Sentinel lymph node biopsy in medullary thyroid microcarcinomas.

The aim of this prospective study was to analyze accuracy of sentinel lymph node biopsy with methylene blue dye for intraoperative detection of lateral metastases in clinically N0M0 medullary microcarcinomas with calcitonin <1,000 pg/mL and selection of true-positive patients for one-time therapeutic lateral dissection. In addition to total thyroidectomy and central neck dissection, all patients had bilateral sentinel biopsy of jugulo-carotid regions after methylene blue injection to decide upon necessity for lateral dissection. If sentinels were benign on frozen section, additional non-sentinels were extirpated, with no further lateral dissection. If sentinels were malignant, one-time lateral dissection was performed. 20 patients were included in this study. Hereditary disease form was observed in 3/20 (15%) of patients with RET proto-oncogene mutation C634F; remaining 17/20 (85%) were negative for germline mutations. There were no allergic reactions to methylene blue and identification rate of sentinels was 100%. In total, 2/20 (10%) cN0 patients had lymphonodal metastases, thus were reclassified as pN1b. Remaining 18/20 (90%) were classified pN0 based on standard pathohistology. Frozen section findings on sentinels were 100% match with standard pathohistology, and there were no skip metastases in lateral compartments. Sensitivity, specificity and accuracy of sentinel biopsy method with methylene dye and frozen section were 100%. Dzodic's sentinel lymph node biopsy method can be used for intraoperative assessment of lateral compartments and optimization of initial surgery of medullary microcarcinomas with calcitonin <1,000 pg/mL. This way, cN0 patients with sentinel metastases can receive one-time lateral dissection, and those without benefit from less extensive surgery.

Evaluation of predictive value of 1H MR spectroscopy for response of neoadjuvant chemotherapy in musculoskeletal tumors.

PURPOSE: Bone and soft tissue tumors are rare. There is a variety of types and each one has its own particular behavior, treatment and patient outcome. The assessment of treatment response following the 3rd cycle of chemotherapy is one of the most important aspects of patient care, as therapeutic options and the timing of surgery may vary depending on the achievement of response. Hence, we focused on the advanced imaging technique, proton magnetic resonance spectroscopy (1H MRS), aiming at improving the diagnostic accuracy and the tumor response to therapy, based on the absolute concentration of choline (Cho) as biomarker of malignancy. METHODS: Twenty patients were studied. All of them had a pathological diagnosis after biopsy. MRI examinations were performed using a 1.5 T MR scanner (Avanto; Siemens, Erlangen, Germany). Single-voxel 1H MR spectroscopy was performed by using a PRESS with TR/TE 1530/100 ms, before chemotherapy and after the 3rd cycle. 1H MRS was processed in LCmodel. RESULTS: Of 20 patients, 7 responded to neoadjuvant chemotherapy and 13 did not. In responders, the mean concentration of tCho before therapy was 4.7±2.5 mmol/kg, which showed statistically significant reduction after therapy. In non-responders, the mean tCho concentration before therapy was 2.9±0.9 mmol/kg which remained the same or increased after the 3rd cycle of neoadjuvant chemotherapy (2.7±2.5 mmol/kg; range from 2.05 to 5.79 with no statistical significance). Compared to reference healthy group, tCho concentrations were increased in all cases. CONCLUSIONS: 1H MRS appears to be valuable technique for evaluation of response to neoadjuvant chemotherapy of patients with musculoskeletal tumors (MSK).

Goblet cell carcinoid of the appendix. Review of the literature a propos of a rare case of endometrial metastases.

BACKGROUND: Carcinoid tumors are rare tumors most commonly found in the gastrointestinal tract. They represent the most common malignancies of the appendix. As a distinct entity from both adenocarcinomas and carcinoids, Goblet cell carcinoid (GCC) was initially described in the literature in 1969. The GCC is almost exclusive to the appendix, but rarely can be found in rectum, ileum and colon. More than 50% of the patients at the time of diagnosis already have advancedstage disease. The most common metastatic sites are the peritoneal surfaces of the pelvis and abdominal cavity, and ovaries in women. Surgery is the main form of treatment in patients with GCC. CASE PRESENTATION: A 49-year-old woman was treated at the Institute of Oncology and Radiology of Serbia with histopathological findings of GCC. In a 8-year period the patient was treated with initial appendectomy and three more operations because of locoregional disease progression. The last operation was performed in March 2016 because of endometrial metastases. Since then the patient is on regular follow up without disease progression. CONCLUSION: GCC is a very rare entity. Multidisciplinary approach is necessary for adequate patient treatment.

