What are the risk factors of failure of enhanced recovery after right colectomy? Results of a prospective study on 140 consecutive cases.

PURPOSE: Nausea and vomiting is the main cause of failure of enhanced recovery protocol (ERP) after right hemicolectomy. METHODS: From January 2013 to January 2018, all patients undergoing right hemicolectomy were prospectively included. Patients undergoing emergency surgery, additional complex procedure or temporary stoma, nasogastric tube (NGT) maintenance, or abdominal drainage were excluded. Failure of ERP was defined as nausea/vomiting precluding oral feeding after POD3 and/or the occurrence of postoperative ileus requiring NGT and/or length of stay (LOS) ≥ 8 days except for patients awaiting admission in rehabilitation unit. Risk factors of failure of ERP were identified using univariate and multivariate analysis. RESULTS: Among 306 patients undergoing right hemicolectomy, 140 fulfilled the inclusion criteria. Postoperative morbidity was 31%, and the mortality rate was nil. The mean postoperative hospital stay was 7 days (range 2-30). Successful ERP was achieved in 83 patients (59%). Causes of failure were major nausea/vomiting precluding oral feeding after POD3 in 36, postoperative ileus requiring NGT in 16 and LOS ≥ 8 days in 36. On multivariate analysis, preoperative anemia (OR 5.2; CI 95%, 1.3-21.1, p = 0.02) and platelet anti-aggregant/anti-coagulant (OR 4.5; CI 95%, 1.7-12.1, p = 0.003) were associated with the risk of failure of ERP. CONCLUSION: This study shows that anemia and medication with antiplatelet/anticoagulation therapy increase the risk of failure of ERP after right hemicolectomy that translates most of the time by nausea/vomiting and postoperative ileus. The presence of these factors should lead to adapt the strategy to improve outcome rather than be considered as contraindication to ERP.

The small height of an anastomotic colonic doughnut is an independent risk factor of anastomotic leakage following colorectal resection: results of a prospective study on 154 consecutive cases.

PURPOSE: The aim of this prospective study was to assess the influence of morphological characteristics of anastomotic doughnuts on the risk of anastomotic leakage (AL) after double-stapled colorectal anastomosis. METHODS: This single-center prospective study enrolled all patients undergoing double-stapled colorectal anastomosis between December 2012 and December 2015. Maximal diameter and minimal and maximal heights and widths of both colonic and rectal doughnuts were measured by surgeons in the operating room. Their influence on the risk of AL was analyzed on uni- and multivariate models. RESULTS: One hundred fifty-four patients were included; 92 (59.7%) were operated on for malignancy. Colorectal anastomoses > and <10 cm above the anal verge were performed in 96 (62.3%) and 58 (37.7%) patients, respectively. AL occurred in 17 (11.0%). The minimal height of the colonic doughnut (CD) was the only measurement significantly associated with an increased risk of AL (p = 0.026). A cutoff value of 4.5 mm for the CD determined on the ROC curve (AUC 0.685, p = 0.013) yielded the best sensitivity (61.4%) and specificity (82.4%) to predict AL. On multivariate analysis, a height of the CD <4.5 mm (OR 5.743, 95% IC 1.476-22.346, p = 0.012), malignant disease (OR 8.821, 95% IC 1.051-74.006, p = 0.045), and American Society of Anesthesiologists score >2 (OR 3.408, 95% IC 1.017-11.418, p = 0.047) were the only independent risk factors of AL. CONCLUSION: The CD's minimal height influences the risk of AL. Its routine measurement during operation, along with other risk factors, could help to decide which patients could benefit from a diverting stoma or the creation of a new anastomosis.

Sigmoid resection with primary anastomosis and ileostomy versus laparoscopic lavage in purulent peritonitis from perforated diverticulitis: outcome analysis in a prospective cohort of 40 consecutive patients.

