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BACKGROUND: The majority of small bowel obstructions (SBO) are caused by adhesion due to abdominal surgery. Internal hernias, a very rare cause of SBO, can arise from exposed blood vessels and nerves during pelvic lymphadenectomy (PL). In this report, we present two cases of SBO following laparoscopic and robot-assisted lateral lymph node dissection (LLND) for rectal cancer, one case each, of which obstructions were attributed to the exposure of blood vessels and nerves during the procedures. CASE PRESENTATION: Case 1: A 68-year-old man underwent laparoscopic perineal rectal amputation and LLND for rectal cancer. Four years and three months after surgery, he visited to the emergency room with a chief complaint of left groin pain. Computed tomography (CT) revealed a closed-loop in the left pelvic cavity. We performed an open surgery to find that the small intestine was fitted into the gap between the left obturator nerve and the left pelvic wall, which was exposed by LLND. The intestine was not resected because coloration and peristalsis of the intestine improved after the hernia was released. The obturator nerve was preserved. Case 2: A 57-year-old man underwent a robot-assisted rectal amputation with LLND for rectal cancer. Eight months after surgery, he presented to the emergency room with a complaint of abdominal pain. CT revealed a closed-loop in the right pelvic cavity, and he underwent a laparoscopic surgery with a diagnosis of strangulated SBO. The small intestine was strangulated by an internal hernia caused by the right umbilical arterial cord, which was exposed by LLND. The incarcerated small intestine was released from the gap between the umbilical arterial cord and the pelvic wall. No bowel resection was performed. The umbilical arterial cord causing the internal hernia was resected. CONCLUSION: Although strangulated SBO due to an exposed intestinal cord after PL has been a rare condition to date, it is crucial for surgeons to keep this condition in mind.
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Background: Endoscopic gastroduodenal stent (GDS) placement is widely used as a safe and effective method to rapidly improve gastrointestinal symptoms of malignant gastric outlet obstruction (MGOO). While previous studies reported the utility of chemotherapy after GDS placement for prognosis improvement, they did not fully address the issue of immortal time bias. Objectives: To examine the association between prognosis and clinical course following endoscopic GDS placement, using a time-dependent analysis. Design: Multicenter retrospective cohort study. Methods: This study included 216 MGOO patients who underwent GDS placement between April 2010 and August 2020. Data of patient baseline characteristics, including age, gender, cancer type, performance status (PS), GDS type and length, GDS placement location, gastric outlet obstruction scoring system (GOOSS) score, and history of chemotherapy before GDS were collected. The clinical course following GDS placement was evaluated by GOOSS score, stent dysfunction, cholangitis, and chemotherapy. A Cox proportional hazards model was used to identify prognostic factors after GDS placement. Stent dysfunction, post-stent cholangitis, and post-stent chemotherapy were analyzed as time-dependent covariates. Results: Mean GOOSS scores before and after GDS were 0.7 and 2.4, respectively, with significant improvement after GDS placement (p < 0.001). The median survival time after GDS placement was 79 [95% confidence interval (CI): 68-103] days. In multivariate Cox proportional hazards model with time-dependent covariates, PS 0-1 [hazard ratio (HR): 0.55, 95% CI: 0.40-0.75; p < 0.001], ascites (HR: 1.45, 95% CI: 1.04-2.01; p = 0.028), metastasis (HR: 1.84, 95% CI: 1.31-2.58; p < 0.001), post-stent cholangitis (HR: 2.38, 95% CI: 1.37-4.15; p = 0.002), and post-stent chemotherapy (HR: 0.01, 95% CI: 0.002-0.10; p < 0.001) significantly affected prognosis after GDS placement. Conclusion: Post-stent cholangitis and tolerability to receive chemotherapy after GDS placement influenced prognosis in MGOO patients.
