A 13-Steroid Serum Panel Based on LC-MS/MS: Use in Detection of Adrenocortical Carcinoma.

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare malignancy, with an annual incidence of 1 or 2 cases per million. Biochemical diagnosis is challenging because up to two-thirds of the carcinomas are biochemically silent, resulting from de facto enzyme deficiencies in steroid hormone biosynthesis. Urine steroid profiling by GC-MS is an effective diagnostic test for ACC because of its capacity to detect and quantify the increased metabolites of steroid pathway synthetic intermediates. Corresponding serum assays for most steroid pathway intermediates are usually unavailable because of low demand or lack of immunoassay specificity. Serum steroid analysis by LC-MS/MS is increasingly replacing immunoassay, in particular for steroids most subject to cross-reaction. METHODS: We developed an LC-MS/MS method for the measurement of serum androstenedione, corticosterone, cortisol, cortisone, 11-deoxycorticosterone, 11-deoxycortisol, 21-deoxycortisol, dehydroepiandrosterone sulfate, pregnenolone, 17-hydroxypregnenolone, progesterone, 17-hydroxyprogesterone, and testosterone. Assay value in discriminating ACC from other adrenal lesions (phaeochromocytoma/paraganglioma, cortisol-producing adenoma, and lesions demonstrating no hormonal excess) was then investigated. RESULTS: In ACC cases, between 4 and 7 steroids were increased (median = 6), and in the non-ACC groups, up to 2 steroids were increased. 11-Deoxycortisol was markedly increased in all cases of ACC. All steroids except testosterone in males and corticosterone and cortisone in both sexes were of use in discriminating ACC from non-ACC adrenal lesions. CONCLUSIONS: Serum steroid paneling by LC-MS/MS is useful for diagnosing ACC by combining the measurement of steroid hormones and their precursors in a single analysis.

Comparing subtotal parathyroidectomy and total parathyroidectomy with autotransplantation in renal transplant recipients.

Background: Both subtotal parathyroidectomy (SPTX) and total parathyroidectomy with autotransplantation (TPTX + AT) are considered acceptable surgical approaches for renal patients. It is common that parathyroid surgery is performed in patients before they undergo kidney transplantation and there is currently no evidence considering the best surgical approach in this subset of patients. Methods: Two cohorts were identified of consecutive patients who underwent parathyroidectomy for renal hyperparathyroidism by two surgeons at a single institution over equivalent time periods (SPTX and TPTX + AT). A retrospective chart review was performed to assess these techniques, including outcomes following kidney transplantation. Results: There were 125 patients analysed, with 56 patients who underwent SPTX and 69 who underwent TPTX + AT. Both cohorts effectively reduced PTH post operatively. There were 22 patients in the SPTX cohort and 26 in the TPTX + AT cohort that subsequently received kidney transplants. There were no cases of recurrent hyperparathyroidism and one of hypoparathyroidism (4.5%) in the SPTX patients post-transplant. There was one case of recurrent hyperparathyroidism (3.8%) and four of persistent hypoparathyroidism (15.4%) in the TPTX + AT patients post-transplant. Conclusions: Surgery for renal hyperparathyroidism requires a careful balance of the extent of parathyroid resection to prevent persistent/recurrent disease and avoid permanent hypoparathyroidism. SPTX may be a more appropriate option in kidney transplant candidates in order to minimise the risk of long-term hypoparathyroidism.

Lesion-based indicators predict long-term outcomes of pheochromocytoma and paraganglioma- SIZEPASS.

