PGC-1ß regulates HER2-overexpressing breast cancer cells proliferation by metabolic and redox pathways.

Breast cancer is a prevalent neoplastic disease among women worldwide which treatments still present several side effects and resistance. Considering that cancer cells present derangements in their energetic homeostasis, and that peroxisome proliferator-activated receptor- gamma coactivator 1 (PGC-1) is crucial for cellular metabolism and redox signaling, the main objective of this study was to investigate whether there is a relationship between PGC-1 expression, the proliferation of breast cancer cells and the mechanisms involved. We initially assessed PGC-1ß expression in complementary DNA (cDNA) from breast tumor of patients bearing luminal A, luminal B, and HER2-overexpressed and triple negative tumors. Our data showed that PGC-1ß expression is increased in patients bearing HER2-overexpressing tumors as compared to others subtypes. Using quantitative PCR and immunoblotting, we showed that breast cancer cells with HER2-amplification (SKBR-3) have greater expression of PGC-1ß as compared to a non-tumorous breast cell (MCF-10A) and higher proliferation rate. PGC-1ß expression was knocked down with short interfering RNA in HER2-overexpressing cells, and cells decreased proliferation. In these PGC-1ß-inhibited cells, we found increased citrate synthase activity and no marked changes in mitochondrial respiration. Glycolytic pathway was decreased, characterized by lower intracellular lactate levels. In addition, after PGC-1ß knockdown, SKBR-3 cells showed increased reactive oxygen species production, no changes in antioxidant activity, and decreased expression of ERRα, a modulator of metabolism. In conclusion, we show an association of HER2-overexpression and PGC-1ß. PGC-1ß knockdown impairs HER2-overexpressing cells proliferation acting on ERRα signaling, metabolism, and redox balance.

Octogenarians: an increasing challenge for acute care and colorectal surgeons. An outcomes analysis of emergency colorectal surgery in the elderly.

AIM: Emergency surgery is associated with higher mortality rates, especially in elderly patients presenting with emergent colorectal disease. The aim of this study was to determine the outcomes in elderly patients following emergency colorectal resection, with particular focus on octogenarians who presented a sixfold higher mortality rate with respect to other patients. METHOD: This study examined 355 patients who underwent surgery at an Emergency Department for complications of colorectal disease between January 2007 and December 2009. Morbidity and mortality were analyzed on the basis of patients' characteristics and presentation. Univariate and logistic regression analyses were performed on morbidity and mortality risk factors. RESULTS: Two-hundred and fifteen patients of > 65 years of age were included, 93 of whom were ≥ 80 years of age. The global mortality rate was 16%. In patients ≥ 80 years of age the mortality rate was 30%. The difference in mortality rate between patients < 80 years of age vs patients ≥ 80 years of age was 24%. In resected patients ≥ 80 years of age, American Society of Anesthesiology grade, colonic ischaemia, neurological comorbidity and anastomotic dehiscence were identified as independent risk factors in both univariate and logistic regression analyses. The morbidity rate was approximately 17%, and no significant difference in morbidity was found between the two groups. CONCLUSION: The results of this study show that fitness status and micro vascular impairment impact significantly on mortality in the elderly, particularly in octogenarians. Although the outcomes observed were compatible with the literature, the six fold higher mortality rate observed in the most elderly patients identifies a group for which death prevention is best achieved with aggressive resuscitation and intensive postoperative care, rather than timing of surgery.

Small bowel intussusception: what is the role of laparoscopy?

Small bowel intussusception in adults is a rare surgical disease which almost always occurs as a complication of either benign or malignant lesion of the bowel that is working as a leading point. In adults, the surgical approach consists of the resection of the bowel involved to ensure the excision of the lesion below. The authors report a case of ileocecal intussusception occurred in a young woman, 35 years old, observed for abdominal pain and signs of small bowel occlusion. She underwent surgical resection of the ileocecal segment with laparoscopic approach. The authors discuss the feasibility of the laparoscopic approach in this rare surgical disease and its benefits in terms of patient's postoperative comfort and outcome.

Squamous and adenosquamous cell carcinomas of the gallbladder.

