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The optimal treatment strategy for neoadjuvant chemotherapy in elderly patients with pancreatic cancer (PC) remains unclear. Hence, this study was aimed at evaluating the safety and feasibility of neoadjuvant-modified FOLFIRINOX (mFOLFIRINOX) in elderly patients with PC. We retrospectively collected data from 62 patients who received neoadjuvant mFOLFIRINOX between May 2015 and October 2023 and comparatively analyzed the clinicopathological data and outcomes between the non-elderly group (age: <75 years) and elderly group (age: >75 years). The non-elderly and elderly groups comprised 39 and 23 patients, respectively. Although elevated levels of aspartate aminotransferase (p = 0.0173) and alanine aminotransferase (p = 0.0378) and nausea (p = 0.0177) were more frequent in the elderly group, the incidence of severe adverse events was similar between the groups. Intergroup differences in resection rate (p = 0.3381), postoperative severe complication rates (p = 0.2450), and postoperative hospital stay (p = 0.3496) were not significant. Furthermore, no significant intergroup differences were found in survival in either the whole or the resection cohorts. The perioperative and postoperative outcomes of elderly patients treated with neoadjuvant mFOLFIRINOX were comparable with those of non-elderly patients. Neoadjuvant mFOLFIRINOX should be considered a feasible option for elderly patients with PC.
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The present study aimed to identify preoperative and perioperative risk factors for postoperative infectious complications in older patients with gastric cancer. The present retrospective study included 504 patients with gastric cancer aged >65 years who underwent radical gastrectomy. After determining the cutoff values for various perioperative factors in the receiver operating characteristic curve analysis, preoperative and perioperative risk factors for the development of infectious complications after gastrectomy were examined using logistic regression analysis. Of the 504 patients who underwent gastrectomy, 95 (18.8%) developed infectious complications of grade II-V based on the Clavien-Dindo classification. In an analysis restricted to preoperative factors, male sex, low prognostic nutritional index, high visceral fat area and total gastrectomy were independent risk factors for infectious complications after gastrectomy. Among all perioperative factors, a low prognostic nutritional index and long operative duration were identified as independent risk factors for infectious complications after gastrectomy. The patients were divided into five groups according to the number of positive preoperative risk factors for infectious complications, and the incidence of infectious complications differed among the five groups (0 factors, 6.7%; 1 factor, 10.4%; 2 factors, 18.9%; 3 factors, 27.8%; and 4 factors, 47.6%; P<0.001). Older patients with gastric cancer who have a number of preoperative risk factors require careful consideration of the indication for gastrectomy and a shorter operative time to reduce infectious complications.
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BACKGROUND/AIM: We evaluated the usefulness of prophylactic mini-tracheostomy (PMT) and perioperative administration of tazobactam/piperacillin (TAZ/PIPC) in high-risk patients after esophagectomy. PATIENTS AND METHODS: We retrospectively studied 89 consecutive high-risk patients who underwent esophagectomy for esophageal cancer between January 2013 and December 2021. We defined patients with two or more of the following factors as high risk: age ≥70 years, performance status ≥1, respiratory dysfunction, liver dysfunction, cardiac dysfunction, renal dysfunction, diabetes mellitus, albumin <3.5 g/dl, and Brinkman index >600. Standard management was administered to the first 50 patients (standard group). PMT and TAZ/PIPC were administered to the next 39 patients (combination group). Patient characteristics and short-term outcomes were compared before and after propensity-score matching. RESULTS: Before propensity-score matching, 24-hour urine creatinine clearance, retrosternal route, 3-field lymph node dissection, and open abdominal approach were more common, postoperative pneumonia (13% vs. 36%, p=0.045) and complications of grade ≥3b (2.6% vs. 22%, p=0.01) were less frequent, and the postoperative hospital stay was shorter (median: 23 vs. 28 days, p=0.022) in the combination group than in the standard group. In propensity-score matching, patient characteristics, except for 24-h creatinine clearance and reconstructive route, were matched for 23 paired patients. Postoperative pneumonia (8.7% vs. 39%, p=0.035) and complications of grade ≥3b (0% vs. 26%, p=0.022) were less frequent and postoperative hospital stay was shorter (median: 22 vs. 25 days, p=0.021) in the combination group than in the standard group. CONCLUSION: PMT with TAZ/PIPC can potentially prevent postoperative pneumonia in high-risk patients after esophagectomy.
