RESUMO
PURPOSE: Few studies have so far focused on the preoperative presence of venous thromboembolism (VTE) in lung cancer patients undergoing surgery. In this study, we investigated the prevalence and risk factors for preoperative deep venous thrombosis (DVT) in patients scheduled to undergo lung cancer surgery. METHODS: Between June 2013 and December 2018, 948 consecutive patients underwent lung cancer surgery in Kindai University Hospital. Four patients did not undergo screening for DVT; thus, 944 patients were enrolled in this study. Preoperatively, venous ultrasonography of the lower extremities was performed in patients deemed at risk for DVT, and the prevalence and risk factors for preoperative DVT were examined. RESULTS: Ninety-one patients (9.6%) were diagnosed with preoperative DVT, and postoperative symptomatic pulmonary thromboembolism occurred in one patient (0.11%). A multivariable logistic regression analysis demonstrated that female sex, age ≥ 72 years, history of VTE, a Wells score ≥ 2 points, chronic obstructive pulmonary disease (COPD), and lower hemoglobin levels were significantly associated with preoperative DVT. CONCLUSION: Female sex, age ≥ 72 years, history of VTE, Wells score ≥ 2 points, COPD, and lower hemoglobin levels were identified to be independent risk factors for preoperative DVT. Monitoring for these risk factors and management considering them should help improve the outcomes after lung cancer surgery.
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Neoplasias Pulmonares/cirurgia , Trombose Venosa/epidemiologia , Trombose Venosa/etiologia , Fatores Etários , Idoso , Feminino , Hemoglobinas/deficiência , Humanos , Neoplasias Pulmonares/complicações , Masculino , Complicações Pós-Operatórias , Período Pré-Operatório , Prevalência , Doença Pulmonar Obstrutiva Crônica , Embolia Pulmonar , Fatores de Risco , Fatores Sexuais , Resultado do Tratamento , Ultrassonografia , Trombose Venosa/diagnóstico por imagemRESUMO
PURPOSE: A high plasma level of either fibrinogen or D-dimer has been shown to correlate with a poor prognosis in patients with surgically resected non-small-cell lung cancer (NSCLC). The present study aimed to identify whether or not both markers combined had a superior prognostic value to either alone. METHODS: Of the 1344 patients who underwent surgical resection for NSCLC at our institution between January 2007 and December 2016, 1065 had preoperative plasma fibrinogen and D-dimer data available and were included in the analysis. RESULTS: The recurrence-free survival (RFS) and overall survival (OS) rates were similar for patients with high plasma levels of either or both fibrinogen (> 4.0 g/L) or D-dimer (> 1.0 µg/mL); therefore, these three groups were combined for a further analysis into a single group with high plasma levels of either or both proteins. The high-level group had significantly lower 5-year RFS (53% vs. 68%, p < 0.001) and 5-year OS (65% vs. 80%, p < 0.001) rates than patients with normal plasma levels of fibrinogen and D-dimer (control group). CONCLUSIONS: Our results suggest that preoperative tests for both plasma fibrinogen and D-dimer are necessary to identify patients with surgically resected NSCLC likely to have a poor RFS and OS.
