ABSTRACT
PURPOSE: To assess the clinical indications for, and prognostic impact of surgery after, chemotherapy for type 4 gastric cancer. METHODS: The subjects of this retrospective study were 67 patients who received chemotherapy for type 4 gastric cancer. The patients were grouped into those with progressive disease (PD group) and those without PD (non-PD group), according to the tumor response to chemotherapy. RESULTS: Distant metastases developed in 58 patients. With regard to tumor response, there were 16 patients in the PD group and 51 patients in the non-PD group. The prognosis of the PD group patients was significantly poorer than that of the non-PD group patients (p < 0.0001). R0 resection was performed for 21 of 23 patients who underwent surgery after chemotherapy. Multivariate analysis revealed tumor response and surgery as independent prognostic factors (p = 0.0001 and p = 0.0009, respectively). Moreover, multivariate analysis of the surgery group revealed that metastatic nodal status (N0-1 vs. N2-3) and residual tumor status (R0 vs. R1-2) were significant independent prognostic factors (p = 0.0258 and p = 0.0458, respectively). CONCLUSION: The findings of this study suggest that surgery after chemotherapy for type 4 gastric cancer may improve the prognosis of responders with N0-1 status, who undergo curative R0 resection.
Subject(s)
Antineoplastic Agents/therapeutic use , Gastrectomy/methods , Stomach Neoplasms/drug therapy , Stomach Neoplasms/surgery , Adult , Aged , Aged, 80 and over , Combined Modality Therapy , Disease Progression , Female , Humans , Male , Middle Aged , Multivariate Analysis , Prognosis , Retrospective Studies , Stomach Neoplasms/classification , Stomach Neoplasms/pathologyABSTRACT
OBJECTIVE: Although chemotherapy has been clinically recommended as the initial treatment for patients with peritoneal dissemination of gastric cancer, poor prognosis has been noted among the same patients. However, the prognostic significance of conversion surgery after chemotherapy remains unclear. The present study therefore aimed to assess the clinical impact of conversion surgery among patients with peritoneal dissemination of gastric cancer. METHODS: A total of 93 patients with peritoneal dissemination of gastric cancer undergoing chemotherapy between February 2002 and October 2019 were retrospectively enrolled and subsequently divided into progressive disease (PD) and non-PD groups based on tumor response to chemotherapy. RESULTS: Among the included patients, 17 developed distant metastases at another site besides peritoneal dissemination. Based on tumor response, 24 and 69 patients were determined to have PD and non-PD, respectively, with the former having significantly poorer prognosis than the latter (p < 0.0001). A total of 19 patients underwent conversion surgery after chemotherapy, with the presence or absence of conversion surgery being significantly correlated with age, first-line chemotherapy regimen, and tumor response (p = 0.0134, p = 0.0337, and p = 0.0024, respectively). Patients in the non-PD group who underwent conversion surgery or chemotherapy alone had 3-year overall survival rates of 55.6 and 6.6%, respectively. Multivariate analysis identified conversion surgery alone as an independent prognostic factor in the non-PD group (p < 0.0001). CONCLUSION: Our retrospective study demonstrated that conversion surgery for gastric cancer with peritoneal dissemination might improve the prognosis of responders who developed no peritoneal dissemination after chemotherapy.