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Neoplasias Esofágicas , Esofagectomia , Combinação Piperacilina e Tazobactam , Pneumonia , Complicações Pós-Operatórias , Humanos , Masculino , Feminino , Idoso , Esofagectomia/efeitos adversos , Esofagectomia/métodos , Neoplasias Esofágicas/cirurgia , Pneumonia/prevenção & controle , Pneumonia/etiologia , Pneumonia/epidemiologia , Combinação Piperacilina e Tazobactam/uso terapêutico , Combinação Piperacilina e Tazobactam/administração & dosagem , Pessoa de Meia-Idade , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/etiologia , Antibacterianos/uso terapêutico , Antibacterianos/administração & dosagem , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND: To improve the prognosis of patients with metastatic colorectal cancer (mCRC), investigating predictive biomarkers of their prognosis and chemotherapeutic responsiveness is necessary. This study aimed to analyze the clinical significance of serum proteinase-3 (PRTN3) as a predictor for prognosis and chemosensitivity, especially to bevacizumab therapy, in mCRC. METHODS: This single-center retrospective observational study enrolled 79 patients with mCRC in our hospital and 353 patients with colorectal cancer in the TCGA database. Preoperative serum PRTN3 levels were measured using an enzyme-linked immunosorbent assay. The clinicopathological characteristics and prognosis according to serum PRTN3 levels were then evaluated. PRTN3 expression in tumor and stromal cells was evaluated immunohistochemically. The impact of PRTN3 levels on angiogenesis and bevacizumab sensitivity was evaluated using the tube formation assay. RESULTS: Serum PRTN3 levels were an independent poor prognostic factor for progression-free survival (PFS) (hazard ratio, 2.082; 95% confidence interval, 1.118-3.647; P=0.010) in patients with mCRC. Similarly, prognostic analysis with TCGA data sets showed poorer overall survival in patients with PRTN3 expression than that in patients without PRTN3 expression, especially in patients with stage IV. Immunohistochemical analysis of resected specimens revealed that stromal neutrophils expressed PRTN3, and their expression level was significantly correlated with serum PRTN3 levels. Interestingly, the effectiveness of first-line chemotherapy was significantly poorer in the high serum PRTN3 level group. High serum PRTN3 was significantly associated with poor PFS (hazard ratio, 3.027; 95% confidence interval, 1.175-7.793; P=0.0161) in patients treated with bevacizumab, an anti-angiogenic inhibitor. The tube formation assay revealed that PRTN3 administration notably augmented angiogenesis while simultaneously attenuating the anti-angiogenic influence exerted by bevacizumab therapy. CONCLUSIONS: Serum PRTN3 levels could be a novel predictive biomarker of PFS of first-line chemotherapy, especially for bevacizumab therapy, in patients with mCRC.