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INTRODUCTION: Freshly isolated uncultured adipose tissue-derived stromal cells (u-ADSCs), containing miscellaneous cells like the relatively abundant mesenchymal stem cells, are attractive for repair and regenerative therapy. However, the detailed characteristics and therapeutic efficacy of u-ADSCs obtained from disease-affected hosts are unknown. We compared the properties of u-ADSCs obtained from wild-type mice and from a mouse model of non-alcoholic steatohepatitis (NASH). METHODS: The NASH model was established by feeding C57BL/6J mice an atherogenic high-fat diet for 4 (NASH (4w)) or 12 weeks (NASH (12w)), followed by the isolation and characterization of u-ADSCs. Wild-type u-ADSCs or NASH-derived u-ADSCs were administered to mice with NASH cirrhosis, followed by analyses of hepatic inflammatory cells, antigen profiles, fibrosis, and gene expression. RESULTS: Wild-type u-ADSCs and NASH-derived u-ADSCs did not show marked differences in surface antigen profiles. In NASH (4w) u-ADSCs, but not NASH (12w) u-ADSCs, the frequencies of the leukocyte markers CD11b, CD45, and CD44 were elevated; furthermore, we observed an increase in the M1/M2 macrophage ratio only in NASH (12w) u-ADSCs. Only in NASH-4w u-ADSCs, the expression levels cell cycle-related genes were higher than those in u-ADSCs. Wild-type u-ADSCs administered to mice with NASH-related cirrhosis decreased the infiltration of CD11b+, F4/80+, and Gr-1+ inflammatory cells, ameliorated fibrosis, and had a restorative effect on liver tissues, as determined by gene expression profiles and the NAFLD activity score. The therapeutic effects of NASH (4w) u-ADSCs and NASH (12w) u-ADSCs on NASH-related cirrhosis were highly similar to the effect of wild-type u-ADSCs, including reductions in inflammation and fibrosis. CONCLUSIONS: NASH-derived u-ADSCs, similar to wild-type u-ADSCs, are applicable for reparative and regenerative therapy in mice with NASH.
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A 60-year-old male patient had alcoholic chronic pancreatitis. Three months prior, he had undergone an exchange of pancreatic duct stents. In December 201X-1, magnetic resonance imaging and computed tomography (CT) scan results showed a caput pancreatic mass and common bile duct dilatation. We considered that it was because of chronic pancreatitis and decided to follow up by imaging studies. Further, in March 201X, a CT scan result revealed worsening of the mass and bile duct dilation. We assessed the mass by endoscopic ultrasound and fine-needle aspiration. Histological findings revealed to an interstitial tissue infiltrated by several neutrophils and plasma cells and abscess-forming inflammation like sulfur granule. The mass was improved by antibiotic administration for 6 months.
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Actinomicosis , Neoplasias Pancreáticas , Actinomicosis/diagnóstico por imagen , Actinomicosis/tratamiento farmacológico , Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico , Endosonografía , Humanos , Masculino , Persona de Mediana Edad , Conductos Pancreáticos , Tomografía Computarizada por Rayos XRESUMEN
There is limited evidence supporting the usefulness of endoscopic retrograde pancreatic drainage (ERPD) for symptomatic pancreaticojejunal anastomotic stenosis (sPJS). We examined the usefulness of ERPD for sPJS. We conducted a retrospective analysis of 10 benign sPJS patients. A forward-viewing endoscope was used in all sessions. Following items were evaluated: technical success, adverse events, and clinical outcome of ERPD. The technical success rate was 100% (10/10) in initial ERPD; 9 patients had a pancreatic stent (no-internal-flap: n = 4, internal-flap: n = 5). The median follow-up was 920 days. Four patients developed recurrence. Among them, 3 had a stent with no-internal-flap in initial ERPD, the stent migrated in 3 at recurrence, and a stent was not placed in 1 patient in initial ERPD. Four follow-up interventions were performed. No recurrence was observed in 6 patients. None of the stents migrated (no-internal-flap: n = 1, internal-flap: n = 5) and no stents were replaced due to stent failure. Stenting with no-internal-flap was associated with recurrence (p = 0.042). Mild adverse events developed in 14.3% (2/14). In conclusions, ERPD was performed safely with high technical success. Recurrence was common after stenting with no-internal-flap. Long-term stenting did not result in stent failure.Clinical trial register and their clinical registration number: Nos. 58-115 and R2-9.