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Biomarcadores Tumorais/sangue , Transtornos da Coagulação Sanguínea/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Fibrinogênio/análise , Neoplasias Pulmonares/cirurgia , Pneumonectomia , Trombofilia/diagnóstico , Tromboembolia Venosa/diagnóstico , Idoso , Transtornos da Coagulação Sanguínea/etiologia , Carcinoma Pulmonar de Células não Pequenas/complicações , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Intervalo Livre de Doença , Feminino , Fibrinólise , Humanos , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/mortalidade , Masculino , Período Pré-Operatório , Prognóstico , Taxa de Sobrevida , Trombofilia/etiologia , Tromboembolia Venosa/etiologiaRESUMO
Colonic diverticular disease has been increasing in prevalence in Japan due to the rapidly aging population. Colonic diverticular bleeding can result in hemorrhagic shock requiring blood transfusion, and it carries a high risk of recurrence within 1 year. Colonic diverticulitis can cause abscess, fistula formation, and perforation of the colon that may require surgery, and it often recurs. As a result, patients with colonic diverticular disease are often bothered by required frequent examinations, re-hospitalization, and a consequent decrease in quality of life. However, the management of diverticular disease differs between Japan and Western countries. For example, computed tomography (CT) is readily accessible at Japanese hospitals, so urgent CT may be selected as the first diagnostic procedure for suspected diverticular disease. Endoscopic clipping or band ligation may be preferred as the first endoscopic procedure for diverticular bleeding. Administration of antibiotics and complete bowel rest may be considered as first-line therapy for colonic diverticulitis. In addition, diverticula occur mainly in the sigmoid colon in Western countries, whereas the right side or bilateral of the colon is more commonly involved in Japan. As such, diverticular disease in the right-side colon is more prevalent in Japan than in Western countries. Against this background, concern is growing about the management of colonic diverticular disease in Japan and there is currently no practice guideline available. To address this situation, the Japanese Gastroenterological Association decided to create a clinical guideline for colonic diverticular bleeding and colonic diverticulitis in collaboration with the Japanese Society of Gastroenterology, Japan Gastroenterological Endoscopy Society, and Japanese Society of Interventional Radiology. The steps taken to establish this guideline involved incorporating the concept of the GRADE system for rating clinical guidelines, developing clinical questions (CQs), accumulating evidence through a literature search and review, and developing the Statement and Explanation sections. This guideline includes 2CQs for colonic diverticulosis, 24 CQs for colonic diverticular bleeding, and 17 CQs for diverticulitis.
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Diverticulose Cólica/terapia , Hemorragia Gastrointestinal/terapia , Doença Diverticular do Colo/diagnóstico , Doença Diverticular do Colo/terapia , Diverticulose Cólica/diagnóstico , Hemorragia Gastrointestinal/diagnóstico , HumanosRESUMO
PURPOSE: The morbidity and mortality associated with lung cancer surgery in patients on chronic hemodialysis (CHD) is high; however, the relationship between the severity of postoperative complications and clinicopathological features is unclear. METHODS: Among 1214 consecutive patients who underwent pulmonary resection for primary lung cancer in our institute between 2004 and 2015, we identified 21 patients on CHD, who were the subjects of this study. Life-threatening postoperative complications were defined as grade 4 and 5 per the Clavien-Dindo classification. RESULTS: Fourteen (67%) of these 21 patients suffered postoperative complications, which were life threatening in 5. There was a higher frequency of interstitial pneumonia (IP) in the patients with life-threatening postoperative complications than in those with complications that were not life threatening (p = 0.032). The rates of acute exacerbation and 90-day mortality in the patients with IP were 50% and 75%, respectively. The overall survival (OS) rate of the patients with life-threatening postoperative complications was significantly lower than that of those with complications that were not life threatening (1- and 3-year OS rates: 40% and 0% vs. 80% and 57%, respectively, p = 0.001). CONCLUSIONS: Postoperative mortality and morbidity were high in patients on CHD who underwent pulmonary resection, especially if they had coexisting IP. Although IP is not a contraindication to pulmonary resection, the surgical strategy for CHD patients with IP should be considered carefully.