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Neoplasias do Colo , Neoplasias Colorretais , Mieloblastina , Neoplasias Retais , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/uso terapêutico , Biomarcadores , Neoplasias do Colo/tratamento farmacológico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Fluoruracila , Peptídeo Hidrolases , Prognóstico , Intervalo Livre de Progressão , Neoplasias Retais/tratamento farmacológico , Mieloblastina/sangueRESUMO
BACKGROUND/AIM: Colorectal cancer (CRC) is the third most common cancer worldwide, and metastasis is strongly associated with poor prognosis in patients with CRC. We have previously found that the expression and phosphorylation of paxillin (PXN) play an important role in the metastatic potential of breast cancer. This study examined the potential role of PXN in CRC metastasis. MATERIALS AND METHODS: Resected tumor specimens from 92 patients with CRC were subjected to immunohistochemical analysis of PXN levels. Three human CRC cell lines, HCT116, LoVo, and SW480 were used for scratch and transwell invasion assays to examine the effects of PXN over-expression. RNA sequencing was performed to obtain the expression profiles under PXN over-expression. RESULTS: High levels of PXN were significantly correlated with advanced stage, higher carcinoembryonic antigen and carbohydrate antigen 19-9 levels, and poorer overall survival. The migration ability of CRC cells was enhanced by exogenous PXN over-expression, but this enhancement was not observed in cells harboring exogenously mutated PXN at Tyr31 or Tyr88 phosphorylation sites. In PXN-over-expressing cells, TNF-α signaling via NF-[Formula: see text]B was positively enriched. CONCLUSION: PXN expression and phosphorylation at Tyr31 or Tyr88 may influence the migration and invasion of CRC cells. PXN expression and phosphorylation at Tyr31 or Tyr88 are promising targets for evaluating prognosis and treating CRC.
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Neoplasias Colorretais , Regulação Neoplásica da Expressão Gênica , Paxilina , Humanos , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Neoplasias Colorretais/patologia , Metástase Neoplásica , Paxilina/genética , Paxilina/metabolismo , Fosforilação , PrognósticoRESUMO
BACKGROUND/AIM: In gastric cancer, accurate determination of human epidermal growth factor receptor type 2 (HER2) status is crucial for treatment decision-making. However, the optimal formalin fixation time of gastric cancer specimens for HER2 status determination remains unestablished. Here, we investigated real-world data on formalin overfixation and its effect on HER2 status determination in gastric cancer. PATIENTS AND METHODS: We comprehensively analyzed HER2 testing results in 228 gastric cancer specimens, including those subjected to formalin overfixation. Subsequently, we divided 52 resected specimens of advanced gastric cancer into three groups and studied the effects of short-term (6-72 h) and long-term (1 and 2 weeks) fixation on HER2 status determination using immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). RESULTS: A total of 21.5% (49/228) of the specimens were HER2-positive, whereas 78.5% (179/228) were negative. Among the HER2-negative specimens, no biopsies were overfixed, whereas 12.5% (9/72) of the surgical resection specimens were overfixed. The HER2 status of the 6-72-h group was 82.7% and 76.9% identical to that of the 1- and 2-week groups, when determined using IHC, and 73.1% and 36.5%, when determined using FISH, respectively. However, HER2 determination was not feasible in 26.9% and 63.5% of the specimens in the 1- and 2-week groups, respectively. CONCLUSION: Formalin overfixation may hinder the determination of HER2 status and should be avoided in gastric cancer sample preparation.
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Biomarcadores Tumorais , Neoplasias Gástricas , Humanos , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Imuno-Histoquímica , Neoplasias Gástricas/genética , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/metabolismo , Hibridização in Situ Fluorescente , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , FormaldeídoRESUMO
INTRODUCTION: Laparoscopic spleen-preserving distal pancreatectomy (LSDP) is widely performed to treat benign and low-grade malignant diseases. Although preservation of splenic vessels may be desirable considering the risk of postoperative complications, it is sometimes difficult due to tumor size, inflammation, and proximity of the tumor and splenic vessels. Herein, we present the first case of LSDP with splenic artery resection and splenic vein preservation. MATERIALS AND SURGICAL TECHNIQUE: A 40-year-old woman with a pancreatic tumor was referred to our hospital. Contrast-enhanced computed tomography (CT) revealed a tumor in the pancreatic tail that was in contact with the splenic artery and distant from the splenic vein. The splenic artery and vein were separated from the pancreas near the dissection line. The splenic artery was resected after pancreatic dissection using a linear stapler. After the pancreatic tail was separated from the splenic hilum while preserving the splenic vein, the distal side of the splenic artery was resected, and the specimen was removed. The postoperative course was uneventful and the patient was discharged on postoperative Day 9. Four months after surgery, postoperative follow-up CT findings showed neither splenic infarction nor gastric varices. DISCUSSION: This technique is an alternative method of splenic preservation when there is no attachment of the tumor to the splenic vein or uncontrolled expected bleeding of the splenic artery using the Kimura technique.
