Goiter surgery recommendations in sub-Saharan Africa in humanitarian cooperation.

Background: The standard treatment for endemic goiter is usually total thyroidectomy. In low- and middle-income countries, the management of thyroid disease, which is commonplace in fully developed countries, is not always possible. The purpose of this study is to establish a treatment algorithm to calculate the extent of thyroidectomy based on the risk factors of each patient. Methods: This is a retrospective observational study conducted during the period between 2017 and 2019. A total of 287 patients with thyroid pathology were treated in Maragua Hospital (Kenya). The results of surgical treatment were analyzed after the implementation of an individualized treatment protocol. Results: One hundred and sixty patients with different types of goiter underwent surgery: solitary nodule (54.4%), multi-nodular goiter (30.6%), diffuse goiter (10.6%), and intrathoracic goiter (3.8%). The techniques used were hemithyroidectomy (78.8%), Dunhill thyroidectomy (9.4%), bilateral subtotal thyroidectomy (6.9%), and total thyroidectomy (3.1%). There was no mortality. The surgical morbidity rate was 16% (only one major complication (3b)). Two cases of dysphonia were resolved in the first week. There were three cases of symptomatic hypocalcaemia, two of which resolved in the first week and the other of which was definitive. The follow-up at 6 months was 67%. The cancer rate found in the resection specimens was 5%. Discussion: The implementation of individualized surgical protocols for thyroid surgery in sub-Saharan Africa can improve outcomes. The cooperation projects can increase access to complex surgical treatment for patients with limited resources in low- and middle-income countries.

Malignant prediction in paragangliomas: analysis for clinical risk factors.

INTRODUCTION: Paragangliomas are infrequent neuroendocrine tumours whose only criterion for malignancy is presence of metastases; thus, all paragangliomas show malignant potential. Actually, different risk factors have been analyzed to predict metastases but they remain unclear. PURPOSE: To analyze clinical, histological, and genetic factors to predict the occurrence of metastasis. PATIENTS AND METHOD: A multicentre retrospective observational analysis was performed between January 1990 and July 2019. Patients diagnosed with paraganglioma were selected. Clinical, histological, and genetic features were analyzed for the prediction of malignancy. RESULTS: A total of 83 patients diagnosed with paraganglioma were included, of which nine (10.8%) had malignant paraganglioma. Tumour size was greater in malignant tumours than in benign (6 cm vs. 4 cm, respectively; p = 0.027). The most frequent location of malignancy was the thorax-abdomen-pelvis area observed in six cases (p = 0.024). No differences were observed in histological differentiation, age, symptoms, and catecholaminergic production. The most frequent genetic mutation was SDHD followed by SDHB but no differences were observed between benign and malignant tumours. In the univariate analysis for predictive factors for malignancy, location, tumour size, and histological differentiation showed statistical significance (p = 0.025, p = 0.014, and p = 0.046, respectively); however, they were not confirmed as predictive factors for malignancy in the multivariate analysis. CONCLUSION: In this study, no risk factors for malignancy have been established; therefore, we recommend follow-up of all patients diagnosed with paraganglioma.

Humanitarian Surgical Missions in Times of COVID-19: Recommendations to Safely Return to a Sub-Saharan Africa Low-Resource Setting.

BACKGROUND: Since the declaration of the pandemic, humanitarian medicine has been discontinued. Until now, there have been no general recommendations on how humanitarian surgical missions should be organized. METHODS: Based on our experience in the field of humanitarian surgical missions to Sub-Saharan Africa, a panel of recommendations in times of COVID-19 was developed. The fields under study were as follows: (1) Planning of a multidisciplinary project; (2) Organization of the infrastructure; (3) Screening, management and treatment of SARS-COV-2; (4) Diagnostic tests for SARS-COV-2; (5) Surgical priorization and (6) Context of patients during health-care assistance. We applied a risk bias measurement to obtain a consensus among humanitarian health-care providers with experience in this field. RESULTS: A total of 94.36% of agreement were reached for the approval of the recommendations. Emergency surgery must be a priority, and elective surgery adapted. For emergency surgery, we established a priority level 1a (< 24 h) and 1b (< 72 h). For an elective procedure, according our American College of Surgeon adaptation score, process with more than 60 points should be reconsidered. Due to the low life expectancy in many African countries, we consider 45-50 years as age of risk. In case of SARS-COV-2 active infection or high clinical suspicion, the screening, management and treatment should be following the international guidelines adapted to duration of the stay, available infrastructure, size of the cooperation team and medical resources. CONCLUSIONS: Humanitarian surgical mission in times of COVID-19 is a challenge that must extrapolate the established recommendations to the local cooperation environment.

