Heritable genomic diversity in breast cancer driver genes and associations with risk in a Chilean population

BACKGROUND: Driver mutations are the genetic components responsible for tumor initiation and progression. These variants, which may be inherited, influence cancer risk and therefore underlie many familial cancers. The present study examines the potential association between SNPs in driver genes SF3B1 (rs4685), TBX3 (rs12366395, rs8853, and rs1061651) and MAP3K1 (rs72758040) and BC in BRCA1/2-negative Chilean families. METHODS: The SNPs were genotyped in 486 BC cases and 1258 controls by TaqMan Assay. RESULTS: Our data do not support an association between rs4685:C > T, rs8853:T > C, or rs1061651:T > C and BC risk. However, the rs12366395-G allele (A/G + G/G) was associated with risk in families with a strong history of BC (OR = 1.2 [95% CI 1.0-1.6] p = 0.02 and OR = 1.5 [95% CI 1.0-2.2] p = 0.02, respectively). Moreover, rs72758040-C was associated with increased risk in cases with a moderate-to-strong family history of BC (OR = 1.3 [95% CI 1.0-1.7] p = 0.02 and OR = 1.3 [95% CI 1.0-1.8] p = 0.03 respectively). Finally, risk was significantly higher in homozygous C/C cases from families with a moderate-to-strong BC history (OR = 1.8 [95% CI 1.0-3.1] p = 0.03 and OR = 1.9 [95% CI 1.1-3.4] p = 0.01, respectively). We also evaluated the combined impact of rs12366395-G and rs72758040-C. Familial BC risk increased in a dose-dependent manner with risk allele count, reflecting an additive effect (p-trend = 0.0002). CONCLUSIONS: Our study suggests that germline variants in driver genes TBX3 (rs12366395) and MAP3K1 (rs72758040) may influence BC risk in BRCA1/2-negative Chilean families. Moreover, the presence of rs12366395-G and rs72758040-C could increase BC risk in a Chilean population.

Linfonodo centinela en cáncer de mama: correlación entre detección isotópica y quirúrgica / Pre and intraoperative scintigraphic detection of sentinel nodes in breast cancer

Background: Sentinel node detection localizes the first node that drains a malignant lesion aiming to detect tumor dissemination. Aim: To assess the yield of sentinel node detection in breast cancer, using pre or intraoperative scintigraphy. Material and Methods: Review of medical records of patients with breast cancer who had a scintigraphic detection of sentinel nodes. Lymph node scintigraphy and surgery were performed in the same day. Results: We studied 174 women aged 53 ± 13 years, operated with a diagnosis of breast cancer, including six highly suspicious lesions in the contralateral breast (totaling 180 studied breasts). Preoperative scintigraphy showed a sentinel node in 174 of 180 breasts (97%). Intraoperative gamma probe confirmed the presence of the sentinel node in the same 174 breasts and detected an additional one reaching a detection yield of 97%. Four patients in whom a sentinel node was not detected in the preoperative scintigraphy, had macrometastases. Frozen section biopsies were available in 177 of 180 breasts. Metastases were informed in 45 patients who underwent axillary lymph node dissection, plus one additional patient with a suspicious lesion. Conclusions: A high rate of sentinel node detection in the preoperative scintigraphy was observed. Most sentinel nodes not detected with nuclear medicine had macrometastases. In 71% of patients, the detection of sentinel node avoided axillary lymph node dissection.

Gastrectomía extendida en cáncer gástrico: Evaluación de la morbilidad y mortalidad postoperatoria / Complications and mortality of extended gastrectomy for gastric cancer

Background: Extended gastrectomy allows a complete tumor excision in patients with advanced gastric cancer. Aim: To compare the surgical results of extended (ER) and non-extended gastrectomy (NER) among patients with gastric cancer, and determine factors associated with complications and mortality. Material and Methods: Review of medical records of patients with gastric cancer who underwent complete resection between 2002 and 2008 in an oncological hospital. Demographics, patient-related and therapeutic features were compared between groups, and independent factors were established with multivariate analysis. Results: Seventy four patients, (44 men, median age 62 years) underwent an ER and 103 patients, (56 men, median age 61 years) a NER. Specifically, ER included splenectomy alone in 27 patients, splenectomy associated with other procedure in 24, partial esophagectomy in 18, distal pancreatectomy in 13, hemicolectomy in 8, total esophagectomy in 7, partial hepatectomy in 4, and adrenalectomy in 1. Postoperative complications were observed in 19 patients treated with an ER (26 percent) and in 11 patients treated with a NER (11 percent), p < 0.05. Serious complications were higher in patients who underwent an ER compared with NER (6 patients (8 percent) vs. 4 (4 percent), respectively) p < 0.05. In the same way, mortality was higher in patients treated with ER when it was compared with NER (4 patients (5 percent) vs two (2 percent), respectively), p < 0.05. ER and serum albumin levels were independent factors associated to a higher risk of mortality and rate of complications. Conclusions: ER was associated with a higher rate of general and severe complications, and mortality.

