Sylvie Maweja

Leçons retenues après 274 surrénalectomies laparoscopiques

Aims: To define the role of minimally invasive videoassisted surgery in the surgical management of adrenal disease and discuss the respective indications of the trans and retroperitoneal video assisted approaches. Materials and Methods: During the last 8 years (1994–2001), 330 adrenalectomies were performed in 305 patients: 274 (83%) laparoscopic approaches and 56 (17%) open approach. Open surgery was reserved for patients presenting with large or malignant tumours (29 cases), multiple and/or extraadrenal phaeochromocytomas (13 cases), previous intraabdominal intestinal surgery (10 cases), and in those requiring concomitant intraabdominal surgery (4 cases). Laparoscopic adrenalectomy was performed using the lateral transperitoneal approach for 89 Conn’s syndrome, 67 Cushing’s syndrome, 2 virilising tumours, 51 phaeochromocytomas and 65 non secretory tumours greater than 4 cm in diameter. Nineteen patients underwent bilateral adrenalectomy. Results: There were no deaths. Twenty patients (7.3%) had a complication. Eleven cases required open conversion (4%) because of difficulties with dissection (8 cases), peroperative suspicion of malignancy (2 cases), and one pneumothorax. The average size of tumours was 34 mm (7–110 mm). There were 18 malignant tumours (6.5%): 8 adrenocortical carcinomas, 1 leiomyosarcoma, and 9 metastases. All patients with hormonally secreting tumours were cured of their endocrinopathy. There was 1 death secondary to hepatic metastases in a patient with an adrenocortical carcinoma. Conclusion: Most adrenal tumours are suitable for video assisted excision. The only absolute contraindication is an invasive carcinoma requiring an extended excision. The lateral, transperitoneal approach is the most suitable for tumours greater than 5–6 cm in diameter. Both the transperitoneal or retroperitoneal approaches are suitable for smaller tumours depending on operator choice and experience. However in the presence of a large right lobe of liver or previous intraabdominal surgery the retroperitoneal approach may be preferable.

Article originalLeçons retenues après 274 surrénalectomies laparoscopiquesLaparoscopic adrenalectomy: Lessons learned from 274 consecutives procedures☆

Aims: To define the role of minimally invasive videoassisted surgery in the surgical management of adrenal disease and discuss the respective indications of the trans and retroperitoneal video assisted approaches. Materials and Methods: During the last 8 years (1994–2001), 330 adrenalectomies were performed in 305 patients: 274 (83%) laparoscopic approaches and 56 (17%) open approach. Open surgery was reserved for patients presenting with large or malignant tumours (29 cases), multiple and/or extraadrenal phaeochromocytomas (13 cases), previous intraabdominal intestinal surgery (10 cases), and in those requiring concomitant intraabdominal surgery (4 cases). Laparoscopic adrenalectomy was performed using the lateral transperitoneal approach for 89 Conn’s syndrome, 67 Cushing’s syndrome, 2 virilising tumours, 51 phaeochromocytomas and 65 non secretory tumours greater than 4 cm in diameter. Nineteen patients underwent bilateral adrenalectomy. Results: There were no deaths. Twenty patients (7.3%) had a complication. Eleven cases required open conversion (4%) because of difficulties with dissection (8 cases), peroperative suspicion of malignancy (2 cases), and one pneumothorax. The average size of tumours was 34 mm (7–110 mm). There were 18 malignant tumours (6.5%): 8 adrenocortical carcinomas, 1 leiomyosarcoma, and 9 metastases. All patients with hormonally secreting tumours were cured of their endocrinopathy. There was 1 death secondary to hepatic metastases in a patient with an adrenocortical carcinoma. Conclusion: Most adrenal tumours are suitable for video assisted excision. The only absolute contraindication is an invasive carcinoma requiring an extended excision. The lateral, transperitoneal approach is the most suitable for tumours greater than 5–6 cm in diameter. Both the transperitoneal or retroperitoneal approaches are suitable for smaller tumours depending on operator choice and experience. However in the presence of a large right lobe of liver or previous intraabdominal surgery the retroperitoneal approach may be preferable.