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Constricción Patológica/patología , Páncreas/patología , Anciano , Anciano de 80 o más Años , Colangiopancreatografia Retrógrada Endoscópica/métodos , Drenaje/métodos , Endosonografía/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pancreatoyeyunostomía/métodos , Estudios Retrospectivos , Stents , Resultado del Tratamiento , Ultrasonografía Intervencional/métodosRESUMEN
BACKGROUND: Malignant afferent loop obstruction (mALO) can cause cholangitis, pancreatitis, and perforation due to blind loop dilatation. However, peritoneal dissemination, lymph node metastasis, and recurrence of the tumor are the main causes of mALO, and most cases are in the advanced stage with thoracicoabdominal fluid retention, for which surgery and percutaneous transhepatic treatment are challenging. At our hospital, endoscopic metal stent placement (EMSP) has been applied for such mALO. We retrospectively investigated the usefulness of EMSP for mALO. METHODS: We conducted a retrospective analysis of 11 mALO patients with EMSP between January 2008 and December 2018. The following items were evaluated: the characteristics of patients, technical success and adverse events of EMSP, clinical efficacy, and outcome after EMSP. RESULTS: The surgical procedures and reconstruction methods were distal gastrectomy with Billroth II reconstruction for 3 patients, pancreaticoduodenectomy with modified-Child reconstruction for 7, choledochojejunostomy with Roux-en-Y reconstruction for 1. The cause of mALO was peritoneal dissemination for 6 patients, local recurrence for 3, lymph node metastasis for 1, and afferent loop invasion for 1. EMSP was attempted in 13 sessions for 11 patients, and successful in 12 of 13 sessions. There were no adverse events. The clinical efficacy was high in successful EMSP. The median survival time after EMSP was 118 days. Ten patients died of primary disease and one patient died of uncontrollable cholangitis after the failure of EMSP. mALO recurred and EMSP was repeated for 2 of 10 patients who died of primary disease. CONCLUSIONS: The success rate of EMSP for mALO was high in patients with poor general conditions due to advanced-stage malignant tumors and it was able to be safely performed, suggesting its high clinical efficacy. The incidence of mALO recurrence after EMSP was low.
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Anastomosis en-Y de Roux/métodos , Anastomosis Quirúrgica/métodos , Endoscopía/métodos , Gastroenterostomía/métodos , Stents/normas , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
Highlight Kida and colleagues described their method for successfully performing biliary self-expandable metallic stenting with the through-the-scope technique using an ultra-slim endoscope for malignant biliary obstruction with duodenal stenosis. This procedure may be useful in cases of duodenal stenosis in which it is difficult to reach the major duodenal papilla.