Cáncer de la unión gastroesofágica: Evaluación de los resultados quirúrgicos, sobrevida alejada y factores pronósticos en enfermos con terapia resectiva / Adenocarcinoma of the esophagogastric junction: Retrospective analysis of 39 patients

Background: The long-term survival of adenocarcinoma of the esophago-gastric junction is poor and depends on the possibility of performing a complete surgical excision and the absence of lymph node involvement. Aim: To report surgical results and survival of patients with adenocarcinoma of the esophago-gastric junction. Material and Methods: Retrospective review of medical records of patients with adenocarcinoma of the esophago-gastric junction, subjected to a curative surgical procedure between 2000 and 2008. Deaths that occurred within 60 days of the operation were considered operative mortality. Tumor stage was determined using TNM and Siewert pathological classifications. Results: Thirty-nine patients aged 40 to 80years (27 men), were operated. According to Siewert classification, seven patients had type I, six type II and 26 type III tumors. Twenty-two patients were subjected to a total gastrectomy with partial excision of distal esophagus and mediastinal reconstruction, 10patients were subjected to a trans-hiatal esophagectomy and seven to a total esophagogastrectomy. According to postoperative staging, five patients were in stage I, 12 in stage II, nine in stage III and 13 in stage IV. Median, three and five year's survival figures were 21.4 months, 33 and 25 percent, respectively. Lymph node and perineural involvement was associated with a lower survival. Well differentiated and stage I tumors had a better survival. Multivariate analysis showed that the presence of a type III tumor, N3 lymph node involvement and vascular permeation were independent predictors' ofa lower survival. Conclusions: Among patients with adenocarcinoma of the esophago-gastric junction, type III tumors, lymph node involvement and vascular permeations are associated with a lower survival.

Melanoma primario del esófago tratado con esofagectomía: Casos clínicos / Esophageal melanoma: Report of two cases

Esophageal melanomas correspond to 0.1 to 0.2 percent of esophageal tumors. We report two patients with the disease. The first patient is a 51 year-old woman pre-sentingwith dysphagia and weight loss. An upper gastrointestinal endoscopy showed a polypoid ulcerated lesion in the middle third of the esophagus. The pathological study ofthe biopsy disclosed a malignant melanoma. The patient was subjected to an esophagectomy with a satisfactory postoperative evolution. Four months later, liver metastases were detected and the patient died eleven months after the operation. The second patient is a 59 year-old mole that consulted by dysphagia. An endoscopy showed a pigmented esophageal lesion whose pathological diagnosis was a malignant melanoma. The patient was subjected to an esophagectomy and sixteen months after surgery there was no evidence of relapse.

Carcinoma hepatocelular variedad fibrolamelar metastásico en menores de 20 años: Reporte de 2 casos tratados con intención curativa y revisión de la literatura / Fibrolamellar liver carcinoma: Report of two cases

Fibrolamellar hepatocellular carcinoma (FLC) is a rare histologic variant of hepatocellular carcinoma that appears most commonly in teenagers and young adults. The diagnosis is often made incidentally and surgical resection is the only curative treatment. Here we report two cases of incidental FLC involving a 19 year-old male, initially diagnosed with screening abdominal ultrasound, and a 14 year-old female that presented with abdominal pain. Diagnostic workup consisted of abdominal PET/CT and MRI Imaging studies and tissue diagnosis was confirmed with percutaneous liver biopsy. Both patients were treated with radical liver resection/tumor excision. However, tumor recurrence was observed in both during short-term follow-up. The male patient was treated successfully with surgical treatment however the female patient succumbed top regression of disease.