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2.
Gastric Cancer ; 24(2): 535-543, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33118118

ABSTRACT

BACKGROUND: The appropriate surgical procedure for patients with upper third early gastric cancer is controversial. We compared total gastrectomy (TG) with proximal gastrectomy (PG) in this patient population. METHODS: A multicenter, non-randomized trial was conducted, with patients treated with PG or TG. We compared short- and long-term outcomes between these procedures. RESULTS: Between 2009 and 2014, we enrolled 254 patients from 22 institutions; data from 252 were included in the analysis. These 252 patients were assigned to either the PG (n = 159) or TG (n = 93) group. Percentage of body weight loss (%BWL) at 1 year after surgery, i.e., the primary endpoint, in the PG group was significantly less than that of the TG group (- 12.8% versus - 16.9%; p = 0.0001). For short-term outcomes, operation time was significantly shorter for PG than TG (252 min versus 303 min; p < 0.0001), but there were no group-dependent differences in blood loss and postoperative complications. For long-term outcomes, incidence of reflux esophagitis in the PG group was significantly higher than that of the TG group (14.5% versus 5.4%; p = 0.02), while there were no differences in the incidence of anastomotic stenosis between the two (5.7% versus 5.4%; p = 0.92). Overall patient survival rates were similar between the two groups (3-year survival rates: 96% versus 92% in the PG and TG groups, respectively; p = 0.49). CONCLUSIONS: Patients who underwent PG were better able to control weight loss without worsening the prognosis, relative to those in the TG group. Optimization of a reconstruction method to reduce reflux in PG patients will be important.


Subject(s)
Gastrectomy/methods , Stomach Neoplasms/surgery , Stomach/surgery , Adult , Aged , Aged, 80 and over , Anastomosis, Surgical , Female , Gastrectomy/mortality , Humans , Male , Middle Aged , Neoplasm Staging , Operative Time , Prognosis , Prospective Studies , Stomach/pathology , Stomach Neoplasms/mortality , Stomach Neoplasms/pathology , Survival Rate , Treatment Outcome , Weight Loss
3.
Transplant Proc ; 50(5): 1238-1242, 2018 Jun.
Article in English | MEDLINE | ID: mdl-29880341

ABSTRACT

BACKGROUND: In this study we present our new surgical procedure, laparoendoscopic single-site surgery plus 1 for donor nephrectomy (LESS+1-DN), which shortens warm ischemic time (WIT) and improves surgical outcomes. METHODS: From January 2013 to February 2017, 15 patients who underwent LESS-DN and 41 patients who underwent LESS+1-DN at our institution were evaluated retrospectively. Patients were divided into 3 groups: group A, 15 cases of LESS-DN; group B, the first 15 patients who underwent LESS+1-DN; and group C, 26 patients who underwent subsequent LESS+1-DN. To reduce WIT, we clearly defined the roles of the surgeon and first assistant in the 26 subsequent LESS+1-DN cases. The surgeon dissected the renal pedicle and harvested the kidney graft using a recovery bag and the first assistant held the recovery bag. RESULTS: The mean operative time in group C (213.7 minutes) was significantly shorter than that in groups A (253.3 minutes) and B (253.8 minutes). The WIT in group C (195.2 seconds) was significantly shorter than that in groups A (389.8 seconds) and B (313.2 seconds). Open conversion was required in 1 case in group A. None of the donors required conversion to open surgery and no perioperative complications occurred in groups B and C. Linear regression analysis of the LESS+1-DN operative times and consecutive case numbers demonstrated a shallow learning curve (R2 = 0.392, P < .05). CONCLUSION: Our new procedure that divides the roles of the operator and the first assistant contributed significantly to a shortening of WIT. Dividing roles can facilitate a safer laparoscopic donor nephrectomy.


Subject(s)
Kidney Transplantation/methods , Nephrectomy/methods , Tissue and Organ Harvesting/methods , Warm Ischemia/methods , Adult , Aged , Conversion to Open Surgery/statistics & numerical data , Female , Humans , Laparoscopy/methods , Learning Curve , Length of Stay , Living Donors , Male , Middle Aged , Operative Time , Retrospective Studies
4.
Dis Esophagus ; 31(7)2018 Jul 01.
Article in English | MEDLINE | ID: mdl-29617733