PURPOSE: This prospective study aimed to compare outcomes after laparoscopic peritoneal lavage (LPL) and sigmoid resection with primary colorectal anastomosis (RPA). METHODS: From June 2010 to June 2015, 40 patients presenting with Hinchey III peritonitis from perforated diverticulitis underwent LPL or RPA. Patients with Hinchey II or IV peritonitis and patients who underwent an upfront Hartmann procedure were excluded. Primary endpoint was overall 30-day or in-hospital postoperative morbidity after surgical treatment of peritonitis. RESULTS: Twenty-five patients underwent RPA and 15 LPL. Overall postoperative morbidity and mortality rates were not significantly different after RPA and LPL (40 vs 67 %, p = 0.19; 4 vs 6.7 %, p = 1, respectively). Intra-abdominal morbidity and reoperation rates were significantly higher after LPL compared to RPA (53 vs 12 %, p < 0.01; 40 vs 4 %, p = 0.02, respectively). Multivariate analysis showed that LPL (p = 0.028, HR = 18.936, CI 95 % = 1.369-261.886) was associated with an increased risk of postoperative intra-abdominal septic morbidity. Among 6 patients who underwent reoperation after LPL, 4 had a Hartmann procedure. All surviving patients who had a procedure requiring stoma creation underwent stoma reversal after a median delay of 92 days after LPL and 72 days after RPA (p = 0.07). CONCLUSION: LPL for perforated diverticulitis is associated with a high risk of inadequate intra-abdominal sepsis control requiring a Hartmann procedure in up to 25 % of patients. RPA appears to be safer and more effective. It may represent the best option in this context.

"En bloc" resection of sacral chordomas by combined anterior and posterior surgical approach: a monocentric retrospective review about 29 cases.

PURPOSE: "En bloc" resection of sacral chordomas (SC) with wide margins is statistically linked with a decrease of local recurrence (LR). Nevertheless, surgery potentially leads to complications and neurological deficits. The effectiveness of radiotherapy (RT) and chemotherapy (CT) remains controversial. The aim of the study was to evaluate the margins of tumor resection, the morbidity of "En bloc" resection of SC by combined anterior and posterior surgical approach and to look for predictive factors on survival and LR. METHODS: We performed sacrococcygectomy by surgical combined approach in 29 SC between 1985 and 2012. We analyzed overall survival and survival to LR with survival analysis using Kaplan-Meier method. Complications and morbidity were reported. RESULTS: The mean follow-up was of 77.9 months (0-241 months). We found 18 (62.1%) postoperative infections and 7 (24.1%) wound dehiscences. Eighteen patients had tumor wide margins (62.1%), 6 marginal (20.7%) and 4 intralesional (13.8%). Seven patients had a LR (24.1%). OS rate was 84.4% at 5 and 10 years, survival rate with LR was 64 and 56%, respectively, after 5 and 10 years. Quality of margins (p = 0.106), tumor volume (p = 0.103), postoperative RT (p = 0.245) and postoperative local infection (p = 0.754) did not have effect on LR. CONCLUSION: "En bloc" resection by combined surgical approach seems to be a relevant alternative especially for SC invading the high sacrum above S3. Nevertheless, it yet remains the problem of postoperative infection. Systematic Adjuvant RT might allow better control on LR in association with surgery.

Parathyroid hormone in situ measurement in patients with hyperparathyroidism: single-centre experience of 179 patients.