Subject(s)
Peritoneal Neoplasms/pathology , Stomach Neoplasms/pathology , Stomach Neoplasms/surgery , Adult , Aged , Aged, 80 and over , Female , Gastrectomy , Humans , Kaplan-Meier Estimate , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Invasiveness , Neoplasm Staging , Peritoneal Neoplasms/drug therapy , Prognosis , Retrospective Studies , Stomach Neoplasms/drug therapyABSTRACT
OBJECTIVE: Nivolumab is recommended as a third-line treatment in patients with unresectable advanced or recurrent gastric cancer. Although recent studies have demonstrated the prognostic impact of salvage chemotherapy after immune checkpoint inhibitors in several malignancies, its clinical significance remains unclear in patients with gastric cancer. This study aimed to investigate tumor response to subsequent chemotherapy after nivolumab in patients with advanced gastric cancer and assess the prognostic effect of salvage chemotherapy. METHODS: We retrospectively enrolled 31 patients with unresectable advanced or recurrent gastric cancer receiving nivolumab. RESULTS: Twenty-two and nine patients received nivolumab as third-line and fourth- to sixth-line treatments, respectively. The objective response rate (ORR) and disease control rate (DCR) to nivolumab were 20.0% (4/20) and 55.0% (11/20), respectively. Eleven patients received salvage chemotherapy after nivolumab. The ORR and DCR to salvage chemotherapy were 37.5% (3/8) and 75.0% (6/8), respectively. The median progression-free survival and overall survival following salvage chemotherapy were 285 and 360 days, respectively. CONCLUSION: Our preliminary study indicates that nivolumab exposure may enhance subsequent chemosensitivity in patients with advanced gastric cancer.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Nivolumab/administration & dosage , Stomach Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Antineoplastic Agents, Immunological/administration & dosage , Female , Humans , Irinotecan/administration & dosage , Male , Middle Aged , Organoplatinum Compounds/administration & dosage , Prognosis , Progression-Free Survival , Pyrrolidines/administration & dosage , Retrospective Studies , Salvage Therapy/methods , Stomach Neoplasms/diagnostic imaging , Thymine/administration & dosageABSTRACT
Considering the poor prognosis of most advanced cancers, prevention of invasion and metastasis is essential for disease control. Ras homologous (Rho) guanine exchange factors (GEFs) and their signaling cascade could be potential therapeutic targets in advanced cancers. We conducted in silico analyses of The Cancer Genome Atlas expression data to identify candidate Rho-GEF genes showing aberrant expression in advanced gastric cancer and found FERM, Rho/ArhGEF, and pleckstrin domain protein 1 (FARP1) expression is related to poor prognosis. Analyses in 91 clinical advanced gastric cancers of the relationship of prognosis and pathological factors with immunohistochemical expression of FARP1 indicated that high expression of FARP1 is significantly associated with lymphatic invasion, lymph metastasis, and poor prognosis of the patients (P = 0.025). In gastric cancer cells, FARP1 knockdown decreased cell motility, whereas FARP1 overexpression promoted cell motility and filopodium formation via CDC42 activation. FARP1 interacted with integrin ß5, and a potent integrin αvß5 inhibitor (SB273005) prevented cell motility in only high FARP1-expressing gastric cancer cells. These results suggest that the integrin αvß5-FARP1-CDC42 axis plays a crucial role in gastric cancer cell migration and invasion. Thus, regulatory cascade upstream of Rho can be a specific and promising target of advanced cancer treatment.
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BACKGROUND: The usefulness of sentinel node navigation surgery (SNNS) for early gastric cancer has been demonstrated in a multicenter prospective study. However, quality of life (QOL) after local resection remains unclear. This present study investigated QOL after local resection and distal gastrectomy. METHODS: We examined 69 patients who underwent laparoscopic distal gastrectomy (LADG) (n = 44) and laparoscopic local resection (LLR) (n = 25) in our hospital between September 2011 and May 2018. We conducted a combination of laparoscopic and endoscopic approaches to neoplasia with non-exposure technique (CLEAN-NET) with SNNS as LLR. All patients had pStage I or II and none had received adjuvant chemotherapy. We evaluated QOL using the postgastrectomy syndrome assessment scale questionnaire (PGSAS-45) 1, 6, and 12 months after surgery. RESULTS: In PGSAS-45, no significant differences were observed between LLR and LADG at 1 and 6 months after surgery. At 12 months, the LLR group scored better for some of the subscales (SS). In the endoscopic evaluation, the LLR group showed significant improvements in residual gastritis at 6 months (P = 0.006) and esophageal reflux and residual gastritis at 12 months (P = 0.021 and P = 0.017). A significant difference was observed in the prognostic nutritional index, which was assessed using serum samples, between the two groups at 6 months (P = 0.028). The body weight ratio was better in the LLR group than in the LADG group at 6 and 12 months (P = 0.041 and P = 0.007, respectively). CONCLUSIONS: CLEAN-NET with SNNS preserved a better QOL and nutrition status than LADG in patients with early gastric cancer.
