Ido Mizrahi

Development of a MicroRNA-Based Molecular Assay for the Detection of Papillary Thyroid Carcinoma in Aspiration Biopsy Samples

BACKGROUND Although thyroid nodules are common and diagnosed in over 5% of the adult population, only 5% harbor malignancy. Patients with clinically suspicious thyroid nodules need to undergo fine-needle aspiration biopsy (FNAB). The main limitation of FNAB remains indeterminate cytopathology. Only 20%-30% of the indeterminate nodules harbor malignancy, and therefore up to 80% of patients undergo unnecessary thyroidectomy. The aim of this study was to identify and validate a panel of microRNAs (miRNAs) that could serve as a platform for an FNAB-based diagnostic for thyroid neoplasms. METHODS The study population included 27 consecutive patients undergoing total thyroidectomy for FNAB-based papillary thyroid cancer (n = 20) and benign disorders (n = 7). Aspiration biopsy was performed from the index lesion and from the opposite lobe normal tissue in all study patients at the time of operation. RNA was extracted from all aspiration biopsy samples. Quantitative polymerase chain reaction on a panel of previously selected miRNAs was performed. Polymerase chain reaction results were compared with final histopathology. miRNA from tumor tissues was amplified using the highest value of each miRNA expression in normal tissue as a threshold for malignancy detection. RESULTS Diagnostic characteristics were most favorable for mir-221 in differentiating benign from malignant thyroid pathology. mir-221 was overexpressed in 19 patients (p < 0.0001) with a sensitive yield of 95%. Specificity, negative and positive predictive value, and accuracy of the miRNA panel were 100%, 96%, 100%, and 98%, respectively. CONCLUSIONS miRNA quantification for differential diagnosis of thyroid neoplasms within aspiration biopsy samples is feasible and may improve the accuracy of FNAB cytology.

Multifocality in well-differentiated thyroid carcinomas calls for total thyroidectomy.

BACKGROUND Multifocality is an important factor when recommending surgery for papillary thyroid cancer (PTC). The aim of this study is to assess the incidence and characterize the spread pattern of multifocal PTC (mPTC) in patients undergoing total thyroidectomy. METHODS All thyroidectomies performed between 2003 and 2008 were reviewed identifying 289 patients. Data were obtained for demographics, clinical data, and histopathological findings. RESULTS Of the patients with papillary carcinoma, mPTC was identified in 150 patients (57%), of which 71% had lesions in the contralateral lobe. There were no significant differences in multifocality rate for gender, pathology type, and all tumor size subgroups including ≤1 cm. Pathology examination of representative sections versus the entire gland examination resulted in a significantly lower incidence of contralateral disease (P = .04). CONCLUSIONS Multifocal and contralateral lesions are common in PTC and their incidence is not related to tumor size. Pathology entire gland examination is strongly recommended to properly assess the rate of mPTC.

Differentiating benign from malignant thyroid nodules using micro ribonucleic acid amplification in residual cells obtained by fine needle aspiration biopsy

BACKGROUND Fine needle aspiration biopsy (FNAB) is the most commonly used diagnostic tool to differentiate benign from malignant thyroid nodules. Nevertheless, some FNAB cytology results are not definite. In such cases diagnostic thyroid lobectomy is performed with malignancy rate on final histopathology ranging at 15%-75%. The aim of this study was to improve on the accuracy of FNAB-based cytology by amplification of microRNAs (micro ribonucleic acids [miRs]) from the residual cells left in the FNAB needle after submission for cytology. METHODS Residual cells were collected from the needle cup after FNAB cytology of 77 consecutive patients with thyroid nodules. miR-enriched RNA was extracted for all patients with cytology showing either follicular lesion or suspicion for malignancy (n=11). The expression of miR-21, -31, -146b, -187, -221, and -222 was determined using real-time polymerase chain reaction. Results were compared with final surgical histopathology. RESULTS RNA was successfully extracted from all FNAB specimens. Five patients had FNAB cytology suspicious for malignancy. The miR panel was positive in all five (100%). Six patients had follicular lesions on FNAB. The miR panel was positive in three of four patients (75%) with confirmed malignancy and was negative in two of two (0%) patients with benign pathology results. This corresponded to a specificity of 100%, sensitivity of 88%, and accuracy of 90%. CONCLUSIONS RNA extraction from FNAB residual cells is feasible, and a miR panel amplified from the extracted RNA seems like a promising diagnostic tool in this limited number of patients.

Perioperative outcomes of delayed laparoscopic cholecystectomy for acute calculous cholecystitis with and without percutaneous cholecystostomy.