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Laparoscopia , Neoplasias Pancreáticas , Feminino , Humanos , Adulto , Baço/cirurgia , Baço/irrigação sanguínea , Veia Esplênica/cirurgia , Pancreatectomia/métodos , Artéria Esplênica/diagnóstico por imagem , Artéria Esplênica/cirurgia , Laparoscopia/métodos , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/cirurgiaRESUMO
BACKGROUND/AIM: Staging laparoscopy (SL) for pancreatic cancer (PC) is considered useful to improve accuracy of staging and resectability. However, given the current accuracy of preoperative imaging, the routine application of SL remains unclear. Therefore, we aimed to investigate the importance of SL in patients with PC without radiological distant metastasis. PATIENTS AND METHODS: This was a prospective, cohort, observational study. SL was performed in all patients with PC without radiological distant metastasis before pancreatectomy or chemotherapy at the Yamaguchi University Hospital. RESULTS: Between July 2020 and March 2023, 55 patients underwent SL with peritoneal cytology. The median age was 71, with 53% male patients. SL revealed occult metastasis in six (11%) patients including positive peritoneal cytology (n=6), and peritoneal dissemination (n=1). The resectability of unresectable locally advanced (UR-LA) was associated with a significantly increased risk of occult metastasis (p=0.0211). The median operative time was 40 min, and the median volume of blood loss was 3 ml. There were no severe complications (Clavien-Dindo III or higher). CONCLUSION: SL with peritoneal cytology regardless of previous abdominal surgery is safe and effective to determine accurate staging. Therefore, SL with peritoneal cytology should be considered for patients with PC without radiological distant metastasis, especially in those with UR-LA.
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Laparoscopia , Neoplasias Pancreáticas , Humanos , Masculino , Idoso , Feminino , Estudos Prospectivos , Estadiamento de Neoplasias , Estudos Retrospectivos , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/patologia , Laparoscopia/métodos , Neoplasias PancreáticasRESUMO
BACKGROUND: Since clinically relevant postoperative pancreatic fistula (CR-POPF) can cause intra-abdominal hemorrhage and abscesses, leading to surgery-related deaths after pancreaticoduodenectomy (PD), its preoperative prediction is important to develop strategies for surgical procedures and perioperative management. This study aimed to establish a novel prediction model for CR-POPF using preoperative markers. METHODS: On a training set of 180 patients who underwent PD at the Yamaguchi University Hospital, a combination of CR-POPF predictors were explored using the leave-one-out method with a unique discrete Bayes classifier. This predictive model was confirmed using a validation set of 366 patients who underwent PD at the Osaka University Hospital. RESULTS: In the training set, CR-POPF occurred in 60 (33%)ãof 180 patients and 130 (36%)ãof 366 patients in the validation set using selected markers. In patients with pancreatic ductal adenocarcinoma (PDAC), the main pancreatic duct (MPD) index showed the highest prognostic performance and could differentiate CR-POPF with 87% sensitivity and 81% specificity among 84 patients in the training set. In the validation set, the sensitivity and specificity of the MPD index-based model for 130 PDAC samples were 93% and 87%, respectively. In patients with non-PDAC, the MPD index/body mass index (BMI) combination showed the highest prognostic performance and could differentiate CR-POPF with 84% sensitivity and 57% specificity among 96 patients in the training set. In the validation set, the sensitivity and specificity of the MPD index/BMI-based model for 236 non-PDAC samples were 85% and 53%, respectively. CONCLUSION: We developed a novel prediction model for pancreatic fistulas after PD using only preoperative markers. The MPD index and MPD index/BMI combination will be useful for CR-POPF assessment in PDAC and non-PDAC samples, respectively.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Fístula Pancreática/diagnóstico , Fístula Pancreática/etiologia , Pancreaticoduodenectomia/efeitos adversos , Teorema de Bayes , Fatores de Risco , Estudos Retrospectivos , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/complicações , Carcinoma Ductal Pancreático/cirurgia , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Neoplasias PancreáticasRESUMO
