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1.
Anticancer Res ; 41(2): 783-794, 2021 Feb.
Article in English | MEDLINE | ID: mdl-33517283

ABSTRACT

BACKGROUND/AIM: The inflammatory cytokine IL-8 and its receptor CXCR2 are key signalling pathway molecules in cancer development. We hypothesized that IL-8/CXCR2 signalling promotes tumour progression in oesophageal squamous cell carcinoma (ESCC) patients. MATERIALS AND METHODS: We examined the relationship between IL-8/CXCR2 expression and clinicopathological factors by immunohistochemistry in samples from 63 patients with resectable ESCC. The effects of IL-8/CXCR2 signalling on cell proliferation and gene expression were examined in vitro and in vivo using ESCC cell lines. RESULTS: Increased IL-8/CXCR2 signalling was associated with shorter overall survival (p<0.05) and recurrence-free survival (p<0.05) in ESCC patients. Multivariate analysis identified IL-8/CXCR2 expression as a prognostic factor for surgically treated ESCC (p<0.05). In vitro, IL-8 exposure or over-expression significantly enhanced ESCC cell proliferation. SB225002, a CXCR2-specific antagonist, and IL-8 siRNA significantly suppressed cell proliferation. CONCLUSION: IL-8/CXCR2 expression is an independent prognostic factor for surgically treated ESCC, and IL-8/CXCR2 signalling contributes to ESCC cell proliferation.


Subject(s)
Esophageal Neoplasms/surgery , Esophageal Squamous Cell Carcinoma/surgery , Interleukin-8/metabolism , Receptors, Interleukin-8B/metabolism , Up-Regulation , Aged , Animals , Cell Line, Tumor , Cell Proliferation/drug effects , Esophageal Neoplasms/metabolism , Esophageal Neoplasms/pathology , Esophageal Squamous Cell Carcinoma/metabolism , Esophageal Squamous Cell Carcinoma/pathology , Female , Gene Expression Regulation, Neoplastic/drug effects , Humans , Interleukin-8/antagonists & inhibitors , Interleukin-8/genetics , Male , Mice , Middle Aged , Neoplasm Transplantation , Phenylurea Compounds/pharmacology , Prognosis , RNA, Small Interfering/pharmacology , Receptors, Interleukin-8B/antagonists & inhibitors , Receptors, Interleukin-8B/genetics , Signal Transduction/drug effects , Survival Analysis
2.
Oncol Lett ; 17(3): 3097-3102, 2019 Mar.
Article in English | MEDLINE | ID: mdl-30867739

ABSTRACT

The association between homeobox (HOX)B9 expression and tumor malignancy was identified recently. It was reported that HOXB9 induced tumor angiogenesis, and associated with poor prognosis in patients with breast and colon cancer. On the other hand, regional lymph nodes are the most common site of tumor spread, and lymph node metastasis is a major prognostic factor in gastric cancer. It was hypothesized that HOXB9 promotes tumor lymphangiogenesis and induces tumor progression, invasion and metastasis in gastric cancer. The aim of the present study was to evaluate the correlation between HOXB9 expression, prognosis and clinicopathologic factors in patients with gastric cancer, and to assess the contribution of HOXB9 expression to tumor cell lymphangiogenesis in vitro. HOXB9 expression was evaluated by immunohistochemistry in resected tumor tissues from 58 patients with gastric cancer, and the association between prognosis and clinicopathologic factors was determined. HOXB9 gene was overexpressed in human gastric cancer TMK-1 cells and the effect of HOXB9 overexpression on the expression of vascular endothelial growth factor (VEGF)-C, VEGF-D and VEGF receptor (R)-3 was determined. It was demonstrated that the depth of tumor invasion, the number of node metastases, lymphatic invasion and vascular invasion were significantly associated with HOXB9 expression. Overall survival was decreased in patients with HOXB9 expression. The mRNA expression of VEGF-D but not of VEGF-C and VEGFR-3 was increased in HOXB9-overexpressing TMK-1 cells compared with control cells. In conclusion, HOXB9 expression was positively correlated with gastric cancer progression and lymphangiogenesis marker expression. HOXB9 may be associated with lymphogenic metastasis.