Subject(s)
Gastrectomy/adverse effects , Laparoscopy/methods , Postgastrectomy Syndromes/pathology , Postoperative Complications/pathology , Quality of Life , Sentinel Lymph Node/pathology , Stomach Neoplasms/surgery , Adult , Aged , Aged, 80 and over , Female , Follow-Up Studies , Humans , Male , Middle Aged , Postgastrectomy Syndromes/etiology , Postoperative Complications/etiology , Prognosis , Retrospective Studies , Stomach Neoplasms/pathologyABSTRACT
OBJECTIVE: Chemotherapy is generally recommended as the first-line standard treatment in patients with liver metastasis from gastric cancer. However, the clinical impact of surgical treatment remains unclear in responders after chemotherapy. The present study aimed to investigate the tumor response and prognosis after chemotherapy and to assess the clinical indication of conversion surgery in responders. METHODS: The study retrospectively reviewed the clinical data of 44 patients with liver metastasis from gastric cancer who were treated with chemotherapy between February 2002 and January 2019. These patients were classified into progressive disease (PD) and non-PD groups according to tumor response. RESULTS: Among the 44 patients, 7 and 26 had peritoneal dissemination and ≥5 had metastatic liver nodules. Additionally, 15 and 29 patients had PD and non-PD, respectively. Surgical treatment was significantly correlated with tumor response (p < 0.0321). Prognostic differences between the PD and non-PD groups were significant (p < 0.0001). Moreover, gastrectomy and hepatectomy were significantly correlated with the number of liver metastases (≥5 vs. <5, respectively) in the non-PD group (p = 0.0025 and p = 0.0169, respectively). The 3-year survival rates among patients with non-PD undergoing both gastrectomy and hepatectomy (n = 6), gastrectomy alone (n = 7), and nonsurgical treatments (n = 16) were 100, 66.7, and 0%, respectively (p = 0.0026). Multivariate analysis identified peritoneal dissemination as an independent prognostic factor (p = 0.0225). CONCLUSION: Our preliminary results suggest that conversion surgery for gastric cancer with liver metastasis might be clinically indicated in chemotherapy responders with <5 metastatic liver nodules and without peritoneal dissemination.
Subject(s)
Liver Neoplasms/pathology , Stomach Neoplasms/pathology , Adult , Aged , Aged, 80 and over , Antineoplastic Agents/therapeutic use , Female , Gastrectomy/methods , Humans , Liver Neoplasms/drug therapy , Liver Neoplasms/mortality , Liver Neoplasms/therapy , Male , Middle Aged , Prognosis , Retrospective Studies , Stomach Neoplasms/mortality , Survival RateABSTRACT
BACKGROUND: Patients with esophagogastric junction cancer are increasing in Western and Eastern countries. Conversely, the clinical significance of surgical resection remains controversial in these patients. We report a long-term survivor of recurrent esophagogastric junction adenocarcinoma who underwent constructive multimodal therapy, including surgical resection. CASE PRESENTATION: A 51-year-old man underwent total gastrectomy for esophagogastric junction adenocarcinoma in 2009. In June 2010, computed tomography (CT) indicated a lung nodule and we partially resected the right lower lung. It was pathologically diagnosed as distant metastasis from esophagogastric junction cancer. After lung resection, he received adjuvant chemotherapy with S-1 for 1 year. In September 2014, CT demonstrated a swelling of the upper mediastinal lymph node with abnormal uptake on fluorine-18 fluorodeoxyglucose positron emission tomography. We performed an ultrasonography-guided needle biopsy, and he was diagnosed with lymph nodal recurrence of esophagogastric junction adenocarcinoma by pathological examination and was subsequently treated with capecitabine plus cisplatin plus trastuzumab. Since CT showed a reduction in the metastatic upper mediastinal lymph node after chemotherapy, he underwent upper mediastinal lymphadenectomy in April 2015. Following surgery, we provided radiation therapy to the upper mediastinum and chemotherapy with S-1. At the last report, the patient was alive for 8 years and 3 months since the first surgery. CONCLUSIONS: This case report shows the clinical benefit of constructive multimodal therapy for recurrent esophagogastric junction adenocarcinoma.