BACKGROUND: The prognosis for patients with colorectal cancer (CRC) is determined by tumor characteristics as well as the host immune response. This study investigated the relationship between an immunosuppressive state and patient prognosis by evaluating the systemic and tumor microenvironment (TME) interleukin (IL)-6 levels. METHODS: Preoperative serum IL-6 levels were measured using an electrochemiluminescence assay. Expression of IL-6 in tumor and stromal cells was evaluated immunohistochemically in 209 patients with resected CRC. Single-cell analysis of tumor-infiltrating immune cells was performed using mass cytometry in 10 additional cases. RESULTS: Elevated serum IL-6 levels were associated with elevated stromal IL-6 levels and a poor prognosis for patients with CRC. High IL-6 expression in stromal cells was associated with low-density subsets of CD3+ and CD4+ T cells as well as FOXP3+ cells. Mass cytometry analysis showed that IL-6+ cells among tumor-infiltrating immune cells were composed primarily of myeloid cells and rarely of lymphoid cells. In the high-IL-6-expression group, the percentages of myeloid-derived suppressor cells (MDSCs) and CD4+FOXP3highCD45RA- effector regulatory T cells (eTreg) were significantly higher than in the low-IL-6-expression group. Furthermore, the proportion of IL-10+ cells in MDSCs and that of IL-10+ or CTLA-4+ cells in eTregs correlated with IL-6 levels. CONCLUSION: Elevated serum IL-6 levels were associated with stromal IL-6 levels in CRC. High IL-6 expression in tumor-infiltrating immune cells also was associated with accumulation of immunosuppressive cells in the TME.
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Neoplasias Colorretais , Interleucina-10 , Humanos , Neoplasias Colorretais/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Interleucina-10/metabolismo , Interleucina-6 , Linfócitos do Interstício Tumoral , Prognóstico , Microambiente TumoralRESUMO
AIM: Developing effective adjuvant therapies is essential for improving the surgical outcomes in patients with hepatocellular carcinoma (HCC). Immunotherapy against HCC has become a promising strategy; however, only approximately 30% of all HCC patients respond to immunotherapy. Previously, we generated the novel therapeutic vaccine comprising multi-human leukocyte antigen-binding heat shock protein 70/glypican-3 peptides with a novel adjuvant combination of hLAG-3Ig and poly-ICLC. We also confirmed the safety of this vaccination therapy, as well as its capacity for the effective induction of immune responses in a previous clinical trial. METHODS: In this phase I study, we administered this vaccine intradermally six times before surgery, and 10 times after surgery to patients with untreated, surgically resectable HCC (stage II to IVa). The primary end-points of this study were the safety and feasibility of this treatment. We also analyzed the resected tumor specimens pathologically using hematoxylin-eosin staining and immunohistochemistry for heat shock protein 70, glypican 3, CD8 and programmed death-1. RESULTS: A total of 20 human leukocyte antigen-matched patients received this vaccination therapy with an acceptable side-effect profile. All patients underwent planned surgery without vaccination-related delay. Immunohistochemical analyses revealed that potent infiltration of CD8+ T cells into tumors with target antigen expression was observed in 12 of 20 (60%) patients. CONCLUSIONS: This novel therapeutic vaccine was safe as perioperative immunotherapy for patients with HCC, and has the potential to strongly induce CD8+ T cells infiltration into tumors.