Multifocality as independent prognostic factor in papillary thyroid cancer - A multivariate analysis.

PURPOSE: The incidence of multifocality of papillary thyroid carcinoma (PTC) ranges from 18 to 87.5% The mechanisms of multifocal spreading, correlation with tumor size, histology variants of PTC, lymph node metastases, and prognostic impact remains unclear. The purpose of this study was to clarify the prognostic significance of multifocality on relapse and survival rates of patients with PTC by analyzing the correlation of multifocality with patient age, gender, tumor size, histological variants of PTC, presence of lymph node metastases and extent of surgery. METHODS: 153 patients with PTC were included in this study. Patients with pT4 tumors or initially distant metastases were excluded from study. Total thyroidectomy was done in all 153 patients. Central and level III and IV lateral neck lymph node dissection was done in 76.5% of the patients, followed by modified radical neck dissection if positive. RESULTS: Multifocality was found in 43 (28%) whole thyroid gland specimens, and was significantly more frequent in patients older than 45 years and in tumors greater than 4 cm in diameter (p<0.01). Presence of multifocality didn't significantly correlate with gender, histology variants of PTC or lymph node metastases. In a median follow up of 84 months locoregional relapse occurred in 8.4% and 1.3% of the patients, while 7.2% patients died due to PTC. The incidence of relapse was significantly higher (p<0.01), and relapse free interval and survival were significantly shorter (p=0.0095, p=0.0004, respectively) in patients with multifocal PTC. Cox multivariate regression analysis showed that multifocality was independent prognostic factor for both disease-free interval (DFI) and cancer-specific survival (CSS) of patients with PTC. CONCLUSION: Due to high incidence of multifocality and potential prognostic impact, total thyroidectomy should be advocated in all patients with PTC, aiming to reduce relapse rate and improve DFI and CSS.

Prognostic importance of steroid receptor status for disease free and overall survival after surgical resection of isolated liver metastasis in breast cancer patients.

PURPOSE: Breast cancer (BC) is the most common malignancy among women, while isolated operable liver metastases (LMs) from BC are very rare and occur in only 1-5% of the patients. Besides, positive steroid receptor (SR) status for oestrogen and/or progesterone is known as a factor which improves disease free survival (DFS) and overall survival (OS). The primary aim of this study was to examine the impact of SR status on DFS and OS after liver metastasectomy in female patients with primary BC. METHODS: We analyzed 32 medical records of female patients diagnosed and treated for primary BC with LMS as the first and only site of disease progression, at the Institute of Oncology and Radiology of Serbia (IORS), during 2006- 2009. All of them underwent primary BC surgery as well as LMs resection. RESULTS: Patients with metachronous BC and LMs and positive SR status in both BC and LM (BC+/LM+) had a median time from BC to LM occurrence (TTLM) of 36 months, compared to BC+/LM- and BC-/LM- subgroups, whose medians for TTLM were 30.5 and 14.5 months, respectively (p<0.01). For all patients, positive SR status showed high correlation with longer DFS and OS after LM resection (medians according survival analysis for DFS/OS in subgroups BC-/LM-, BC+/LM- and BC+-LM+ were 10/19, 25/45, 50/not reached months respectively; p<0.01 for DFS/ OS). Cox regression analysis confirmed that the subgroup of patients with BC-/LM- had 10.8 and 18.8 higher risk of events for DFS (disease relapse or death) and event for OS (death only), respectively, compared to BC+/LM+ subgroup of patients. CONCLUSION: Positive SR status in BC and LM has a high impact not only on time from BC to LM occurrence, but also on longer DFS and OS after LM resection.

Lymph node metastases in clinically N0 patients with papillary thyroid microcarcinomas - a single institution experience.