ABSTRACT

Reflux following an esophagectomy with gastric conduit reconstruction in the posterior mediastinum is a clinically significant problem. In this study, we investigated the frequency and impact of reflux on the quality of life (QOL) among 158 patients who underwent an esophagectomy for esophageal cancer using an original questionnaire and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Version 3.0 (EORTC QLQ-C30). Reflux frequency was assessed using the original questionnaire. The number of patients who complained of reflux every day, two or three times a week, once a week, or less than once a week was 16 (10.1%), 21 (13.3%), 26 (16.5%), and 60 (38.0%), respectively. Out of 35 patients (22.2%) reported no reflux symptoms. Patients were divided into two groups: those with reflux ≥ once/week (63 patients) and those with low frequency of symptoms (95 patients). Time elapsed following surgery was the only factor to influence reflux frequency. Reflux frequency decreased within two years of surgery; however, the frequency plateaued after more than two years. QOL was assessed using the EORTC QLQ-C30. The ≥ once/week reflux group had a significantly lower global health status score than the low-frequency reflux group (59.6 ± 24.2 vs. 70.8 ± 20.7; P = 0.007). In addition, the ≥ once/week reflux group had a significantly lower social functioning score than the low-frequency reflux group (81.6 ± 24.1 vs. 88.4 ± 19.8; P = 0.035). Regarding symptoms, the ≥ once/week reflux group had significantly higher scores for fatigue, nausea, and vomiting, dyspnea and insomnia compared to the low-frequency reflux group (fatigue: 42.4 ± 21.9 vs. 28.9 ± 18.4, P < 0.001; nausea and vomiting: 17.3 ± 17.1 vs. 4.9 ± 10.6, P < 0. 001; dyspnea: 29.2 ± 26.0 vs. 21.7 ± 26.8, P = 0.043; insomnia: 22.2 ± 31.1 vs. 10.5 ± 21.7, P = 0.015). Thus, reflux after an esophagectomy was associated with a lower QOL.


Subject(s)
Esophagectomy/adverse effects , Gastroesophageal Reflux/psychology , Plastic Surgery Procedures/adverse effects , Postoperative Complications/psychology , Quality of Life/psychology , Aged , Esophageal Neoplasms/surgery , Esophagectomy/methods , Esophagogastric Junction/surgery , Female , Gastroesophageal Reflux/epidemiology , Gastroesophageal Reflux/etiology , Humans , Male , Mediastinum/surgery , Middle Aged , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Postoperative Period , Plastic Surgery Procedures/methods , Surveys and Questionnaires , Treatment Outcome
6.
Dis Esophagus ; 31(4)2018 Apr 01.
Article in English | MEDLINE | ID: mdl-29190316

ABSTRACT

Although no consensus is available on the treatment of esophageal squamous cell carcinoma (ESCC) invading adjacent organs (T4), establishing effective induction treatments is crucial to altering an unresectable status and achieving curative resection. Here, we evaluated the efficacy of chemotherapy using 5-fluorouracil, cisplatin, and docetaxel (DCF) as the initial induction treatment for T4 ESCC. Fifty patients without distant metastasis who underwent initial induction chemotherapy using DCF for T4 ESCC were propensity score-matched with 50 patients who underwent radiotherapy concurrent with cisplatin and 5-fluorouracil (CRT). In the DCF group, 24 (48.0%) patients underwent surgery, achieving a 64% clinical response rate compared to 72.0% for induction CRT. CRT was also performed in another 24 (48.0%) patients in the DCF group in whom surgical resection was not indicated. The DCF group had significantly higher overall resectability than the CRT group (78.0% vs. 48.0%, P = 0.0017). The esophageal perforation rate during induction treatments was significantly lower in the DCF group than the CRT group (4.0% vs. 18.0%, P = 0.0205). Prognosis was significantly better in the DCF group than the CRT group (5-year cancer-specific survival 42.1% vs. 22.2%, P = 0.0146). Thus, induction DCF chemotherapy in patients with T4 ESCC reduced esophageal perforation and increased overall resectability, leading to better survival than CRT alone. Therefore, DCF chemotherapy may be an effective and safe option for initial induction treatment of T4 ESCC.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Carcinoma, Squamous Cell/therapy , Cisplatin/administration & dosage , Esophageal Neoplasms/therapy , Fluorouracil/administration & dosage , Induction Chemotherapy/methods , Taxoids/administration & dosage , Aged , Carcinoma, Squamous Cell/pathology , Chemoradiotherapy/methods , Docetaxel , Esophageal Neoplasms/pathology , Esophageal Squamous Cell Carcinoma , Esophagoscopy/statistics & numerical data , Female , Humans , Male , Middle Aged , Propensity Score , Treatment Outcome
7.
Dis Esophagus ; 30(11): 1-8, 2017 Nov 01.
Article in English | MEDLINE | ID: mdl-28881906