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Doenças Pulmonares Intersticiais/mortalidade , Neoplasias Pulmonares/cirurgia , Pneumonectomia/efeitos adversos , Pneumonectomia/mortalidade , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/mortalidade , Diálise Renal/efeitos adversos , Diálise Renal/mortalidade , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Feminino , Humanos , Doenças Pulmonares Intersticiais/epidemiologia , Doenças Pulmonares Intersticiais/etiologia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/classificação , Complicações Pós-Operatórias/epidemiologia , Índice de Gravidade de Doença , Taxa de Sobrevida , Fatores de TempoRESUMO
BACKGROUND: The local recurrence of rectal cancer classifies 4 types, anterior, posterior, lateral compartment and anastomotic site. This study evaluates outcome of laparoscopic lateral lymph node dissection(LLND)against the lateral lymph node recurrence. METHOD: Five patients were diagnosed as the lateral lymph node recurrence and underwent laparoscopic LLND. We diagnosed the lateral lymph node recurrence by CT, MRI and PET-CT. All cases revealed abnormal uptake on PET-CT. RESULT: The median of age is 63. Three patients are male. About primary tumor, 4 patients had tumor below peritoneal reflection and one patient above it. Two patients received neoadjuvant(chemo)radiotherapy(RT group)and one of them underwent laparoscopic LLND at the first operation. The median period from operation to recurrence was 25 months. Before re-operation, 3 patients received chemotherapy. Pathological assessments confirmed pathological complete response(pCR) in all three cases. The median of operation time and bleeding were 257 min and 0 mL, respectively. No complications, more than Grade III(Clavien-Dindo classification)happened. The median follow-up period from re-operation was 34 months. Four patients have no recurrence and one presents lung metastasis. All 5 patients are alive. CONCLUSION: Laparoscope magnifies various pelvic structures. Therefore we perform operation more exactly and safety. In the case of local recurrence, especially lateral compartment, tumor is easy to invade adjacent structures. Then, it is often difficult to do R0 resection. If we find the recurrence lesions earlier and induce neoadjuvant chemotherapy, we can improve R0 resection rate.
Assuntos
Neoplasias Retais/terapia , Idoso , Terapia Combinada , Feminino , Humanos , Excisão de Linfonodo , Linfonodos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Neoplasias Retais/patologia , RecidivaRESUMO
The current case was 73-year-oldwoman. She was referredto our hospital for an abnormal shadow of chest X-ray in the upper right lung field. Chest CT showed 3.5 cm of tumor located at the apex of right lobe with invasion of the chest wall. The tumor was diagnosed as squamous cell carcinoma using CT guided needle biopsy(superior sulcus tumor, clinical T3N0M0, Stage II B). The neoadjuvant therapy, 4 courses of chemotherapy(CBDCA plus PTX)andconcurrent radiotherapy(45 Gy/25 Fr)was performed. Chest CT revealed that tumor size was decreased to 2.3 cm in a diameter, and therapeutic effect was decided as partial response(34%). Upper right lobectomy combinedwith the chest wall(1th to 3th ribs)andmed iastinal lymph node dissection were performed. The pathological specimens showed no residual cancer cells(Ef3, pathological complete response[pCR]). She discharged without complications at 10 days after surgery. It is important to collect cases which obtainedpCR for development of more effective preoperative therapy.
Assuntos
Carcinoma de Células Escamosas/terapia , Quimiorradioterapia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/terapia , Idoso , Carcinoma de Células Escamosas/diagnóstico por imagem , Feminino , Humanos , Neoplasias Pulmonares/patologia , Pneumonectomia , Resultado do TratamentoRESUMO
The programmed death-1/programmed death-ligand 1 (PD-L1) pathway is a negative feedback pathway that suppresses the activity of T cells. Previous studies reported that high PD-L1 expression on tumor cells (TC) was associated with poor survival in patients with colorectal cancer; however, the prognostic evaluation of these studies was limited because they included patients at various disease stages. The purpose of the present study was to evaluate the relationship between PD-L1 status in the immune microenvironment and the clinicopathological features of stage III colorectal cancer. Two hundred and thirty-five patients were included in the analysis. PD-L1 expression on TC and tumor-infiltrating mononuclear cells (TIMC) was evaluated by immunohistochemistry. The median follow-up of thisi study was 52.9 months. A total of 8.1% of stage III colorectal cancer showed high PD-L1 expression on TC and 15.3% showed high PD-L1 expression on TIMC. Patients with high PD-L1 expression on TC had significantly shorter disease-free survival (DFS) than patients with low expression (hazard ratio [HR] 2.36; 95% confidence interval [CI], 1.21-4.62; P = 0.012). In addition, patients with high PD-L1 expression on TIMC were associated with longer DFS than patients with low expression (HR 0.40; 95% CI, 0.16-0.98; P = 0.046). These findings suggest that PD-L1 expression status may be a new predictor of recurrence for stage III colorectal cancer patients and highlight the necessity of evaluating PD-L1 expression on TC and TIMC separately in the tumor microenvironment.