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BACKGROUND/AIM: The aim of the present study was to compare human epidermal growth factor receptor 2 (HER2) expression before and after trastuzumab-based chemotherapy in patients with advanced HER2-positive gastric cancer. MATERIALS AND METHODS: We assessed HER2 expression using immunohistochemistry and/or fluorescence in situ hybridization in pre-treatment biopsied specimens and post-treatment resected specimens obtained from seven patients with advanced HER2-positive gastric cancer receiving trastuzumab-based chemotherapy. RESULTS: Four patients maintained the HER2-positive status and three patients had a change in HER2 expression from positive to negative. In patients showing the loss of HER2 expression after treatments, HER2-positive tumor cells with a dominant histological type disappeared, and HER2-negative tumor cells with another dominant histological type were identified. CONCLUSION: HER2 expression can change after trastuzumab-based chemotherapy in patients with advanced HER2-positive gastric cancer. Continuous monitoring of HER2 expression after treatments may be utilized to determine whether the continued use of trastuzumab is advisable.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Receptor, ErbB-2/antagonists & inhibitors , Receptor, ErbB-2/genetics , Stomach Neoplasms/drug therapy , Stomach Neoplasms/genetics , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Biomarkers, Tumor , Combined Modality Therapy , Female , Humans , Immunohistochemistry , In Situ Hybridization, Fluorescence , Male , Middle Aged , Molecular Targeted Therapy , Multimodal Imaging/methods , Neoplasm Metastasis , Neoplasm Staging , Receptor, ErbB-2/metabolism , Recurrence , Stomach Neoplasms/diagnosis , Stomach Neoplasms/metabolism , Trastuzumab/administration & dosage , Treatment OutcomeABSTRACT
BACKGROUND: The neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) are representative blood markers of systemic inflammatory responses. However, the clinical significance of the combination of these markers is unclear. This study aimed to investigate the NLR and PLR in patients with advanced gastric cancer treated with chemotherapy and assess the clinical utility of a new blood score combining the NLR and PLR (NLR-PLR score) as a predictor of tumor response and prognosis. METHODS: We retrospectively analyzed 175 patients with gastric cancer receiving chemotherapy or chemoradiotherapy. These patients were categorized into progressive disease (PD) and non-PD groups according to tumor response. The NLR and PLR before treatment were examined, and the cut-off values were determined. The NLR-PLR score ranged from 0 to 2 as follows: score of 2, high NLR (> 2.461) and high PLR (> 248.4); score of 1, either high NLR or high PLR; score of 0, neither high NLR nor high PLR. RESULTS: With regard to tumor response, 64 and 111 patients had PD and non-PD, respectively. The NLR-PLR score was significantly higher in patients with PD than in those with non-PD (p = 0.0009). The prognosis was significantly poorer in patients with a higher NLR-PLR score than in those with a lower NLR-PLR score (p < 0.0001). Multivariate analysis demonstrated that the NLR-PLR score was an independent prognostic factor for prediction of overall survival (p = 0.0392). CONCLUSION: Low-cost stratification according to the NLR-PLR score might be a promising approach for predicting tumor response and prognosis in patients with advanced gastric cancer.
Subject(s)
Blood Platelets , Chemoradiotherapy , Lymphocytes , Neutrophils , Stomach Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/blood , Female , Humans , Kaplan-Meier Estimate , Lymphocyte Count , Male , Middle Aged , Multivariate Analysis , Platelet Count , Prognosis , Retrospective Studies , Treatment OutcomeABSTRACT
A 57-year-old woman was admitted to our hospital for treatment of gastric cancer presenting as a type 2 tumor in the lower third of the stomach. According to pre-therapeutic imaging examinations and laparoscopy, she was diagnosed with advanced gastric cancer, cT4a(SE)N2M0, Stage â ¢. Therefore, neoadjuvant chemotherapy was planned, and she received the SOX regimen. After 3 courses of chemotherapy, post-therapeutic imaging examinations showed that the primary gastric tumor and metastatic lymph nodes had reduced in size. We performed distal gastrectomy with D2 lymphadenectomy. Final pathological examinations demonstrated that no viable tumor cells remained in the resected stomach and dissected lymph nodes (Grade 3). SOX may be useful as neoadjuvant chemotherapy to improve prognosis in patients with advanced gastric cancer. Herein, we report a case of advanced gastric cancer with pathological complete response after neoadjuvant chemotherapy with the SOX regimen.