ABSTRACT

Although 3-field lymph node dissection (3-FLD) is often performed for thoracic esophageal squamous cell carcinoma (ESCC), the clinical effects of cervical lymph node dissection in addition to mediastinal and abdominal dissections on postoperative complications remain unclear. A total of 367 ESCC patients who underwent curative esophagectomy for thoracic esophageal cancer in our hospital from 2010 to 2015 were included in the study: 157 patients who underwent 2-field lymph node dissection (2-FLD) and 210 patients who underwent 3-FLD. Clinicopathological parameters and postoperative complications based on the Clavien-Dindo classification were compared between the two groups. We performed propensity score matching (PSM) analyses to compare the groups with well-balanced backgrounds. In terms of patient background, clinical T (p < 0.001), N (p < 0.001), and M (p = 0.002) stage of tumor was significantly more advanced; therefore, preoperative treatment was more frequently performed in the 3-FLD group than in the 2-FLD group (91.0% vs. 79.0%, P< 0.001). However, perioperative parameters including operation time, blood loss, and the number of dissected mediastinal and abdominal lymph nodes did not differ between the groups. In terms of postoperative complications, the occurrence rate of pneumonia increased significantly in patients with 3-FLD compared to 2-FLD (grade III or higher: 10.5% vs. 3.2%, P= 0.025). Although the duration of systemic inflammatory response syndrome (SIRS) was longer in the 3-FLD group than in the 2-FLD group (median 3 days vs. 2 days, P= 0.025), other postoperative parameters (including the highest level of postoperative serum C-reactive protein, intensive care unit stay, re-operation rate, and postoperative hospital stay) were similar between the groups. After PSM, the differences in the background between the groups disappeared. PSM analysis showed that there was no significant difference in each complication between the groups. The duration of SIRS tended to be longer in the 3-FLD group than in the 2-FLD group, but the difference was not significant. The field of lymphadenectomy negatively impacted the short-term outcome in ESCC patients in terms of pneumonia and inflammatory response. However, because the results of the PSM analyses indicate that the short-term outcome was similar between the two groups, 3-FLD could be as feasible as 2-FLD in ESCC patients.


Subject(s)
Carcinoma, Squamous Cell/surgery , Esophageal Neoplasms/surgery , Esophagectomy/methods , Lymph Node Excision/methods , Lymph Nodes/surgery , Postoperative Complications/etiology , Abdomen , Adult , Aged , Aged, 80 and over , C-Reactive Protein/analysis , Carcinoma, Squamous Cell/blood , Carcinoma, Squamous Cell/pathology , Esophageal Neoplasms/blood , Esophageal Neoplasms/pathology , Esophageal Squamous Cell Carcinoma , Female , Humans , Length of Stay , Lymph Nodes/pathology , Male , Mediastinum , Middle Aged , Neck , Operative Time , Pneumonia/etiology , Postoperative Period , Propensity Score , Prospective Studies , Retrospective Studies , Systemic Inflammatory Response Syndrome/etiology , Time Factors , Treatment Outcome
8.
Transplant Proc ; 48(3): 874-7, 2016 Apr.
Article in English | MEDLINE | ID: mdl-27234756

ABSTRACT

BACKGROUND: Persistent hyperparathyroidism in kidney transplant recipients may be prolonged for a few years, and in these cases, parathyroidectomy is indicated even if graft function is satisfactory. The aim of this study was to characterize the parathyroid glands in long-term dialysis recipients and determine the pathogenesis of persistent hyperparathyroidism. METHODS: We analyzed 44 parathyroid glands resected from 11 patients who underwent parathyroidectomy after kidney transplantation. The histopathologic types and weights of all the parathyroid glands were evaluated. RESULTS: The mean dialysis period was 15.8 years, and the time from kidney transplantation to parathyroidectomy ranged from 3.5 to 89 months. Nodular hyperplasia was present in parathyroid glands in all cases. The mean glandular weight was 396.0 ± 299.0 mg, and the maximum glandular weight was 3200 mg. Seven patients who underwent parathyroidectomy >1 year after kidney transplantation (late PT) were compared with 4 patients who underwent parathyroidectomy within 10 months after transplantation (early PT). The maximum (442.9 vs 1503 mg; P = .018) and mean (312.5 ± 177.4 mg vs 1135.6 ± 977.7 mg; P = .001) glandular weights were significantly lower in patients who underwent late PT compared with those who received early PT. Based on the histopathologic type and glandular weight of each parathyroid gland, nodular hyperplasia in glands ≤150 mg was common in patients who underwent late PT. CONCLUSIONS: The presence of nodular hyperplasia in parathyroid glands with a low weight may be involved in long-lasting persistent hyperparathyroidism in patients undergoing long-term dialysis.