Prediction of hypocalcemia after total thyroidectomy using indocyanine green angiography of parathyroid glands: A simple quantitative scoring system.

BACKGROUND: Hypocalcemia is one of the most common complications after total thyroidectomy. Recently, indocyanine green (ICG) angiography of the parathyroid glands (PGs) has been suggested as a reliable tool for predicting postoperative hypocalcemia. The aim of our study was to evaluate the performance of a simple quantitative score based on ICG angiography of the PGs (4-ICG score) for predicting postoperative hypocalcemia. METHODS: Thirty nine consecutive patients who underwent total thyroidectomy for multinodular goiter were included. For each patient, the 4-ICG score was calculated, adding the individual viability value of the four PGs. Discrimination and correlation analyses were performed. RESULTS: In 32/39 patients, the four PGs were identified. Patients with postoperative hypocalcemia (n = 6, 19%) had a lower 4-ICG score (2.5 [1.8-3.3] vs. 4.0 [3.0-6.0]; p = 0.003). The 4-ICG score showed good discrimination in terms of predicting postoperative hypocalcemia (AUC = 0.875 (0.710-0.965); p = 0.001) and a good correlation with postoperative parathyroid function. CONCLUSIONS: The 4-ICG score predicts postoperative hypocalcemia and correlates well with postoperative parathyroid function in patients undergoing total thyroidectomy for multinodular goiter.

Prophylactic thyroidectomy in multiple endocrine neoplasia 2 (MEN2) patients with the C634Y mutation: A long-term follow-up in a large single-center cohort.

BACKGROUND: Medullary thyroid carcinoma (MTC) is the main cause of death in multiple endocrine neoplasia 2A (MEN2A) patients. It is therefore important to treat this disease at an early stage. The mutation in codon 634 is considered to be associated with an aggressive clinical course, whereas the C634Y mutation may result in a more indolent course. Prophylactic thyroidectomy is performed before thyroid disease occurs. However, controversy surrounds this disease regarding levels of calcitonin (Ct) and age. In this context, few studies have investigated this mutation over a long period. OBJECTIVE: To analyze a large cohort of patients with the C634Y mutation who received prophylactic thyroidectomy. MATERIALS AND METHODS: In a group of 110 MEN2 patients, we analyzed those with the C634Y mutation who had received prophylactic thyroidectomy (absence of clinical and radiological thyroid disease) treated in a tertiary referral hospital between 1983 and 2016. MTC is related to age and Ct. Statistical analysis was performed using the χ2 test, partial correlations, and logistic regression. RESULTS: Fifty patients with a mean age of 12 ±â€¯9 years were analyzed; 56% of these had MTC (100% stage I). There was no case of hypoparathyroidism or permanent recurrent damage. MTC was associated mainly with age (OR 1.38). One 5-year-old patient presented with MTC. Mean follow-up time was 16 ±â€¯6 years, and no cases of recurrence were observed. CONCLUSIONS: Performing prophylactic thyroidectomy in patients with the C634Y mutation allows us to cure the disease without causing long-term complications. Our results support the notion that age <5 years should be a criterion for carrying out prophylactic thyroidectomy in these patients.

Chyle fistula as complication of thyroid surgery in malignant pathology. / Fístula quilosa como complicación de la cirugía tiroidea en patología maligna.