PURPOSE: To register the frequency of central and lateral lymph node metastases (LNMs) from papillary thyroid microcarcinomas (PTMCs), and to assess whether sentinel lymph node (SLN) biopsy of the lateral compartment is an accurate technique to select patients with true positive but clinically negative lymph nodes for one-time selective lateral neck dissection (sLND). The correlation between tumor characteristics (size, multifocality, bilaterality, capsular invasion) and LNMs was analyzed. METHODS: During a 10-year-period (2004-2013), 111 clinically N0 patients with PTMCs had total thyroidectomy, central neck dissection and SLN biopsy of the lateral neck compartment in our institution. SLN mapping was performed by subcapsular injection of 0.2 to 0.5ml of 1% methylene blue dye. If SLNs were positive on frozen section, one-time sLND was done. RESULTS: Forty per cent of PTMCs were multicentric. LNMs were detected in 25% of the patients and isolated central LNMs were found in 18% of the patients. Lateral LMNs were present in 7% of the patients, of which 4% were isolated, skip LNMs. All these patients had therapeutic sLND. Specificity and sensitivity of SLN biopsy were 100% and 57%, positive and negative predictive values were 100% and 97%, respectively. Method's accuracy was 97%. CONCLUSIONS: SLN biopsy of the lateral neck compartment is more precise than physical examination and ultrasonography for detection of lateral LNMs in clinically N0 patients with PTMCs. Intraoperative assessment of lateral lymph nodes (SLNs) provides one-time therapeutic dissection for patients with occult LNMs at initial operation, reducing the need for additional operations. This method provides appropriate disease staging and optimizes treatment.

Recurrent Laryngeal Nerve Liberations and Reconstructions: A Single Institution Experience.

BACKGROUND: Recurrent laryngeal nerve (RLN) palsy rates vary from 0.5 to 10%, even 20% in thyroid cancer surgery. The aim of this paper was to present our experience with RLN liberations and reconstructions after various mechanisms of injury. METHODS: Patients were treated in our institution from year 2000 to 2015. First group (27 patients) had large benign goiters, locally advanced thyroid/parathyroid carcinomas, or incomplete previous surgery of malignant thyroid disease. Second group (5 patients) had reoperations due to RLN paralysis on laryngoscopy. Liberations and reconstructions of injured RLNs were performed. RESULTS: Surgical exploration of central compartment enabled identification of the RLN injury mechanism. Liberations were performed in 11 patients, 2 months to 16 years after RLN injury, by removing misplaced ligations. Immediate or delayed (18 months to 23 years) RLN reconstructions were performed in 21 patients, by direct suture or ansa cervicalis-to-RLN anastomosis (ARA). RLN liberation provided complete voice recovery within 3 weeks in all patients. Patients with direct sutures had better phonation 1 month after reconstruction. Improved phonation was observed 2-6 months after ARA in 43% of patients. CONCLUSIONS: Vocal cords do not regain normal movement once being paralyzed after RLN transection, but they restore tension during phonation by reconstruction. Nerve liberation is a useful method which enables patients with RLN paresis/paralysis a significant improvement in phonation, even complete voice recovery. Reinnervation of vocal cords, using one of the mentioned techniques, should be a standard in thyroid and parathyroid surgery, with aim to improve quality of patient's life.

Prognostic factors and outcomes of cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy in patients with advanced ovarian cancer - A single tertiary institution experience.

PURPOSE: Ovarian cancer (OC) ranks fifth in mortality among females cancer patients. Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) have radically changed the treatment of OC. The aim of this study was to evaluate overall survival (OS) and disease-free survival (DFS) in our patient population after the application of combined CRS and HIPEC treatment. METHODS: The study included patients who met defined inclusion and exclusion criteria and had undergone CRS of peritoneal carcinomatosis from 2006 to 2011. Tumor extension was intraoperatively calculated using peritoneal cancer index (PCI). After CRS had been performed, selected patients underwent closed HIPEC. Assessment of successful surgery was estimated with the completeness of cytoreduction score. RESULTS: The study involved 31 patients. The median DFS was 19 months. The DFS for 1 and 2-year period were 69.2 and 35.2%, respectively. The mean OS was 51 months. The 1-, 2- and 5-year OS was 85.4, 63.3 and 56.3%, respectively. PCI ranged from 1 to 24 and the majority (77.4%) of the patients had PCI score below 13. The most frequent carcinomatosis was observed in the omentum (80.6%), followed by adnexae (61.3%), uterus (58.1%), colon (58.1%). spleen (25.8%), diaphragm (25.8%), small intestine (19.4%), bursa omentalis 19.4, liver (9.7%), and pancreas (3.2%). CONCLUSION: The results of the current study are in concordance with the literature which clearly favors combined the CRS and HIPEC treatment. The reported data suggest that this method could be successfully applied in our region and outline the necessity of future multicentric studies that will involve major regional hospitals.