Subject(s)
Hyperparathyroidism, Secondary/etiology , Kidney Transplantation/adverse effects , Parathyroid Glands/pathology , Renal Dialysis/adverse effects , Female , Fluid Therapy/adverse effects , Follow-Up Studies , Humans , Hyperparathyroidism, Secondary/pathology , Hyperparathyroidism, Secondary/surgery , Male , Middle Aged , Parathyroid Glands/surgery , Parathyroidectomy , Time Factors
9.
Br J Surg ; 103(1): 97-104, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26506079

ABSTRACT

BACKGROUND: [(18) F]fluorodeoxyglucose (FDG)-PET has been used to evaluate the response of primary tumours to neoadjuvant therapy for oesophageal cancer. The clinical significance of the number of PET-positive nodes before and after therapy has not been investigated previously. METHODS: [(18) F]FDG-PET was performed before and 2-3 weeks after completion of neoadjuvant chemotherapy to identify the number of PET-positive nodes, and these numbers were assessed in relation to metabolic changes in the primary tumour. RESULTS: Of 302 patients in total, 90 had no PET-positive nodes, 83 had one, 59 had two and 70 patients had three or more positive nodes before therapy. After treatment, the numbers were: none in 207 patients, one in 59, two in 20 and three or more in 16 patients. The number of PET-positive nodes after treatment was influenced by both the number of PET-positive nodes before therapy and the response to preoperative therapy, and correlated with the number of metastatic lymph nodes. Overall survival was longer in patients who had no PET-positive nodes after treatment than in those who had one or more. Multivariable analysis identified the numbers of PET-positive nodes before and after chemotherapy as independent prognostic factors, together with clinical response, tumour depth and lymph node involvement. CONCLUSION: The number of PET-positive nodes after treatment correlated with survival in patients with oesophageal cancer who underwent neoadjuvant chemotherapy.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Squamous Cell/drug therapy , Esophageal Neoplasms/drug therapy , Esophagectomy , Lymph Nodes/diagnostic imaging , Positron-Emission Tomography , Adult , Aged , Antineoplastic Agents/administration & dosage , Carcinoma, Squamous Cell/diagnostic imaging , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/surgery , Chemotherapy, Adjuvant , Esophageal Neoplasms/diagnostic imaging , Esophageal Neoplasms/mortality , Esophageal Neoplasms/surgery , Female , Fluorodeoxyglucose F18 , Humans , Lymphatic Metastasis , Male , Middle Aged , Multivariate Analysis , Radiopharmaceuticals , Treatment Outcome
10.
Br J Cancer ; 112(2): 352-6, 2015 Jan 20.
Article in English | MEDLINE | ID: mdl-25490524

ABSTRACT

BACKGROUND: Circulating tumour DNA (ctDNA) is an emerging candidate biomarker for malignancies and may be useful for monitoring the disease status of gastric cancer. METHODS: We performed targeted deep sequencing of plasma cell-free DNA (cfDNA) by massively parallel sequencing in patients with tumours harbouring TP53 mutations. The quantitative values of TP53-ctDNA during the clinical course were compared with the tumour status. RESULTS: Three out of ten patients with TP53 mutations in primary tumours showed detectable TP53 mutation levels in preoperative cfDNA. Although the cfDNA concentrations were not always reflective of the disease course, the ctDNA fraction correlated with the disease status. CONCLUSIONS: ctDNA may serve as a useful biomarker to monitor gastric cancer progression and residual disease.


Subject(s)
Biomarkers, Tumor/blood , DNA, Neoplasm/blood , Stomach Neoplasms/blood , Aged , Aged, 80 and over , DNA Mutational Analysis , Disease Progression , High-Throughput Nucleotide Sequencing , Humans , Lymphatic Metastasis , Male , Neoplasm, Residual , Prospective Studies , Stomach Neoplasms/pathology , Stomach Neoplasms/surgery , Tumor Suppressor Protein p53/genetics
11.
Br J Surg ; 100(11): 1490-7, 2013 Oct.
Article in English | MEDLINE | ID: mdl-24037571