Aim: We seek a simple and reliable tool to predict malignant behavior of pheochromocytoma and paraganglioma (PPGL). Methods: This single-center prospective cohort study assessed size of primary PPGLs on preoperative cross-sectional imaging and prospectively scored specimens using the Pheochromocytoma of the Adrenal Gland Scaled Score (PASS). Multiplication of PASS points with maximum lesion diameter (in mm) yielded the SIZEPASS criterion. Local recurrence, metastasis or death from disease were surrogates defining malignancy. Results: 76 consecutive PPGL patients, whereof 58 with pheochromocytoma and 51 female, were diagnosed at a mean age of 52.0 ± 15.2 years. 11 lesions (14.5%) exhibited malignant features at a median follow-up (FU) of 49 months (range 4-172 mo). Median FU of the remaining cohort was 139 months (range 120-226 mo). SIZEPASS classified malignancy with an area under the curve (AUC) of 0.97 (95%CI 0.93-1.01; p<0.0001). Across PPGL, SIZEPASS >1000 outperformed all known predictors of malignancy, with sensitivity 91%, specificity 94%, and accuracy 93%, and an odds ratio of 72 fold (95%CI 9-571; P<0.001). It retained an accuracy >90% in cohorts defined by location (adrenal, extra-adrenal) or mutation status. Conclusions: The SIZEPASS>1000 criterion is a lesion-based, clinically available, simple and effective tool to predict malignant behavior of PPGLs independently of age, sex, location or mutation status.

Defining the feasibility of same day adrenalectomy - A prospective matched cohort study.

Background: Despite technical advances, day surgery still accounts for <1 % of adrenal procedures. We investigated feasibility and safety of same day adrenalectomy (SDA). Methods: Between We recruited 30 patients with primary hyperaldosteronism (PHA) or Cushing's syndrome (CS) into a prospective matched, single centre cohort study to evaluate the impact of exposure to a same day discharge pathway (SDA cohort; n = 10) or inpatient adrenalectomy (PIPA cohort; n = 20). We compared results to a matched cohort (n = 40) from our prospective in-patient adrenalectomy registry (RIPA cohort). Results: Mean age was 51.3 ± 8.5 years, with 43 % female, 3.3 % ASA I and 96.7 % ASA II. Lesion size was 17 ± 9 mm (range 5-40 mm). 80 % of patients presented with PHA. The predefined primary endpoint (discharge on same calendar day without major complications, emergency presentation or readmission) was achieved in 100 % of SDA, but none of the in-patients (χ2 = 57; p < 0.0001). The secondary endpoint (discharge within 23 h of surgery without major complications, emergency presentation or readmission) was achieved in 100 % of SDA, 90 % of PIPA (n.s.), 33 % of RIPA (33 %; χ2 = 14.6 p < 0.001), and 51.5 % of IPA patients (χ2 = 8.5 p < 0.01). Combining SDA and PIPA cohorts, 93.3 % of treatment episodes met widely used (WHO, United States) definitions of day surgery as completion of the hospital care episode within 23 h. Patients admitted for SDA were highly satisfied (100 %). Conclusion: Same day discharge after adrenalectomy is feasible, safe, and well-perceived in appropriately selected patients with PHA and Cushing's syndrome.

Margin Free Resection Achieves Excellent Long Term Outcomes in Parathyroid Cancer.

Long-term outcomes of parathyroid cancer remain poorly documented and unsatisfactory. This cohort includes 25 consecutive parathyroid cancer patients with median follow-up of 10.7 years (range 4.1−26.5 years). Pre-operative work-up in the center identified a suspicion of parathyroid cancer in 17 patients. En bloc resection, including the recurrent laryngeal nerve in 4/17 (23.5%), achieved cancer-free resection margins (R0) in 82.4% and lasting loco-regional disease control in 94.1%. Including patients referred after initial surgery elsewhere, R0 resection was achieved in merely 17/25 (68.0%) of patients. Cancer-positive margins (R1) in 8 patients led to local recurrence in 50%. On multivariate analysis, only margin status prevailed as independent predictor of recurrence free survival (χ2 19.5, p < 0.001). Local excision alone carried a 3.5-fold higher risk of positive margins than en bloc resection (CI95: 1.1−11.3; p = 0.03), and a 6.4-fold higher risk of locoregional recurrence (CI95: 0.8−52.1; p = 0.08). R1-status was associated with an 18.0-fold higher risk of recurrence and redo surgery (CI95: 1.1−299.0; p = 0.04), and a 22.0-fold higher probability of radiation (CI95: 1.4−355.5; p = 0.03). In patients at risk, adjuvant radiation reduced the actuarial risk of locoregional recurrence (p = 0.05). When pre-operative scrutiny resulted in upfront oncological surgery achieving cancer free margins, it afforded 100% recurrence free survival at 5- and 10-year follow-up, whilst failure to achieve clear margins caused significant burden by outpatient admissions (176 vs. 4 days; χ2 980, p < 0.001) and exposure to causes for concern (1369 vs. 0 days; χ2 11.3, p = 0.003). Although limited by cohort size, our study emphasizes the paradigm of getting it right the first time as key to improve survivorship in a cancer with excellent long-term prognosis.