Context: The measurement of parathyroid hormone(PTH) in situ (PTHis) by fine-needle aspiration (FNA) has been proposed as a tool to preoperatively help localize parathyroid glands detected on ultrasound. However, the accuracy of PTHis is highly variable according to the few available studies. Aim: We aimed to develop and validate the PTHis procedure and assessed the performance of PTHis in a large series of patients with hyperparathyroidism and/or undetermined cervical lesions. Patients and methods: The technique set-up consisted of PTHis measurement in thyroid samples from patients with thyroid nodules and patients with high circulating PTH levels (tertiary hyperparathyroidism). Consecutive patients were recruited at one tertiary referral centre from 2017 to 2020 and submitted to ultrasound-guided FNA-PTHis determination. Results: During the method set-up, we obtained undetectable PTHis levels in all non-parathyroid tissues after sample dilutions. PTHis was higher in patients with hyperparathyroidism (n = 145; 1817 ± 3739 ng/L; range: <4.6-31 140) than in those with thyroid or undetermined cervical lesions (n= 34; <4.6 ng/mL; P < 0.0001). When evaluating PTHis performance in histologically proven samples (158 lesions from 121 patients), PTHis was detectable in 85/97 parathyroid lesions (87%; range: 22-31;140 ng/L) and undetectable in all non-parathyroid lesions (n = 61; P < 0.0001). The specificity and positive predictive value were 100%, and the sensitivity was 87.6%. False-negative lesions (n= 12) were smaller (9.4 ± 5.9 mm) and more often consisted of hyperplasias (75%) than true-positive lesions (16.1 ± 8.4 mm and 33%, P = 0.009 and P = 0.0089, respectively). The method was safe and well tolerated. Four educational cases are also provided. Conclusions: PTHis determination is a safe and well-tolerated procedure that enhances the specificity of ultrasound-detected lesions. If accurately set-up, it confirms the parathyroid origin of uncharacterized cervical lesions.

Loss of KDM1A in GIP-dependent primary bilateral macronodular adrenal hyperplasia with Cushing's syndrome: a multicentre, retrospective, cohort study.

BACKGROUND: GIP-dependent primary bilateral macronodular adrenal hyperplasia with Cushing's syndrome is caused by aberrant expression of the GIP receptor in adrenal lesions. The bilateral nature of this disease suggests germline genetic predisposition. We aimed to identify the genetic driver event responsible for GIP-dependent primary bilateral macronodular adrenal hyperplasia with Cushing's syndrome. METHODS: We conducted a multicentre, retrospective, cohort study at endocrine hospitals and university hospitals in France, Canada, Italy, Greece, Belgium, and the Netherlands. We collected blood and adrenal samples from patients who had undergone unilateral or bilateral adrenalectomy for GIP-dependent primary bilateral macronodular adrenal hyperplasia with Cushing's syndrome. Adrenal samples from patients with primary bilateral macronodular adrenal hyperplasia who had undergone an adrenalectomy for overt or mild Cushing's syndrome without evidence of food-dependent cortisol production and those with GIP-dependent unilateral adrenocortical adenomas were used as control groups. We performed whole genome, whole exome, and targeted next generation sequencing, and copy number analyses of blood and adrenal DNA from patients with familial or sporadic disease. We performed RNA sequencing on adrenal samples and functional analyses of the identified genetic defect in the human adrenocortical cell line H295R. FINDINGS: 17 patients with GIP-dependent primary bilateral macronodular adrenal hyperplasia with Cushing's syndrome were studied. The median age of patients was 43·3 (95% CI 38·8-47·8) years and most patients (15 [88%]) were women. We identified germline heterozygous pathogenic or most likely pathogenic variants in the KDM1A gene in all 17 patients. We also identified a recurrent deletion in the short p arm of chromosome 1 harboring the KDM1A locus in adrenal lesions of these patients. None of the 29 patients in the control groups had KDM1A germline or somatic alterations. Concomitant genetic inactivation of both KDM1A alleles resulted in loss of KDM1A expression in adrenal lesions. Global gene expression analysis showed GIP receptor upregulation with a log2 fold change of 7·99 (95% CI 7·34-8·66; p=4·4 × 10-125), and differential regulation of several other G protein-coupled receptors in GIP-dependent primary bilateral macronodular hyperplasia samples compared with control samples. In vitro pharmacological inhibition and inactivation of KDM1A by CRISPR-Cas9 genome editing resulted in an increase of GIP receptor transcripts and protein in human adrenocortical H295R cells. INTERPRETATION: We propose that GIP-dependent primary bilateral macronodular adrenal hyperplasia with Cushing's syndrome results from a two-hit inactivation of KDM1A, consistent with the tumour suppressor gene model of tumorigenesis. Genetic testing and counselling should be offered to these patients and their relatives. FUNDING: Agence Nationale de la Recherche, Fondation du Grand défi Pierre Lavoie, and the French National Cancer Institute.