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Antígeno B7-H1/metabolismo , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Intervalo Livre de Doença , Humanos , Imuno-Histoquímica/métodos , Linfócitos do Interstício Tumoral/metabolismo , Linfócitos do Interstício Tumoral/patologia , Prognóstico , Microambiente Tumoral/fisiologiaRESUMO
BACKGROUND: The use of laparoscopic surgery for colorectal cancer has become widespread recently. However, the safety and oncological outcomes of laparoscopic surgery for primary advanced colorectal cancer need extensive investigation. We analyzed the short- and long-term outcomes after laparoscopic multivisceral resection for primary colon cancer with suspected invasion of other organs at a single institution. METHODS: Between January 2000 and December 2014, 118 patients underwent laparoscopic multivisceral resection for primary colon cancer invading or adhering to adjacent organs or structures; their short- and long-term outcomes were retrospectively evaluated. RESULTS: The median operating time was 254 min (range 130-1051 min), and median blood loss was 48 ml (range 0-2777 ml). The overall conversion rate was 6.8%. The postoperative complication rate was 17.8%. The number of patients with R0 and R1 resection was 112 (94.9%) and 6 (5.1%), respectively. At a median follow-up period of 32 months (range 0-157 months), the local recurrence rate in patients who underwent R0 resection was 1.8%, while for R1 resection it was 66.7%. In multivariate analysis, R1 resection and LN metastases were found to be predictors of poor prognosis. The cancer-specific 5-year survival was 87% when R0 resection was achieved; within these, the 5-year survival rates for patients with stages II, III, and IV disease were 94, 81, and 40%, respectively. CONCLUSIONS: Laparoscopic en bloc multivisceral resection for clinically suspected T4 colon cancer is a safe and feasible procedure for precisely selected patients, attaining satisfactory oncological outcomes when R0 resection is achieved.
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Colectomia/métodos , Neoplasias Colorretais/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Perda Sanguínea Cirúrgica , Colectomia/efeitos adversos , Neoplasias Colorretais/patologia , Feminino , Seguimentos , Humanos , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Duração da Cirurgia , Complicações Pós-Operatórias , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do TratamentoRESUMO
We present a case of bilateral lymph node metastases of rectal cancer treated with chemotherapy and surgery. The patient was a 65-year-old man with upper rectal cancer. Laparoscopic low anterior resection(LAR)was performed. Pathological findings were tub2>por>muc, pT3, ly2, v3, pN2, pM0. Six months after surgery, the CEA level was elevated. CT and PET-CT confirmed bilateral metastasis to the lymph nodes. Five courses of FOLFOX4 plus bevacizumab were administered, and then, we performed laparoscopic bilateral lymph node dissection. Pathological assessments confirmed scarring and fibrosis, that is, a pathological complete response(pCR)was achieved. Two years and 6 months after surgery, no recurrence was detected. After chemotherapy or chemoradiotherapy, we should perform surgery to prevent local recurrence, especially to the lateral lymph nodes.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Retais/tratamento farmacológico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Bevacizumab/administração & dosagem , Terapia Combinada , Fluoruracila/administração & dosagem , Humanos , Laparoscopia , Leucovorina/administração & dosagem , Metástase Linfática , Masculino , Compostos Organoplatínicos/administração & dosagem , Neoplasias Retais/patologia , Neoplasias Retais/cirurgia , RecidivaRESUMO
Mutant selective epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), such as rociletinib and AZD9291, are effective for tumors with T790M secondary mutation that become refractory to first-generation EGFR-TKI. However, acquired resistance to these prospective drugs is anticipated considering the high adaptability of cancer cells and the mechanisms remain largely obscure. Here, CNX-2006 (tool compound of rociletinib) resistant sublines were established by chronic exposure of HCC827EPR cells harboring exon 19 deletion and T790M to CNX-2006. Through the analyses of these resistant subclones, we identified two resistant mechanisms accompanied by MET amplification. One was bypass signaling by MET amplification in addition to T790M, which was inhibited by the combination of CNX-2006 and MET-TKI. Another was loss of amplified EGFR mutant allele including T790M while acquiring MET amplification. Interestingly, MET-TKI alone was able to overcome this resistance, suggesting that oncogenic dependence completely shifted from EGFR to MET. We propose describing this phenomenon as an "oncogene swap." Furthermore, we analyzed multiple lesions from a patient who died of acquired resistance to gefitinib, then found a clinical example of an oncogene swap in which the EGFR mutation was lost and a MET gene copy was gained. In conclusion, an "oncogene swap" from EGFR to MET is a novel resistant mechanism to the EGFR-TKI. This novel mechanism should be considered in order to avoid futile inhibition of the original oncogene.