3.
Case Rep Gastroenterol ; 12(3): 578-585, 2018.
Article in English | MEDLINE | ID: mdl-30323733

ABSTRACT

We report a patient with highly advanced gastric carcinoma who was treated successfully with chemoradiotherapy (CRT) comprising S-1 and cisplatin. The patient was a 71-year-old male who was diagnosed with advanced gastric carcinoma by esophagogastroduodenoscopy (EGD) by medical examination. EGD demonstrated type 3 advanced gastric carcinoma in the posterior wall of the upper gastric body. An abdominal computed tomography (CT) scan showed that the gastric wall was thickened due to gastric primary tumor, and large lymph nodes (LNs) including the lesser curvature LN, anterosuperior LN along the common hepatic artery and some para-aortic LNs were detected. The patient was diagnosed with stage IV advanced gastric carcinoma according to the Japanese classification of gastric carcinoma (cT4a, cN3, cM1 [para-aortic LN], cStage IV). Preoperative CRT was carried out in an attempt to downstage the disease. Remarkable reduction of the primary tumor and metastatic LNs was observed after initial CRT, and radiological examination determined that a partial response had been achieved. Adverse effects included grade 2 anorexia and grade 3 ALP elevation (919 U/ml). No grade 4 or more severe adverse event was observed. After CRT, although we recommended curative surgery, the patient refused surgical treatment and opted for conservative treatment. Thus, we continued S-1 oral administration for 1 year. Five months after beginning CRT, upper endoscopy showed that the tumor had maintained regression and scar formation, in which no cancer cells were detected by endoscopic biopsy. The patient is doing well and has maintained a clinical complete response for more than 42 months without curative surgery. CRT could be considered as an option for treatment of patients with locally advanced gastric carcinoma diagnosed as unresectable, or for those who refuse surgical treatment.

4.
Gastric Cancer ; 21(3): 508-515, 2018 May.
Article in English | MEDLINE | ID: mdl-28744619

ABSTRACT

BACKGROUND: Laparoscopic wedge resection (LWR) is widely performed for managing gastric submucosal tumors (SMTs). Despite the development of novel procedures such as laparoscopy-endoscopy cooperative surgery (LECS) and nonexposed endoscopic wall-inversion surgery (NEWS), the most appropriate surgical intervention for gastric SMTs remains unclear. METHODS: We retrospectively reviewed patient characteristics, surgical outcomes, postoperative courses, results of histopathological examinations, and surgical costs of 71 consecutive patients who underwent LWR, LECS, or NEWS for gastric SMTs from January 2010 to June 2016 in our institute. RESULTS: LWR, LECS, and NEWS were performed in 31, 14, and 26 cases, respectively. Patient backgrounds were comparable between groups. LWR was not performed for esophagogastric (E-G) junction tumors to avoid postoperative stricture, and LECS was not performed for ulcerated tumors to prevent tumor dissemination. NEWS was considered for tumors smaller than 3 cm for transoral extraction. Resected specimen area of the LWR group was significantly larger than that of the other groups. Further, the LWR group had a significantly higher complication rate. Compared to the LECS group, postoperative serum C-reactive protein level was significantly lower and postoperative hospitalization was significantly shorter in the NEWS group. Also, operation costs were significantly lower in the NEWS group. CONCLUSIONS: The surgical procedure for gastric SMTs must be carefully chosen according to tumor size, location, and presence or absence of ulceration. For selected patients, NEWS is suggested to be an appropriate option for the treatment of gastric SMTs.


Subject(s)
Gastrectomy/methods , Gastrointestinal Stromal Tumors/surgery , Minimally Invasive Surgical Procedures/methods , Stomach Neoplasms/surgery , Adult , Aged , Female , Gastrointestinal Stromal Tumors/pathology , Humans , Male , Middle Aged , Stomach Neoplasms/pathology
5.
Oncol Lett ; 14(4): 4220-4224, 2017 Oct.
Article in English | MEDLINE | ID: mdl-28943930

ABSTRACT

Comprehensive gene screening with transposons is a novel procedure for the systematic identification of resistant genes. The present study aimed to use this technique to identify candidate radioresistant genes in esophageal squamous cell carcinoma. A transposon is a base sequence that can translocate to another location in the genome at random. By inserting the cytomegalovirus promotor as a transcriptional activator in the transposon, the following gene in the new location becomes overexpressed and the gene located at the transposon insertion site is downregulated. Consequently, various transposon-tagged cells, which have differentially overexpressed or downregulated genes using the transposon method can be obtained. Following the irradiation of transposon-tagged cells, candidate radioresistant genes can be selected in order to detect the location of the transposon in the cells that have survived. A total of 11 genes were detected as candidate radioresistant genes. Cytochrome c oxidase 1 (MT-CO1), an enzyme involved in apoptosis through the activation of the caspase cascade, was one of the candidate genes identified. The relative expression level of MT-CO1 was 0.12 in MT-CO1-downregulated cells which was significantly lower compared with the expression level in parent TE4 cells (P<0.001). The survival rate was 28.7% in MT-CO1-downregulated cells and 10.5% in parent TE4 cells 9 days following 5-Gy irradiation. The activity of cytochrome c and caspase-3 following irradiation was significantly lower in the MT-CO1-downregulated radioresistant cells compared with in TE4 cells. In conclusion, the novel gene screening technique demonstrated to be useful for detecting candidate radioresistant genes in esophageal squamous cell carcinoma. The results of the present study revealed that the downregulation of MT-CO1 induced radioresistance occurs by inhibiting the activation of the caspase cascade in radioresistant esophageal cancer cells.