INTRODUCTION: Cervical chyle fistula (CF) is exceptional, and there is no agreement on its treatment. The study objective was to assess the efficacy of conservative and surgical treatment in this condition. METHOD: Study population: Patients undergoing thyroid surgery who experience CF after the procedure. Study groups: 1) Group with conservative treatment: CF with flow rates less than 300cm3/day, late or collected in the neck; and 2) Group with surgical treatment: early CF with flow rates greater than 300 cm3/day. STUDY VARIABLES: Cure rates and rate of conversion to surgery were analyzed. RESULTS: Nine patients experienced CF. Conservative treatment was started in all of them, in 67% (n=6) with curative intent. Fifty percent of treated cases were resolved (n=3). The remaining patients were hospitalized after more than 150 days of treatment to add absolute diet and parenteral nutrition. The condition resolved in one patient, and the other two were referred for surgery. In the remaining patients (33%, n=3), surgery was indicated as the initial definitive treatment. A cervical approach, with ligature and transfixion stitch of the thoracic duct, was used. In one of the patients, who also had chylothorax, thoracoscopy was also performed. In the two patients where conservative treatment failed, cervicotomy was indicated, identifying in both the lymphatic reflux point. Fistula resolved in all operated patients. CONCLUSIONS: Conservative treatment was effective in 66% of low flow CFs. Surgery effectively and rapidly resolves fistulas with a high flow or not responding to conservative treatment.

Evaluation of the thyroid nodule with high-resolution ultrasonography and elastography without fine needle aspiration biopsy. / Evaluación del nódulo tiroideo con ecografía y elastografía de alta resolución sin la punción-aspiración con aguja fina.

INTRODUCTION: Fine needle aspiration biopsy (FNAB) is the gold standard screening technique used in the diagnostic protocol for thyroid nodules. However, it is not free of complications. OBJECTIVE: To identify thyroid nodules in which FNAB could be avoided during the diagnostic process by means of the use of a high-resolution ultrasonography or elastography. MATERIAL AND METHOD: A prospective, non-randomized study was carried out. Single thyroid nodules and dominant nodules of multinodular goiter were included. Patients who had undergone thyroid surgery in the past were excluded. All patients underwent a high-resolution ultrasound and elastography, and, subsequently, a FNAB. We analyzed the ultrasound variables in 2D and Doppler, followed by the elastographic variables, and the results of the FNAB according to Bethesda. To correlate the data, the nodules were classified as benign or malignant. Student's t test, the Chi-square test and a logistic regression analysis were applied for the statistical analysis. RESULTS: A total of 221 thyroid nodules were analyzed, 32 of which were malignant (14%). The most predictive ultrasound findings of malignancy (P<.05) were a hypoechoic or complex echostructure (OR=11.832), the presence of microcalcifications (OR=9.637) and chaotic vascularization observed in the Doppler (OR=46.464). With regard to the elastography, elastographic patterns i and ii were seen to be associated with benignity (P=.0004 and P<.0001, respectively). When type i or ii elastography was combined with an ultrasound showing a non-hypoechoic nor complex echostructure, without microcalcifications nor chaotic vascularization in the Doppler ultrasound, 100% of the cases were benign with a specificity of 100% and a sensitivity of 14%. CONCLUSIONS: The combination of a high-resolution ultrasound with an elastography makes it possible to select cases where a FNAB does not have to be performed. Cases susceptible to a periodic follow-up without the use of a FNAB are those without a hypoechoic nor complex structure, no microcalcifications, non-chaotic vascularization and a type i or ii elastography.

Prognostic factors of follicular thyroid carcinoma.

INTRODUCTION: Most prognostic studies in differentiated carcinoma have included a high number of papillary carcinomas and few follicular carcinomas, and not all of their conclusions therefore apply to the latter. OBJECTIVE: To analyze the prognostic factors of follicular thyroid carcinoma. SELECTION CRITERIA: Patients with histological diagnosis of follicular carcinoma who had undergone potentially curative surgery, had no disseminated disease at diagnosis, and had been followed up for at least 5 years. STUDY VARIABLES: Tumor recurrence was defined as: 1) tumor lesions with cytological analysis suggesting malignancy and/or 2) patients with total thyroidectomy with thyroglobulin levels >2 ng/mL. Clinical, therapeutic, and histological parameters were analyzed to assess prognostic factors. RESULTS: Recurrence was found in 25 (38%) of the 66 study patients during a follow-up period of 99 ± 38 months. Most patients with recurrence (n=20) had increased Tg levels without anatomical location, and were initially treated with radioactive I131. In the remaining 5 cases, surgical excision of the lesion was performed, and three patients required surgery during the follow-up period. Two patients died due to the disease (3%), and two other patients (3%) currently have distant metastases. Mean disease-free interval was 154 ± 14 months, and rates of disease-free patients at 5, 10, 15, and 20 years were 71, 58, 58, and 58% respectively. Clinical factors influencing recurrence included 1) age (p=0.0035); 2) sex (p=0.0114); and 3) cervical pain (p=0.0026). Histological/surgical factors associated with recurrence included 1) infiltration into neighboring structures (p=0.0000); 2) type of carcinoma (p=0.0000); 3) size (p=0.0162); 4) vascular invasion (p=0.0085); and 5) adenopathies (p=0.046). In the multivariate study, cervical pain (p=0.018) and extrathyroid invasion (p=0.045) continued to be significant factors. CONCLUSIONS: In follicular carcinoma, rates of disease-free patients are 71% at 5 years and 58% at 10 years, and the main predictive factors are presence of local clinical symptoms and infiltration into neighboring structures.