Subject(s)
Antineoplastic Agents , Neoadjuvant Therapy , Oxaliplatin , Stomach Neoplasms , Antineoplastic Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols , Female , Gastrectomy , Humans , Middle Aged , Oxaliplatin/therapeutic use , Stomach Neoplasms/drug therapyABSTRACT
BACKGROUND/AIM: We previously described the safety of distal jejunal pouch with Roux-en-Y reconstruction after total gastrectomy. The present prospective study evaluated its clinical benefit. PATIENTS AND METHODS: Forty-five patients with gastric cancer were preoperatively assigned to groups who underwent Roux-en-Y reconstruction with jejunal pouch (PRY) (n=23) or without pouch (RY) (n=22). Age, sex, grade of lymph node dissection, splenectomy and mode of laparotomy were analyzed, and body mass index (BMI), volume of food intake at one sitting and blood chemistry (total protein, hemoglobin, iron and cholesterol) were periodically assessed in both groups. RESULTS: Post-surgical mortality and severe morbidity did not occur. Three and four patients in the PRY and RY groups, respectively, died of gastric cancer recurrence during the study. BMI at six months after surgery was significantly higher in the PRY than in the RY group (p<0.05). The percentage of food intake at one year after the procedure was significantly higher in the PRY than in the RY group (p<0.05). CONCLUSION: The distal jejunal pouch ameliorated postoperative weight loss and increased food intake. A distal jejunal pouch with PRY reconstruction may confer significant clinical advantages after total gastrectomy. The long-term clinical benefit of this procedure should be evaluated.
Subject(s)
Anastomosis, Roux-en-Y/rehabilitation , Gastrectomy/adverse effects , Jejunum/surgery , Neoplasm Recurrence, Local/prevention & control , Postoperative Complications/prevention & control , Stomach Neoplasms/surgery , Aged , Female , Follow-Up Studies , Humans , Male , Middle Aged , Prognosis , Prospective Studies , Quality of Life , Plastic Surgery Procedures , Stomach Neoplasms/pathologyABSTRACT
BACKGROUND: Sex-determining region Y-box 9 (SOX9) is an important transcription factor for the development and differentiation of cells and their organization. In the present study, the clinical significance of SOX9 expression in oesophageal squamous cell carcinoma was examined. MATERIALS AND METHODS: SOX9 expression in surgical specimens of primary tumours were immunohistochemically investigated in 175 patients with oesophageal squamous cell carcinomas. RESULTS: SOX9 was expressed (moderately or strongly) in 62.9% of samples. Expression of SOX9 was significantly positively correlated with depth of invasion, advanced stage, lymphatic and venous invasion, and poor prognosis. Univariate analysis showed that depth of invasion, lymph node metastasis, distant metastasis, stage, lymphatic invasion, venous invasion, and SOX9 expression were prognostic factors. Multivariate analysis indicated that depth of invasion and stage were independent prognostic factors, but SOX9 expression was not. CONCLUSION: SOX9 expression is related to prognosis in patients with oesophageal squamous cell carcinoma, although it is not an independent prognostic factor.
Subject(s)
Biomarkers, Tumor/genetics , Carcinoma, Squamous Cell/genetics , Esophageal Neoplasms/genetics , Prognosis , SOX9 Transcription Factor/genetics , Adult , Aged , Carcinoma, Squamous Cell/pathology , Esophageal Neoplasms/pathology , Esophageal Squamous Cell Carcinoma , Female , Gene Expression Regulation, Neoplastic , Humans , Lymph Nodes/pathology , Lymphatic Metastasis , Male , Middle AgedABSTRACT
Currently, immune checkpoint blockade against members of the B7/CD28 family is being used as a new molecular-targeted therapy, in patients with unresectable advanced or recurrent gastric cancer. Although human endogenous retrovirus-H long terminal repeat-associating protein 2 (HHLA2) is a novel molecule of the B7/CD28 family, the clinical impact of its expression remains uncertain in gastric cancer. Consequently, we examined HHLA2 expression in blood specimens from patients with gastric cancer, and investigated the relationship between its expression and clinicopathological factors to assess its potential power as a prognostic blood predictor. Untreated peripheral blood specimens were obtained from 111 patients with gastric cancer and 20 healthy volunteers. HHLA2 mRNA expression levels were determined using quantitative RT-PCR assay. Blood specimens obtained from patients with gastric cancer had significantly lower copies of HHLA2 mRNA than those obtained from healthy volunteers (P < 0.0001). Furthermore, HHLA2 expression was significantly correlated with the depth of tumor invasion (P = 0.0331), distant metastasis (P < 0.0001), and stage of disease (P = 0.0032). The 5-year survival rate was significantly higher in patients with high HHLA2 expression compared with the patients with low expression (P = 0.0001). These findings demonstrate that assessment of HHLA2 expression levels in the blood could be utilized to predict tumor aggressiveness in patients with gastric cancer.