6.
Inflamm Res ; 66(9): 803-811, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28573312

ABSTRACT

OBJECTIVE AND DESIGN: An animal experiment was performed to demonstrate the anti-inflammatory effects of an alpha-lipoic acid (ALA) derivative, dihydrolipoyl histidinate zinc complex (DHLHZn) for acute lung injury (ALI) and to investigate the mechanism of action. MATERIAL: Rats were randomly divided into three experimental groups: control group (n = 17), DHLHZn(-) group (n = 11, ALI model rats), and DHLHZn(+) group (n = 12, ALI model rats treated by DHLHZn). TREATMENT: Lipopolysaccharides (LPS, 10 mg/kg) were administered intratracheally in the DHLHZn(-) group and the DHLHZn(+) group. For the DHLHZn(+) group, DHLHZn (100 mg/kg) was administered intraperitoneally 2 h prior to LPS administration. METHODS: Four hours after LPS administration, bronchoalveolar lavage fluid (BALF) and lung tissue were collected. The findings were analyzed using the Mann-Whitney U test. RESULTS: Total number of cells, number of neutrophils and lymphocytes, levels of various inflammatory cytokines, and NF-kB p65 concentration of BALF were significantly lower in the DHLHZn(+) group than in the DHLHZn(-) group (p < 0.05). ALI pathology scores were significantly lower in the DHLHZn(+) group than in the DHLHZn(-) group (p < 0.001). CONCLUSIONS: Anti-inflammatory effects of DHLHZn for ALI were demonstrated by BALF and histopathological findings. The mechanism of action of DHLHZn was considered to be via inhibition of the NF-kB signaling pathway. DHLHZn is thus suggested to be a new prophylactic agent for ALI.


Subject(s)
Acute Lung Injury/drug therapy , Anti-Inflammatory Agents/therapeutic use , Histidine/analogs & derivatives , Thioctic Acid/analogs & derivatives , Acute Lung Injury/immunology , Acute Lung Injury/pathology , Animals , Anti-Inflammatory Agents/pharmacology , Bronchoalveolar Lavage Fluid/cytology , Cell Count , Cytokines/immunology , Histidine/pharmacology , Histidine/therapeutic use , Lung/drug effects , Lung/immunology , Lung/pathology , Male , NF-kappa B/immunology , Rats, Sprague-Dawley , Thioctic Acid/pharmacology , Thioctic Acid/therapeutic use
7.
Int J Cancer ; 140(1): 188-196, 2017 Jan 01.
Article in English | MEDLINE | ID: mdl-27521503

ABSTRACT

Paclitaxel is a standard second-line gastric cancer treatment in Japan. Trastuzumab could be active as second-line chemotherapy for taxane/trastuzumab-naïve patients with epidermal growth factor 2 (HER2)-positive advanced gastric cancer. Patients aged ≥20 years with HER2-positive, previously treated (except for trastuzumab and taxane), unresectable or recurrent gastric adenocarcinoma underwent combined trastuzumab (first and subsequent doses of 8 and 6 mg kg-1 , respectively, every 3 weeks) and paclitaxel (days 1, 8, 15, every 4 weeks) treatment. Study endpoints were best overall response, progression-free survival, overall survival, and safety. From September 2011 to March 2012, 47 Japanese patients were enrolled. Forty patients discontinued treatment after a median of 128.5 (range 4-486) days. Complete and partial responses were obtained in one and 16 patients (response rate of 37% [95% CI 23-52]), respectively. Median progression-free survival and overall survival were 5.1 (95% CI 3.8-6.5) and 17.1 (95% CI 13.5-18.6) months, respectively. Grade 3/4 adverse events were neutropenia (32.6%), leukopenia (17.4%), anemia (15.2%) and hypoalbuminemia (8.7%). There was no clinically significant cardiotoxicity or cumulative toxicity. Three (disturbed consciousness, pulmonary fibrosis, and rapid disease progression) grade 5 events occurred. In conclusion, trastuzumab combined with paclitaxel was well tolerated and was a promising regimen for patients with HER2-positive, previously treated, advanced or recurrent gastric cancer.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Neoplasm Recurrence, Local/drug therapy , Paclitaxel/administration & dosage , Receptor, ErbB-2/metabolism , Stomach Neoplasms/drug therapy , Trastuzumab/administration & dosage , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Disease-Free Survival , Drug Administration Schedule , Female , Humans , Japan , Male , Middle Aged , Neoplasm Recurrence, Local/metabolism , Paclitaxel/adverse effects , Stomach Neoplasms/metabolism , Survival Analysis , Trastuzumab/adverse effects , Treatment Outcome
8.
Asian J Endosc Surg ; 10(1): 47-50, 2017 Feb.
Article in English | MEDLINE | ID: mdl-27739194