Self-expanding removable plastic stents for the protection of surgical anastomoses after esophageal replacement in a porcine model.

BACKGROUND: Esophageal replacement by biological graft is associated with a high risk of anastomotic leak-related mediastinitis. OBJECTIVE: To determine whether a self-expanding plastic stent can help avoid anastomotic leak after full-thickness replacement of the esophagus in a porcine model. DESIGN: Experimental feasibility study in a porcine model. SUBJECTS: Twelve pigs were analyzed in the study. INTERVENTIONS: Replacement of a 2-cm-long segment of the cervical esophagus by an aortic allograft was performed in 12 pigs, with 6 pigs used as graft donors. Animals were divided into 2 groups depending on whether a self-expanding removable plastic stent protecting the 2 aortoesophageal anastomoses was inserted (n = 7) or not (n = 5), and were allowed to eat 24 hours postoperatively. MAIN OUTCOME MEASUREMENTS: The relative occurrence of mediastinitis caused by anastomotic leakage in stented and nonstented groups was assessed; endoscopic evaluation and histological analysis of the graft area were performed 1 month after esophageal replacement. RESULTS: All animals (n = 5) without stent insertion died of anastomotic leakage within 20 days of surgery. Two of the 7 stented animals died at day 2, and 5 survived 1 month in good clinical condition. Two stent migrations were noted. Stent extraction was followed by the development of a fibrous stricture. CONCLUSIONS: The use of a self-expanding plastic stent seems to allow leak-free healing after circumferential replacement of the esophagus by a biological graft in a porcine model.

Hyperparathyroidism in Patients With X-Linked Hypophosphatemia.

X-linked hypophosphatemia (XLH) is characterized by increased activity of circulating FGF23 resulting in renal phosphate wasting and abnormal bone mineralization. Hyperparathyroidism may develop in XLH patients; however, its prevalence, pathogenesis, and clinical presentation are not documented. This observational study (CNIL 171036 v 0) recruited XLH adult patients in a single tertiary referral center. Each patient was explored in standardized conditions and compared with two healthy volunteers, matched for sex, age, and 25-OH vitamin D concentrations. The primary endpoint was the proportion of patients with hyperparathyroidism. The secondary endpoints were the factors influencing serum parathyroid hormone (PTH) concentrations and the prevalence of hypercalcemic hyperparathyroidism. Sixty-eight patients (51 women, 17 men) were enrolled and matched with 136 healthy volunteers. Patients had higher PTH concentrations compared with healthy controls (53.5 ng/L, interquartile range [IQR] 36.7-72.7 versus 36.0 ng/L, IQR 27.7-44.0, p < .0001). Hyperparathyroidism was observed in 17 patients of 68 (25%). In patients, a positive relationship between PTH and calcium concentrations and a negative relationship between PTH and phosphate concentrations were observed. Seven (10%) patients (3 premenopausal women, 1 postmenopausal woman, and 3 men) were diagnosed with hypercalcemic hyperparathyroidism. All underwent parathyroid surgery, with consecutive normalization of calcium and PTH concentrations. Hyperparathyroidism is a frequent complication in XLH adult patients. Disruption of the physiological regulation of PTH secretion contributes to parathyroid disease. Early-onset hypercalcemic hyperparathyroidism can be effectively and safely cured by surgical resection. © 2020 American Society for Bone and Mineral Research.

Selective modification of a native protein in a patient tissue homogenate using palladium nanoparticles.

We have developed new benign palladium nanoparticles able to catalyze the Suzuki-Miyaura cross-coupling reaction on human thyroglobulin (Tg), a naturally iodinated protein produced by the thyroid gland, in homogenates from patients' tissues. This represents the first example of a chemoselective native protein modification using transition metal nanoobjects in near-organ medium.