ABSTRACT

BACKGROUND: Several studies have examined the clinical significance of metabolic response in primary tumours by [(18) F]fluorodeoxyglucose positron emission tomography ((18) F-FDG-PET) in patients with oesophageal cancer who undergo neoadjuvant therapy. The relevance of the metabolic response in lymph nodes is unclear. METHODS: Consecutive patients with oesophageal cancer who underwent neoadjuvant chemotherapy followed by surgery were studied. (18) F-FDG-PET was performed before and 2-3 weeks after completion of neoadjuvant chemotherapy, assessing FDG uptake in primary tumours and lymph nodes considered to be metastatic. RESULTS: Before therapy, 156 (73·9 per cent) of 211 patients had PET-positive nodes, of whom 89 (57.1 per cent) had no evidence of metabolic activity in these lymph nodes following chemotherapy. There was a significant relationship between post-treatment lymph node status assessed by FDG-PET and numbers of pathologically confirmed metastatic lymph nodes. Patients with post-treatment PET-positive nodes had shorter survival than those without (5-year survival rate 25 versus 62·6 per cent; P < 0·001). There was no difference in survival between patients with PET-positive nodes before but not after therapy and patients who had PET-negative nodes throughout (5-year survival rate 59 versus 71 per cent respectively; P = 0·207). Multivariable analysis identified post-treatment nodal status assessed by FDG-PET and tumour depth as independent prognostic factors. CONCLUSION: Identification of PET-positive lymph nodes after completion of chemotherapy is a predictor of poor prognosis of patients with oesophageal cancer scheduled for surgery. FDG-PET lymph node status after neoadjuvant chemotherapy is more important than that before chemotherapy.


Subject(s)
Carcinoma, Squamous Cell/drug therapy , Esophageal Neoplasms/drug therapy , Fluorodeoxyglucose F18 , Radiopharmaceuticals , Carcinoma, Squamous Cell/diagnostic imaging , Carcinoma, Squamous Cell/surgery , Disease-Free Survival , Esophageal Neoplasms/diagnostic imaging , Esophageal Neoplasms/surgery , Female , Humans , Lymph Nodes/diagnostic imaging , Lymphatic Metastasis , Male , Middle Aged , Multimodal Imaging/methods , Multimodal Imaging/mortality , Neoadjuvant Therapy , Radionuclide Imaging , Treatment Outcome
12.
Br J Cancer ; 108(5): 1119-25, 2013 Mar 19.
Article in English | MEDLINE | ID: mdl-23403818

ABSTRACT

BACKGROUND: NY-ESO-1 antibodies are specifically observed in patients with NY-ESO-1-expressing tumours. We analysed whether the NY-ESO-1 humoral immune response is a useful tumour marker of gastric cancer. METHODS: Sera from 363 gastric cancer patients were screened by enzyme-linked immunosorbent assay (ELISA) to detect NY-ESO-1 antibodies. Serial serum samples were obtained from 25 NY-ESO-1 antibody-positive patients, including 16 patients with curative resection and 9 patients who received chemotherapy alone. RESULTS: NY-ESO-1 antibodies were detected in 3.4% of stage I, 4.4% of stage II, 25.3% of stage III, and 20.0% of stage IV patients. The frequency of antibody positivity increased with disease progression. When the NY-ESO-1 antibody was used in combination with carcinoembryonic antigen and CA19-9 to detect gastric cancer, information gains of 11.2% in stages III and IV, and 5.8% in all patients were observed. The NY-ESO-1 immune response levels of the patients without recurrence fell below the cutoff level after surgery. Two of the patients with recurrence displayed incomplete decreases. The nine patients who received chemotherapy alone continued to display NY-ESO-1 immune responses. CONCLUSION: When combined with conventional tumour markers, the NY-ESO-1 humoral immune response could be a useful tumour marker for detecting advanced gastric cancer and inferring the post-treatment tumour load in seropositive patients.


Subject(s)
Antibodies, Neoplasm/blood , Antigens, Neoplasm/immunology , Biomarkers, Tumor/blood , Membrane Proteins/immunology , Stomach Neoplasms/immunology , Aged , Antigens, Tumor-Associated, Carbohydrate/analysis , Carcinoembryonic Antigen/analysis , Disease Progression , Female , Humans , Immunity, Humoral , Male , Middle Aged , Prognosis , Stomach Neoplasms/diagnosis , Stomach Neoplasms/pathology , Tumor Burden
14.
Br J Cancer ; 106(8): 1415-23, 2012 Apr 10.
Article in English | MEDLINE | ID: mdl-22433967