[Prognostic value of clinical, histopathological and immunohistochemical features in medullary thyroid cancer]. / Valor pronóstico de las características clínicas, histopatológicas e inmunohistoquímicas en el carcinoma medular de tiroides.

BACKGROUND AND OBJECTIVE: To analyze the importance of various clinical, histopathological and immunohistochemical features in the prognosis of resected medullary thyroid carcinoma. PATIENTS AND METHODS: A total of 55 cases of medullary thyroid carcinoma consecutively operated were investigated. The data referring to clinical features were collected in the patient's clinical history. The histopathological and immunohistochemical features of the tumors were taken from their pathological anatomy report. RESULTS: Survival at one year was 96 ± 2%; at 5 years 91 ± 4%; at 10 years 88 ±6%; at 15 years 83 ± 7%; and at 20 years 61 ± 14%. Among epidemiological features, tumor type was significantly related with the disease (best familial prognosis; P=.035); among histopathological features, the presence of C cell hyperplasia and the presence of tumor necrosis had a significant relationship (P=.0005 and P=.039); among immunohistochemical features, positivity for p53 and for c-erb-b2 (P=.023 and P=.022); and finally, among staging data, TNM clinical staging (P=.015), size (P=.046) and the presence of distant metastases (P=.002). According to Cox's regression model, the only variables indicating a poor prognosis were: the existence of necrosis (P=.039; OR=6.513) and tumor size>4 cm (P=.027; OR=14.196). CONCLUSIONS: The survival rate was mainly determined by tumor size and the presence of tumor necrosis. None of the immunohistochemical markers had a significant influence on survival.

[Histological and immunohistochemical profile of sporadic and familial medullary thyroid carcinoma]. / Perfil histológico e inmuno-histoquímico del carcinoma medular de tiroides esporádico y familiar.

INTRODUCTION: The histological and immunohistochemical profile of medullary thyroid carcinoma is ill-defined. The objective of this study was to determine the epidemiological, histological, and immunohistochemical characteristics of medullary carcinoma and to analyze whether differences exist between sporadic and familial carcinomas. PATIENTS AND METHODS: Fifty-five histologically confirmed tumors were studied. Histological slides were reviewed and immunohistochemical staining of the archival paraffin blocks was performed. RESULTS: Nineteen of the 55 carcinomas (35%) were sporadic, and 36 (65%) familial. Sex distribution was similar, but familial carcinoma was more common in patients under 40 years of age (p<0.001). A solid growth pattern and plasmacytoid cells were found in most cases. C-cell hyperplasia and multicentricity were more frequent findings in familial carcinoma, while tumor necrosis, hemorrhagic foci, vascular invasion, and neovascularization were more common in the sporadic type. Immunohistochemical staining was positive for calcitonin, CEA, bcl-2, and p53 protein. With regard to staging, familial carcinomas were diagnosed in the earliest stages, when they were smaller and there were no lymph node metastases (p<0.01). CONCLUSIONS: Familial cases were more frequent when there was more C-cell hyperplasia and multicentricity. Sporadic cases more frequently showed foci of necrosis, hemorrhage, vascular invasion, and neovascularization. Neither histopathological nor immunohistochemical criteria are useful for differentiating between familial and sporadic forms.

Pheochromocytoma in MEN 2A syndrome. Study of 54 patients.