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Colangitis/etiología , Colangitis/cirugía , Endoscopios , Neoplasias Pancreáticas/complicaciones , Stents Metálicos Autoexpandibles , Anciano de 80 o más Años , Colangitis/diagnóstico por imagen , Medios de Contraste , Úlcera Duodenal/cirugía , Diseño de Equipo , Gastrectomía , Humanos , Masculino , Invasividad NeoplásicaRESUMEN
BACKGROUND: Combination therapy with fluorouracil, platinum, and trastuzumab (Tmab) is the first-line treatment for human epidermal growth factor receptor 2 (HER2)-positive gastric cancer, and there is currently no established second-line therapy. We evaluated the efficacy and safety of weekly paclitaxel plus Tmab as second-line chemotherapy for HER2-positive gastric cancer patients. PATIENTS AND METHODS: Eligible patients were older than or equal to 20 years, had histologically confirmed gastric adenocarcinoma that was HER2 positive (immunohistochemistry 3+ or immunohistochemistry 2+ and fluorescence in-situ hybridization positive or dual color in-situ hybridization positive), and had been treated previously with chemotherapy (pretreated or not with Tmab). Patients received weekly paclitaxel plus Tmab as the second-line chemotherapy. The primary endpoint was the overall response rate (ORR; threshold ORR=20% and expected ORR=35%). RESULTS: Twenty-eight patients were enrolled. ORR was 21.4%. The median progression-free survival (PFS) was 4.6 months. The median overall survival (OS) was 9.6 months. No significant differences were observed in ORR, PFS, or OS between the Tmab beyond progression (TBP) group (n=20) and the non-TBP group (n=8). However, in the TBP group, a therapeutic effect was associated with the duration of PFS in the first-line Tmab treatment [≥6 months PFS in the first-line Tmab treatment (n=10) vs. <6 months (n=10); ORR: 40 and 10%, P=0.303, PFS: 6.2 and 2.8 months, P=0.005, OS: 15.8 and 6.5 months, P=0.006, respectively]. CONCLUSION: Weekly paclitaxel plus Tmab was not superior as second-line chemotherapy for HER2-positive gastric cancer patients, but may be effective for patients who showed better responses to Tmab-combined chemotherapy in the first-line treatment.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Receptor ErbB-2/metabolismo , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/enzimología , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Esquema de Medicación , Femenino , Humanos , Inmunohistoquímica , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Paclitaxel/administración & dosificación , Paclitaxel/efectos adversos , Neoplasias Gástricas/patología , Trastuzumab/administración & dosificación , Trastuzumab/efectos adversosRESUMEN
Background: Colorectal cancer (CRC), the most common malignancy worldwide, causes inflammation. We explored the inflammatory pathophysiology of CRC by assessing the peripheral blood parameters. Methods: The differences in gene expression profiles of whole blood cells and cell subpopulations between CRC patients and healthy controls were analyzed using DNA microarray. Serum cytokine/chemokine concentrations in CRC patients and healthy controls were measured via multiplex detection immunoassays. In addition, we explored correlations between the expression levels of certain genes of peripheral CD4+ cells and serum chemokine concentrations. Results: The gene expression profiles of peripheral CD4+ cells of CRC patients differed from those of healthy controls, but this was not true of CD8+ cells, CD14+ cells, CD15+ cells, or CD19+ cells. Serum IL-8 and eotaxin-1 levels were significantly elevated in CRC patients, and the levels substantially correlated with the expression levels of certain genes of CD4+ cells. Interestingly, the relationships between gene expression levels in peripheral CD4+ cells and serum IL-8 and eotaxin-1 levels resembled those of monocytes/macrophages, not T cells. Conclusions: Serum IL-8 and eotaxin-1 concentrations increased and were associated with changes in the gene expression of peripheral CD4+ cells in CRC patients.
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Linfocitos T CD4-Positivos , Quimiocina CCL11/sangre , Neoplasias Colorrectales/sangre , Neoplasias Colorrectales/genética , ADN/sangre , Interleucina-8/sangre , Estudios de Casos y Controles , Neoplasias Colorrectales/inmunología , Expresión Génica , Humanos , Análisis de Secuencia por Matrices de Oligonucleótidos , TranscriptomaRESUMEN
A man in his 60s visited our hospital because of a pancreatic head tumor. Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) revealed that the tumor consisted of a neuroendocrine carcinoma (NEC) and adenocarcinoma, including signet-ring cell carcinoma, and that the ratio of these components was approximately 50:50. Therefore, he was diagnosed with mixed adenoneuroendocrine carcinoma (MANEC). Because of liver and lymph node metastases, systemic chemotherapy was initiated using a regimen for the NEC component based on an increase in neuron-specific enolase (NSE). Although the patient achieved stable disease after two chemotherapy cycles, the tumor increased in size after three cycles, which was associated with a gradual increase in carcinoembryonic antigen and a decrease in NSE level. An EUS-FNA reexamination revealed that the adenocarcinoma component accounted for 90 % of the tumor. Thus, an adenocarcinoma chemotherapy regimen was started, and a slight reduction in tumor size was observed. Here, we report an extremely rare and remarkable case of MANEC of the pancreas that demonstrates the effectiveness of EUS-FNA for helping to decide the chemotherapy regimen.