ABSTRACT

BACKGROUND: Lin28 is a negative regulator of the tumour suppressor microRNA, let-7, suggesting its role in tumourigenesis. However, the clinical significance of Lin28 expression in oesophageal cancer has not been elucidated. METHODS: Lin28 and Lin28B expression was examined by immunohistochemistry in 161 tissues from patients with oesophageal cancer who had undergone curative surgery. The relationship between the expressions of Lin28 and Lin28B and various clinicopathological factors was examined. In vitro assays were conducted to determine the role of Lin28 in aggressiveness of oesophageal cancers using oesophageal cancer cell line. RESULTS: Lin28 and Lin28B were overexpressed in oesophageal cancer cells compared with non-cancerous epithelial cells, especially in the invasive front. High expression of Lin28 and Lin28B correlated significantly with lymph node metastasis and poor prognosis. High expression of Lin28B expression correlated significantly with low expression of let-7. Multivariate analysis also identified Lin28B expression as an independent prognostic factor. In vitro assays showed that the proliferative and invasive activities were significantly reduced in Lin28B-knockdown cells, compared with control cells. CONCLUSION: High expression of Lin28 is associated with poor prognosis and high tumour aggressiveness in oesophageal cancer and these effects are mediated through increased proliferation and invasiveness of oesophageal cancer cells.


Subject(s)
DNA-Binding Proteins/metabolism , Esophageal Neoplasms/metabolism , Esophageal Neoplasms/pathology , RNA-Binding Proteins/metabolism , Cell Proliferation , DNA-Binding Proteins/biosynthesis , DNA-Binding Proteins/genetics , Esophageal Neoplasms/diagnosis , Esophageal Neoplasms/genetics , Female , Humans , Immunohistochemistry , Male , Middle Aged , Prognosis , RNA-Binding Proteins/biosynthesis , RNA-Binding Proteins/genetics , Real-Time Polymerase Chain Reaction
15.
Br J Cancer ; 106(5): 947-54, 2012 Feb 28.
Article in English | MEDLINE | ID: mdl-22333595

ABSTRACT

BACKGROUND: Recently, PFTK1 was identified as a member of the cyclin-dependent kinase family; however, its expression and clinical significance in oesophageal squamous cell carcinoma (ESCC) have not been evaluated. METHODS: PFTK1 expression was initially examined by expression microarray in 77 ESCC patients. Using independent samples of 223 patients, PFTK1 expression was evaluated immunohistochemically to assess the relationship between expression and various clinicopathological parameters. The association between PFTK1 and the response to chemotherapy was also investigated in pretreatment samples of 85 patients who received chemotherapy as first treatment. RESULTS: Significant upregulation of PFTK1 expression was noted in ESCC compared with normal epithelium. PFTK1 expression was positive in 51.6% (115 out of 223) of the tumours, but did not correlate with any clinicopathological parameter. The 5-year overall survival rate was poorer in patients positive for PFTK1 (43.6%) than those with negative expression (66.2%, P<0.001). Uni- and multivariate analyses identified PFTK1 as an independent marker of prognosis (RR=2.428, 95% CI=1.615-3.711, P<0.001). Out of 85 biopsy samples, 40 (47.1%) tumours showed PFTK1-positive expression, and the response rate to chemotherapy was significantly lower than PFTK1-negative tumours (27.9% vs 72.1%, P<0.001). CONCLUSION: PFTK1 is not only useful as a prognostic marker, but also as a predictor of the response to chemotherapy.


Subject(s)
Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/metabolism , Cyclin-Dependent Kinases/metabolism , Esophageal Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/metabolism , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/pathology , Cyclin-Dependent Kinases/genetics , Esophageal Neoplasms/metabolism , Esophageal Neoplasms/mortality , Esophageal Neoplasms/pathology , Female , Follow-Up Studies , Gene Expression Regulation, Neoplastic , Humans , Male , Middle Aged , Survival Rate , Treatment Outcome
16.
Br J Cancer ; 104(4): 707-13, 2011 Feb 15.
Article in English | MEDLINE | ID: mdl-21206495

ABSTRACT

BACKGROUND: Although multidrug resistance protein 2 (MRP2) confers chemoresistance in some cancer types, its implication on oesophageal squamous cell carcinoma (ESCC) remains unclear. METHODS: We evaluated MRP2 expression by immunohistochemistry and RT-PCR using 81 resected specimens from ESCC patients who did or did not receive neo-adjuvant chemotherapy (NACT), including 5-fluorouracil, doxorubicin, and cisplatin (CDDP). Correlation between MRP2 expression and response to chemotherapy was also examined in 42 pre-therapeutic biopsy samples and eight ESCC cell lines. RESULTS: MRP2-positive immunostaining was more frequently observed in ESCCs with NACT than in those without NACT (27.3 vs 5.4%). The MRP2-positive patients showed poorer prognosis than MRP2-negative patients (5-year survival rate, 25.6 vs 55.7%). Concordantly, ESCC with NACT showed 2.1-fold higher mRNA expression of MRP2 than those without NACT (P=0.0350). In pre-therapeutic biopsy samples of patients with NACT, non-responders showed 2.9-fold higher mRNA expression of MRP2 than responders (P=0.0035). Among the panel of ESCC cell lines, TE14 showed the highest MRP2 mRNA expression along with the strongest resistance to CDDP. Inhibition of MRP2 expression by small-interfering RNA reduced chemoresistance to CDDP. CONCLUSION: Our data suggested that MRP2 is one of molecules, which regulate the sensitivity to chemotherapy including CDDP in advanced ESCC patients.