ABSTRACT
BACKGROUND: The sentinel node (SN) detection by dual tracer method using indocyanine green (ICG) and a radioisotope (RI) has been recommended for early gastric cancer. However, institutions are limited due to radioactivity in the RI method. The greatest advantage of the RI method is that it objectively assesses RI uptake as a numerical value. The aim of the present study was to verify the usefulness of ICG fluorescence intensity in SN. METHODS: Seventeen patients with early gastric cancer were enrolled in this study. RI uptake by each lymph node was measured using Navigator GPS and fluorescence nodes were identified using the hyper eye medical system (HEMS). Fluorescence intensity in fluorescence nodes was evaluated using ICG intensity imaging software (Mizuho, Japan) of the HEMS. RESULTS: The total number of dissected lymph nodes was 227, with an average of 13.3 per patient. The numbers of HN, FN-S, and FN-B were 64, 77, and 34. RI uptake was significantly greater by FN-S than by non-FN-S (P = 0.0016). The median fluorescence intensity value was higher in HN than in non-HN (P < 0.001). A correlation was observed between RI uptake and fluorescence intensity. Dissecting FNs with fluorescence intensity levels of 1-6 resulted in 92.1% dissection of HNs. CONCLUSION: It is possible that the evaluation of fluorescence intensity is useful for selected SNs instead of RI tracer. If fluorescence intensity is measurable in surgery, an infrared fluorescence method using ICG may be useful and safe for the detection of SN in early gastric cancer.
Subject(s)
Optical Imaging/methods , Sentinel Lymph Node/pathology , Stomach Neoplasms/pathology , Contrast Media , Fluorescence , Fluorescent Dyes/pharmacokinetics , Humans , Indocyanine Green , Lymph Node Excision , Lymphatic Metastasis/pathology , Radiopharmaceuticals/pharmacokinetics , Stomach Neoplasms/surgery , Technetium/pharmacokineticsABSTRACT
Although postoperative management of gastric cancer is determined by pathological stage based on the tumor-node-metastasis classification, predicting disease recurrence and prognosis in patients undergoing gastrectomy is clinically difficult. We investigated the depth of tumor invasion and tumor size in resected specimens from patients with gastric cancer and assessed the clinical utility of primary tumor score (PTS) calculated by tumor depth and size as a prognostic marker. We classified 247 patients with gastric cancer into three groups based on cut-off values for deeper tumor invasion (pT2-T4) and larger tumor size (≥ 45 mm) as a PTS of 2 (both abnormalities), 1 (one abnormality), or 0 (neither abnormality). PTS correlated significantly with lymph node metastasis, lymphovascular invasion, and stage (P < 0.0001 each). Survival differences among groups based on PTS were significant (P < 0.0001). Multivariate analysis identified PTS alone as an independent prognostic factor (P = 0.0363). PTS derived from primary tumor information alone is a potentially useful marker for predicting tumor progression and prognosis in postoperative patients with gastric cancer.