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Carcinoma Neuroendocrino/patología , Carcinoma de Células en Anillo de Sello/patología , Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico/métodos , Tumor Mixto Maligno/patología , Neoplasias Pancreáticas/patología , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma Neuroendocrino/diagnóstico , Carcinoma Neuroendocrino/tratamiento farmacológico , Carcinoma de Células en Anillo de Sello/diagnóstico , Carcinoma de Células en Anillo de Sello/tratamiento farmacológico , Humanos , Masculino , Tumor Mixto Maligno/diagnóstico , Tumor Mixto Maligno/tratamiento farmacológico , Imagen Multimodal , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/tratamiento farmacológico , Tomografía de Emisión de Positrones , Tomografía Computarizada por Rayos XRESUMEN
Gastric adenocarcinoma of the fundic gland (chief cell-predominant type, GA-FG-CCP) is a rare variant of well-differentiated adenocarcinoma, and has been proposed to be a novel disease entity. GA-FG-CCP originates from the gastric mucosa of the fundic gland region without chronic gastritis or intestinal metaplasia. The majority of GA-FG-CCPs exhibit either a submucosal tumor-like superficial elevated shape or a flat shape on macroscopic examination. Narrow-band imaging with endoscopic magnification may reveal a regular or an irregular microvascular pattern, depending on the degree of tumor exposure to the mucosal surface. Pathological analysis of GA-FG-CCPs is characterized by a high frequency of submucosal invasion, rare occurrences of lymphatic and venous invasion, and low-grade malignancy. Detection of diffuse positivity for pepsinogen-I by immunohistochemistry is specific for GA-FG-CCP. Careful endoscopic examination and detailed pathological evaluation are essential for early and accurate diagnosis of GA-FG-CCP. Nearly all GA-FG-CCPs are treated by endoscopic resection due to their small tumor size and low risk of recurrence or metastasis.
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Adenocarcinoma/diagnóstico , Adenocarcinoma/patología , Células Principales Gástricas/patología , Fundus Gástrico/patología , Gastroscopía/métodos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/patología , Biomarcadores de Tumor , Biopsia , Diagnóstico Diferencial , Fundus Gástrico/citología , Fundus Gástrico/cirugía , Humanos , Inmunohistoquímica , Laparoscopía/métodos , Imagen de Banda Estrecha/métodos , Recurrencia Local de Neoplasia , Pepsinógeno A/inmunología , Pólipos/diagnóstico , Guías de Práctica Clínica como Asunto , Neoplasias Gástricas/cirugíaRESUMEN
Recently, a new disease entity termed gastric adenocarcinoma of fundic gland type (GA-FG) was proposed. We treated five cases of GA-FG with endoscopic submucosal dissection. All tumors were small and located in the upper third of the stomach. Four tumors were macroscopically identified as 0-IIa and one was identified as 0-IIb. Narrow-band imaging with magnifying endoscopy showed an irregular microvascular pattern in 2 cases and a regular microvascular pattern in the remainder. All tumors arose from the deep layer of the lamina propria mucosae and showed submucosal invasion. Lymphatic invasion was seen only in one case, while no venous invasion was recognized. All tumors were positive for pepsinogen-Iâ and MUC6 by immunohistochemistry. None showed p53 overexpression, and the labeling index of Ki-67 was low in all cases. All cases have been free from recurrence or metastasis. Herein, we discussed the clinicopathological features of GA-FG in comparison with past reports.