Can we use frozen section analysis of sentinel lymph nodes mapped with methylene blue dye for decision making upon one-time axillary dissection in breast carcinoma surgery in developing countries?

PURPOSE: To evaluate the accuracy of intraoperative frozen section analysis (FSA) of sentinel lymph nodes (SLNs) mapped using methylene blue dye (MBD) and its usefulness for selecting patients with breast carcinomas and positive axillary lymph nodes (ALNs) for one-time axillary dissection. METHODS: 152 female patients with T1/T2 breast carcinomas and clinically negative ALNs were selected for mapping using MBD (1%) from October 2010 to December 2011. Patients underwent FSA of mapped SLNs and ALN dissection. The accuracy of SLN-FSA was tested by comparing these findings with the definite histopathology (HP) of SLNs, as well as of other ALNs. Sensitivity, specificity, positive and negative predictive values were calculated. RESULTS: There was a 98%-match between FSA and definite HP findings of SLNs, suggesting high accuracy of FSA in this series. None of 3 patients with false-negative SLNs on FSA had additional axillary nodal metastases. One out of 20 (5%) patients with metastases in other ALNs had "clear" SLNs, both on FSA and definite HP (false-negative). Accuracy reached 94.1%. CONCLUSIONS: SLN-FSA enables adequate selection of patients for one-time axillary node dissection. MBD mapping technique is cheap, feasible and enables easy and precise detection of the first draining ALNs. Using FSA of SLNs mapped with MBD, patients with breast carcinoma benefit from complete surgical treatment during one hospitalization, the risk of undergoing anaesthesia twice is reduced, as well as the treatment cost, which is important in developing countries.

Surgical management of well-differentiated thyroid carcinoma in children and adolescents: 33 years of experience of a single institution in Serbia.

Well-differentiated thyroid carcinoma in children and adolescents is rare but demonstrates aggressive behavior. Gross lymph node metastases and distant metastases are common upon first clinical presentation. During a 33-year period (1981-2014) at the Institute of Oncology and Radiology of Serbia, 62 children and adolescents underwent surgery due to well-differentiated thyroid carcinoma. Mean age was 16.7 (range 7-21) years. At the time of diagnosis 6% of patients had lung metastases. Total thyroidectomy or completion thyroidectomy was performed for all patients followed by central neck dissection and frozen section examination of jugular-carotid compartments. Median follow-up was 10.9 (range 0.69-33.05) years and median tumor size was 20 (range 2-60) mm. Papillary carcinoma was found in 96%, and follicular and Hürthle cell carcinoma in 2% of patients. Multifocal tumors were found in 50% and capsular invasion in 60% of patients. Lymphonodal metastases in either central or lateral neck compartments were found in 73% of patients. Multifocality and capsular invasion were significantly more frequent in patients less than 16 years of age (both p < 0.01). Median disease-free interval had not been reached and overall survival rate was 100%. Well-differentiated thyroid carcinoma in children and adolescents is characterized by a high rate of loco-regional aggressiveness, multifocality, capsular invasion, lymph node metastases and distant metastases at the time of diagnosis. Adequate surgical approaches should be performed for both primary and recurrent disease in young patients with well-differentiated thyroid carcinoma in order to achieve loco-regional disease control and longer disease-free survival.

Lymphatic drainage, regional metastases and surgical management of papillary thyroid carcinoma arising in pyramidal lobe--a single institution experience.

Papillary thyroid carcinoma (PTC) arising in pyramidal lobe (PL) is very rare. The aim of this study was to determine the incidence of single PTC focus in PL and its lymphonodal metastases, as well as to present a single surgeon experience in management of PL PTC. We performed a retrospective analysis of records of all patients surgically treated for PTC in our institution from year 2003 to 2013. Only patients with single PTC focus in PL were included. Out of total 753 patients, majority (66.52%) had PTC focus in one of the lobes, while only 3 patients (0.4%) had solitary PTC focus in PL. They were all females, aged 36, 41 and 22. During surgery, methylene-blue dye was injected peritumorally. After frozen section analysis of excised PL and isthmus and confirmation of malignancy, we performed total thyroidectomy with central neck dissection, as well as sentinel lymph node biopsy in both jugulo-carotid regions. Pathology showed encapsulated PTC stage T1 and solitary metastasis in Delphian lymph node of the youngest patient. All patients were disease free in the follow-up. PTC single focus in PL is very rare and only individual experiences can be discussed regarding the extent of the surgery.