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BACKGROUND/AIM: Chemotherapy combined with anti-EGFR or anti-VEGF monoclonal antibodies (mAb) is widely used to treat patients with metastatic colorectal cancer (mCRC). Here, we investigated the effects of these antibodies on T-cell infiltration and T-cell receptor (TCR) repertoire variation in CRC liver metastases. MATERIALS AND METHODS: Ten patients with mCRC received chemotherapy in combination with anti-EGFR (n=6) or anti-VEGF (n=4) mAb. T-cell infiltration was examined for CD3 and CD8 by carrying out immunohistochemistry on biopsy or surgical specimens from liver metastases before and after treatment. TCR repertoire analysis was carried out on specimens with post-treatment CD3+ T-cell infiltration. RESULTS: T-cell infiltrations were approximately 83% (5/6) and 50% (2/4), following treatment with anti-EGFR or anti-VEGF mAb, respectively. TCR repertoire analysis revealed higher clonality and lower diversity of TCR alpha and beta (TRA and TRB) in the anti-VEGF mAb group than that in the anti-EGFR group mAb. Furthermore, the percentage of the common TCR clones between infiltrating T cells and T cells in peripheral blood was significantly lower in the anti-VEGF mAb group compared to that in the anti-EGFR mAb group. CONCLUSION: The population of T cells infiltrating liver metastases in the anti-VEGF mAb group differed from that in the anti-EGFR mAb group.
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Antineoplásicos , Neoplasias Colorretais , Neoplasias Hepáticas , Humanos , Linfócitos T , Anticorpos Monoclonais/farmacologia , Receptores de Antígenos de Linfócitos T alfa-beta , Antineoplásicos/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Receptores de Antígenos de Linfócitos TRESUMO
BACKGROUND/AIM: Colorectal cancer is the third most common cancer globally, and the poor prognosis of patients with metastatic colorectal cancer (mCRC) warrants urgent attention. We previously obtained 10 candidate serum biomarkers for mCRC. Our aim with this study was to determine the prognostic performance of the pre-treatment serum C-C motif chemokine ligand 7 (CCL7) concentration in patients with mCRC. PATIENTS AND METHODS: Protein concentrations of CCL7 were examined using ELISA and immunohistochemistry for serum (n=110) and surgical specimens (n=85), respectively, of patients with mCRC. The relationship between protein concentration and prognosis was examined using Cox regression analysis, receiver operator characteristic curve analysis and the Kaplan-Meier method. RESULTS: The overall survival (OS) of patients with high concentrations of serum CCL7 was significantly poorer than that of patients with low concentrations. Patients with a high CCL7 concentration in the stroma had significantly poorer outcomes than those with a low concentration. The concentrations of carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 were significantly higher in the high-CCL7 group, compared to those in the low-CCL7 group. Univariate and multivariate analysis revealed that serum CCL7 concentration was a significant prognostic factor for mCRC. The combination of serum CCL and CEA concentrations was also useful in this regard (area under the curve=0.71). CONCLUSION: The combined pre-treatment serum levels of CCL7 and CEA are useful prognostic biomarkers for mCRC.