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Adenocarcinoma/cirugía , Gastrectomía/métodos , Fundus Gástrico/cirugía , Gastroscopía/métodos , Neoplasias Gástricas/cirugía , Adenocarcinoma/química , Adenocarcinoma/patología , Anciano , Biomarcadores de Tumor/análisis , Biopsia , Femenino , Fundus Gástrico/química , Fundus Gástrico/patología , Humanos , Inmunohistoquímica , Masculino , Imagen de Banda Estrecha , Estadificación de Neoplasias , Neoplasias Gástricas/química , Neoplasias Gástricas/patología , Resultado del TratamientoRESUMEN
A 29-year-old man with ulcerative colitis presented to the hospital complaining of persistent back pain. Pancreatic enzymes and tumor markers were elevated; imaging showed diffuse narrowing of the main pancreatic duct associated with diffuse pancreatic enlargement. We therefore performed an endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) biopsy of the pancreas using a 19-gauge needle. Histopathology revealed interlobular fibrosis, neutrophil infiltration in the intralobular ducts and acini, and very few immunoglobulin G4-positive cells. The patient was diagnosed with type 2 autoimmune pancreatitis and started on oral steroids; subsequently, we observed an improvement in the pancreatic enlargement and duct narrowing. Histologically proven type 2 autoimmune pancreatitis is rare in Japan.
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Enfermedades Autoinmunes/patología , Pancreatitis/patología , Adulto , Enfermedades Autoinmunes/tratamiento farmacológico , Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico , Humanos , Masculino , Imagen Multimodal , Tomografía de Emisión de Positrones , Tomografía Computarizada por Rayos XRESUMEN
PURPOSE: To report a rare and complicated case of immunoglobulin (Ig) G4-related periaortitis involving both the aortic wall and the retroperitoneum without aneurysmal formation. CASE REPORT: A 79-year-old man with IgG4-related periaortitis suffered aortic rupture despite a normal caliber aorta after 6 months of steroid therapy (20 mg/d). Endovascular repair with an aortic cuff sealed the rupture. Steroid therapy was halted 2 weeks later due to infection. Four months later, a biopsy during esophagogastroduodenoscopy to investigate gastrointestinal bleeding suggested a relapse of IgG4-RD in the duodenum. Subsequent aortoduodenal fistula formation proved fatal. Generally, IgG4-related periaortitis does not result in such complications due to the absence of aneurysm formation and a thick aortic wall. CONCLUSIONS: Our report highlights a rare case of IgG4-related periaortitis where complications resulted following steroid therapy and surgical intervention, emphasizing the difficulties in dealing with IgG4-related cardiovascular lesions.
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Aneurisma de la Aorta Abdominal/cirugía , Rotura de la Aorta/cirugía , Aortitis/inmunología , Enfermedades Duodenales/inmunología , Procedimientos Endovasculares/efectos adversos , Inmunoglobulina G/análisis , Fístula Intestinal/inmunología , Fístula Vascular/inmunología , Anciano , Aneurisma de la Aorta Abdominal/diagnóstico , Aneurisma de la Aorta Abdominal/inmunología , Rotura de la Aorta/diagnóstico , Rotura de la Aorta/inmunología , Aortitis/complicaciones , Aortitis/diagnóstico , Aortitis/tratamiento farmacológico , Aortografía/métodos , Biopsia , Implantación de Prótesis Vascular , Enfermedades Duodenales/diagnóstico , Endoscopía Gastrointestinal , Infecciones por Escherichia coli/inmunología , Infecciones por Escherichia coli/microbiología , Resultado Fatal , Hemorragia Gastrointestinal/inmunología , Humanos , Huésped Inmunocomprometido , Fístula Intestinal/diagnóstico , Masculino , Factores de Riesgo , Esteroides/efectos adversos , Factores de Tiempo , Tomografía Computarizada por Rayos X , Fístula Vascular/diagnósticoRESUMEN
A 70-year-old female underwent follow-up colonoscopy after colonic polypectomy. The colonoscopy revealed the presence of a 7-mm submucosal tumor in the sigmoid colon. The tumor surface was smooth and covered with normal mucosa. It was diagnosed as a submucosal tumor, and polypectomy was performed. Histopathological examination of the resected specimen revealed moderately to poorly differentiated adenocarcinoma measuring 2 × 5 × 3 mm with marked peritumoral lymphocytic infiltration and lymphoid follicle formation. It was diagnosed as carcinoma with lymphoid stroma (lymphoepithelioma-like carcinoma), SM (1,800 µm), ly2, v0, budding; grade 1. We confirmed the indication for noncurative additional surgical resection and performed laparoscopic sigmoid colectomy. No metastases were observed in the dissected lymph nodes.