Subject(s)
Carcinoma, Squamous Cell/genetics , Drug Resistance, Neoplasm/genetics , Esophageal Neoplasms/genetics , Multidrug Resistance-Associated Proteins/physiology , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biomarkers, Pharmacological/analysis , Biomarkers, Pharmacological/metabolism , Biomarkers, Tumor/analysis , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/mortality , Cell Line, Tumor , Cisplatin/administration & dosage , Doxorubicin/administration & dosage , Drug Resistance, Multiple/drug effects , Drug Resistance, Multiple/genetics , Drug Resistance, Neoplasm/drug effects , Esophageal Neoplasms/drug therapy , Esophageal Neoplasms/metabolism , Esophageal Neoplasms/mortality , Female , Fluorouracil/administration & dosage , Gene Expression Regulation, Neoplastic/drug effects , Humans , Immunohistochemistry , Male , Middle Aged , Multidrug Resistance-Associated Protein 2 , Multidrug Resistance-Associated Proteins/genetics , Multidrug Resistance-Associated Proteins/metabolism , Neoadjuvant Therapy , RNA, Small Interfering/pharmacology , Survival Analysis
17.
Br J Cancer ; 101(8): 1298-306, 2009 Oct 20.
Article in English | MEDLINE | ID: mdl-19755983

ABSTRACT

BACKGROUND: Cytokeratins (CKs) are structural marker proteins specific for epithelial cells. However, recent studies indicate their involvement in cancer progression. METHODS: We evaluated CK18 and its filament partner, CK8 expression, by immunohistochemistry in 210 resected specimens from patients with oesophageal squamous cell carcinoma (OSCC). We also analysed the relationship between their expression and various clinicopathological parameters including prognosis. RESULTS: Neither CK18 nor CK8 was expressed in non-cancerous squamous epithelium whereas proper oesophageal glands expressed both CKs. Ninety (42.9%) tumours were CK18 positive and 85 (40.5%) CK8 positive, and the concordance rate for immunohistochemical classification for CK18 and CK8 was 82.4%. CK18 expression correlated with poorly differentiated tumours, use of neo-adjuvant chemotherapy, and advanced stage. Prognosis of patients with CK18-positive tumours was poorer than that of patients with negative OSCC (P<0.001). A similar trend was noted for CK8 expression. Multivariate analysis identified pT (P=0.020), pN number (P=0.001), and CK18 expression (P=0.004) as independent prognostic factors. CK18 expression in 83 pretreatment biopsy specimens was detected in 47 cases (56.6%) and also correlated with prognosis (P=0.045). CONCLUSION: CK18/CK8 expression correlated with progression of OSCC. The significant correlation with prognosis and stable expression in biopsy specimen suggest usefulness of CK18 in selection of treatment strategies for OSCC.


Subject(s)
Biomarkers, Tumor/analysis , Carcinoma, Squamous Cell/chemistry , Esophageal Neoplasms/chemistry , Keratin-18/analysis , Keratin-8/analysis , Adult , Aged , Aged, 80 and over , Biopsy , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/pathology , Esophageal Neoplasms/mortality , Esophageal Neoplasms/pathology , Female , Humans , Immunohistochemistry , Male , Middle Aged , Prognosis , Survival Rate
18.
Br J Cancer ; 99(8): 1307-15, 2008 Oct 21.
Article in English | MEDLINE | ID: mdl-18827816

ABSTRACT

Gene expression profiling is a valuable tool for identifying differentially expressed genes in studies of disease subtype and patient outcome for various cancers. However, it remains difficult to assign biological significance to the vast number of genes. There is an increasing awareness of gene expression profile as an important part of the contextual molecular network at play in complex biological processes such as cancer initiation and progression. This study analysed the transcriptional profiles commonly activated at different stages of gastric cancers using an integrated approach combining gene expression profiling of 222 human tissues and gene regulatory dynamic mapping. We focused on an inferred core network with CDKN1A (p21(WAF1/CIP1)) as the hub, and extracted seven candidates for gastric carcinogenesis (MMP7, SPARC, SOD2, INHBA, IGFBP7, NEK6, LUM). They were classified into two groups based on the correlation between expression level and stage. The seven genes were commonly activated and their expression levels tended to increase as disease progressed. NEK6 and INHBA are particularly promising candidate genes overexpressed at the protein level, as confirmed by immunohistochemistry and western blotting. This integrated approach could help to identify candidate players in gastric carcinogenesis and progression. These genes are potential markers of gastric cancer regardless of stage.