Asporin Is a Fibroblast-Derived TGF-β1 Inhibitor and a Tumor Suppressor Associated with Good Prognosis in Breast Cancer.

Background Breast cancer is a leading malignancy affecting the female population worldwide. Most morbidity is caused by metastases that remain incurable to date. TGF-β1 has been identified as a key driving force behind metastatic breast cancer, with promising therapeutic implications. Methods and Findings Employing immunohistochemistry (IHC) analysis, we report, to our knowledge for the first time, that asporin is overexpressed in the stroma of most human breast cancers and is not expressed in normal breast tissue. In vitro, asporin is secreted by breast fibroblasts upon exposure to conditioned medium from some but not all human breast cancer cells. While hormone receptor (HR) positive cells cause strong asporin expression, triple-negative breast cancer (TNBC) cells suppress it. Further, our findings show that soluble IL-1β, secreted by TNBC cells, is responsible for inhibiting asporin in normal and cancer-associated fibroblasts. Using recombinant protein, as well as a synthetic peptide fragment, we demonstrate the ability of asporin to inhibit TGF-β1-mediated SMAD2 phosphorylation, epithelial to mesenchymal transition, and stemness in breast cancer cells. In two in vivo murine models of TNBC, we observed that tumors expressing asporin exhibit significantly reduced growth (2-fold; p = 0.01) and metastatic properties (3-fold; p = 0.045). A retrospective IHC study performed on human breast carcinoma (n = 180) demonstrates that asporin expression is lowest in TNBC and HER2+ tumors, while HR+ tumors have significantly higher asporin expression (4-fold; p = 0.001). Assessment of asporin expression and patient outcome (n = 60; 10-y follow-up) shows that low protein levels in the primary breast lesion significantly delineate patients with bad outcome regardless of the tumor HR status (area under the curve = 0.87; 95% CI 0.78–0.96; p = 0.0001). Survival analysis, based on gene expression (n = 375; 25-y follow-up), confirmed that low asporin levels are associated with a reduced likelihood of survival (hazard ratio = 0.58; 95% CI 0.37–0.91; p = 0.017). Although these data highlight the potential of asporin to serve as a prognostic marker, confirmation of the clinical value would require a prospective study on a much larger patient cohort. Conclusions Our data show that asporin is a stroma-derived inhibitor of TGF-β1 and a tumor suppressor in breast cancer. High asporin expression is significantly associated with less aggressive tumors, stratifying patients according to the clinical outcome. Future pre-clinical studies should consider options for increasing asporin expression in TNBC as a promising strategy for targeted therapy.

Risk of upper gastrointestinal cancer after bariatric operations

The authors discuss the potential influence of obesity surgery on the risk of cancer, focusing on the upper GI tract directly affected by operations. There is currently no substantiation for an increased risk of cancer after bariatric surgery, because there are only about 25 reports of subsequent cancer of the esophagus and the stomach. However, this review emphasizes the need to detect potential precancerous conditions before surgery. Candidates for postoperative endoscopic surveillance may include patients >15 years after gastric surgery, but also patients symptomatic for gastroesophageal reflux disease in whom a high incidence of Barretts metaplasia has been reported. The greatest concern is a delay in diagnosis from inadequate investigation due to mistaking serious upper GI symptoms as a consequence of the past operation.

Place actuelle de la chirurgie vidéo-assistée dans le traitement de l’hyperparathyroïdie primaire

