Residents' perspectives: Does the Saudi general surgery residency training program apply CanMEDS competencies and prepare future leaders?

BACKGROUND: This study investigates leadership skills and Canadian Medical Education Directives for Specialists (CanMEDS) competencies acquisition within the General Surgery Residency Training Program (GSRTP). The Saudi Commission for Health Specialties (SCFHS) incorporates the CanMEDS Competency Framework into its curriculum to prepare the resident for healthcare needs. METHODS: This is a descriptive-analytical study. A questionnaire was used to collect data from 117 General Surgery residents (GS) at seven institutes in Jeddah, Saudi Arabia. RESULTS: The GS residents reported an acceptable self-perceived level of Clinical Leadership Skills (mean ± standard deviation). The most dominant skill was working with others (1.98 ± 1.03), followed by demonstrating personal qualities (2.07 ± 0.88), the ability to manage services (2.21 ± 1.37), improving services (2.22 ± 1.84) and last, setting directions (2.39 ± 0.95). Regarding the CanMEDS competencies, the respondents showed a generally positive perception with an "agree" level (Mean = 1.83). Of the CanMEDS competency roles, Collaborator ranked first followed by Professional and then Communicator. Leader competency ranked fourth followed by Health Advocate, Medical Expert and last, Scholar. CONCLUSION: The GSRTP residents showed satisfactory self-assessed clinical leadership skills and acquirement of the CanMEDS competencies during their training, which will prepare them to lead in the future.

CONTEXTE: Cette étude se penche sur les compétences en leadership et l'acquisition de compétences CanMEDS (Canadian Medical Education Directives for Specialists - directives canadiennes en formation médicale pour les spécialistes) au sein du GSRTP (programme de formation en résidence en chirurgie générale). La SCFHS (commission saoudienne pour les spécialistes de la santé) intègre le cadre des compétences CanMEDS dans son programme pour préparer les résidents aux besoins en matière de soins de santé. MÉTHODES: Il s'agit d'une étude descriptive et analytique. Un questionnaire a été utilisé pour collecter des données auprès de 117 résidents en chirurgie générale dans sept instituts médicaux à Djeddah, Arabie saoudite. RÉSULTATS: Les résidents en chirurgie générale ont rapporté un niveau perçu acceptable de compétences en leadership clinique (moyenne ± écart type) La compétence la plus dominante était le travail avec les autres (1,98 ± 1,03), suivi par la démonstration de qualités personnelles (2,07 ± 0,88), la capacité de gérer les services (2,1 ± 1,37), l'amélioration des services (2,22 ± 1,84) et, finalement, l'établissement des orientations (2,39 ± 0,95). En ce qui a trait aux compétences CanMEDS, les répondants ont montré une perception généralement positive avec un niveau « d'accord ¼ (moyenne = 1,83). En ce qui a trait aux rôles associés aux compétences CanMEDS, celui de collaborateur s'est classé au premier rang, suivi par celui de professionnel et ensuite de communicateur. Le rôle de chef de file s'est classée quatrième en matière de compétence, suivie de défenseur de la santé, d'expert médical et, finalement, d'érudit. CONCLUSION: Les résidents du GSRTP ont montré une satisfaction en matière de compétences de leadership clinique autoévaluées et d'acquisition des compétences CanMEDS lors de leur formation, laquelle les préparera à jouer un rôle de premier plan dans l'avenir.

Genetic relationship between Hashimoto`s thyroiditis and papillary thyroid carcinoma with coexisting Hashimoto`s thyroiditis.

