los resultados clínicos de pacientes sometidos a resección quirúrgica por cáncer colorrectal. Consulte Video Resumen http://links.lww.com/DCR/B267.


Subject(s)
Adenocarcinoma/surgery , Colorectal Neoplasms/surgery , Lymphocytes , Neutrophils , Serum Albumin/metabolism , Adenocarcinoma/blood , Adenocarcinoma/pathology , Adult , Aged , Aged, 80 and over , Body Mass Index , Colorectal Neoplasms/blood , Colorectal Neoplasms/pathology , Disease-Free Survival , Female , Humans , Inflammation/blood , Japan , Leukocyte Count , Lymphocyte Count , Male , Margins of Excision , Middle Aged , Neoplasm Grading , Neoplasm Metastasis , Neoplasm Staging , Nutritional Status , Prognosis , Proportional Hazards Models , Retrospective Studies , Survival Rate
18.
Gastric Cancer ; 23(4): 716-724, 2020 07.
Article in English | MEDLINE | ID: mdl-31927674

ABSTRACT

BACKGROUND: Standard gastrectomy with systematic lymphadenectomy as an additional surgery after endoscopic resection (ER) causes a deterioration in long-term quality of life. If the sentinel lymph node (SN) basin concept can be applied in post-ER gastric cancer, minimal surgery can be applied without reducing the curability. This retrospective multicenter cohort study aimed to verify the validity of the SN basin concept in post-ER gastric cancer. PATIENTS AND METHODS: Individual data of 132 patients who underwent SN mapping after ER were collected from 8 university hospitals in Japan from 2001 to 2016. Tracers were injected endoscopically in the submucosal layer at four sites around the post-ER scar. We compared the SN basin distribution of post-ER gastric cancer with that of 275 patients with non-ER gastric cancer. RESULTS: Two cases of SN were unidentified, both involving a single tracer (SN detection rate: 98.5%). Nine cases (6.8%) of lymph node metastasis were found, of which eight had a metastatic lymph node within the SNs and one had a non-SN metastasis within the SN basin. The diagnostic sensitivity of SN mapping for lymph node metastasis was 88.9% in post-ER group and 95.7% in non-ER group (P = 0.490); the accuracy was 99.2% and 99.6% (P = 0.539), respectively. Regarding the SN basin, no significant intergroup differences were found regardless of the primary tumor location. CONCLUSIONS: Our findings clarified the feasibility of SN mapping based on the SN basin concept in patients with gastric cancer who previously underwent ER.


Subject(s)
Early Detection of Cancer/methods , Gastrectomy/methods , Gastroscopy/methods , Lymph Node Excision/methods , Sentinel Lymph Node Biopsy/methods , Sentinel Lymph Node/pathology , Stomach Neoplasms/pathology , Adult , Aged , Aged, 80 and over , Female , Follow-Up Studies , Humans , Male , Middle Aged , Prognosis , Retrospective Studies , Sentinel Lymph Node/surgery , Stomach Neoplasms/surgery
19.
Surg Today ; 50(6): 551-559, 2020 Jun.
Article in English | MEDLINE | ID: mdl-31863190

ABSTRACT

PURPOSE: The clinical significance of the red blood cell distribution width (RDW) in patients with rectal cancer undergoing preoperative chemoradiotherapy (CRT) followed by surgery has not been fully evaluated. METHODS: In this retrospective study, we investigated the association between the RDW and the prognosis in 120 patients with locally advanced rectal cancer (LARC). We also performed a subgroup analysis limited to patients with pathological TNM stage I-II (ypN[-]) LARC. RESULTS: The RDW standard deviation was used to evaluate the RDW. We set 47.1% as the cut-off value of the RDW for the assessment of the prognosis. The RDW exhibited a significant negative relationship with the serum hemoglobin and albumin levels. An elevated RDW was an independent prognostic factor for the overall survival (OS) and disease-free survival (DFS) in patients with LARC. In addition, an elevated RDW predicted a poor OS and DFS in patients with pathological TNM stage I-II (ypN[-]) LARC. CONCLUSIONS: The RDW is a promising predictor of a poor survival and recurrence in patients with LARC treated by CRT.


Subject(s)
Biomarkers, Tumor/blood , Chemoradiotherapy, Adjuvant , Digestive System Surgical Procedures , Erythrocyte Count , Rectal Neoplasms/diagnosis , Rectal Neoplasms/therapy , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Neoplasm Staging , Preoperative Period , Prognosis , Rectal Neoplasms/blood , Retrospective Studies
20.
Surg Today ; 50(3): 223-231, 2020 Mar.
Article in English | MEDLINE | ID: mdl-31485750

ABSTRACT

PURPOSE: Gastric cancer (GC) is a common malignancy, especially in East Asian countries. There is emerging evidence that circulating neutrophil and platelet levels correlate with cancer progression. We evaluated the short- and long-term outcomes of GC patients systemically, to compare the original neutrophil-platelet score (NPS) and our modified NPS (mNPS). METHODS: We analyzed the original pre-operative NPS and the mNPS of 621 GC patients. RESULTS: Racial differences between the United Kingdom and East Asian countries accounted for compelling deviation in classification using the original NPS, which could not reliably stratify the prognoses of Japanese GC patients. We developed the mNPS using appropriate cutoff levels for pre-operative neutrophils and platelets, and demonstrated that the pre-operative mNPS was significantly correlated with all of the well-established clinicopathological factors for disease development, including advanced T stage, venous and lymphatic vessel invasion, lymph node/peritoneal /distant metastasis, and tumor-node-metastasis stage. The pre-operative mNPS could stratify prognostication for both overall survival (OS) and disease-free survival (DFS): a high pre-operative mNPS was an independent prognostic factor for the OS and DFS of GC patients and also an independent predictor of post-operative surgical site infection after gastrectomy. CONCLUSION: Calculating the mNPS could help clinicians to stratify the surgical and oncological risks of patients with GC.


Subject(s)
Biomarkers, Tumor/blood , Leukocyte Count , Neutrophils , Platelet Count , Stomach Neoplasms/diagnosis , Stomach Neoplasms/surgery , Humans , Prognosis , Treatment Outcome
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