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Quimiocina CCL7 , Neoplasias do Colo , Neoplasias Colorretais , Neoplasias Retais , Humanos , Biomarcadores Tumorais , Antígeno Carcinoembrionário , Quimiocina CCL7/sangue , Quimiocina CCL7/química , Neoplasias do Colo/diagnóstico , Neoplasias do Colo/metabolismo , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/metabolismo , Ligantes , Prognóstico , Neoplasias Retais/diagnóstico , Neoplasias Retais/metabolismo , Estudos RetrospectivosRESUMO
OBJECTIVE: Irinotecan is a useful anticancer drug for colorectal cancer treatment. UGT1A1*28 and *6 gene polymorphisms are known risk factors for irinotecan-associated toxicity. However, severe adverse effects due to irinotecan have been observed even in patients who do not harbor UGT1A1*28 or *6. We investigated gene polymorphisms in the whole exome to identify useful biomarkers for irinotecan toxicity other than UGT1A. METHODS: A total of 178 patients with metastatic colorectal cancer (mCRC) and 87 patients with pancreatic cancer were treated with FOLFIRI, FOLFOX, FOLFOXIRI, modified FOLFIRINOX, or gemcitabine plus nab-paclitaxel. Genome-wide screening was performed using whole-exome sequencing (WES), and validation analysis was performed using qPCR with a hydrolysis probe. RESULTS: Using WES after a doublet chemotherapy regimen comprising irinotecan and 5-fluorouracil (n = 15), seven single nucleotide polymorphisms (SNPs) were identified as candidate biomarkers for irinotecan-associated toxicity of neutropenia. Among the seven SNPs, an SNP in R3H domain and coiled-coil containing 1 (R3HCC1; c.919G > A, rs2272761) showed a significant association with neutropenia (>grade 3) after doublet chemotherapy. Patients receiving irinotecan including triplet chemotherapy, FOLFOXIRI for mCRC (n = 23) or modified FOLFIRINOX for pancreatic cancer (n = 40), also showed significant linear trends between R3HCC1 polymorphism and neutropenia (p = 0.017 and 0.046, respectively). No significant association was observed in patients treated with irinotecan-free regimens, FOLFOX for mCRC (n = 66), and gemcitabine plus nab-paclitaxel for pancreatic cancer (n = 47). CONCLUSION: Thus, an SNP in the R3HCC1 gene may be a useful biomarker for the toxicity of irinotecan-containing chemotherapy for mCRC and pancreatic cancer.
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Neoplasias do Colo , Neoplasias Colorretais , Neutropenia , Neoplasias Pancreáticas , Neoplasias Retais , Humanos , Irinotecano , Polimorfismo de Nucleotídeo Único , Camptotecina/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Fluoruracila , Neoplasias do Colo/tratamento farmacológico , Neutropenia/induzido quimicamente , Neoplasias Retais/tratamento farmacológico , Leucovorina/efeitos adversos , Neoplasias PancreáticasRESUMO
During the postoperative follow-up for adrenal tumor for a 78-year-old male patient, a contrast-enhanced computed tomography scan revealed wall thickness with contrast effect in the cystic duct, enlarged lymph nodes along the ileocecal artery, and nodal shadow in the lower lobe of the left lung. First, the collected bile juice at ERC was submitted to cytology multiple times however, no malignant findings were noted. Next, a staging laparoscopy was performed; but the pathological findings of the enlarged lymph nodes and the abdominal lavage cytology showed no malignancy. A nodule in the lower lobe of the left lung was resected for diagnostic and therapeutic purposes, and the pathological diagnosis was primary adenocarcinoma of the lung. Finally the patient underwent exploratory laparotomy for diagnostic purposes. An intraoperative ultrasound- guided needle biopsy for mass lesion located in the medial section of the left liver was performed, and malignant lymphoma was suspected by the intraoperative pathological diagnosis. Cholecystectomy was performed to confirm the histological type, leading to the diagnosis of diffuse large B cell lymphoma. After surgery, the patient underwent 6 courses of rituximab plus CHOP therapy, and the bile duct stricture was improved.