Hashimoto's thyroiditis (HT) is present in the background of around 30% of papillary thyroid carcinomas (PTCs). The genetic predisposition effect of this autoimmune condition is not thoroughly understood. We analyzed the microarray expression profiles of 13 HT, eight PTCs with (w/) coexisting HT, six PTCs without (w/o) coexisting HT, six micro PTCs (mPTCs), and three normal thyroid (TN) samples. Based on a false discovery rate (FDR)-adjusted p-value ≤ 0.05 and a fold change (FC) > 2, four comparison groups were defined, which were HT vs. TN; PTC w/ HT vs. TN; PTC w/o HT vs. TN; and mPTC vs. TN. A Venn diagram displayed 15 different intersecting and non-intersecting differentially expressed gene (DEG) sets, of which a set of 71 DEGs, shared between the two comparison groups HT vs. TN ∩ PTC w/ HT vs. TN, harbored the relatively largest number of genes related to immune and inflammatory functions; oxidative stress and reactive oxygen species (ROS); DNA damage and DNA repair; cell cycle; and apoptosis. The majority of the 71 DEGs were upregulated and the most upregulated DEGs included a number of immunoglobulin kappa variable genes, and other immune-related genes, e.g., CD86 molecule (CD86), interleukin 2 receptor gamma (IL2RG), and interferon, alpha-inducible protein 6 (IFI6). Upregulated genes preferentially associated with other gene ontologies (GO) were, e.g., STAT1, MMP9, TOP2A, and BRCA2. Biofunctional analysis revealed pathways related to immunogenic functions. Further data analysis focused on the set of non-intersecting 358 DEGs derived from the comparison group of HT vs. TN, and on the set of 950 DEGs from the intersection of all four comparison groups. In conclusion, this study indicates that, besides immune/inflammation-related genes, also genes associated with oxidative stress, ROS, DNA damage, DNA repair, cell cycle, and apoptosis are comparably more deregulated in a data set shared between HT and PTC w/ HT. These findings are compatible with the conception of a genetic sequence where chronic inflammatory response is accompanied by deregulation of genes and biofunctions associated with oncogenic transformation. The generated data set may serve as a source for identifying candidate genes and biomarkers that are practical for clinical application.

Comparison of microarray expression profiles between follicular variant of papillary thyroid carcinomas and follicular adenomas of the thyroid.

BACKGROUND: Follicular variant of papillary thyroid carcinoma (FVPTC) and follicular adenoma (FA) are histologically closely related tumors and differential diagnosis remains challenging. RNA expression profiling is an established method to unravel molecular mechanisms underlying the histopathology of diseases. METHODS: BRAF mutational status was established by direct sequencing the hotspot region of exon 15 in six FVPTCs and seven FAs. Whole-transcript arrays were employed to generate expression profiles in six FVPTCs, seven FAs and seven normal thyroid tissue samples. The threshold of significance for differential expression on the gene and exon level was a p-value with a false discovery rate (FDR) < 0.05 and a fold change cutoff > 2. Two dimensional average linkage hierarchical clustering was generated using differentially expressed genes. Network, pathway, and alternative splicing utilities were employed to interpret significance of expression data on the gene and exon level. RESULTS: Expression profiling in FVPTCs and FAs, all of which were negative for a BRAF mutation, revealed 55 transcripts that were significantly differentially expressed, 40 of which were upregulated and 15 downregulated in FVPTCs vs. FAs. Amongst the most significantly upregulated genes in FVPTCs were GABA B receptor, 2 (GABBR2), neuronal cell adhesion molecule (NRCAM), extracellular matrix protein 1 (ECM1), heparan sulfate 6-O-sulfotransferase 2 (HS6ST2), and retinoid X receptor, gamma (RXRG). The most significantly downregulated genes in FVPTCs included interaction protein for cytohesin exchange factors 1 (IPCEF1), G protein-coupled receptor 155 (GPR155), Purkinje cell protein 4 (PCP4), chondroitin sulfate N-acetylgalactosaminyltransferase 1 (CSGALNACT1), and glutamate receptor interacting protein 1 (GRIP1). Alternative splicing analysis detected 87 genes, 52 of which were also included in the list of 55 differentially expressed genes. Network analysis demonstrated multiple interactions for a number of differentially expressed molecules including vitamin D (1,25- dihydroxyvitamin D3) receptor (VDR), SMAD family member 9 (SMAD9), v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (KIT), and RXRG. CONCLUSIONS: This is one of the first studies using whole-transcript expression arrays to compare expression profiles between FVPTCs and FAs. A set of differentially expressed genes has been identified that contains valuable candidate genes to differentiate both histopathologically related tumor types on the molecular level.

Effect of BRAF mutational status on expression profiles in conventional papillary thyroid carcinomas.