Resume Introduction . – Au cours de ces dernieres annees, plusieurs techniques de parathyroidectomie mini-invasive ont ete rapportees. Cette etude retrospective a pour but de preciser la place actuelle de la parathyroidectomie video-assistee (PVA) dans notre pratique de la chirurgie de l’hyperparathyroidisme primaire (HPT I). Patients et methodes. – En 5 ans (1998-2002), 528 patients porteurs d’un HPT I ont ete operes dans le service. Une PVA a ete proposee a tous les patients presentant un HPT I sporadique, sans goitre associe et sans antecedent de chirurgie thyroparathyroidienne, et chez qui une echographie et une scintigraphie Mibi systematiquement pratiquees en preoperatoire, etaient en faveur d’une lesion unique. La PVA a ete pratiquee par voie laterocervicale avec insufflation lorsque l’imagerie etait en faveur d’une lesion retrothyroidienne ou par voie mediane sans insufflation lorsque la lesion etait en situation cervicale anterieure. Chez tous les patients, la radicalite de l’exerese parathyroidienne a ete verifiee par des dosages rapides de PTH (rPTH). En postoperatoire, la calcemie, la phosphoremie et les taux de PTH ont ete evalues a j1, j8 puis 1 mois plus tard et 1 an plus tard. Tous les patients ont eu un controle de la mobilite de leurs cordes vocales en pre et postoperatoire. Resultats. – La parathyroidectomie a ete pratiquee par cervicotomie transverse conventionnelle chez 228 patients (43 %) et par un abord video-assiste chez 300 patients (57 %). Les 228 patientes operes par cervicotomie transverse presentaient une contre-indication a une PVA : goitre nodulaire associe necessitant eventuellement une thyroidectomie concomitante (99 cas), antecedents de chirurgie cervicale (42 cas), suspicion de lesions multiglandulaires (25 cas), absence de localisation preoperatoire (48 cas), causes diverses (14 cas). L’indication d’une PVA a ete retenue chez 300 patients presentant un HPT I sporadique : 282 patients ont ete operes par voie laterale, 17 par voie centrale et un par thoracoscopie. La duree operatoire mediane a ete de 50 min (20-130 min). Chez 42 patients (14 %), une conversion en cervicotomie transverse a ete necessaire : 11 adenomes non trouves, difficultes de dissection en rapport avec des adenomes volumineux ou adherents aux structures voisines chez 7 patients, faux positifs de l’imagerie dans 11 cas, non observation d’une decroissance de plus de 50 % des taux de rPTH chez 13 patients. Chez 10 de ces 13 patients, la conversion a confirme l’existence de lesions multiglandulaires, mais chez les 3 autres, il s’agissait d’un faux negatif de la rPTH. La mortalite a ete nulle. Un patient a presente une paralysie recurrentielle definitive. Un patient presente un HPT I persistant et un autre un probable HPT I recidivant. Conclusion. – Une PVA peut etre proposee a plus de la moitie des patients presentant une HTP I. Dans notre experience, parathyroidectomie conventionnelle et PVA sont devenues complementaires. A condition de selectionner rigoureusement les patients, les resultats precoces de la PVA sont comparables a ceux de la chirurgie conventionnelle. Le risque reel d’HPT I recidivant ne pourra etre evalue qu’apres plusieurs annees de suivi.

Oncological and surgical outcome after oncoplastic breast surgery

Abstract Background : Oncoplastic surgery combines breast-conserving treatment and plastic surgery techniques. The aim of the study was to identify breast and tumor-related characteristics that contribute to the rate of complications and recurrence. Material & Methods : This retrospective study included 72 patients with a median follow-up of 32 months. For each patient, a comprehensive set of data was collected, including epidemiology, tumor characteristics, preoperative information, detailed pathology reports, radiotherapy treatment and type of surgical technique. The rate of complications, recurrence and survival were studied. Results : Complete tumor removal was performed with clear margins in all patients but in 25 of them margins were less than 2 mm. One patient had local recurrence and another developed distant metastases. The study showed that the size of the margin was not predictive of recurrence as long as not positive; the greater the resection volume, the larger the excision margin. The resection size was the only factor influencing complications and no specific tumor-related factor significantly increased the complication rate. Surgical complications did not delay the initiation of chemotherapy and radiotherapy. Conclusion : This is the first oncoplastic study where both tumor and breast characteristics were analyzed using the most recent criteria of the literature. Oncoplastic surgery can be considered as oncologically safe. The resection size was the sole significant risk factor for postoperative complications. Complications after oncoplastic breast surgery did not differ neoadjuvant therapy. Long-term event-free survival was excellent (96% at 7 years).