INTRODUCTION The role of percutaneous cholecystostomy (PC) in the management of patients with acute calculous cholecystitis (ACC) remains controversial. The aim of this study is to report operative outcomes in a large cohort of patients undergoing PC before their delayed laparoscopic cholecystectomy (DLC). METHODS All patients who underwent DLC because of ACC between 2003 and 2012 were included. Outcomes of patients with and without previous PC were compared. RESULTS Of 639 patients who underwent DLC because of ACC at our institution during a 10-year time interval beginning 2003, 163 (25.5%) patients had PC before their DLC. Patients who underwent PC were older (64 ± 1 years vs 48 ± 0.8 years, P < .001) and had more comorbid conditions (P < .001). Accumulated duration of stay was longer in the PC group (16.2 ± 0.4 days vs 9.7 ± 0.1 days, P < .001). Rate of conversion to open procedure was greater in the PC group (11% vs 4%, P = .001) and operative time was longer (142 ± 4 minutes vs 107 ± 4 minutes, P < .001). Patients in the PC group had a greater rate of biliary-related complications (10% vs 4%, P = .003) and surgical-site infections; both superficial (5% vs 1%, P = .004) and deep (7% vs 3%, P = .04). On multivariable analysis PC was an independent risk factor for conversion to open cholecystectomy (odds ratio 2.67 95% CI 1.18-6.72) as well as to biliary-related complications (odds ratio 4.85 95% CI 1.57-14.92). CONCLUSION DLC for ACC in patients with previous PC is associated with longer duration of stay, more readmissions, and, most importantly, greater conversion rate, biliary related complications, and surgical-site infections.

Internal mammary artery injury during central venous catheter insertion for TPN: rare but fatal.

Vascular injuries caused by subclavian central venous catheter (CVC) insertion can be associated with major complications. Such injuries differ in clinical presentation as well as optimal management, which ranges from observation only to surgical or endovascular repair. We report an injury to a branch of the internal mammary artery following an attempt to introduce a subclavian CVC, resulting in a massive hemothorax. This very rare injury was diagnosed and treated by angiography and embolization; however, the patient later succumbed to multi-organ failure. Suspicion of such an injury in a similar clinical setting should result in immediate angiography that can be lifesaving. To the best of our knowledge, this is the only report of such an adverse event in an adult.

Role of laparoscopy in rectal cancer: A review

Despite established evidence on the advantages of laparoscopy in colon cancer resection, the use of laparoscopy for rectal cancer resection is still controversial. The initial concern was mainly regarding the feasibility of laparoscopy to achieve an adequate total mesorectal excision specimen. These concerns have been raised following early studies demonstrating higher rates of circumferential margins positivity following laparoscopic resection, as compared to open surgery. Similar to colon resection, patients undergoing laparoscopic rectal cancer resection are expected to benefit from a shorter length of hospital stay, less analgesic requirements, and a faster recovery of bowel function. In the past decade there have been an increasing number of large scale clinical trials investigating the oncological and perioperative outcomes of laparoscopic rectal cancer resection. In this review we summarize the current literature available on laparoscopic rectal cancer surgery.

Next-Generation Sequencing Identifies a Highly Accurate miRNA Panel That Distinguishes Well-Differentiated Thyroid Cancer from Benign Thyroid Nodules

Background: Fine needle aspiration biopsy (FNAB) is the gold-standard procedure for diagnosing malignant thyroid nodules. Indeterminate cytology is identified in 10% to 40% of cases, and molecular testing may guide management in this setting. Current commercial options are expensive, and are either sensitive or specific. The aim of this study was to utilize next-generation sequencing (NGS) technology to identify informative diversities in the miRNA expression profile of benign versus malignant thyroid nodules. Methods: Ex vivo FNAB samples were obtained from thyroid specimens of patients who underwent thyroidectomy at a referral center. miRNA levels were determined using NGS and multiplexing technologies. Statistical analyses identified differences between normal and malignant samples and miRNA expression profiles that associate with malignancy were established. The accuracy of the miRNA signature in predicting histologic malignancy was validated using a group of patient specimens with indeterminate cytology results. Results: A total of 274 samples were obtained from 102 patients undergoing thyroidectomy. Of these samples, 71% were benign and 29% were malignant. Nineteen miRNAs were identified as statistically different between benign and malignant samples and were used to classify 35 additional nodules with indeterminate cytology (validation). The miRNA panels sensitivity, specificity, negative and positive predictive values, and overall accuracy were 91%, 100%, 87%, 100%, and 94%, respectively. Conclusions: Using NGS technology, we identified a panel of 19 miRNAs that may be utilized to distinguish benign from malignant thyroid nodules with indeterminate cytology. Impact: Our panel may classify indeterminate thyroid nodules at higher accuracy than commercially available molecular tests. Cancer Epidemiol Biomarkers Prev; 27(8); 858–63. ©2018 AACR.