BACKGROUND: Whereas 40 % to 70 % of papillary thyroid carcinomas (PTCs) are characterized by a BRAF mutation (BRAFmut), unified biomarkers for the genetically heterogeneous group of BRAF wild type (BRAFwt) PTCs are not established yet. Using state-of-the-art technology we compared RNA expression profiles between conventional BRAFwt and BRAFmut PTCs. METHODS: Microarrays covering 36,079 reference sequences were used to generate whole transcript expression profiles in 11 BRAFwt PTCs including five micro PTCs, 14 BRAFmut PTCs, and 7 normal thyroid specimens. A p-value with a false discovery rate (FDR) < 0.05 and a fold change > 2 were used as a threshold of significance for differential expression. Network and pathway utilities were employed to interpret significance of expression data. BRAF mutational status was established by direct sequencing the hotspot region of exon 15. RESULTS: We identified 237 annotated genes that were significantly differentially expressed between BRAFwt and BRAFmut PTCs. Of these, 110 genes were down- and 127 were upregulated in BRAFwt compared to BRAFmut PTCs. A number of molecules involved in thyroid hormone metabolism including thyroid peroxidase (TPO) were differentially expressed between both groups. Among cancer-associated molecules were ERBB3 that was downregulated and ERBB4 that was upregulated in BRAFwt PTCs. Two microRNAs were significantly differentially expressed of which miR492 bears predicted functions relevant to thyroid-specific molecules. The protein kinase A (PKA) and the G protein-coupled receptor pathways were identified as significantly related signaling cascades to the gene set of 237 genes. Furthermore, a network of interacting molecules was predicted on basis of the differentially expressed gene set. CONCLUSIONS: The expression study focusing on affected genes that are differentially expressed between BRAFwt and BRAFmut conventional PTCs identified a number of molecules which are connected in a network and affect important canonical pathways. The identified gene set adds to our understanding of the tumor biology of BRAFwt and BRAFmut PTCs and contains genes/biomarkers of interest.

Comprehensive survey of HRAS, KRAS, and NRAS mutations in proliferative thyroid lesions from an ethnically diverse population.

BACKGROUND: The distribution and kind of rat sarcoma viral oncogenes homolog (RAS) mutations, as well as their clinical impact on different types of thyroid lesions, vary widely among the different populations studied. We performed a comprehensive mutational survey in the highly related RAS genes HRAS, KRAS, and NRAS in a case series of proliferative thyroid lesions with known BRAF mutational status, originating from an ethnically diverse group. MATERIALS AND METHODS: Mutational hotspot regions encompassing codons 12, 13, and 61 of the RAS genes were directly sequenced in 381 cases of thyroid lesions. In addition, the putative NRAS hotspot region encompassing codon 97 was sequenced in 36 thyroid lesions. The case series included lesions of Hashimoto's thyroiditis (HT), nodular goiters, hyperplastic nodules, follicular adenomas (FAs), Hurthle cell variants of FA, papillary thyroid carcinomas (PTCs), follicular variants of PTC (FVPTCs), microcarcinomas of PTC (micro PTCs; tumor size ≤1 cm), follicular TCs (FTCs), Hurthle cell variants of FTC, and non-well-differentiated TCs (NWDTCs). RESULTS: We identified RAS mutations in 16 out of 57 (28.1%) FAs, 2 out of 8 (25%) NWDTCs, 8 out of 42 (19.0%) FVPTCs, 2 out of 10 (20.0%) FTCs, 1 out of 12 (8.3%) Hurthle cell variants of FA, 3 out of 46 (6.5%) goiters, 1 out of 18 (5.6%) hyperplastic nodules, 3 out of 56 (5.4%) micro PTCs, 2 out of 115 (1.7%) PTCs, 0 out of 7 (0%) Hurthle cell variants of FTC, and 0 out of 10 (0%) HT lesions. NRAS codon 61 mutation was the predominant form, followed by HRAS codon 61 mutation. Only three mutations affected RAS codons 12 and 13, two of which were identified in goiters. No codon 97 mutation was detected in the examined FVPTCs. An as yet undescribed deletion of KRAS codon 59 was identified in one FA. DISCUSSION: RAS mutations in our case series were commonly associated with follicular-patterned thyroid lesions. Our data suggest that FAs with a RAS mutation may constitute precursor lesions for TC with follicular histology. The newly-discovered KRAS codon 59 deletion is one of the first reported codon deletions in a RAS hotspot region.