Mediastinal Parathyroid Cancer.

Parathyroid cancer (PC) is rare, but its pre-operative recognition is important to choose appropriate access strategies and achieve oncological clearance. This study characterizes features of mediastinal parathyroid cancer (MPC) and explores criteria aiding in the pre-operative recognition of malignancy. We assembled data from 502 patients with mediastinal parathyroid neoplasms (MPNs) from a systematic review of the literature 1968−2020 (n = 467) and our own patient cohort (n = 35). Thirty-two of the 502 MPNs (6.4%) exhibited malignancy. Only 23% of MPC patients underwent oncological surgery. Local persistence and early recurrence at a median delay of 24 months were frequent (45.8%), and associated with a 21.7-fold (95%CI 1.3−351.4; p = 0.03) higher risk of death due to disease. MPCs (n = 30) were significantly larger than cervical PC (n = 330), at 54 ± 36 mm vs. 35 ± 18 mm (χ2 = 20; p < 0.0001), and larger than mediastinal parathyroid adenomas (MPA; n = 226) at 22 ± 15 mm (χ2 = 33; p < 0.01). MPC occurred more commonly in males (60%; p < 0.01), with higher calcium (p < 0.01) and parathyroid hormone (PTH) levels (p < 0.01) than MPA. Mediastinal lesions larger than 3.0 cm and associated with a corrected calcium ≥ 3.0 mM are associated with a more than 100-fold higher odds ratio of being malignant (OR 109.2; 95%CI 1.1−346; p < 0.05). The composite 3 + 3 criterion recognized 74% of all MPC with an accuracy of 83%. Inversely, no MPN presenting with a calcium < 3.0 mM and size < 3.0 cm was malignant. When faced with pHPT in mediastinal location, consideration of the 3 + 3 rule may trigger an oncological team approach based on simple, available criteria.

Clusterin in stool: a new biomarker for colon cancer screening?

OBJECTIVES: The identification of useful markers for early diagnosis of human colon cancer is a major goal still in progress. Clusterin is a pleiotropic protein with a broad range of functions. It has recently drawn much attention because of its association with cancer promotion and metastasis. It is involved in prosurvival and apoptosis processes that are carried out by two different isoforms. Secreted clusterin isoform (sCLU) is cytoprotective and its prosurvival function is the basis of the current phase I/II clinical trials against prostate, lung, and breast cancers. We have already shown that in colorectal cancer (CRC) there is an increased expression of sCLU. In this report, we investigated whether sCLU is released in the blood and stool of colon cancer patients in order to study sCLU as a potential diagnostic molecular marker for colon cancer screening. METHODS: The quantitative expression of sCLU was determined by dot blot immunodosage in the serum and stool of CRC patients (n=63) and age-matched controls without clinical history of neoplasia, CRC, or systemic or bowel inflammatory disease (n=50). Unpaired t-tests and Mann-Whitney U-tests were used for continuous variables. The diagnostic performance of clusterin was appraised by means of receiver operating characteristic (ROC) curves. RESULTS: We found a significant increase of sCLU in the serum and stool of CRC patients (P=0.0002 and P<0.000, respectively) as compared with controls. ROC curves provided cutoff points showing a trade-off between sensitivity and specificity. With a cutoff point of 88.5 microg/ml, sCLU in blood showed a 55.6% sensitivity and 100% specificity, and with a cutoff point of 34.6 microg/g, the stool test reached 66.7% sensitivity and 84% specificity in discriminating between nonneoplastic and colorectal neoplastic lesions. Human cancer xenografts in nude mice indicated a positive correlation between increasing serum clusterin level and tumor size. CONCLUSIONS: This study highlights the potential of clusterin detection in stool to be a valuable tool to improve the effectiveness and efficiency of large-scale clinical cancer screening.