ABSTRACT

Situs inversus totalis (SIT) is a rare congenital condition in which abdominal and thoracic organs are transposed from normal positions. Laparoscopy-assisted distal gastrectomy for situs inversus totalis is technically difficult and has rarely been reported. Here, we report the case of man in his 40s with situs inversus totalis and a preoperative diagnosis of stage IA gastric cancer (cT1b, cN0, cM0). We successfully performed laparoscopy-assisted distal gastrectomy with D1+ lymph node dissection and Billroth I reconstruction. To ensure a safe procedure, we evaluated the vessels preoperatively with 3-D CT angiography. Furthermore, we performed the surgery by reversing our surgical positions, using a two-monitor method, and then reconstructing under direct vision through the incision. The surgery was performed with minimal blood loss, and no severe postoperative complications were observed. Histopathological examination revealed poorly to moderately differentiated stage IA (pT1b, pN0, pM0) adenocarcinoma. No recurrence has been observed as of 2 years postoperatively.


Subject(s)
Adenocarcinoma/surgery , Gastrectomy/methods , Laparoscopy/methods , Situs Inversus/complications , Stomach Neoplasms/surgery , Adenocarcinoma/complications , Adult , Humans , Male , Stomach Neoplasms/complications
9.
Gan To Kagaku Ryoho ; 43(11): 1367-1373, 2016 Nov.
Article in Japanese | MEDLINE | ID: mdl-27899777

ABSTRACT

PURPOSE: To determine factors affecting physical activity in outpatients with gastrointestinal cancer. METHODS: This observational study applied the International Physical Activity Questionnaire(IPAQ)to identify factors affecting physical activity in outpatients(male, n=51; female, n=24; mean age, 64.2±10.2 years)with gastrointestinal cancer undergoing chemotherapy. Relationships between the main outcome measures, total weekly physical activity score(TPA)and total weekly energy expenditure(TEE), and patient background factors were analyzed. RESULTS: The median duration of induction chemotherapy in the 75 outpatients who completed the IPAQ was 242.5(range 7-2,294)days. The TPA and TEE tended to decrease in older patients and were lower in all patients compared with age-specific standard values for healthy persons. Both values tended to increase to a greater extent among patients who worked than among those who did not, and being employed was significantly associated with Eastern Cooperative Oncology Group performance status(ECOG-PS). The TEE tended to be lower among patients with adverse events(AE)such as pain. CONCLUSION: Progressive cachexia, changes in lifestyle, and AE affected physical activity among outpatients with gastrointestinal cancer undergoing chemotherapy. Comprehensive support by an oncology team would probably play an important role in encouraging elderly patients to participate in physical activity.


Subject(s)
Antineoplastic Agents/therapeutic use , Exercise , Gastrointestinal Neoplasms/physiopathology , Adult , Aged , Antineoplastic Agents/adverse effects , Energy Intake , Female , Gastrointestinal Neoplasms/drug therapy , Humans , Male , Middle Aged , Outpatients , Surveys and Questionnaires
10.
BMC Cancer ; 16: 514, 2016 07 21.
Article in English | MEDLINE | ID: mdl-27439769

