Fabrice Menegaux

Identification of CD8+CD25+Foxp3+ suppressive T cells in colorectal cancer tissue

Background: The antitumoral immune response is one determinant of colorectal cancer (CRC) outcome. Recent work suggests that Foxp3+CD25+CD4+ regulatory T cells (T4reg) might hamper effective immunosurveillance of emerging cancer cells and impede effective immune responses to established tumours. In this descriptive study, we analysed blood and tissue regulatory T cell populations in patients with CRC. Methods: Blood and tissue regulatory Foxp3+ T cells from 40 patients with CRC were compared to regulatory Foxp3+ T cells from normal colonic tissue and from blood of 26 healthy volunteers. Flow cytometry was used to quantify and phenotype all Foxp3+ T cell populations. Correlations were sought with the tumour stage and with micro-invasive status. The suppressive capacity of regulatory Foxp3+ T cells was assessed by their effect on CD4+CD25− T cell proliferation in vitro and by their capacity to inhibit cytokine production by conventional T cells. Results: We found a significant increase of CD8+CD25+Foxp3+ cells (T8reg) in blood and CRC tissue; their phenotype was close to that of T4reg. T8reg cells infiltrating CRC were activated, as suggested by increased cytoxic T lymphocyte-associated antigen-4, glucocorticoid-induced tumour necrosis factor-related protein, and transforming growth factor (TGF)β1 expression compared to T8reg from normal autologous colonic tissue. Moreover, T8reg were able to suppress CD4+CD25− T cell proliferation and Th1 cytokine production ex vivo, demonstrating that tumour-infiltrating T8reg have strong suppressive capacities. T8reg numbers correlated with the tumour stage and with micro-invasive status. Finally, interleukin 6 and TGFβ1 synergistically induced the generation of CD8+CD25+Foxp3+ T cells ex vivo. Conclusions: We have identified a new regulatory T cell population (CD8+Foxp3+) in colorectal tumours. After isolation from cancer tissue these CD8+Foxp3+ cells demonstrated strong immunosuppressive properties in vitro. These data suggest that these cells may contribute to tumoral immune escape and disease progression.

Secondary thyroidectomy in patients with prior thyroid surgery for benign disease: A study of 203 cases

BACKGROUNDnThe goal of this study was to evaluate the complication rate of secondary thyroidectomy in patients with prior thyroid surgery for benign disease.nnnMETHODSnOver an 8-year period, 203 thyroid reoperations were performed on 202 patients. All information relating to operative procedures, pathology, and complications was recorded prospectively.nnnRESULTSnThere were 24 men and 178 women with a mean age of 52 years. Prior surgery was unilateral in 136 cases (67%) and bilateral in 67 cases (33%), and 14 patients (6.9%) had more than 1 previous thyroid operation. For euthyroid or pretoxic recurrent nodular goiter, 190 reoperations were performed and 13 reoperations were performed for recurrent thyrotoxicosis. Twenty-three cancers were found in a specimen (11.4%). Completion thyroidectomy was done in 143 patients. Postoperative complications occurred in 21 patients (10.4%): recurrent laryngeal nerve palsy (7 patients), hypocalcemia (8 patients), hematoma requiring surgical evacuation (5 patients), and wound infection (1 patient). Complications remained permanent in 4 patients (2%).nnnCONCLUSIONSnThe permanent complication rate is higher in thyroid reoperations than in primary thyroid operations. However, we believe that this 2% rate is low enough to allow reoperation whenever it is necessary, provided precise operative rules are respected.

Influence of Experience on Performance of Individual Surgeons in Thyroid Surgery: Prospective Cross Sectional Multicentre Study

Objective To determine the association between surgeons’ experience and postoperative complications in thyroid surgery. Design Prospective cross sectional multicentre study. Setting High volume referral centres in five academic hospitals in France. Participants All patients who underwent a thyroidectomy undertaken by every surgeon in these hospitals from 1 April 2008 to 31 December 2009. Main outcome measures Presence of two permanent major complications (recurrent laryngeal nerve palsy or hypoparathyroidism), six months after thyroid surgery. We used mixed effects logistic regression to determine the association between length of experience and postoperative complications. Results 28 surgeons completed 3574 thyroid procedures during a one year period. Overall rates of recurrent laryngeal nerve palsy and hypoparathyroidism were 2.08% (95% confidence interval 1.53% to 2.67%) and 2.69% (2.10% to 3.31%), respectively. In a multivariate analysis, 20 years or more of practice was associated with increased probability of both recurrent laryngeal nerve palsy (odds ratio 3.06 (1.07 to 8.80), P=0.04) and hypoparathyroidism (7.56 (1.79 to 31.99), P=0.01). Surgeons’ performance had a concave association with their length of experience (P=0.036) and age (P=0.035); surgeons aged 35 to 50 years had better outcomes than their younger and older colleagues. Conclusions Optimum individual performance in thyroid surgery cannot be passively achieved or maintained by accumulating experience. Factors contributing to poor performance in very experienced surgeons should be explored further.