BACKGROUND: Pheochromocytoma occurs in nearly 50% of MEN 2A (multiple endocrine neoplasia, type 2A) cases. Many issues related to this tumor are still the subject of debate: the diagnostic management in patients who have had positive genetic study results (RET mutation), variations related to mutation, the best surgical option, and the real relapse rate during long-term follow-up. The aim of this study is to present our experience with this unusual disease, looking for answers to some of these questions. PATIENTS AND METHODS: Of 169 patients belonging to 19 MEN 2A families, 54 (32%) presented with pheochromocytoma. The following variables have been studied: (1) clinical and diagnostic data [age, mutation, clinical features, results of catecholamines and catabolites in a 24-h urine sample, computerized tomography (CT) scan and iodine-131 meta-iodobenzylguanidine (MIBG) scintigraphy results, and the means of diagnostic, clinical, or genetic screening]; (2) surgical treatment; and (3) follow-up and recurrence. The mean follow-up time was 92.5 months (range: 12-120 months). RESULTS: The mean age of the 54 patients was 37.9 years (range: 14-71 years); 33 were women. Most (96.3%) mutations were found in exon 11. The most frequent mutations were Cys634Tyr (in 33 cases [61.1%]) and Cys634Arg (in 14 [25.9%]). The diagnosis of pheocromocytoma was made after the diagnosis of MTC in 26 cases (48.2%), simultaneously in 21 (38.9%), and prior in the 7 remaining cases (12.9%). At the time of diagnosis 28 patients (51.8%) were asymptomatic and 26 (48.2%) had clinical features related to pheochromocytoma. In 6 patients (11.1%), the values of catecholamines and catabolites in urine were normal. In the cases with high values, the most useful isolated determination was that of metanephrines (82%), followed by adrenaline (76%). The CT scan did not provide a correct diagnosis in 6 patients with bilateral lesions, and one patient with a bilateral tumor was not diagnosed by MIBG. The combination of CT scan and MIBG diagnosed 100% of cases. The pheochromocytoma was bilateral in 27 cases, with a total number of 81 pathological glands detected. A laparascopic approach was used in 30 cases and a laparotomy in 24. The mean tumor size was 4.5 cm (range: 1-18 cm). Five patients with unilateral resection relapsed (18.5%), and the mean relapse time was 43.2 months (range: 12-120 months). There was a greater frequency of pheochromocytoma in those subjects who had the Cys634Arg mutation (p < 0.03). In addition, the Cys634Arg mutation is more frequent in bilateral cases. There are no prognostic factors for recurrence. CONCLUSIONS: Pheochromocytoma in MEN 2A is related to the type of mutation, which can be early onset and is frequently asymptomatic. Its diagnosis requires catecholamines determinations as well as a CT scan. Correct diagnosis of bilaterality is established by CT and MIBG. Laparoscopic adrenalectomy is the treatment of choice.

Protamine 2 precursors, protamine 1/protamine 2 ratio, DNA integrity and other sperm parameters in infertile patients.

BACKGROUND: The protamine 1-to-protamine 2 ratio (P1/P2) is altered in the sperm cells of some infertile patients. Also, evidence for increased protamine 2 precursors (pre-P2) in a few patients has been reported. But so far, there have been no studies measuring simultaneously these two variables in a large number of patients. METHODS: We measured the P1/P2 ratio and the presence of pre-P2 using, for the first time, an antibody specific to the precursor pre-P2, together with other sperm parameters in 224 infertile patients. Additionally, the DNA integrity was assessed by terminal transferase dUTP nick-end labelling (TUNEL) in a subset of the samples. RESULTS: Pre-P2 levels show a significant positive correlation with the P1/P2 ratio, with the presence of other proteins and, at low pre-P2 levels, with TUNEL-positive sperm. An inverse correlation with sperm count, normal morphology and motility was detected. CONCLUSIONS: The levels of pre-P2 may provide clues into the pathogenic mechanisms of infertility. The increased proportion of pre-P2 in some patients with increased P1/P2 ratio suggests an involvement of pre-P2 processing. The positive correlation between TUNEL-positive sperm and pre-P2 at low pre-P2/P2 ratios also suggests a link between deficient protamine processing and decreased DNA integrity.

Results of surgery for toxic multinodular goiter.