Long-term quality of voice is usually acceptable after initial hoarseness caused by a thyroidectomy or a parathyroidectomy.

BACKGROUND: Vocal cord (VC) palsy following a thyroidectomy or parathyroidectomy can result in significant morbidity for the patient. We aimed to investigate the incidence of VC palsy in a tertiary referral Institution, track the management of these cases and record the long-term outcomes and VC recovery rates. METHODS: Retrospective review of all thyroidectomy/parathyroidectomy operations performed over 11 years. Patients with an unequivocal hoarse voice postoperatively were included. We analysed the patient's clinical characteristics and voice outcomes, operative, pathology and laryngoscopy reports during their follow-up. RESULTS: Ten patients fitted the inclusion criteria and were analysed. Median age at date of operation was 47.5 years (range, 16-81 years) and the M:F ratio was 1:2.3 (M:3, F:7). The median FU was 62.5 months (range, 12-144 months). The median hospital stay was 1.5 days (range, 1-87 days). There were 7 recurrent laryngeal nerve (RLN) injuries by manipulation, 1 case of RLN resection, 1 inadvertent division (with primary nerve repair) and 1 RLN was shaved off the thyroid. Long-term voice outcomes for the 7 patients with an RLN manipulation injury were: 3/7 patients had normal voice, 3/7 had moderate hoarseness and 1/7 had long-term hoarseness. The long-term voice outcome of the patient with RLN shaving off the thyroid gland was excellent while the 2 remaining patients (RLN resection and inadvertent division) needed 12 and 18 months respectively to achieve a normal quality of voice. Four out of the 10 patients had permanent VC palsy in the long-term and their voice outcomes varied: 1 patient had a normal voice, 2 patients had moderate hoarseness and 1 patient had persistent hoarseness. Only 1/10 patients did not show any voice improvement after 12 months. CONCLUSIONS: In the vast majority of cases post-operative hoarseness due to RLN palsy improves in the long-term, albeit voice may not return completely to normal.

Dynamics of liver trauma: tearing of segments III and IV at the level of the hepatic ligament.

The liver is the most commonly injured intra-abdominal organ. Liver mass is the key factor in determining the extent of the inertial force and consequently of damage in the case of sudden deceleration. In this respect, high-speed accidents usually produce characteristic lesions where the III-IV segments tear at the level of the hepatic ligament causing grade I-III liver injuries. The pathophysiology of such traumas is the subject of the present contribution. All trauma patients who sustained a blunt abdominal injury from January 1 to December 31 2004 were identified by the trauma registry at the Policlinico di Tor Vergata In order to select high-speed and sudden deceleration traumas, clinical records were reviewed for demographics, severity of injury, severity of liver injury, associated concomitant injuries, and management scheme. The grade of liver injury was determined on the basis of the initial CT or the intraoperative findings. A total of 159 patients who incurred abdominal injuries due to blunt trauma were identified. In 14 (8.8 percent) one or more liver lesions were associated. Among the low-grade injuries, 3 were grade I, and 8 grade II. Forty percent were high-grade injuries consisting in 6 grade III and 1 grade IV. We observed no grade V or grade VI injuries in this series. The most frequent occurrence was a tear between hepatic segments III and IV caused by the acute impact of the liver on the hepatic ligament. A hepatic injury caused by the round ligament was diagnosed intraoperatively in 1 out of 5 liver trauma patients (20 percent) and preoperatively in 4 out of 5 (80 percent) in our one-year abdominal blunt trauma series. Our clinical contribution underlines the high frequency of such lesions that seems to be related to, and characteristic of, high-speed trauma. In these cases immediate deceleration due to the impact may be a relevant factor in the pathophysiology of the lesion.