Concurrent Medullary, Papillary, and Follicular Thyroid Carcinomas and Simultaneous Cushing's Syndrome

Background: Papillary thyroid carcinoma is the most common thyroid cancer (85%). Follicular thyroid carcinoma is the second most common type of thyroid cancer, accounting for up to 10% of all thyroid cancers. Medullary thyroid carcinoma accounts for only 5-8% of thyroid cancers. Concurrent medullary, follicular, and papillary carcinomas of the thyroid gland are extremely rare and reported scarcely. Case Report: A 72-year-old male presented with nonspecific neck pain. The workup revealed a nodular thyroid gland with a follicular lesion on fine-needle aspiration. Total thyroidectomy was performed and pathological examination identified a 25-mm follicular carcinoma, two papillary microcarcinomas, and two medullary microcarcinomas. The genetic workup was negative and no other family members were diagnosed with any endocrinopathy. Two months after surgery, the patient was diagnosed with Cushings syndrome that was treated with laparoscopic left adrenalectomy. On 3-year follow-up, the patient is asymptomatic with no evidence of recurrent disease. Conclusion: We present a rare case of a patient with follicular, papillary, and medullary thyroid carcinoma, and Cushings syndrome. To date, no known genetic mutation or syndrome can account for this combination of neoplastic thyroid and adrenal pathologies, although future research may prove differently.

Preoperative localization modalities in primary hyperparathyroidism: Correlation with postoperative cure

Background: Accurate preoperative localization is critical to the success of minimally invasive parathyroidectomy. This investigation aimed to assess the correlation among preoperative imaging results, intraoperative findings, and postoperative cure rates in patients undergoing operation for primary hyperparathyroidism. Methods: A retrospective review of all patients who underwent operation for primary hyperparathyroidism between June 2010 and March 2016 was performed. Results: During the study period, 398 patients underwent parathyroidectomy. The overall cure rate was 97.5%. The ultrasonography performed by the surgeon was superior to the ultrasonography performed by the radiologist and to the sestamibi scan in lateralizing the adenoma correctly (80% vs 62% vs 70%, P < .001, respectively), and had the greatest sensitivity (93%) and accuracy (80%) among all tests (P < .001). Age ≥65 was found to be associated with lesser cure rates (94% vs 99.2%, P = .003). The number of positive preoperative studies correlated with cure rate, ranging from 80% for patients with 0 positive studies, to 100% in those with 4 positive studies (P = .0004). In patients with a negative sestamibi and an ultrasonography performed by the radiologist, there was no significant difference in the cure rates among those with no preoperative computed tomography, a positive preoperative computed tomography, or a negative preoperative computed tomography. Conclusion: An ultrasonography performed by an experienced surgeon is an extremely valuable preoperative localization modality. The cure rate obtained is proportional to the number of positive imaging studies. In patients with negative ultrasonography performed by a nonexperienced radiologist and a negative sestamibi scan, the performance of computed tomography does not seem to increase cure rate. Patients with no positive preoperative scans represent a challenging subgroup, with cure rates of approximately 80%.

Thyroidectomy Practice After Implementation of the 2015 American Thyroid Association Guidelines on Surgical Options for Patients With Well-Differentiated Thyroid Carcinoma

Importance The recommended extent of surgery for well-differentiated thyroid carcinoma has been modified considerably in the updated 2015 American Thyroid Association guidelines published in January 2016. To date, the changes in clinical practice after publication of these new guidelines have not been demonstrated. Objective The aim of this study was to evaluate clinical practice changes associated with implementation of the updated guidelines on the surgical procedure rates of total thyroidectomy, thyroid lobectomy, and completion thyroidectomy at a single tertiary medical center. Design, Setting, and Participants This is a retrospective cohort study of 169 patients at the Hadassah–Hebrew University Medical Center, Jerusalem, Israel. Patients with pathologically proved, well-differentiated thyroid carcinoma who underwent surgery between January 1, 2013, and December 31, 2014, were compared with patients who underwent surgery from January 1 to December 31, 2016. A total of 434 thyroidectomy procedures were performed during the study period, and 251 had pathologically proved, well-differentiated thyroid carcinoma. Patients with tumors larger than 4 cm, involved lymph nodes, or bilateral nodules were excluded. Main Outcomes and Measures Primary outcomes were the rate of up-front total thyroidectomy vs lobectomy and the rates of completion thyroidectomy before and after the implementation of the new guidelines. Results Of the 169 patients in the final analysis, 118 (69.8%) were included from 2013 to 2014 and 51 (30.2%) in 2016. The mean (SD) age for the entire cohort was 44 (13.8) years, and 129 (76.3%) were women. Up-front total thyroidectomy was performed in 72 of 118 patients (61.0%) prior to the 2015 American Thyroid Association guidelines and 16 of 51 (31.4%) following their implementation (odds ratio, 0.29; 95% CI, 0.14-0.59). The rate of completion thyroidectomy also significantly decreased between these periods (73.9% vs 20.0%; odds ratio, 0.09; 95% CI, 0.04-0.19). Conclusions and Relevance The updated 2015 American Thyroid Association guidelines implementation was associated with a significant decrease in the rates of both up-front total thyroidectomy and completion thyroidectomy. According to these findings, only 1 of 5 patients who undergoes thyroid lobectomy will require a completion procedure.