Assuntos
Resistencia a Medicamentos Antineoplásicos/genética , Receptores ErbB/genética , Neoplasias Pulmonares/tratamento farmacológico , Proteínas Proto-Oncogênicas c-met/genética , Acrilamidas/administração & dosagem , Linhagem Celular Tumoral , Receptores ErbB/antagonistas & inibidores , Gefitinibe , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Mutação , Oncogenes , Inibidores de Proteínas Quinases/administração & dosagem , Pirimidinas/administração & dosagem , Quinazolinas/administração & dosagemRESUMO
Anastomotic stricture reportedly often recurs following barium peritonitis, regardless of whether the anastomotic diameter is initially sufficient. However, the causes of repetitive stricture have not been clarified. We report a case that suggests the pathophysiology of recurrent anastomotic strictures following barium peritonitis. The patient was a 39-year-old Japanese man with idiopathic perforation of the descending colon after undergoing an upper gastrointestinal barium contrast study. After emergency peritoneal lavage and diverting colostomy, created using the perforated region, the patient recovered uneventfully and 3 months later, the colostomy was closed and the perforated colon was resected. However, 7 months after colostomy closure, abdominal distention gradually developed, and colonoscopy revealed an anastomotic stricture. The patient was referred to our hospital where he underwent resection of the anastomotic stricture. The surgical specimen exhibited barium granulomas not only in the subserosa of the entire specimen, but also in the submucosa and lamina propria localized in the anastomotic site. These findings suggest that barium was embedded in the submucosa and lamina propria with manipulation of the stapled anastomosis and that the barium trapped in the anastomotic site caused persistent inflammation, resulting in an anastomotic stricture.
Assuntos
Anastomose Cirúrgica/efeitos adversos , Sulfato de Bário/efeitos adversos , Colo Descendente , Meios de Contraste/efeitos adversos , Enema/efeitos adversos , Granuloma/etiologia , Granuloma/patologia , Enteropatias/etiologia , Enteropatias/patologia , Perfuração Intestinal/etiologia , Peritonite/etiologia , Adulto , Colo Descendente/patologia , Colo Descendente/cirurgia , Colostomia , Constrição Patológica , Humanos , Perfuração Intestinal/parasitologia , Perfuração Intestinal/cirurgia , Masculino , Lavagem Peritoneal , Peritonite/terapia , Resultado do TratamentoRESUMO
OBJECTIVE: To perform a retrospective analysis of UFT and oral leucovorin combination adjuvant chemotherapy for Stage III colon cancer patients over 76 years old, in order to evaluate both treatment efficacy and toxicity. SUBJECTS: Between 2002 and 2011, 333 Stage III colon cancer patients had surgery performed in our institute, and we studied 25 of them on our chemotherapy regimen. RESULTS: Patients'median age was 78 years old, with 12 men and 13 women. Of all the patients, 19 had Stage IIIa and 6 had Stage IIIb. The 3-year disease-free survival rates for Stage III and Stage IIIa patients were 65. 1% and 83. 1%, respectively, and the 3-year overall survival rate for Stage III was 79. 9%. With regard to toxicity, liver function disorder was observed in 8% of the patients, being the adverse event that occurred the most, but there was no Grade 3 or 4 toxicity. CONCLUSION: UFT and oral leucovorin combination adjuvant chemotherapy for Stage III colon cancer patients over 76 years showed a good response, especially for Stage III a.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Quimioterapia Adjuvante , Ensaios Clínicos Fase III como Assunto , Neoplasias do Colo/patologia , Feminino , Humanos , Leucovorina/administração & dosagem , Masculino , Estadiamento de Neoplasias , Estudos Retrospectivos , Tegafur/administração & dosagem , Uracila/administração & dosagemRESUMO