ABSTRACT
As an antagonist of bone morphogenetic proteins (BMPs), 2, 4 and 7, gremlin1 plays a role in regulating organogenesis, tissue differentiation and angiogenesis. However, there is little information regarding gremlin1 in gastrointestinal cancer. We attempted to clarify how gremlin1 expression affects the clinical features and biological properties of gastric cancer. A total of 232 gastric cancer patients who received R0 gastrectomy at Kagoshima University Hospital were enrolled. Gremlin1 expression in gastric cancer was detected by immunohistochemical and western blotting methods. Correlations between clinicopathological parameters and gremlin1 expression were analyzed. Gremlin1 was identified in the cytoplasm and nucleus of all gastric cancer cell lines and some regions of surgical specimens of gastric cancer. One hundred and seventeen of the 232 patients (50.4%) were classified as gremlin1-positive based on gremlin1 expression. Gremlin1 positivity was correlated with shallower tumor depth, smaller tumor size, less nodal involvement and vessel invasion (p < 0.05). The 5-year survival rate of the gremlin1-positive group was 81%, which was significantly higher than the gremlin1-negative group (p < 0.01). Multivariate analysis revealed that gremlin1 was not selected as an independent prognostic marker. Gremlin1 expression in gastric cancer may be a useful prognostic marker that is involved with the BMP signaling pathway. Furthermore, gremlin1 may have clinical use as a diagnostic and treatment tool.
Subject(s)
Adenocarcinoma/pathology , Biomarkers, Tumor/metabolism , Intercellular Signaling Peptides and Proteins/metabolism , Stomach Neoplasms/pathology , Adenocarcinoma/metabolism , Adenocarcinoma/surgery , Adult , Aged , Aged, 80 and over , Female , Follow-Up Studies , Humans , Male , Middle Aged , Neoplasm Invasiveness , Prognosis , Stomach Neoplasms/metabolism , Stomach Neoplasms/surgery , Survival Rate , Tumor Cells, CulturedABSTRACT
Immune checkpoint inhibitor therapy has been clinically introduced for several malignancies, and its effectiveness has been confirmed by clinical trials. In particular, programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) are widely known as important immune checkpoint molecules associated with the mechanisms of immune escape by malignant tumor cells. In addition, liquid biopsy of blood specimens has the clinical benefit of providing a simple, repeatable sampling tool. Non-invasive liquid biopsy has recently been spotlighted as a promising approach to predicting tumor progression and prognosis. This study assessed the clinical significance of PD-L1 mRNA expression in blood specimens obtained from patients with gastric cancer. Peripheral blood specimens were collected before treatment from 124 patients with gastric cancer. The PD-L1 mRNA expression was evaluated by quantitative RT-PCR. Programmed death-ligand 1 mRNA expression was significantly higher in patients with advanced gastric cancer than in patients with early gastric cancer (P = .002). Moreover, PD-L1 expression correlated significantly with depth of tumor invasion, distant metastasis, and stage (P = .001, P < .001, and P < .001, respectively). Patients with high PD-L1 expression showed significantly poorer prognosis than those with low PD-L1 expression (P < .0001). Multivariate analysis indicated PD-L1 expression as an independent prognostic factor. Expression of PD-L1 in peripheral blood may offer an immunological predictor of tumor progression and disease outcome in patients with gastric cancer.
Subject(s)
B7-H1 Antigen/genetics , Stomach Neoplasms/genetics , Up-Regulation , Adult , Aged , Aged, 80 and over , B7-H1 Antigen/blood , Biomarkers, Tumor/blood , Biomarkers, Tumor/genetics , Cell Line, Tumor , Female , Gene Expression Regulation, Neoplastic , Humans , Liquid Biopsy , Male , Middle Aged , Prognosis , Stomach Neoplasms/bloodABSTRACT
BACKGROUND: While chemoradiation therapy (CRT) is one of the most useful treatments for esophageal squamous cell carcinoma (ESCC), it is important to predict response prior to treatment by using markers because some patients respond well and others do not. METHODS: Fifty-nine patients with ESCC were treated with neoadjuvant CRT at the Kagoshima University Hospital. The expression of seven types of biomarker candidate proteins in biopsy specimens of untreated primary tumors was evaluated to determine whether it correlated with response and prognosis. RESULTS: The positive expression rates were 47% for p53, 83% for CDC25B, 68% for 14-3-3sigma, 76% for p53R2, 75% for ERCC1, 32% for Gli-1, and 54% for Nrf2. In terms of histological response, tumor grade of the 59 patients was 48.8% for grade 1 as the non-responder, 29.2% for grade 2, and 22.0% for grade 3 as the responder. CRT was significantly effective in p53(-), p53R2(-), ERCC1(-), and Nrf2(-) tumors, while p53(-), p53R2(-), and ERCC1(-) were factors independently correlated with effective histological response. Their combined expression of two or three negative expressions had 100% effective response and was a significant prognostic factor. CONCLUSION: Our results suggest that two or three negative expressions of p53, p53R2, and ERCC1 in biopsy specimens of primary tumors were associated with a favorable response to CRT for ESCC. Assessment of tumor suppressor and DNA repair protein expressions in biopsy specimens may be useful for the potential utility of CRT therapy for patients with ESCC prior to treatment.