The closure of arteriovenous fistula in kidney transplant recipients is associated with an acceleration of kidney function decline

Background The creation of arteriovenous fistula (AVF) may retard chronic kidney disease progression in the general population. Conversely, the impact of AVF closure on renal function in kidney transplant recipients (KTRs) remains unknown. Methods From 2007 to 2013, we retrospectively categorized 285 KTRs into three groups: no AVF (Group 0, n = 90), closed AVF (Group 1, n = 114) and left-open AVF (Group 2, n = 81). AVF closure occurred at 653 ± 441 days after kidney transplantation (KTx), with a thrombosis:ligation ratio of 19:95. Estimated glomerular filtration rate (eGFR) was determined using the Modification of Diet in Renal Disease equation. Linear mixed models calculated the slope and intercept of eGFR decline versus time, starting at 3 months post-KTx, with a median follow-up of 1807 days (95% confidence interval 1665–2028). Results The eGFR slope was less in Group 1 (−0.081 mL/min/month) compared with Group 0 (−0.183 mL/min/month; P = 0.03) or Group 2 (−0.164 mL/min/month; P = 0.09). Still, the eGFR slope significantly deteriorated after (−0.159 mL/min/month) versus before (0.038 mL/min/month) AVF closure (P = 0.03). Study periods before versus after AVF closure were balanced to a mean of 13.5 and 12.5 months, respectively, with at least 10 observations per patient (n = 99). Conclusions In conclusion, a significant acceleration of eGFR decline is observed over the 12 months following the closure of a functioning AVF in KTRs.

Surgical management of adrenal tumours lessons from a 10 years personal experience

Abstract Objective: To review our personal experience of the last 10 years with adrenal surgery in order to define the indications of laparoscopic adrenalectomy (LA) and open adrenalectomy (OA), respectively. Patients and methods: From November 1993 to June 2003, we performed 105 adrenalectomies on 97 patients (29 males and 68 females). The lesions resected were preoperatively considered non-secreting in 47 cases (45%) and hormonally active in 58 cases (55%). In 78 patients (80%), La was performed and 84 adrenal glands were resected. In 19 patients (20%), OA was considered the best modality of resection and 21 adrenal glands were resected. The average tumour size was 37.2 mm (range 25-90) in LA group and 82.6 mm (30-260) in the OA group. All the LA were performed using a trans-peritoneal approach. Depending on the particularities of the lesions and of the patients, the OA were performed by anterior or lumbar incisions. Results: There was no mortality. Conversion from LA to open surgery was necessary in two patients. Mean operating time was 110 minutes for LA and 135 minutes for OA. Two (2.6%) patients suffered complications after LA and 4 (19%) after OA. Conclusions: In our experience, trans-peritoneal LA proved to be a safe and reliable procedure for benign adrenal disease. In our institution, it has become the gold standard technique for the resection of adrenal tumours, except for those suspected or proven malignant.

Mutations of calcium-sensing receptor gene: two novel mutations and overview of impact on calcium homeostasis

OBJECTIVE Genetic disorders of calcium metabolism arise in a familial or sporadic setting. The calcium-sensing receptor (CASR) plays a key role in maintaining calcium homeostasis and study of the CASR gene can be clinically useful in determining etiology and appropriate therapeutic approaches. We report two cases of novel CASR gene mutations that illustrate the varying clinical presentations and discuss these in terms of the current understanding of CASR function. PATIENTS AND METHODS A 16-year-old patient had mild hypercalcemia associated with low-normal urinary calcium excretion and normal-to-high parathyroid hormone (PTH) levels. Because of negative family history, familial hypocalciuric hypercalcemia was originally excluded. The second patient was a 54-year-old man with symptomatic hypocalcemia, hyperphosphatemia, low PTH, and mild hypercalciuria. Familial investigation revealed the same phenotype in the patients sister. The coding region of the CASR gene was sequenced in both probands and their available first-degree relatives. RESULTS The first patient had a novel heterozygous inactivating CASR mutation in exon 4, which predicted a p.A423K change; genetic analysis was negative in the parents. The second patient had a novel heterozygous activating CASR mutation in exon 6, which predicted a p.E556K change; the affected sister of the proband was also positive. CONCLUSIONS We reported two novel heterozygous mutations of the CASR gene, an inactivating mutation in exon 4 and the first activating mutation reported to date in exon 6. These cases illustrate the importance of genetic testing of CASR gene to aid correct diagnosis and to assist in clinical management.