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Neoplasias dos Ductos Biliares , Colangiocarcinoma , Linfoma , Masculino , Humanos , Idoso , Neoplasias dos Ductos Biliares/diagnóstico , Neoplasias dos Ductos Biliares/cirurgia , Neoplasias dos Ductos Biliares/patologia , Ductos Biliares/patologia , Colangiocarcinoma/diagnóstico , Ductos Biliares Intra-Hepáticos/patologiaRESUMO
An 81-year-old man with a history of left hemiplegia due to a cerebral hemorrhage was admitted to a clinic because of tarry stools. Endoscopic findings revealed an ulcerative lesion with hemorrhage in the descending duodenum. The patient was transferred to our hospital for treatment. Because endoscopic hemostasis was impossible, interventional radiology(IVR) hemostasis was performed using coil embolization for the feeding artery. Simultaneously, angiography showed stenosis of the root of the celiac axis due to arch ligament syndrome and an aneurysm of the inferior pancreaticoduodenal artery (IPDA). Due to the risk of rebleeding, subtotal stomach-preserving pancreatoduodenectomy was performed after the patient's overall condition had stabilized. Despite dissecting the arcuate ligament, the hepatic artery flow did not improve. Hence, a direct arterial anastomosis between the middle colic artery and the gastroduodenal artery was performed. Furthermore, due to the proximity of the IPDA aneurysm to the superior mesenteric artery, IVR embolization for the IPDA aneurysm was performed on postoperative day 8, and he was transferred to a rehabilitation hospital on postoperative day 57. The pathological result was invasive intraductal papillary mucinous carcinoma(IPMC). The patient has been an outpatient with no recurrence 12 months postoperatively.
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Aneurisma , Embolização Terapêutica , Idoso de 80 Anos ou mais , Humanos , Masculino , Aneurisma/complicações , Aneurisma/cirurgia , Artéria Celíaca/cirurgia , Duodeno , Hemorragia/terapia , Ligamentos , Artéria Mesentérica Superior , Pâncreas , SíndromeRESUMO
Aim: To identify preoperative factors, especially other diseases that cause death, that are associated with the prognosis of gastrectomy in elderly patients with gastric cancer. Methods: This retrospective study included a total of 211 consecutive patients aged ≥75 years who underwent radical gastrectomy due to gastric cancer. Time-dependent receiver operating characteristic curve analysis was performed to determine the optimal cutoff values for various perioperative factors. Risk factors for the overall survival and death from other diseases were analyzed using the Cox proportional hazards model. Results: Among the all perioperative factors, sex, neutrophil-to-lymphocyte ratio, skeletal muscle mass index, and lymph node dissection in accordance with guidelines or not extracted as independent risk factors for death from other diseases. In an analysis restricted to the preoperative factors, sex, neutrophil-to-lymphocyte ratio, and skeletal muscle mass index of the patients were extracted as independent risk factors for death from other diseases and overall survival. We divided the patients into four groups according to the number of preoperative risk factors for death from other diseases and found that the 5-year non-gastric-cancer-related survival was different among the four groups (risk factor 0, 91.7%; risk factor 1, 83.3%; risk factor 2, 56.3%; risk factor 3, 27.2%; P < 0.001). Conclusion: Male sex, low skeletal muscle mass index, and high neutrophil-to-lymphocyte ratio are risk factors for non-gastric-cancer-related death and the overall survival of elderly patients undergoing gastrectomy. Cautious treatment strategies are needed for elderly gastric cancer patients with many risk factors.
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BACKGROUND: We recently reported the relapse-free survival (RFS) significance of the combination of CD4+ and forkhead box P3+ (FOXP3) T-cell densities identified by immunohistochemistry in patients with stage I, II, and III colorectal cancer (CRC) who underwent curative resections. This study was designed to determine the optimal combination of markers that predict recurrence in patients with T factors of T3/T4a stage II CRC by applying a novel Bayes decision rule. METHODS: Using 137 cancer tissue specimens from T3/T4a stage II patients, 12 clinicopathologic and immune factors were analysed as predictive candidates for recurrence. RESULTS: Our study showed that the combination of low CD4+ and low FOXP3+ T-cell densities resulted in extremely poor RFS. CONCLUSIONS: Adjuvant chemotherapy may be considered for patients with a combination of low CD4+ and low FOXP3+ T-cell densities. The discovery of this new prognostic indicator is important for the appropriate management of patients undergoing curative resection for T3/T4a stage II CRC.