Subject(s)
Biomarkers, Tumor/metabolism , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/secondary , Chemoradiotherapy , Esophageal Neoplasms/metabolism , Esophageal Neoplasms/pathology , Neoadjuvant Therapy , Biomarkers, Tumor/genetics , Carcinoma, Squamous Cell/therapy , Esophageal Neoplasms/therapy , Female , Follow-Up Studies , Humans , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Invasiveness , Prognosis , Retrospective Studies , Survival RateABSTRACT
BACKGROUND: Perforation of the horizontal duodenum is very rare due to the presence in retroperitoneal space. It depicts an unusual clinical picture and is difficult to diagnose, leading to increased morbidity and mortality. The treatment strategies are usually varied and based on small series of cases, literature reviews, and expert opinions. CASE PRESENTATION: Here, we presented three cases of horizontal duodenal perforation in three different clinical processes. The first case, a 30-year-old male patient, presented with abdominal pain and hematemesis after experiencing a physical assault on the previous day. Computed tomography (CT) scan showed rupture of the horizontal duodenum. It was repaired by side-to-side duodenojejunostomy. Postoperatively, he had anastomotic leakage, disseminated intravascular coagulation, and pulmonary failure and recovered after a long hospital stay. The second case, an 81-year-old female, had duodenal perforation with endoscopic coagulation of the bleeding diverticulum. Segmental resection of the duodenum and side-to-side duodenojejunostomy were performed. Postoperatively, there was slight anastomotic leakage, but surgical intervention was not needed. The third case, an 89-year-old female, was a patient with obstructive jaundice due to pancreas head carcinoma, who developed perforation of the horizontal duodenum during endoscopic retrograde cholangiopancreatography (ERCP). After unsuccessful conservative management, duodenojejunostomy at the perforated site and gastric bypass were performed. The postoperative course was uneventful. CONCLUSION: Early suspicion and investigation is necessary for cases of abdominal injuries. CT scan is the investigation of choice. The management options should be based on the clinical condition of the patient, comorbidities, surgical expertise, existing guidelines, and available resources.
ABSTRACT
Sentinel node navigation surgery (SNNS) has been recognized as a minimally invasive tool for individualized lymphadenectomy in patients with early gastric cancer (EGC). The aim of this study was to compare clinicopathological factors, adverse events, and clinical outcomes between sentinel node mapping (SNM) and SN dissection (SND) groups and assess the clinical utility of SNNS in patients with EGC. The clinical data of 157 patients with EGC, diagnosed as clinical T1N0M0 with tumors ≤ 40 mm, undergoing SNNS between March 2004 and April 2016 were retrospectively reviewed. Twenty-seven patients were excluded from the analysis. In the remaining 130 patients, 59 and 71 patients underwent standard lymphadenectomy for SNM and SND, respectively. The sentinel node detection rate in the SNM and SND groups was 98.3% (58/59) and 100% (71/71), respectively. Two (3.5%), 15 (25.9%), and 41 (70.7%) patients having sentinel nodes underwent total gastrectomy, proximal gastrectomy (PG), and distal gastrectomy (DG), respectively, in the SNM group. One (1.4%), 5 (7.0%), 10 (14.1%), 39 (54.9%), and 16 (22.5%) patients underwent PG, DG, segmental gastrectomy, local resection, and endoscopic submucosal dissection, respectively, in the SND group. There was no significant difference in postoperative complications between the SNM and SND groups (P = 0.781). Survival did not differ between the both groups (P = 0.856). The present results suggest that personalized surgery with SND provides technical safety and curability related with a favorable survival outcome in patients with EGC.