Interest of Laparoscopy for "En Bloc" Resection of Primary Malignant Sacral Tumors by Combined Approach: Comparative Study With Open Median Laparotomy.

STUDY DESIGN: Retrospective case-control study. OBJECTIVE: To compare laparoscopy with open median laparotomy for anterior approach in "en bloc" resection of primary malignant sacral tumors (PMST) in combined approach strategy. SUMMARY OF BACKGROUND DATA: Wide margin surgical resection is the "gold standard" treatment of PMST. METHODS: Two groups of patients suffering from PMST and operated for "en bloc" resection by combined approach (anterior and posterior) only differencing for the anterior approach were constituted: "laparoscopy" group (n = 11) and "laparotomy" group (n = 22). Intraoperative morbidity (blood loss, red blood cell transfusion (RBC transfusion), surgical procedure duration) and postoperative morbidity (surgical-site infection (SSI), perineal dysfunctions, local recurrence) were analyzed. Surgical margins were studied. Data of both groups were compared using nonparametric Mann-Whitney test for continuous data and Fisher test for categorical data. Overall survival (OS) and Disease-free survival (DFS) were analyzed by Kaplan-Meier method. RESULTS: Blood loss during anterior approach was less important in "laparoscopy" group 71.9 mL (range 0-400 mL) as compared with 2140 mL (range 0-9000 mL) for "laparotomy" group (P = 0.019). Blood loss during posterior approach was not different between the 2 groups. Total blood loss including anterior and posterior approach was inferior in "laparoscopy" group 2208 mL (range 230-4800 mL) versus 5385.7 mL (range 1400-11500 mL) for "laparotomy" group (P = 0.026). We reported significant difference on blood transfusion (3.7 RBC transfusions (range 0-8) for "laparoscopy group" versus 10.1 RBC transfusions (range 0-35) for "laparotomy" group (P = 0.025)). Surgical duration, quality of surgical margins, perineal dysfunctions and SSI were equivalent for both groups. At a follow-up of 36.6 months for "laparoscopy" group and 115.3 months for "laparotomy" group, OS and DFS were equivalent. CONCLUSION: Use of laparoscopy for anterior approach decreases intraoperative blood loss and intraoperative RBC transfusion without increasing surgical duration, without altering the quality of surgical margins and without impairing long-term outcomes. LEVEL OF EVIDENCE: 4.

Unilateral Adrenalectomy as a First-Line Treatment of Cushing's Syndrome in Patients With Primary Bilateral Macronodular Adrenal Hyperplasia.

CONTEXT: Bilateral adrenalectomy is the reference treatment for Cushing's syndrome (CS) related to primary bilateral macronodular adrenal hyperplasia (PBMAH). It is, however, responsible for definitive adrenal insufficiency. OBJECTIVE: The objective of the study was to evaluate the clinical interest of unilateral adrenalectomy (UA) of the larger gland for the treatment of CS related to PBMAH. DESIGN, SETTING, PATIENTS, AND INTERVENTION: This was a retrospective study in four tertiary French centers including all 15 patients with PBMAH and CS who underwent UA of the larger gland between 2001 and 2015. MAIN OUTCOME MEASURES: Urinary free cortisol, plasma cortisol, ACTH, body mass index, blood pressure, plasma glucose, and lipids were registered pre- and postoperatively and on follow-up. Median follow-up was 60 months (interquartile range 39-105), including 8 of 15 patients followed up for at least 5 years. RESULTS: A normal or low urinary free cortisol was obtained in 15 of 15 patients (100%) postoperatively. Six patients (40%) became adrenal insufficient, of whom three of six recovered a quantitatively normal cortisol secretion on follow-up. Decrease of both body mass index and blood pressure were observed at 1 year, and decrease of blood pressure was persistent 5 years postoperatively. Diabetes was cured in four of six patients. Two patients experienced a recurrence of hypercortisolism, and one was treated with mitotane, whereas the other underwent a second adrenal surgery 9 years after initial UA. CONCLUSION: UA induced remission of hypercortisolism in all patients, with sustained significant clinical improvement. The rates of both definitive adrenal insufficiency and 5-year recurrence were low. UA appears an interesting alternative to bilateral adrenalectomy as a first-line treatment in PBMAH responsible for overt CS.