ABSTRACT

BACKGROUND: The chemokine CXCL12 and its corresponding receptor CXCR4 are key players in the development of several cancers. Therefore, we hypothesized that there is a functional causality between CXCL12 expression and tumor progression in patients with esophageal squamous cell carcinoma (ESCC). METHODS: We performed an immunohistochemical analysis in 79 consecutive patients with ESCC. We performed in vitro and in vivo cell proliferation assays using ESCC cell lines and a newly established transfectant stably overexpressing CXCL12. RESULTS: Immunohistochemistry revealed positive CXCR4 and CXCL12 expression in 48 (61 %) and 62 (78 %) patients, respectively. Additionally, the expression levels did not significantly correlate with any clinicopathological factors. The MIB-1 proliferation index was markedly higher in ESCC with a positive expression of CXCR4 or CXCL12. Positive CXCL12 expression was significantly correlated with lower recurrence-free survival (RFS, p = 0.02). Cox's hazard models revealed CXCL12 expression as an independent predictive factor for recurrence. In vitro, CXCL12 exposure or overexpression enhanced ESCC proliferation; and AMD3100, a specific inhibitor of CXCR4, equally decreased proliferation irrespective of CXCL12 exposure or overexpression. In the mouse model, AMD3100 significantly decreased ESCC tumor size (p = 0.03). CONCLUSIONS: CXCL12 stimulates ESCC proliferation, and its expression levels are related to lower RFS in patients with ESCC. Our findings indicate that positive CXCL12 expression may be a useful marker for predicting the outcome in patients with ESCC and is a potentially new therapeutic target for ESCC.


Subject(s)
Biomarkers, Tumor/analysis , Carcinoma, Squamous Cell/pathology , Chemokine CXCL12/biosynthesis , Esophageal Neoplasms/pathology , Adult , Aged , Animals , Carcinoma, Squamous Cell/metabolism , Cell Proliferation , Disease-Free Survival , Esophageal Neoplasms/metabolism , Esophageal Squamous Cell Carcinoma , Female , Heterografts , Humans , Immunohistochemistry , Kaplan-Meier Estimate , Male , Mice , Mice, Inbred BALB C , Mice, Nude , Middle Aged , Prognosis , Proportional Hazards Models , Real-Time Polymerase Chain Reaction
12.
Ann Surg Oncol ; 23(13): 4247-4252, 2016 12.
Article in English | MEDLINE | ID: mdl-27364500

ABSTRACT

BACKGROUND: In patients with early stage gastric cancer in the middle third of the stomach, pylorus-preserving gastrectomy (PPG) can be an option as function-preserving surgery, although its oncologic safety is not definitively defined. This issues may be overcome using the sentinel node (SN) concept. The aim of this study was to investigate the effectiveness of the SN concept in early gastric cancer patients who are candidates for PPG. METHODS: One hundred fifty-six patients with middle-third location of cT1N0 gastric cancer (single lesion, <4 cm) underwent distal gastrectomy with SN mapping. As a tracer, technetium-99 tin colloid solution and blue dye were endoscopically injected into the submucosal layer surrounding the primary tumor. RESULTS: SN detection rate was 100 % (156 of 156), and the accuracy of the nodal evaluation of metastasis was 99 % (155 of 156). Suprapyloric lymph node (LN; LN No. 5) and infrapyloric LN (LN No. 6) were detected as SNs in 6 and 14 % of the patients, respectively. We also found two cases with metastasis to LN No. 5 or LN No. 6. DISCUSSION: When performing PPG, the possibility of LN metastasis, especially to LN No. 5 and LN No. 6, cannot be underestimated. SN mapping can play an important role to predict the possibility of metastasis to LN No. 5 and LN No. 6.


Subject(s)
Lymph Node Excision , Organ Sparing Treatments , Pylorus/surgery , Sentinel Lymph Node/pathology , Stomach Neoplasms/pathology , Stomach Neoplasms/surgery , Aged , Female , Gastrectomy/methods , Humans , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Staging , Patient Selection , Radiopharmaceuticals , Retrospective Studies , Sentinel Lymph Node/diagnostic imaging , Sentinel Lymph Node/surgery , Technetium Compounds , Tin Compounds , Tumor Burden
13.
Medicine (Baltimore) ; 95(24): e3839, 2016 Jun.
Article in English | MEDLINE | ID: mdl-27310961