Squamous and adenosquamous cell carcinomas (ASC and SCC) are rare subtypes of gallbladder cancer, traditionally considered more aggressive and with a poorer prognosis than adenocarcinoma. We report about two patients affected by an advanced squamous cell carcinoma of the gallbladder. Both had a large tumour in the gallbladder fossa region with infiltration of the liver. Surgical resection was radical in one, but palliative in the other. pTNM was T3 N0 M0, G3, R0 in the former and T3 N0 M0, G2 R1 in the latter. Patients died for local recurrence after 12 and 5 months, respectively. Natural history, clinical findings, prognosis and outcome of this rare gallbladder tumour are discussed on the basis of a review of the English literature. In conclusion, an aggressive and radical surgical treatment of advanced squamous and adenosquamous cell gallbladder carcinomas seems to be indicated for their low proclivity to distant spreading.

Senna vs polyethylene glycol for mechanical preparation the evening before elective colonic or rectal resection: a multicenter controlled trial. French Association for Surgical Research.

HYPOTHESIS: Senna is more efficient than polyethylene glycol as mechanical preparation before elective colorectal surgery. DESIGN: Prospective, randomized, single-blind study. SETTING: Multicenter study (18 centers). PATIENTS: Five hundred twenty-three consecutive patients with colonic or rectal carcinoma or sigmoid diverticular disease, undergoing elective colonic or rectal resection followed by immediate anastomosis. INTERVENTION: Two hundred sixty-two patients were randomly allotted to receive senna (1 package diluted in a glass of water) and 261 to receive polyethylene glycol (2 packages diluted in 2-3 L of water), administered the evening before surgery. All patients received 5% povidone iodine antiseptic enemas (2 L) the evening and the morning before surgery. Ceftriaxone sodium and metronidazole were given intravenously at anesthetic induction. MAIN OUTCOME MEASURES: Degree of colonic and rectal cleanliness. RESULTS: Colonic cleanliness was better (P=.006), fecal matter in the colonic lumen was less fluid (P=.001), and the risk for moderate or large intraoperative fecal soiling was lower (P=.11) with senna. Overall, clinical tolerance did not differ significantly between groups, but 20 patients receiving polyethylene glycol (vs 16 with senna) had to interrupt their preparation, and 15 patients (vs 8 with senna) complained of abdominal distension. Senna, however, was better tolerated (P = .03) in the presence of stenosis. There was no statistically significant difference found in the number of patients with postoperative infective complications (14.7% vs 17.7%) or anastomotic leakage (5.3% vs 5.7%) with senna and polyethylene glycol, respectively. CONCLUSION: Mechanical preparation before colonic or rectal resection with senna is better and easier than with polyethylene glycol and should be proposed in patients undergoing colonic or rectal resection, especially patients with stenosis.

Large extrapleural hematoma in an anticoagulated patient after a thoracic blunt trauma.

We report the 7th case of a traumatic extrapleural hematoma that developed in an anticoagulated patient with a thoracic blunt trauma and rib fractures, and required an emergency surgical treatment. Extrapleural hematoma is a rare and life-threatening condition characterized by a collection of blood between the pleura parietalis and the endothoracic fascia. Related symptoms and chest x-ray findings are not characteristic and may present several hours after the injury, leading to delayed diagnosis and treatment. Etiological, surgical and prognostic implications of this finding are briefly discussed.

Superiority of laparoscopy compared to ultrasonography in diagnosis of widespread liver diseases.

The aim of the study was to compare the results of ultrasonography (US) and laparoscopy in a series of 210 patients referred to our institution for the diagnosis of widespread liver diseases. Among 205 patients, laparoscopy revealed cirrhosis in 114, chronic widespread disease in 70 (chronic persistent hepatitis in 21, chronic active hepatitis in 28, steatosis in 14, acute hepatitis in 5, fibrosis in 2), and absence of liver disease in 21. Four of these cases had minor complications. A corroborative diagnosis was obtained in 122 patients (59.5%). Overall sensitivity of US was 84% with a low specificity due to the high rate of false negatives. From the results of this study we conclude that laparoscopy is a safe and essential diagnostic tool in the final diagnosis of widespread liver diseases and that US is not a reliable screening method because of its incidence of false negatives.