Selection of Patients with Solitary Thyroid Nodules for Operation

OBJECTIVEnTo improve the preoperative selection for operation of patients with solitary thyroid nodules.nnnDESIGNnProspective cohort study.nnnSETTINGnUniversity hospital, France.nnnPATIENTSn155 consecutive patients who presented with solitary thyroid nodules and were operated on.nnnINTERVENTIONSnClinical examination, ultrasound examination, fine needle aspiration biopsy, followed by total thyroid lobectomy with frozen section and final histological examination.nnnMAIN OUTCOME MEASUREnCorrect prediction of thyroid carcinoma or benign adenoma.nnnRESULTSnA logistic regression analysis indicated that absence of rim (p < 0.002), solid and hypoechoic feature (p < 0.003) and malignant or suspicious fine needle aspiration biopsy results (p < 0.0001) were significantly associated with malignancy. Selection for operation by the logistic model would save 40 of 73 patients from operation and 40 of 59 from unnecessarily radical operation. It would detect a similar number of cancers as a strategy based solely on fine needle aspiration cytology.nnnCONCLUSIONSnA combination of the available diagnostic methods provides substantial benefit in the preoperative selection of patients with an isolated thyroid nodule.

Should primary hyperparathyroidism be treated surgically in elderly patients older than 75 years

BACKGROUNDnDiagnosis of primary hyperparathyroidism (PHPT) is increasingly suspected in elderly patients after the discovery of hypercalcemia by routine measurement of serum calcium levels. Surgery is commonly accepted as the optimal treatment of PHPT. We wanted to assess risk and results of neck exploration in elderly patients with PHPT.nnnMETHODSnWe performed a retrospective study of the charts of 78 patients older than 75 years (mean age, 79.1 years) with PHPT who underwent neck exploration during a 15-year period.nnnRESULTSnThe most common presenting symptoms were neurologic and psychiatric disorders (47 patients). Preoperative localization investigations, performed in 72 patients, were successful in 42 of them (sensivity, 58%). Single adenoma, double adenomas, and hyperplasia were found in 74 patients (95%), three patients, and one patient, respectively. Overall postoperative mortality was 3.8% (three patients) with no death since 1984. Significant complications occurred in three patients (4%): one myocardial infarction, one pulmonary embolism, and one cerebral hemorrhage. Average length of postoperative hospital stay was 4 days. Among patients who could be followed up (65 cases with a mean follow-up of 3 years), 94% reported an improvement in their symptoms. This was especially marked for fatigue and intellectual function.nnnCONCLUSIONSnThese data support a liberal approach regarding surgical treatment in elderly patients with PHPT.

Diaphragm pacing improves sleep in patients with amyotrophic lateral sclerosis

Abstract In amyotrophic lateral sclerosis (ALS) patients, respiratory insufficiency is a major burden. Diaphragm conditioning by electrical stimulation could interfere with lung function decline by promoting the development of type 1 muscle fibres. We describe an ancillary study to a prospective, non-randomized trial (NCT00420719) assessing the effects of diaphragm pacing on forced vital capacity (FVC). Sleep-related disturbances being early clues to diaphragmatic dysfunction, we postulated that they would provide a sensitive marker. Stimulators were implanted laparoscopically in the diaphragm close to the phrenic motor point in 18 ALS patients for daily conditioning. ALS functioning score (ALSFRS), FVC, sniff nasal inspiratory pressure (SNIP), and polysomnographic recordings (PSG, performed with the stimulator turned off) were assessed before implantation and after four months of conditioning (n = 14). Sleep efficiency improved (69 ± 15% to 75 ± 11%, p = 0.0394) with fewer arousals and micro-arousals. This occurred against a background of deterioration as ALSFRS-R, FVC, and SNIP declined. There was, however, no change in NIV status or the ALSFRS respiratory subscore, and the FVC decline was mostly due to impaired expiration. Supporting a better diaphragm function, apnoeas and hypopnoeas during REM sleep decreased. In conclusion, in these severe patients not expected to experience spontaneous improvements, diaphragm conditioning improved sleep and there were hints at diaphragm function changes.

Prophylactic lymph node dissection in papillary thyroid carcinoma: is there a place for lateral neck dissection?