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PURPOSE: The repair enzyme RAD18 plays a key role in the post-replication repair process in various organisms from yeast to human, and the molecular function of the RAD18 protein has been elucidated. Single nucleotide polymorphism (SNP) of arginine (Arg, CGA) or glutamine (Gln, CAA) at codon 302 is known on RAD18; however, the association between the SNP and the risk of any human cancers including non-small-cell lung cancer (NSCLC) has not been reported. We therefore investigated the relationship between the polymorphism and the development and progression of human NSCLC. METHODS: The study population included 159 patients with NSCLC and 200 healthy controls. The SNP was genotyped by polymerase chain reaction with the confronting two-pair primer (PCR-CTPP) assay. Genotype frequencies were compared between patients and controls, and the association of genotypes with clinicopathological parameters was also studied. RESULTS: The Gln/Gln genotype was significantly more frequent in NSCLC patients (20.7%) than in healthy controls (11.5%)(P = 0.003). The increased risk was detected in NSCLC patients with the Gln/Gln genotype [Odds ratio (OR) = 2.63, 95% confidence interval (CI)=1.38-4.98]. As to the relationship of the SNP with clinicopathological parameters of NSCLC, significantly higher risks were detected in lung squamous cell carcinoma (LSC) (OR = 4.40, 95% CI = 1.60-12.1). CONCLUSIONS: Our results suggested that Gln/Gln genotype of the RAD18 SNP has the increased risk of NSCLC, especially of LSC. This is the first report to provide evidence for an association between the RAD18 Arg302Gln polymorphism and human NSCLC risk.
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Carcinoma de Pulmón de Células no Pequeñas/genética , Proteínas de Unión al ADN/metabolismo , Neoplasias Pulmonares/genética , Polimorfismo de Nucleótido Simple/genética , Adenocarcinoma/genética , Adenocarcinoma/secundario , Anciano , Alelos , Carcinoma de Células Grandes/genética , Carcinoma de Células Grandes/secundario , Carcinoma de Pulmón de Células no Pequeñas/secundario , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/secundario , Estudios de Casos y Controles , Estudios de Cohortes , Proteínas de Unión al ADN/genética , Femenino , Genotipo , Humanos , Neoplasias Pulmonares/patología , Masculino , Reacción en Cadena de la Polimerasa , Factores de Riesgo , Ubiquitina-Proteína LigasasRESUMEN
To identify the tumor suppressor genes (TSG) associated with non-small cell lung cancers (NSCLC), we performed the loss of heterozygosity (LOH) analysis in NSCLC samples from 66 patients. We focused on the novel hot spot region on 15q14-24 with eight polymorphic microsatellite markers. Frequent allelic loss was detected in 33 of 48 informative cases (69%) at D15S984 on 15q23. We defined the fine map on the region and identified the SIN3A gene as a candidate TSG. The SIN3A gene product is a component of the histone deacetylase (HDAC) complex and plays essential roles in early embryonic development and the proliferation and survival of a variety of cells through the repression of diverse signaling pathways. Our expression analysis revealed more frequent down-regulation of the SIN3A mRNA in 19 of 31 cases (61%) of NSCLCs in comparison to those of other flanking genes (16-42%), albeit the correlation of the decreased expression with the LOH did not attain statistic significance. These results suggest that the attenuated function of SIN3A due to a decreased level of expression may result in epigenetic de-regulation of growth-related genes through histone acetylation, which leads to the tumorigenesis of lung cancer cells. To our knowledge, this is the first evidence of the down-regulation of the SIN3A gene in human cancer.