Background/Aim: Synchronous colorectal cancer, which occurs in approximately 4.8-8.4% of all colorectal cancers, has a genetic profile with a higher rate of v-raf murine sarcoma viral oncogene homolog B1 (BRAF) mutation and microsatellite instability-high than solitary colorectal cancer. However, little information is available on heterogeneity among tumor lesions because of difficulty in performing genetic tests in all lesions in clinical practice. Case Report: A 44-year-old man presented with multiple recurrent lung metastases 42 months after the endoscopic resection of early stage synchronous ascending and sigmoid colon cancers. The genetic testing of sigmoid colon cancer tissue samples, their state being more advanced than that of ascending colon cancer, revealed a v-Ki-ras 2 Kirsten rat sarcoma viral oncogene homolog mutation (G13C) and BRAF wild type. However, the tumor was refractory to initial chemotherapy and rapidly progressed to new liver metastases. Therefore, we suspected that there may be biological heterogeneity between the primary sigmoid colon lesion and liver metastases. Next, we performed next-generation sequencing on circulating tumor DNA from the patient's plasma (Foundation One Liquid CDx®), which revealed the V600E mutation of BRAF, suggesting that there was genetic heterogeneity among the synchronized primary lesions, one of which was responsible for the chemo-refractory rapid-growing liver metastases. Conclusion: Genetic profiling with liquid biopsy at the time of recurrence and metastasis may be useful in patients with multiple synchronous cancers because there is less heterogeneity between primary and metastatic sites.
RESUMO
OBJECTIVE: To perform a retrospective analysis of UFT and oral leucovorin plus PSK combination adjuvant chemotherapy for stage III colon cancer in order to evaluate both treatment efficacy and toxicity. SUBJECTS: Between 2003 and 2009, 273 stage III colon cancer patients underwent surgery in our institute, and we studied 156 of them. RESULTS: Patients' median age was 72 years old; 87 men and 69 women. Of all patients, 119 had stage IIIa and 37 had stage IIIb. The 3-year disease, free survival rates for stage III, stage IIIa and stage IIIb patients were 73. 9%and 80. 6%and 51. 4%, respectively, and the 3-year overall survival rates for stage III was 97. 6%. With regard to toxicity, liver function disorder was observed in 9. 6%of the patients as the most frequent adverse event, but there was no grade 3 or 4 toxicity. CONCLUSION: UFT and oral leucovorin plus PSK combination adjuvant chemotherapy for stage III colon cancer showed a good response especially for stage III a.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Leucovorina/uso terapêutico , Polissacarídeos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/economia , Quimioterapia Adjuvante , Neoplasias do Colo/patologia , Leucovorina/administração & dosagem , Leucovorina/economia , Estadiamento de Neoplasias , Polissacarídeos/administração & dosagem , Polissacarídeos/economia , Recidiva , Estudos Retrospectivos , Tegafur/economia , Tegafur/uso terapêutico , Uracila/economia , Uracila/uso terapêuticoRESUMO
KRAS and epidermal growth factor receptor (EGFR) are the two most frequently mutated proto-oncogenes in adenocarcinoma of the lung. The occurrence of these two oncogenic mutations is mutually exclusive, and they exhibit many contrasting characteristics such as clinical background, pathological features of patients harboring each mutation, and prognostic or predictive implications. Lung cancers harboring the EGFR mutations are remarkably sensitive to EGFR tyrosine kinase inhibitors such as gefitinib or erlotinib. This discovery has dramatically changed the clinical treatment of lung cancer in that it almost doubled the duration of survival for lung cancer patients with an EGFR mutation. In this review, we describe the features of KRAS mutations in lung cancer and contrast these with the features of EGFR mutations. Recent strategies to combat lung cancer harboring KRAS mutations are also reviewed.