BackgroundCervical lymph node (LN) metastases are common in patients with papillary thyroid carcinoma (PTC), and they have a negative impact on recurrence. The management of preoperatively node-negative (N0) PTC is still controversial. The aim of our study was to describe the results of a prophylactic bilateral lymph node dissection (LND) and to investigate its impact on recurrence.MethodsFrom 2003 to 2011, we analyzed 603 consecutive preoperatively N0 PTC patients. For each patient, we reviewed demographics data, tumor characteristics, pattern and risk factors of LN metastasis, and outcome.ResultsLymph node metastases were found in 23xa0% of patients: 19xa0% in the central compartment and 8xa0% in the lateral compartment, including 1xa0% in the lateral compartment on the opposite side from the tumor. Multivariate analysis showed that hyperthyroidism and extrathyroidal invasion of the tumor were significantly associated with LN metastasis. Further analysis showed that localization of the tumor in the upper third of the thyroid lobe and metastatic LN in the central compartment were independent risk factors for lateral LN metastasis. During the 4.3-year follow-up, 23 recurrences were observed (4xa0%), including 5 in the central compartment. Recurrence rates were 2xa0% in the N0 group, 5xa0% in N1a patients, and 22xa0% in N1b patients (pxa0<xa00.001).ConclusionsIn preoperatively N0 PTC patients, LN metastases are frequent in central and ipsilateral lateral compartments. Prophylactic LND in the central and ipsilateral lateral compartments should therefore be recommended in the presence of PTC to identify high-risk patients.

Clinical outcome after laparoscopic adrenalectomy for primary hyperaldosteronism: The role of pathology

BACKGROUNDnPrimary hyperaldosteronism (PHA) is potentially curable by laparoscopic unilateral adrenalectomy (LUA). Pre-operative assessment rarely differentiates adrenal adenoma from hyperplasia. This study aimed to evaluate the results of LUA for PHA according to pathologic findings when an adrenal mass was identified unequivocally on a CT scan.nnnMETHODSnA retrospective analysis of LUA for PHA from July 1997 to May 2008 was performed. The minimal follow-up was 6 months. We considered hypertension to be cured in patients with normal blood pressure without antihypertensive medication (AM). Improvement was defined by a decrease of AM.nnnRESULTSnFifty-seven patients were included. Thirty-six patients (63%) had an adrenal adenoma and 21 (37%) a hyperplasia. The median follow-up was 6.4 years. Hypokalemia was cured in all patients, 33 patients (58%) were cured of their hypertension, and 23 (96% of the 24 noncured patients) were improved with a reduction of the number of AM. Predictive factors for a cure were: gender, age, BMI, duration of hypertension, number of pre-operative AMs, pre-operative arterial systolic blood pressure, creatinin and plasma renin activity. Postoperative predictive factors were pathology, size of the mass, and systolic and diastolic arterial pressures. In the multivariate analysis the only remaining factor was pathology.nnnCONCLUSIONnLUA for PHA cured all patients from their hypokalemia and cured or improved hypertension in 98%. Pre-operative diagnosis of adenoma or hyperplasia is not mandatory but it is important to warn patients that hypertension can persist after adrenalectomy, especially in case of adrenal hyperplasia, although this hypertension is easier to control.

Biliary surgery after heart transplantation

BACKGROUNDnBiliary tract diseases are frequent in heart transplant recipients, with significant morbidity and mortality. Since the first presentation of gallstones in this population is often acute cholecystitis, asymptomatic cholelithiasis should not be considered benign.nnnPATIENTS AND METHODSnWe retrospectively reviewed 18 heart transplant recipients who underwent cholecystectomy from January 1991 to June 1997. We intentionally chose to perform a straightforward open procedure when acute cholecystitis was suspected (3 patients). A laparoscopic cholecystectomy was performed in all the other cases (15 patients) without conversion to open procedure.nnnCONCLUSIONnSince no significant complications were observed in our patients, we believe that transplant recipients with cholelithiasis should undergo laparoscopic cholecystectomy in their posttransplantation course regardless of the symptomatic status of their biliary tract.

Effect of systemic corticosteroids on elective left-sided colorectal resection with colorectal anastomosis

BACKGROUNDnThe impact of systemic steroid therapy on surgical outcome after elective left-sided colorectal resection with rectal anastomosis is not well known.nnnMETHODSnWe compared 606 consecutive patients including 53 patients who were on steroids and undergoing surgery between 1995 and 2005.nnnRESULTSnPostoperative mortality and anastomotic leakage rates were equivalent. The postoperative complications rate, especially infections, was higher in steroid-treated patients than in non-steroid-treated patients: 38% (20 of 53 patients) versus 25% (139 of 553 patients), respectively (P = .046). In the steroid group, univariate analysis revealed 3 significant risk factors for postoperative complications: blood transfusion, preoperative anticoagulation, and chronic respiratory failure. In a multivariate analysis, blood transfusion and chronic respiratory failure remained independent factors for postoperative complications.nnnCONCLUSIONnPatients on steroids have a higher incidence of postoperative complications after elective left-sided colorectal resection with rectal anastomosis.