Carlos Eduardo Pinto

Interferon-inducible guanylate binding protein (GBP)-2: A novel p53-regulated tumor marker in esophageal squamous cell carcinomas

TP53 mutations are common in esophageal squamous cell carcinomas (SCC). To identify biological markers of possible relevance in esophageal SCC, we (i) searched for genes expressed in a p53‐dependent manner in TE‐1, an esophageal SCC cell line expressing the temperature‐sensitive TP53 mutant V272M, and (ii) investigated the expression of one of those genes, the interferon‐inducible Guanylate Binding Protein 2 (GBP‐2), in esophageal SCC tissues. Clontech Human Cancer 1.2 arrays containing 1,176 human cancer gene‐related sequences were used to identify differentially expressed genes in TE‐1 cells at permissive (32°C) and nonpermissive (37°C) temperatures. The expression of GBP‐2 and IRF‐1, its main transcriptional regulator, was analyzed by immunohistochemistry in a retrospective series of 41 esophageal SCC cases with a clear transition zone from noncancer, apparently normal epithelium to invasive cancer. The expression of the GBP‐2 gene is consistently increased in TE‐1 at 32°C in a p53‐dependent manner, as confirmed by inhibition of p53 expression by RNA interference. Increase in GBP‐2 is accompanied by an increase in protein levels of IRF‐1, the main transcriptional regulator of GBP‐2, and in the formation of complexes between p53 and IRF‐1. GBP‐2 expression is significantly higher in esophageal SCC than in adjacent normal epithelium (p < 0.01), in which GBP‐2 staining is limited to the basal layer. Our results suggest that p53 up‐regulates GBP‐2 by cooperating with IRF‐1. The association of GBP‐2 expression with proliferative squamous cells suggests that GBP‐2 may represent a marker of interest in esophageal SCC.

Salvage esophagectomy after exclusive chemoradiotherapy: results at the Brazilian National Cancer Institute (INCA)

Surgical resection is considered the gold standard treatment for esophageal cancer, with global cure rates ranging from 15 to 40%. Exclusive chemoradiotherapy has been used for patients with locally advanced esophageal carcinoma or without clinical conditions for esophagectomy, reaching a 5-year survival rate of up to 30%. However, locoregional control is poor, with local recurrence of 40-60%, being reported in the literature. Maybe, these patients can benefit from salvage surgery. In this study, 15 patients with esophageal cancer submitted to salvage esophagectomy after exclusive chemoradiotherapy treatment were retrospectively analyzed. Salvage esophagectomy was demonstrated to be technically feasible. However, it presents with high surgical morbidity. Currently, salvage esophagectomy is considered the best available treatment to attempt cure in cases of tumor recurrence or persistence after exclusive chemoradiotherapy. All the other types of treatments are regarded as palliative with discouraging survival results.

Esofagectomia de resgate após quimiorradioterapia radical exclusiva: resultados do departamento de cirurgia abdôminopélvica do Instituto Nacional de Câncer

OBJECTIVE: To present the experience and the results from the Abdominopelvic Surgery Section from the National Cancer Institute in the rescue esophagectomy in patients previously submitted to the exclusive chemoradiotherapy as primary treatment. METHOD: 14 patients submitted to the esophagectomy of rescue from March of 1999 to May of 2006 were analyzed retrospectively. RESULTS: The median age was of 63 years (39-72 years). Eight patients were females and six were males. Nine patients presented the tumor in the medium esophagus and five patients presented the disease in the distal esophagus; epidermoid carcinoma occurred in 12 patients and adenocarcinoma in two patients. The median of the surgical time was of 305 minutes (240-430 minutes). Operation with complete resection (R0) of the tumor was performed in 13 patients and one had metastati cresidual disease to lung apices. Total morbidity was of 69.2 % and there was no operative mortality. All patients were discharged. CONCLUSION: The esophagectomy of rescue was shown to be technically viable; however, it presents a high operative morbidity. It represents the best treatment option for the cure of recurrent tumor, or persistent tumor after exclusive radical chemoradiotherapy. All therapies are considered palliatives, with disappointing survival results.

Esofagectomia trans-hiatal versus transtorácica: experiência do Instituto Nacional do Câncer (INCA)

OBJECTIVE: Analyses of morbidity, mortality and overall survival after transhiatal (TH) or transthoracic (TT) esophagectomy. METHODS: Retrospective non randomized study of 68 patients with esophagus neoplasia operated in the Brazilian National Cancer Institute between 1997 and 2005. We divided in two groups: Group 1 - TH (33 patients); and Group 2 - TT (35 patients). RESULTS: The mean age was 40,7 years old (25 - 74 years old), being 73,5% male. Middle third tumors predominated in Group 2 (48,6% vs. 21,2%, p = 0,02). The mean of dissected lymph nodes was biggest in Group 2 (21,6 vs. 17,8 lymph nodes, p = 0,04), however without difference in number of metastatic lymph nodes (4,1 vs. 3,9 linfonodos, p = 0,85). The mean of operative time was higher in Group 2 (410 vs. 270 minutes, p = 0,001). Also the mean of length of stay was higher in Group 2 (19 vs. 14 days, p = 0,001). The operative morbidity was 50%, without statistical difference between the groups (42,4% vs. 57,1%, p = 0,23). Esophageal leakage occurred in 13,2% of cases, also without statistical difference (9,1% vs. 17,1%, p = 0,23). The mortality was 5,8% (04 patients), without statistical difference (1,4% vs. 4,4%, p = 0,83). CONCLUSION: In our study, the morbidity and mortality showed no statistical difference in relation to the access performed, although higher operative time and length of stay were observed in TT access. The 3 and 5-years overall survival also were biggest in TT access, probably due to the biggest frequency of patients on initial stages between the submitted to the TT access.