Assuntos
Adenocarcinoma/genética , Transformação Celular Neoplásica/genética , Genes erbB-1/fisiologia , Genes ras/fisiologia , Neoplasias Pulmonares/genética , Mutação , Adenocarcinoma/patologia , Animais , Transformação Celular Neoplásica/patologia , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/patologia , Modelos Biológicos , Mutação/fisiologia , Ativação Transcricional/genética , Ativação Transcricional/fisiologiaRESUMO
Lung cancer is a major cause of cancer-related mortality worldwide. Currently, adenocarcinoma is its most common histological subtype in many countries. In contrast with small cell lung cancer or squamous cell carcinoma, lung adenocarcinoma often arises in never-smokers, especially in East Asian countries, as well as in smokers. Adenocarcinoma in never-smokers is associated with a lower incidence of genetic alterations (i.e., somatic mutations, loss of heterozygosity, and methylation) than in smokers. In addition, most adenocarcinomas in never-smokers harbor one of the proto-oncogene aberrations that occur in a mutually exclusive manner (EGFR mutation, KRAS mutation, HER2 mutations, or ALK translocation). It is of note that the proliferation and survival of lung cancer cells that harbor one of these oncogenic aberrations depend on the signaling from each aberrantly activated oncoprotein (oncogene addiction). Therefore, most adenocarcinomas in never-smokers can be effectively treated by molecularly targeted drugs that inhibit each oncoprotein. Moreover, from a pathological aspect, lung adenocarcinoma in never-smokers is characterized by terminal respiratory unit-type adenocarcinoma and a particular gene expression profile. Finally, epidemiological analyses have identified many candidate causes of lung cancer in never-smokers (genetic, environmental, and hormonal factors). The elucidation of the particular features of lung cancer unrelated to smoking and the development of new therapeutic modalities may reduce the mortality from lung cancers in the future.
Assuntos
Adenocarcinoma/epidemiologia , Carcinoma Pulmonar de Células não Pequenas/epidemiologia , Neoplasias Pulmonares/epidemiologia , Proteínas Oncogênicas/genética , Adenocarcinoma/etiologia , Adenocarcinoma/patologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Aberrações Cromossômicas , Receptores ErbB/genética , Feminino , Perfilação da Expressão Gênica , Humanos , Neoplasias Pulmonares/etiologia , Neoplasias Pulmonares/patologia , Masculino , Terapia de Alvo Molecular , Mutação , Estadiamento de Neoplasias , Exposição Ocupacional , Proteínas de Fusão Oncogênica/genética , Prognóstico , Proto-Oncogene Mas , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas p21(ras) , Fumar/epidemiologia , Proteína Supressora de Tumor p53/genética , Proteínas ras/genéticaRESUMO
Mucosal prolapse syndrome (MPS) is a benign inflammatory disease of the rectum that causes symptoms such as blood-stained stools and anemia. However, there is no treatment with a proven long-term efficacy for MPS. A 53-year-old man presented with blood-stained stools and anemia due to MPS and was treated conservatively for 1 year. However, his symptoms did not improve. We performed endoscopic submucosal dissection (ESD) for MPS. He has had no symptoms for six years after ESD, and the recurrence of MPS was not seen on endoscopy. This case shows that ESD can be effective for the long-term treatment of symptomatic MPS.
Assuntos
Ressecção Endoscópica de Mucosa , Endoscopia , Humanos , Mucosa Intestinal , Masculino , Pessoa de Meia-Idade , Prolapso , Reto , Resultado do TratamentoRESUMO
A 65 -year-old male was admitted to our hospital because of epigastregia. Computed tomography (CT) and abdominal ultrasonography (AUS) revealed advanced gallbladder cancer and two S5 liver metastases. Selective gallbladder angiogram revealed his cystic vein was draining into the portal vein (P5), so cholecystectomy and S4a+S5-subsegmentectomy were performed. Pathological study of the resected specimens showed three liver metastases. After surgical resection lumbar metastasis was suspected, so radiotherapy and UFT at 300mg/day were started. Next, we started oral administration of S-1 alone (100mg/body) for 4 weeks followed by a 2-week rest period as one course. 100mg/day was changed to 80mg/body after 3 courses because of grade 2 neutropenia. A total of 31 courses of S-1 80mg/day were administered postoperatively for five years. The patient is alive and free of disease five years and ten months after the operation.