BRAF mutations in thyroid tumors from an ethnically diverse group.

BACKGROUND: The molecular etiology of thyroid carcinoma (TC) and other thyroid diseases which may present malignant precursor lesions is not fully explored yet. The purpose of this study was to estimate frequency, type and clinicopathological value of BRAF exon 15 mutations in different types of cancerous and non-cancerous thyroid lesions originating in an ethnically diverse population. METHODS: BRAF exon 15 was sequenced in 381 cases of thyroid lesions including Hashimoto´s thyroiditis, nodular goiters, hyperplastic nodules, follicular adenomas (FA), papillary TC (PTC), follicular variant PTC (FVPTC), microcarcinomas of PTC (micro PTC; tumor size ≤ 1 cm), follicular TC (FTC), and non-well differentiated TC (non-WDTC). RESULTS: We identified BRAF mutations in one of 69 FA, 72 of 115 (63%) PTC, seven of 42 (17%) FVPTC, 10 of 56 (18%) micro PTC, one of 17 (6%) FTC, and one of eight (13%) non-WDTC. Most of the cases showed the common V600E mutation. One case each of PTC, FVPTC, and FTC harbored a K601E mutation. A novel BRAF mutation was identified in a FA leading to deletion of threonine at codon 599 (p.T599del). A rare 3-base pair insertion was detected in a stage III PTC resulting in duplication of threonine at codon 599 (p.T599dup). Patients with PTC harboring no BRAF mutation (BRAFwt) were on average younger than those with a BRAF mutation (BRAFmut) in the PTC (36.6 years vs. 43.8 years). Older age (≥ 45 years) in patients with PTC was significantly associated with tumor size ≥ 4 cm (P = 0.018), vessel invasion (P = 0.004), and distant metastasis (P = 0.001). Lymph node (LN) involvement in PTC significantly correlated with tumor size (P = 0.044), and vessel invasion (P = 0.013). Of notice, taken the whole TC group, family history of thyroid disease positively correlated with capsular invasion (P = 0.025). CONCLUSIONS: Older age is manifold associated with unfavorable tumor markers in our series. The K601E identified in a PTC, FVPTC, and FTC seems to be more distributed among different histological types of TC than previously thought. The T599del is a yet undescribed mutation and the rare T599dup has not been reported as a mutation in PTC so far.

Mutational screening of RET, HRAS, KRAS, NRAS, BRAF, AKT1, and CTNNB1 in medullary thyroid carcinoma.

BACKGROUND: Screening medullary thyroid carcinomas (MTCs) for rearranged during transfection (RET) mutations becomes increasingly important for clinical assessment of the disease. The role of mutations in other genes including RAS (i.e. HRAS, KRAS, and NRAS), v-raf murine sarcoma viral oncogene homolog B1 (BRAF), v-akt murine thymoma viral oncogene homolog 1 (AKT1), and CTNNB1 (ß-catenin) is unknown or not fully explored yet for this disease. MATERIALS AND METHODS: Formalin-fixed and paraffin-embedded (FFPE) material was the primary source for screening 13 sporadic and inherited MTCs and matched non-tumor specimens. Multiplex PCR was included in the PCR protocol. Sequence analysis encompassed mutational hotspot regions in RET exons 5, 8, 10, 11, and 13 to 16; HRAS exons 1 and 2; KRAS exons 1 and 2; NRAS exons 1 and 2; BRAF exon 15; AKT1 exon 2, and CTNNB1 exon 3. RESULTS: We identified RET mutations in seven of 13 MTCs: five RET-positive cases revealed a mutation in exon 16 (M918T) and two a mutation in exon 10 (C618S and C620S). In four of the RET-positive cases, the mutation was inherited, out of which three were reportedly associated with a multiple endocrine neoplasia type 2 (MEN2) syndrome, i.e. MEN2A (C618S), MEN2A/familial MTC (FMTC) (C620S), and MEN2B (M918T). These cases reflect the known MEN2 genotype-phenotype correlation. Three of the five stage IVc MTCs were inherited RET-positive cases. Mutational screening in HRAS, KRAS, NRAS, BRAF, AKT1, and CTNNB1 disclosed one sporadic RET-negative MTC (stage III) with mutation in HRAS codon 13 (G13R). CONCLUSION: Our study supports the clinical relevance of screening MTC patients for RET mutations. The role of RAS mutations, in particular HRAS mutations, in sporadic RET-negative MTC has not been fully explored yet. Mutations in BRAF, AKT1, and CTNNB1 are likely not to play a role in MTC.