ABSTRACT

The number of dissected lymph nodes (LNs), surgical outcomes, and postoperative recurrence-free survival (RFS) were compared between thoracic duct (TD)-preserved and TD-resected groups. The distribution of metastasis in LNs around TD (TDLN) was reviewed. Transthoracic esophagectomy (TTE) with TD resection for esophageal cancer patients has been one of the standard procedures. Because the adipose tissue surrounding the TD contains LNs, TD resection might be necessary for radical LN dissection. However, few studies have investigated the oncological outcome of TTE with TD resection. Two hundred fifty-six consecutive patients who underwent TTE between 2004 and 2015 were retrospectively reviewed and classified into TD-preserved or TD-resected groups. The number of dissected LNs for each LN station and surgical outcomes were compared. RFS was analyzed in 155 patients who underwent TTE before December 2012. Since 2013, the TDLN number was prospectively examined, independent of the regional LNs (n = 72). Of these, the TDLN number for each location (TDLN-Ut/Mt/Lt) was investigated and the correlation between TDLN metastasis and clinicopathological factors was analyzed. The TD was preserved in 89 patients and resected in 167 patients. Patients with TD resection showed significant advanced stage. There was no significant difference in the incidence of postoperative complications, including pneumonia, anastomotic leakage, and chylothorax. The number of dissected mediastinal LNs was significantly increased in the TD-resected group. The 5-year RFS rate of cStage I patients was 67.3% in the TD-preserved group against 90.3% in the TD-resected group, showing a tendency towards RFS extension that did not quite reach statistical significance (P = 0.055). The mean TDLN-Ut/Mt/Lt numbers were 0.89/0.56/0.44, respectively. Eight of 72 (11%) patients displayed TDLN metastasis. Metastatic TDLNs were observed on the same or cranial level of the primary lesion in 7 of 8 patients. Transthoracic esophagectomy with TD resection could increase the number of dissected mediastinal LNs without increase of postoperative complication. TDLN metastasis was observed in patients with advanced disease. A prospective trial, investigating the survival between TD-preserved and TD-resected groups, should be conducted to clarify if TD should be resected in TTE.


Subject(s)
Esophageal Neoplasms/surgery , Esophagectomy/methods , Lymph Node Excision/methods , Lymph Nodes/pathology , Thoracic Duct/surgery , Thoracotomy/methods , Esophageal Neoplasms/diagnosis , Esophageal Neoplasms/secondary , Female , Follow-Up Studies , Humans , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Staging/methods , Prognosis , Retrospective Studies
14.
Oncol Lett ; 11(6): 3631-3636, 2016 Jun.
Article in English | MEDLINE | ID: mdl-27284365

ABSTRACT

Radiotherapy (RT) or chemoradiotherapy (CRT) is a potentially curative, non-surgical treatment option for esophageal cancer, although the rate of local failure within the esophagus remains relatively high. Salvage esophagectomy is not regarded as a common treatment for esophageal cancer, since it is a high-risk surgery with a relatively high surgical mortality rate. Salvage endoscopic resection (ER) for local failure is used for treatment when esophageal cancer is localized and superficial. To evaluate to usefulness of salvage ER, the present study reviewed the clinicopathological records and follow-up data of 37 patients that underwent salvage ER for esophageal cancer, following initial treatment with RT or CRT. Salvage ER was conducted on a total of 78 lesions observed in the 37 patients. Since a thick epithelium and lack of normal vessels on the surface of the mucosa are characteristics of esophageal mucosa following RT or CRT, almost all the lesions were detected using iodine dyeing, and not by narrow band imaging. The growth rate of the detected lesions was relatively high, and early treatment was required. No particular complications occurred during the endoscopic treatment. A total of 11 patients survived for >5 years subsequent to initial endoscopic treatment. Only 4 patients succumbed to esophageal cancer. In conclusion, the present study demonstrated that salvage ER following CRT or RT for esophageal cancer is a minimally invasive, safe, adaptive and curative method for superficial lesions without distant metastases in patients with esophageal cancer with local failure following CRT or RT.

15.
Oncol Lett ; 11(2): 1453-1456, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26893759

ABSTRACT

Xanthogranulomas are known to develop in the gallbladder and kidney. Xanthogranuloma of the stomach is a rare disease, and to the best of our knowledge, only a few cases have been reported to date. The present patient was a 64-year-old man who underwent a wide resection of the stomach following a Billroth-I reconstruction for a gastric ulcer ~40 years prior to the current presentation. Due to tarry stools, a gastrointestinal endoscopy was performed, leading to identification of an ulcerated gastric lesion located at the previous suture line at the lesser curvature of the remnant stomach. This lesion was elevated, appearing to indicate a submucosal tumor. Positron emission tomography revealed uptake of fluorodeoxyglucose radiotracer by the tumor. Although not indicated by the biopsy specimens, a malignant tumor of the remnant stomach was suspected, in the form of a malignant gastrointestinal tumor or remnant gastric cancer. Curative resection of the tumor was successfully performed. Histological examination of the resected specimens revealed xanthogranulomatous inflammation consisting of foamy histiocytes and plasma cells, however, no cancer cells were observed. The tumor was diagnosed as xanthogranulomatous gastritis that mimicked a malignant tumor of the remnant stomach. The present study therefore indicates that inflammatory tumors should be considered in the differential diagnosis of malignant tumors.