Assuntos
Neoplasias da Vesícula Biliar/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Ácido Oxônico/uso terapêutico , Tegafur/uso terapêutico , Idoso , Combinação de Medicamentos , Neoplasias da Vesícula Biliar/diagnóstico por imagem , Neoplasias da Vesícula Biliar/patologia , Neoplasias da Vesícula Biliar/cirurgia , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Masculino , Estadiamento de Neoplasias , Indução de Remissão , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Myxoglobulosis is considered a subtype of appendiceal mucinous neoplasm (AMN). Factors affecting the occurrence of myxoglobulosis include proximal appendiceal obstruction and mucosal secretion at the residual appendiceal mucosa. In addition, myxoglobulosis has also been reportedly associated with persistent chronic inflammation. We report a case of AMN with myxoglobulosis occurring 3 years after perforated barium appendicitis and the importance of caution during surgery for barium peritonitis and elucidate the pathology of myxoglobulosis. CASE PRESENTATION: A 45-year-old man with an AMN underwent laparoscopic ileocecal resection 3 years after peritonitis caused by perforated barium appendicitis. The patient had a medical history of perforated barium appendicitis after barium swallow imaging, which was treated conservatively 3 years ago. Computed tomography (CT) revealed cystic enlargement of the appendix and remnant barium around the appendix. He was then pathologically diagnosed with a low-grade AMN based on the resected specimen, and the appendix filled with white globules was diagnosed as myxoglobulosis. When barium is not absorbed, it causes chronic inflammation. As barium was observed around the appendix, prolonged inflammation, and appendicitis may have contributed to the myxoglobulosis. The circumference of the appendix firmly adhered to the surrounding tissue with barium; hence, it was difficult to perform appendectomy. Barium that enters the anastomotic site causes stenosis of this part; therefore, excision of the ileocecal region in the intestinal part where barium is not present was selected instead of appendectomy. Colonoscopy performed 1 year after surgery and showed no evidence of anastomotic stricture. CONCLUSION: This case suggested that barium peritonitis caused strong adhesions with the surrounding tissue; thus, careful manipulation was necessary to avoid perforating the appendix. Appendectomy and partial cecal resection were predicted to be difficult because of adhesion by barium. In addition, the ileocecal resection was selected because we had to choose an anastomotic site without barium. The perforated appendicitis caused stenosis of the appendix orifice, and barium surrounding the appendix caused persistent chronic inflammation. This was suggested to contribute to the myxoglobulosis.
RESUMO
OBJECTIVES: Colonic diverticular disease is widespread in Western countries and its associated with aging. In Japan, diverticulitis and colovesical fistula are also occurring more frequently. Colonic resection for diverticula-related fistulas is frequently technically demanding because of associated acute or chronic inflammation. We evaluated the safety and efficacy of a standardized laparoscopic procedure. METHODS: Data from 39 consecutive patients who had undergone laparoscopic surgery for colovesical fistula between October 2006 and August 2017 were retrospectively reviewed. RESULTS: The patients' median age was 60 years and comprised 35 men and four women. Sigmoidectomy was performed in 33 patients, Hartmann's procedure in four, and anterior resection in two. The median operative time was 203 minutes and estimated blood loss 15 mL. There were no intraoperative complications or conversion to open surgery. No patients required bladder repair; three had minor postoperative complications, and none had recurrent diverticulitis or fistula at a mean follow-up of 5.1 years. CONCLUSIONS: The magnified vision and minimal invasiveness make a laparoscopic approach the ideal means of managing colovesical fistula. To our knowledge, this is the largest study of colovesical fistula managed by a standardized laparoscopic procedure.