O uso do tubo colônico bipediculado microcirúrgico na reconstrução do esôfago

In some cases of esophageal reconstruction, it is not possible to use the gastric tube. In those cases, the second option is the reconstruction with a colonic segment. In the present paper, the authors present the use of microsurgical technique to improve vascular supply in esophageal reconstructions using the colon. Therefore, the transposed segment becomes perfused by two vascular pedicles: a proximal one and a distal one. The authors describe a case of 52 years-old patient, suffering of middle third esophagus carcinoma, who underwent a primarily esophageal resection with an unsuccessful reconstruction using gastric transposition. A new reconstruction was proposed using a bipedicle microcirurgical colonic tube, four months later. The post operative was uneventful with rehabilitation of swallowing and satisfactory recovery of nutritional state.

Câncer gástrico precoce: revisão de 47 casos do instituto nacional de câncer nos últimos cinco anos

OBJETIVO: O presente estudo visa estudar as caracteristicas dos tumores gastricos precoces diagnosticados em um grande centro de referencia no tratamento do câncer gastrico em nosso pais, o Instituto Nacional de Câncer. METODO: Analisamos retrospectivamente os casos de câncer gastrico precoce da Secao de Cirurgia Abdominopelvica do Hospital do Câncer I no periodo de 1995 a 1999. Resgatamos 47 prontuarios de pacientes portadores de câncer gastrico precoce, dos 296 pacientes submetidos a resseccao gastrica neste periodo. RESULTADOS: Em nosso hospital a incidencia corresponde a cerca de 15,8% dos pacientes submetidos a gastrectomias por câncer gastrico. Constatamos uma incidencia de 1,1:1 com relacao ao sexo F/M e com morbidade de 19,1% e mortalidade de 4,2%. Houve uma predominância do tipo IIc + III e com 27,6% de positividade para o Helicobacter pylori. CONCLUSAO: O câncer gastrico precoce representa o melhor estagio para a resseccao nos tumores do estomago, porem, infelizmente, ainda e pouco diagnosticado em nosso meio, apesar dos avancos nos metodos de diagnostico.

Esofagectomia vídeo-tóraco-laparoscópica com tempo torácico em posição pronada

OBJECTIVE to analyze the National Cancer Institute Abdominopelvic Division (INCA / MS/HC I) initial experience with thoraco-laparoscopic esophagectomy with thoracic stage in prone position. METHODS we studied 19 consecutive thoraco-laparoscopic esophagectomies from may 2012 to august 2014, including ten patients with squamous cells carcinoma (five of the middle third and five of the lower third) and nine cases of gastroesophageal junction adenocarcinoma (six Siewert I and three Siewert II). All procedures were initiated by the prone thoracic stage. RESULTS There were minimal blood loss, optimal mediastinal visualization, oncological radicality and no conversions. Surgical morbidity was 42 %, most being minor complications (58% Clavien I or II), with few related to the technique. The most common complication was cervical anastomotic leak (37%), with a low anastomotic stricture rate (two stenosis: 10.53%). We had one (5.3%) surgical related death, due to a gastric tube`s mediastinal leak, treated by open reoperation and neck diversion. The median Intensive Care Unit stay and hospital stay were two and 12 days, respectively. The mean thoracoscopic stage duration was 77 min. Thirteen patients received neoadjuvant treatment (five squamous cells carcinoma and eight gastroesophageal adenocarcinomas). The average lymph node sample had 16.4 lymph nodes per patient and 22.67 when separately analyzing patients without neoadjuvant treatment. CONCLUSION the thoraco-laparoscopic approach was a safe technique in the surgical treatment of esophageal cancer, with a good lymph node sampling.

Avaliação da reconstrução do trato alimentar com tubo gástrico ou colônico na esofagectomia por câncer de esôfago

BACKGROUND: To describe the main reconstruction techniques of the alimentary tract after esophagectomy due to esophagus cancer in patients enrolled. METHODS: We analyzed retrospectively 68 patients submitted to the esophagectomy between february of 1997 and november of 2005. All of the patients included in the study were submitted to the reconstruction with gastric tube and colon segment and cervical anastomosis. RESULTS: The mean age was 55,4 years (25-74 years). 50 patients were of male gender and 18 patients of female gender. 27 patients presented the tumor localized in the medium esophagus and 41 patients in the distal esophagus, being epidermoid carcinoma in 35 patients and adenocarcinoma in 33 patients. The ressection was performed through transthoracic access in 35 individuals and through transhiatal access in 33. The reconstruction with gastric tube was performed in 58 patients and with colonic tube in 10 patients. The series total morbidity was 52,9%. The operative mortality was 5,8%. The mean survival was of 35 months. CONCLUSION: The esophagectomy with reconstruction with gastric tube and cervical anastomosis is feasible technically; being a routine procedure realized in the patients carriers of esophagus cancer with surgical indication. The reconstruction with the colonic tube is indicated mainly for the patients without possibility of the stomach use for reconstruction of the alimentary tract, being a valid option and with excellent results.

Leiomiossarcoma do esôfago

The authors describe a case of esophageal leiomyosarcoma treated at the Abdominopelvic Surgery Department of the Brazilian National Cancer Institute, including literature review, addressing treatment and prognosis. A 45 year-old female patient complaining of dysphagia, with pre-operative exams sugestive of esophageal leiomyoma. She was submitted to an esophagusgastrectomy with digestive reconstitution using a gastric tube brought through the posterior mediastinum. The histopathological examination and immunohistochemical tests confirmed that the tumor was an esophageal leiomyosarcoma. She is at the 7th year of follow up with no recurrence nor digestive complains.