Stool test for colorectal cancer screening: what is going on?

Given the increasing incidence of colorectal cancer (CRC), performing new and cost-effective stool tests is of particular importance for early diagnosis and treatment. In the present review, we describe the main characteristics, and the performance of the most recently developed stool tests in the screening setting of colorectal tumoral diseases. Most of the studies reported high sensitivity both for adenomas and CRC diagnosis; less than half studies reported also high specificity with respect to stage and localization of the tumor. However, the performance of every single test was extremely variable, reaching >95% specificity for most of DNA-based markers, although lacking sensitivity even in case of invasive CRC. A new potential stool marker of colon cancer is clusterin, a protein of particular interest for its high sensitivity and positive predictive value in patients with highly aggressive CRC.

Massive intestinal infarction following retroperitoneoscopic right lumbar sympathectomy.

The adverse physiological effects of pneumo and retro-peritoneum are relatively well known. However, the clinical implications of compromised mesenteric circulation through several mechanical and physiological mechanisms are not as well recognized. We describe a fatal case of intestinal infarction following an elective retroperitoneoscopic right sympathectomy. The patient was a 88-year-old man who died 30 hours after an uneventful anesthesia and right endoscopic lumbar sympathectomy. An emergency explorative laparotomy revealed a massive intestinal infarction due to thrombosis of the superior mesenteric artery. We reviewed the literature on laparoscopic procedures and mesenteric ischemia. To our knowledge, this is the first reported case of intestinal infarction following retro-pneumoperitoneum. We conclude that the presence of a severe multidistrectual? arteriopathy may represent a major risk factor in retroperitoneoscopic procedures.

Teaching subfascial perforator veins surgery: survey on a 2-day hands-on course.

BACKGROUND: The present paper describes a training method with objective evaluation to enhance video-assisted surgical skills in subfascial endoscopic perforator veins surgery (SEPS). Training was scheduled during a 2-day intensive course. METHODS: Hands-on exercises were performed (i) on a simulator to assess whether specific training exercises were helpful in attainment of skills; (ii) on a known animal model that uses the swine abdominal wall and which allows practice in endoscopic dissection and perforator veins (PV) using appropriate instrumentation in an environment that is a reasonable surrogate for the human calf; and (iii) assisting a senior surgeon performing SEPS. Thirty surgeons without experience in SEPS were trained to perform a sequence of standardized drills connected with the SEPS technique. The SEPS simulator consisted of an artificially constructed subfascial space of the leg in which false perforator veins had to be localized, and cut. The participants performed a sequence of drills three times in order to improve their dexterity. The same exercises were then performed on a swine model. The model consisted of the arteries and veins penetrating the rectus fascia and passing into the overlying cutaneous trunci muscle and hypodermis on either side of the midline between the arch of the ribs cranially and the umbilicus caudally. Trainees were required to achieve operative space in the animal subcutaneous fat, to reach and identify the "perforating" subcutaneous vessels, and to interrupt some of them with a 5-mm clamp coagulator ultrasonic scalpel. The time required to perform each dexterity drill was recorded in seconds. Finally, the day after, trainees were asked to drive the senior operator during clinical SEPS performed on eight patients, suggesting the following manoeuvres in order to: (i) enter the subfascial space of the leg; (ii) make operative space; (iii) identify the incompetent perforator vein(s); and (iv) coagulate and divide them with the ultrasonic scalpel. Each of these four steps scored 1 point. RESULTS: All the trainees showed a steady improvement in skill acquisition on the SEPS simulator (P < 0.001), and on the animal model with the single-port technique (P < 0.001). These results reflect positively on the animal model using the dual-port technique, and on the scores achieved in the operating theatre during clinical SEPS. CONCLUSIONS: The validity of the 2-day course was demonstrated by significant improvement in performance with increasing skill on the training models, and in clinical practice.