17.
Gastric Cancer ; 19(4): 1080-1087, 2016 Oct.
Article in English | MEDLINE | ID: mdl-26621524

ABSTRACT

BACKGROUND: Sentinel node (SN) mapping using dye and radioisotope (RI) tracer has been reported to be feasible in cases of early gastric cancer. Because accurate diagnosis of micrometastasis is sometimes difficult in the limited time available during surgery, a faster and simpler method of improving the intraoperative diagnostic precision of lymph node metastasis is needed. The amount of tracer deposited in an SN can be determined from its radioactivity; however, the significance of the RI count has not been fully discussed. We investigated the clinical impact of the RI count when used as an adjunct to conventional lymph node dissection when diagnosing lymphatic metastasis in cases of early gastric cancer. METHODS: From 2008 to 2009, patients with clinically diagnosed T1N0M0 gastric cancers who underwent gastrectomy and SN mapping were enrolled. SNs were examined by intraoperative and postoperative pathology. The RI count was measured for each SN with a handheld gamma probe; the correlation between nodal metastasis and the RI count was assessed. RESULTS: A total of 308 SNs were harvested from 72 patients. Patients with SN metastasis had significantly higher total RI counts than those without SN metastasis (p = 0.007). Among cases with SN metastasis, RI counts were also significantly elevated in metastasis-positive nodes, stations, and basins. In these cases, the most of SNs having the highest RI count in each case had metastasis including isolated tumor cells. CONCLUSION: In early gastric cancer patients, a high RI count from an SN was correlated with lymph node metastasis. Therefore, RI counting may aid efficient pathological diagnosis and focused lymph node dissection.


Subject(s)
Adenocarcinoma/secondary , Radiopharmaceuticals , Sentinel Lymph Node Biopsy , Sentinel Lymph Node/pathology , Stomach Neoplasms/pathology , Adenocarcinoma/diagnostic imaging , Adenocarcinoma/surgery , Early Detection of Cancer , Female , Follow-Up Studies , Gastrectomy , Humans , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Staging , Prognosis , Sentinel Lymph Node/diagnostic imaging , Sentinel Lymph Node/surgery , Stomach Neoplasms/diagnostic imaging , Stomach Neoplasms/surgery
18.
Gastric Cancer ; 19(3): 876-86, 2016 Jul.
Article in English | MEDLINE | ID: mdl-26304171

ABSTRACT

BACKGROUND: S-1 is an oral anticancer drug, containing tegafur (a prodrug of 5-fluorouracil, 5-FU), 5-chloro-2,4-dihydroxypyridine, and potassium oxonate. As renal dysfunction is known to increase exposure of 5-FU following S-1 administration, the incidence of severe adverse reactions is increased in patients with impaired renal function. However, no reliable information on its dose modification for patients with renal dysfunction has been provided. METHODS: We conducted a prospective pharmacokinetic study to develop an S-1 dosage formula based on renal function. Sixteen cancer patients with various degrees of renal function received a single dose of S-1 at 40 mg/m(2). A series of blood samples were collected at predefined times within 24 h to assess the plasma concentration profiles of 5-FU, 5-chloro-2,4-dihydroxypyridine, and tegafur. A mathematical model for the relationship between renal function and exposure of 5-FU was constructed by a population pharmacokinetic analysis. RESULTS: The clearance of 5-FU following S-1 administration was related to body surface area and creatinine clearance in the range 15.9-108.8 mL/min as estimated by the Cockcroft-Gault equation. The S-1 dosage formula was derived as follows:[Formula: see text]where AUC is the area under the concentration-time curve, CLcr is creatinine clearance, and BSA is body surface area. The recommended daily doses of S-1 in Asia and Europe were also proposed as nomograms according to exposure matching to the previously reported area under the concentration-time curve of 5-FU, which confirmed the efficacy and toxicity in pivotal registration studies. CONCLUSIONS: We have developed a novel formula for determining the S-1 dosage on the basis of renal function. Further validation is needed to confirm the formula for practical application.