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Carcinoma de Pulmón de Células no Pequeñas/genética , Cromosomas Humanos Par 15 , Genes Supresores de Tumor , Pérdida de Heterocigocidad , Neoplasias Pulmonares/genética , Proteínas Represoras/genética , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mutación , Complejo Correpresor Histona Desacetilasa y Sin3RESUMEN
The RAD18 gene, located on the human chromosome 3p24-p25, plays a crucial role in post-replication repair (PRR) in various organisms from yeast to humans. In the human RAD18 gene, one coding single nucleotide polymorphism (SNP) at codon 302, encoding either arginine (Arg, CGA) or glutamine (Gln, CAA), was reported. Although the molecular function of the RAD18 protein came to be elucidated, the association between the RAD18 Arg302Gln polymorphism and the risk of human cancer development was not examined. Therefore, we investigated the relationship between the polymorphism and the development of human primary colorectal cancer (CRC). The Arg302Gln polymorphism in 100 patients with CRC and 200 healthy controls were genotyped by the polymerase chain reaction with confronting two-pair primer (PCR-CTPP) assay. The Gln/Gln genotype was significantly more frequent in CRC (18.0%) than in the healthy controls (11.5%) (p=0.046). The increased risk was detected in CRC patients with the Gln/Gln genotype (Odds ratio [OR], 2.10; 95% confidence interval [CI], 1.00 to 4.40). When the relationship of the SNP with clinicopathological parameters of CRC was investigated, particularly in the well-differentiated grade and in the lymph node metastasis (N1) CRC patients, significantly higher risks were detected (OR, 7.00; 95% CI, 1.19-41.1 and OR, 3.71; 95% CI, 1.30-10.6, respectively). These results suggested that the RAD18 Arg302Gln polymorphism is associated with the risk of CRC. This report provides evidence for an association between the RAD18 Arg302Gln polymorphism and human CRC risk.
Asunto(s)
Neoplasias Colorrectales/genética , Proteínas de Unión al ADN/genética , Polimorfismo de Nucleótido Simple , Anciano , Estudios de Cohortes , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Japón , Masculino , Distribución Aleatoria , Factores de Riesgo , Fumar , Ubiquitina-Proteína LigasasRESUMEN
PURPOSE: Total pelvic exenteration (TPE) is the standard procedure for locally advanced rectal cancer involving the prostate and seminal vesicles. We evaluated the feasibility of bladder-sparing surgery as an alternative to TPE. METHODS: Eleven patients with advanced primary or recurrent rectal cancer involving the prostate or seminal vesicles, or both, underwent bladder-sparing extended colorectal resection with radical prostatectomy. The procedures performed were abdominoperineal resection (APR) with prostatectomy (n = 6), colorectal resection using intersphincteric resection combined with prostatectomy (n = 4), and abdominoperineal tumor resection with prostatectomy (n = 1). Local control and urinary and anal function were evaluated postoperatively. RESULTS: Cysto-urethral anastomosis (CUA) was performed in seven patients and catheter-cystostomy was performed in four patients. Coloanal or colo-anal canal anastomosis was also performed in four patients. There was no mortality, and the morbidity rate was 38%. All patients underwent complete resection with negative surgical margins. After a median follow-up period of 26 months there was no sign of local recurrence, and ten patients were alive without disease, although distant metastases were found in three patients. Five patients had satisfactory voiding function after CUA, and three had satisfactory evacuation after intersphincteric resection (ISR). CONCLUSION: These bladder-sparing procedures allow conservative surgery to be performed in selected patients with advanced rectal cancer involving the prostate or seminal vesicles, without compromising local control.