Giant recurrent intrathoracic goitre treated by clamshell thoracotomy and reverse sternotomy.

A 59-year-old man with a giant recurrent intrathoracic goitre was admitted for completion thyroidectomy for recurrent severe retrosternal pain. The patient had undergone a cervical thyroidectomy elsewhere 13 years earlier, during which only the cervical part of the goitre had been resected. Owing to the previous operation with an expected scar around the innominate vein, and the goitre's size and localisation obstructing the upper chest aperture, we chose an alternate access. Clamshell thoracotomy with reverse sternotomy allows central vascular control and excision of large goitres bypassing predictable problems at the cervicothoracic junction. Surgery was performed with minimal blood loss and with excellent functional outcome. The described access adds to the repertoire to deal with this unusual situation.

What is a reliable CT scan for diagnosing splenosis under emergency conditions?

Splenosis is a condition in which splenic tissue is present in a non-anatomical position. Implants of splenic tissue can mimic neoplasms and only specific examinations can confirm the correct diagnosis. Here we report a case of a 23-year-old male patient with a history of surgical splenectomy during childhood after trauma. He was admitted to the emergency department with acute bowel obstruction. An abdominal-pelvic computed tomography (CT) scan revealed small bowel obstruction and the presence of two rounded, solid masses located in the rectal-vescical pouch. Quantitative analyses of the different density values in the arterial phase and early portal venous phase demonstrated that these lesions were highly vascularised (92 and 97 Hounsfield Units, respectively). The hypothesis of an ectopic splenic mass was made after evaluation of the CT images and clinical history. The acute bowel obstruction caused by adhesive intestinal syndrome was resolved by surgical adhesiolysis. The smallest mass adherent to the rectum was removed. Histopathologic examination confirmed the benign nature of the lesion, which consisted of splenic tissue.

A dry lab for medical engineers?

INTRODUCTION: We describe a teaching and training method with objective evaluation to improve medical engineering students' knowledge and analysis skills about Minimally Invasive Surgery (MIS) instrumentation and techniques through hands-on experience. Training has been scheduled during a three-month course. METHODS: Twenty medical engineering students were trained to perform three times on a pelvic trainer a sequence of standardized drills connected with the selected MIS techniques, in order to improve their dexterity. The time required to perform each dexterity drill was recorded in seconds.Then, the participants were divided into groups and asked to write an essay about an instrument they chose, analyzing and criticizing the instrument itself. RESULTS: All the trainees showed steady improvement in skill acquisition on the laparoscopic simulator and discussed their essays, making proposals in order to improve the instrument they tested. CONCLUSION: Significant improvement in performance with increasing skillness has been measured; during the course and during their discussion the participants showed deep knowledge of the instrument, ability to analyze and criticize it and ability to make improvement proposals.Dry lab experience for medical engineering students is useful for teaching and improving analysis and management of laparoscopic devices, allowing identification of problems and developing better devices.

Diagnostic lobectomy for unilateral follicular nodules of the thyroid gland.

We describe our technique of diagnostic lobectomy (DL) and the rationale it is based on. We define DL as a minimally invasive procedure consisting of total lobectomy and isthmusectomy, with preservation of the omolateral recurrent laryngeal nerve and parathyroid glands, but without digital exploration of the contralateral lobe. The fact that re-entry into the previously explored field to complete thyroidectomy increases the risk of complications must be taken into consideration. The subjects were 63 consecutive patients who underwent surgery for unilobar follicular neoplasms of the thyroid gland between January 1997 and December 2002. There were 49 follicular adenomas and 14 carcinomas. In the 14 patients with thyroid cancer, total thyroidectomy was performed within 2 weeks after the first operation in a sterile environment with normal anatomical cleavage plains, avoiding any risk of injury to the laryngeal nerves and parathyroid glands. It is concluded that DL is a safe and suitable surgical procedure for patients with follicular-structured lesions of the thyroid gland.