Subject(s)
Gene Expression Profiling , Stomach Neoplasms/genetics , Stomach Neoplasms/pathology , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/genetics , Blotting, Western , Cell Transformation, Neoplastic/genetics , Cyclin-Dependent Kinase Inhibitor p21/biosynthesis , Cyclin-Dependent Kinase Inhibitor p21/genetics , Disease Progression , Female , Gene Expression , Humans , Immunohistochemistry , In Situ Hybridization, Fluorescence , Male , Middle Aged , Oligonucleotide Array Sequence Analysis , Reverse Transcriptase Polymerase Chain Reaction , Transcription, Genetic
19.
Dis Esophagus ; 21(2): 132-8, 2008.
Article in English | MEDLINE | ID: mdl-18269648

ABSTRACT

For esophageal cancer patients, the gastric tube is the first choice as an esophageal substitute, with the colon or the jejunum being used when the stomach cannot be used. We retrospectively compared these two methods from the viewpoint of peri-operative complications and long-term bodyweight alteration. From 1998 to 2005 53 patients who had undergone subtotal esophagectomy due to thoracic esophageal cancers were given reconstruction with the colon (28 cases) or the jejunum (25 cases). Both intestines were reconstructed via the subcutaneous route and were anastomosed to the internal mammalian artery and vein for a supercharged blood supply. There was no difference in operating time and blood loss. Compared with the colon reconstruction group, the hospital stay of the jejunum reconstruction group was significantly shorter (65 days vs 45 days, P = 0.0120) and the incidence of anastomotic leakage tended to be less (13 cases, 46%vs 6 cases, 24%, P = 0.1507), while other operative morbidity did not differ between the two groups. Bodyweight loss, which is a serious postoperative sequela after esophagectomy, was less in the jejunum group than in the colon group, showing a significant difference at 12 months after surgery. Our retrospective study revealed the jejunum to be superior to the colon for the reconstruction after esophagectomy along with gastrectomy, with respect to anastomotic leakage and bodyweight loss. The next step will be to conduct a prospective large cohort study.


Subject(s)
Colon/transplantation , Esophageal Neoplasms/surgery , Esophagectomy , Esophagus/surgery , Gastrectomy , Jejunum/transplantation , Aged , Female , Humans , Male , Middle Aged , Retrospective Studies , Time Factors
20.
Dis Esophagus ; 21(2): 144-50, 2008.
Article in English | MEDLINE | ID: mdl-18269650

ABSTRACT

(18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) is used for pre-treatment staging and evaluation of response to pre-operative therapy in advanced thoracic esophageal cancers. To evaluate the clinical significance of PET diagnosis of superficial thoracic esophageal cancers, FDG-PET was conducted preoperatively in 41 patients with such cancers without pre-operative therapy. We compared the PET diagnosis with clinicopathological findings with respect to both the primary tumor and lymph node (LN) metastasis. Of the 41 superficial thoracic esophageal cancers, 21 (51.2%) were PET positive for primary tumors. Although tumor length and histological type did not correlate with FDG uptake by primary tumors, non-flat (elevated or depressed) tumors showed significantly stronger FDG uptake than flat ones. Of 28 tumors infiltrating the deep submucosal layer, 19 (67.9%) were PET positive, while only two (15.4%) of 13 tumors infiltrating only the mucosa or shallow submucosal layer were PET positive. Manova identified FDG uptake as the only independent risk factor for deep submucosal invasion (odds ratio, 7.407; P = 0.0279). In 13 patients with pathological LN metastasis, although no LN metastasis was detected by FDG-PET, FDG uptake by the primary tumors was the only risk factor for LN metastasis (P = 0.0318). PET-negative tumors tended to reflect longer disease-free survival than PET-positive tumors, although this was not significant. FDG-PET is useful for detecting tumors infiltrating the middle or deep submucosal layer (sm2/sm3), and for predicting LN metastasis in patients with superficial thoracic esophageal cancers. FDG-PET is helpful for decision-making regarding treatment of such patients.


Subject(s)
Carcinoma, Squamous Cell/diagnostic imaging , Esophageal Neoplasms/diagnostic imaging , Fluorodeoxyglucose F18 , Positron-Emission Tomography , Radiopharmaceuticals , Carcinoma, Squamous Cell/pathology , Esophageal Neoplasms/pathology , Female , Humans , Male , Middle Aged
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