Subject(s)
Antimetabolites, Antineoplastic/pharmacokinetics , Fluorouracil/pharmacokinetics , Oxonic Acid/pharmacokinetics , Renal Insufficiency/blood , Stomach Neoplasms/drug therapy , Tegafur/pharmacokinetics , Aged , Antimetabolites, Antineoplastic/administration & dosage , Antimetabolites, Antineoplastic/adverse effects , Drug Combinations , Female , Follow-Up Studies , Humans , Male , Middle Aged , Neoplasm Staging , Oxonic Acid/administration & dosage , Oxonic Acid/adverse effects , Prognosis , Prospective Studies , Renal Insufficiency/chemically induced , Stomach Neoplasms/blood , Tegafur/administration & dosage , Tegafur/adverse effects , Tissue Distribution
19.
Gastric Cancer ; 19(4): 1088-1094, 2016 Oct.
Article in English | MEDLINE | ID: mdl-26545881

ABSTRACT

BACKGROUND: The sentinel node (SN) concept is safely applied and validated in early gastric cancer. Gastric lymph nodes are divided into five basins with the main gastric arteries, and the anterosuperior lymph nodes with the common hepatic artery (No. 8a) are classified in the right gastric artery (r-GA) basin. Although No. 8a are considered to have lymphatic flow from the r-GA basin, there might be additional multiple lymphatic flows into No. 8a. The aim of this study is to analyze the lymphatic flows to No. 8a and to investigate the clinical significance of No. 8a as a sentinel node (SN No. 8a). METHODS: Four hundred and twenty-nine patients with cT1N0 or cT2N0 gastric cancer underwent SN mapping. We used technetium-99 tin colloid solution and blue dye as a tracer. RESULTS: We detected SN No. 8a in 35 (8.2 %) patients. In these patients, we detected SN No. 8a with SNs that belonged to the left gastric artery (l-GA) basin (66 %), right gastroepiploic artery (r-GEA) basin (54 %), and right gastric artery (r-GA) basin (46 %). In addition, celiac artery lymph nodes were detected as SNs significantly more frequently. Function-preserving surgery was performed significantly less often in patients with SN No. 8a (p =0.018). CONCLUSIONS: We found that SN No. 8a seemed to have lymphatic flow not only from the r-GA basin, but also from the l-GA basin or r-GEA basin. When SN No. 8a are detected, we should be careful to perform function-preserving surgery, even in SN-negative cases.


Subject(s)
Adenocarcinoma/secondary , Hepatic Artery/pathology , Radiopharmaceuticals , Sentinel Lymph Node Biopsy , Sentinel Lymph Node/pathology , Stomach Neoplasms/pathology , Adenocarcinoma/diagnostic imaging , Adenocarcinoma/surgery , Female , Follow-Up Studies , Gastrectomy , Hepatic Artery/diagnostic imaging , Hepatic Artery/surgery , Humans , Laparoscopy , Lymph Node Excision , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Staging , Prognosis , Sentinel Lymph Node/diagnostic imaging , Sentinel Lymph Node/surgery , Stomach Neoplasms/diagnostic imaging , Stomach Neoplasms/surgery
20.
Ann Surg Oncol ; 23(2): 511-21, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26104543

ABSTRACT

BACKGROUND: Remnant gastric cancer (RGC) is one of the less prevalent gastric cancers. The purpose of this study was to explore the clinicopathological characteristics and results of the operation of RGC following distal gastrectomy. In particular, we examined factors related to prognosis. METHODS: Between January 1970 and December 2012, 122 patients with RGC following distal gastrectomy underwent further surgery and were analyzed retrospectively. RESULTS: Initial gastric diseases included benign (49 patients, 40.2 %) and malignant diseases (73 patients, 59.8 %). Reconstructions by initial surgery included Billroth I (80 patients, 65.6 %) and Billroth II (42 patients, 34.4 %). Tumors were located at anastomotic (44 patients, 36.1 %) and nonanastomotic sites (78 patients, 63.9 %). There were 59 patients (48.4 %) classified with pathological (p) stage I, 19 as p stage II (15.6 %), 22 as p stage III (18.0 %), and 22 (18.0 %) as p stage IV. A total of 100 patients (82.0 %) underwent curative resection, and 22 underwent noncurative resection. The number of cases of postoperative morbidity, 90-day mortality, and adjuvant chemotherapy were 23 (18.9 %), 3 (2.5 %), and 20 (16.4 %), respectively. Univariate and multivariate analyses were performed to identify the prognostic factors of RGC. Multivariate analysis revealed historical periods, pathological venous invasion, curative resection, and postoperative morbidity to be independent prognostic factors. CONCLUSIONS: The prognosis of patients with RGC can be improved by aggressively performing curative resection without causing complications.


Subject(s)
Adenocarcinoma/surgery , Gastrectomy/mortality , Gastric Stump/surgery , Plastic Surgery Procedures , Stomach Neoplasms/surgery , Adenocarcinoma/pathology , Aged , Female , Follow-Up Studies , Gastric Stump/pathology , Humans , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Invasiveness , Neoplasm Staging , Prognosis , Retrospective Studies , Risk Factors , Stomach Neoplasms/pathology , Survival Rate , Time Factors
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