Consensus-based management of differentiated thyroid cancer in a tertiary care set-up.

INTRODUCTION: This study describes the experience of a tertiary care hospital in the management of differentiated thyroid cancer. Thyroid cancer accounts for less than 1% of all human malignancy. Nevertheless, it is the commonest endocrine malignancy constituting 90% of endocrine cancers. It is the commonest cancer in Saudi Arabian women second to breast cancer. This fact makes differentiated thyroid cancer an important tumor and a challenging disease. METHODS: The medical records of patients diagnosed to have differentiated thyroid cancer in King Faisal Specialist Hospital and Research Centre, Jeddah, Saudi Arabia between 1st January 2000 and 30th September 2006 were reviewed retrospectively. The data included patient's demographic details, clinical diagnoses, co-morbid conditions, relevant investigations, imaging studies, medical and surgical treatment offered, types of surgeries performed, radioactive iodine therapy given, and the complications and outcome of management. Management of these patients follows a clinical care pathway set up by the hospital Thyroid Cancer Group representing various multidisciplinary team members. RESULTS: One hundred and eight medical records were reviewed. Of these, 72 (66.7%) patients were females and 36 (33.3%) were males. Median age for the females was 40 years, and for males 45 years. Ninety patients (83.3%) had a papillary carcinoma, four patients (3.7%) had a follicular carcinoma and fourteen patients (13%) had other types, namely medullary thyroid carcinoma, anaplastic carcinoma and lymphoma. A total of 78 patients underwent various forms of surgery in our hospital and the remaining patients underwent operation in the district hospitals before they were referred to our centre for further management. Complications included bleeding (1.8%), voice changes (4.5%), and hypocalcaemia (3.8%). The overall outcome showed that 99 patients (91.7%) were alive and well at the time of analysis, 4 patients (3.7%) died and 5 patients (4.6%) were lost to follow up. CONCLUSIONS: This hospital-based epidemiological study, the largest one done in the western part of Saudi Arabia, showed that differentiated thyroid cancer behavior and the management approach we adopt is not different from other centres of excellence. In spite of the relatively higher number of redo surgery we performed in these patients, yet the incidence of recurrent laryngeal nerve injury and hypocalcaemia are similar to what is published in the literature.

Laparoscopic treatment of hepatic hydatid cysts with a liposuction device.

OBJECTIVE: We describe herein a surgical technique, whereby we use a liposuction device for the laparoscopic treatment of hepatic hydatid cysts (HHC). METHODS: Ten patients with 12 hepatic hydatid cysts were treated with this technique. All patients received pre- and postoperative antiscolecidal medications. The laparoscopic technique consisted of partial aspiration of the cyst fluid and replacement of the aspirated fluid with 10% Betadine. The Betadine solution was left in situ for 10 minutes. Evacuation of the cyst contents was carried out with the liposuction device. The residual cavity was unroofed by partial excision of the ectocyst. A drain was left alongside the cyst. No intra- or postoperative complications were encountered. RESULTS: All patients were mobilized freely, were allowed to eat a regular meal 6 hours after recovery from anesthesia, and were discharged on the third postoperative day. All patients resumed their normal household and work activities by the tenth postoperative day. The patients were regularly followed up every 2 months for 2 years. At follow-up in the surgical clinic, no evidence of recurrence was noted either clinically, serologically, or by imaging techniques. CONCLUSION: We conclude that the laparoscopic treatment of HHC is feasible and advantageous. We believe that the use of a liposuction device facilitates rapid and efficient evacuation of the viscid organic contents of the cyst and helps in the obliteration of the residual cavity.