Lung and heart-lung transplantation for systemic sclerosis patients. A monocentric experience of 13 patients, review of the literature and position paper of a multidisciplinary Working Group.

Systemic sclerosis per se should not be considered as an a priori contraindication for a pre-transplantation assessment in patients with advanced interstitial lung disease and/or pulmonary hypertension. For lung or heart-lung transplantation, a multidisciplinary approach, adapting the pre-transplant assessment to systemic sclerosis and optimizing systemic sclerosis patient management before, during and after surgery should improved the short- and long-term prognosis. Indications and contraindications for transplantation have to be adapted to the specificities of systemic sclerosis. A special focus on the digestive tract involvement and its thorough evaluation are mandatory before transplantation in systemic sclerosis. As the esophagus is almost always involved, isolated gastro-oesophageal reflux disease, pH metry and/or manometry abnormalities should not be a systematic per se contraindication for pre-transplantation assessment. Corticosteroids may be harmful in systemic sclerosis as they are associated with acute renal crisis. A low dose corticosteroids protocol for immunosuppression is therefore advisable in systemic sclerosis.

Esophageal replacement by allogenic aorta in a porcine model.

BACKGROUND: Esophageal replacement is a challenging problem requiring complex reconstruction. In response to the recent success of tracheal replacement by fresh allogenic aorta in humans, we assessed in a pig model the feasibility of circumferential segmental esophageal replacement by a fresh aortic allograft. METHODS: A 4-cm long aortic allograft was interposed after a circumferential 2-cm long resection of the cervical esophagus in 18 minipigs. Anastomoses were protected temporarily by self-expanding polyester-silicone stents (Polyflex; Boston Scientific, Montigny-le-Bretonneux, France). No immunosuppression was given. When stenosis occurred after stent removal or migration, a new stent was inserted. After clinical and endoscopic evaluation, pigs were killed sequentially at 1, 3, 6 and 12 months for analysis. RESULTS: Mortality during the first month was 33%. Four animals died from stent migration during the entire follow-up. Maintenance of a lumen through the graft area by a stent was necessary for 6 months, in order to avoid stenosis occurrence. After the sixth postoperative month, esophageal lumen remained patent until the twelfth month, allowing an apparently normal feeding and weight gain. Gradual contraction of the graft area was observed with time. Sequential histologic analysis showed an inflammatory reaction that decreased with time and a progressive epithelialization of the graft area which became similar to native esophageal epithelium. After 12 months, islets of smooth muscle organized as fascicules or in bundles were visible within the fibrotic tissue. CONCLUSION: Short esophageal replacement by fresh aortic allograft, under the cover of a temporary maintenance of the lumen of the graft area by an esophageal stent, allows the restitution of a patent esophageal lumen and nutritional autonomy.

Esophageal reconstruction after caustic injury: is there still a place for right coloplasty?

BACKGROUND: Through a systematic policy of using the right colon as an esophageal substitute, the authors analyze the reliability of this transplant for reconstruction after digestive caustic injury. METHODS: From 1995 to 2005, a right coloplasty was attempted in 81 patients after total esophagogastrectomy (n = 57) or for esophageal stricture (n = 24). RESULTS: The use of the right colon was not possible in 10 patients (12%) because of insufficient blood supply. In addition, postoperative right colic graft necrosis occurred in 5 patients. Cervical fistula occurred in 25 patients (31%). Opening of the thoracic inlet was associated with a lower rate of this complication (P = .04). At the end of the follow-up, 71 patients (88%) recovered oral feeding. CONCLUSION: Attempt to use the right colon as an esophageal substitute failed in 18% of the patients. Despite high rates of cervical complications, in part linked to the peculiar setting of caustic injury, functional results remains satisfactory.