PURPOSE: We analyzed the clinical and histological features of patients operated on for toxic multinodular goiter (TMG) to determine the clinical profile and evaluate the surgical results. METHODS: We reviewed 672 patients who underwent surgery for multinodular goiter (MG), 112 (17%) of whom had hyperthyroidism, and analyzed the epidemiological, clinical, and surgical variables. RESULTS: The patients with TMG tended to be older than those with nontoxic MG, with a greater evolution time of the goiter and a higher rate of positive antithyroid antibodies. In the multivariate analysis, the only feature characteristic of TMG, as opposed to nontoxic MG, was the evolution time. Morbidity was 34%, representative of the fact that that most of the patients were seen before the establishment of our endocrine surgical unit. The hyperthyroid symptoms resolved in all patients, but 4 of 17 patients who underwent partial surgical resection showed signs of relapse within a follow-up period of 98 +/- 71 months. CONCLUSIONS: TMG is characterized by a long evolution time and is most effectively treated by total thyroidectomy, which achieves complete remission from symptoms, without relapse, and is necessary if there is associated carcinoma. However, the incidence of complications may be high if this procedure is not carried out by surgeons with experience in endocrine surgery.

[Relation between clinical presentation and prognosis of patients with papillary thyroid microcarcinoma]. / Relación entre la forma de presentación y el pronóstico del microcarcinoma papilar tiroideo.

BACKGROUND AND OBJECTIVE: We aimed to analyze patients with papillary thyroid microcarcinoma (PTM) in order to establish the prognosis according to the differences observed between those diagnosed before surgery and those diagnosed postoperatively. PATIENTS AND METHOD: Retrospective study of 83 PTM patients who were distributed in 2 groups. Clinical, histological and follow-up data were compared. Survival and disease-free interval (DFI) were analyzed in both groups. RESULTS: Group A (diagnosed before surgery): 30 patients (36.1%); group B (diagnosed postoperatively): 53 patients (63.9%). Five group A patients had a relapse. Overall survival was 98.8% and overall DFI was 94% (83.3% in group A and 100% in group B, p = 0.01). CONCLUSIONS: It is useful to differentiate patients with PTM diagnosed before surgery from those whose PTM was diagnosed after since their evolution is different.

Prophylactic thyroidectomy in MEN 2A syndrome: experience in a single center.

BACKGROUND: Genetic study of the RET proto-oncogene has modified the management, treatment, and prognosis of medullary thyroid carcinoma (MTC), multiple endocrine neoplasia 2A (MEN 2A), for patients with less advanced tumor stages. Classically, the diagnosis was based on an increase in basal and poststimulus peak calcitonin (bCT and pCT). Prophylactic thyroidectomy, based on results of genetic testing, may reduce recurrences in MTC. STUDY DESIGN: Of 82 MTC (MEN 2A) patients genetically diagnosed and surgically treated at our center, 22 received a prophylactic thyroidectomy (RET +, bCT and pCT with normal values and asymptomatic). We analyzed age, gender, phenotype, RET mutation, cervical ultrasound, laboratory tests (bCT, pCT, and CEA), surgery, histologic data, TNM, and followup. RESULTS: The 22 patients belonged to 8 families with MTC (MEN 2A). Mean age was 15.2 years (range 5 to 36 years). The RET mutation in 21 patients was Cys-->Tyr and in the remaining patient both in codon 634 in exon 11. The median values of bCT and pCT were 38 pg/mL (range < 15 to 75 pg/mL) and 148.5 pg/mL (range < 15 to 250 pg/mL), respectively. Total thyroidectomy was performed in 8 patients (age < or = 10 years) and associated central neck dissection in 14 patients (age> 10 years). Histologic study showed 7 C-cell hyperplasias and 15 MTCs (8 bilateral); the median size was 0.2 cm (range < 0.1 to 0.7cm); 1 patient had metastatic adenopathies. According to TNM, 7 were stage 0, 14 were stage I, and 1 was stage III. Postsurgery bCT and pCT values were normal in all patients, with a curative rate of 100%. MTC patients compared with C-cell hyperplasia patients were older on average, had higher mean bCT, mean pCT, and mean CEA. CONCLUSIONS: Prophylactic thyroidectomy based on genetic testing allows identification and treatment of patients at an early stage of the disease and decreases recurrence rates. pCT values above the upper limit of normal may be markers for the presence of MTC and should be considered in selecting operative procedures for these patients.