Survival prognostic factors in patients with colorectal peritoneal carcinomatosis treated with cytoreductive surgery and intraoperative hyperthermic intraperitoneal chemotherapy: a single institution experience.

PURPOSE: The aim of this research was to examine overall (OS) and disease-free survival (DFS) in patients with colorectal peritoneal carcinomatosis (CRC-PC), treated with cytoreductive surgery (CRS) and intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC), as well as to analyse factors of prognostic significance. METHODS: We included 61 patients with pathological/and computerized tomography (CT) confirmation of CRC-PC, treated with CRS+HIPEC from 2005 to 2012. Peritoneal Cancer Index (PCI) score was used for quantitative assessment of the CRC-PC extent. We performed CRS following the Sugarbaker's principles in all patients with PCI ≤20 and only in 3/61 (4.92%) patients with PCI >20. HIPEC (oxaliplatin 410 mg/m(2) in 2000mL isotonic solution and 41?C) was performed using RanD Performer® HT perfusion system during 30-60 min. Cox proportional hazard regression was used to determine significant factors for OS and DFS. RESULTS: The follow-up ranged from 1 to 83 months (median 22). Median OS was 51 months (95% confidence interval/ CI 22+). Median DFS for patients without residual disease (57/61, 93.44%) was 23 months (95% CI 16+). One-, 2- and 6-year OS (DFS) were 78.6% (68.3%), 58.7% (46.7%) and 50.5% (38.1%), respectively. By the end of the study, 55.74% of the patients were still alive. Cox multivariate analysis indicated PCI score as a parameter of highly prognostic significance for patients treated with CRS+HIPEC (p<0.001). Patients with PCI (13 (vs PCI ≥13) had significantly longer OS and DFS (p<0.001), also confirmed for PCI subcategories (PCI <7 vs 7≤ PCI <13 vs PCI ≥13). All patients with PCI <7 are still alive. CONCLUSION: Our study indicates that CRS+HIPEC significantly improves the survival of CRC-PC patients. This treatment modality should be considered as the most suitable in well-selected patients with this disease.

Adrenal Cysts: To Operate or Not to Operate?

Adrenal cysts are uncommon and usually asymptomatic, and therefore are usually incidentally discovered adrenal lesions. They have a broad pathohistological spectrum that includes pseudocysts and endothelial (vascular), parasitic, and epithelial (mesothelial) cysts. Although most adrenal cysts are benign and hormonally non-functional lesions, some can have ambiguous imaging appearances and mimic malignant adrenal neoplasms. On the other hand, the actual malignant neoplasms could undergo cystic transformation. Additionally, immune cell infiltrations, thrombosis, or haemorrhage seen in sepsis can frequently cause adrenal cyst development, raising a question about the possible connection between severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) and adrenal cystic lesions. Due to the disease's rarity, the likelihood of malignancy, and the lack of specific guidelines, the management of adrenal cysts is always challenging especially in a young person. This review discusses the important diagnostic and the current treatment possibilities for adrenal cystic lesions. Aiming to emphasize clinical dilemmas and help clinicians navigate the challenges when encountering a patient with an adrenal cyst in everyday practice, we based our review on a practical question-answer framework centred around the case of a young woman with an incidentally discovered large adrenal cyst.

Right thyroid hemiagenesis with adenoma and hyperplasia of parathyroid glands -case report.

BACKGROUND: Thyroid hemiagenesis is a rare anomaly, more commonly seen on the left side (ratio 4:1) and in females (ratio 3:1). The first to describe this anomaly was Handfield Jones in 1852. CASE PRESENTATION: We present a 66 year old female patient with right thyroid hemiagenesis, parathyroid adenoma on the side of hemiagenesis and parathyroid hyperplasia on the contralateral side. The patient had neck pain and was diagnosed as Hashimto thyroiditis with hyperparathyroidism. Parathyroid hormone, thyroglobulin antibodies (Tg-Ab) and thyroid peroxidase antibodies (TPO-Ab) were elevated. Neck ultrasound and technetium 99mTc-methoxyisobutyl isonitrile (MIBI) scintigraphy confirmed the right thyroid hemiagenesis, but not adenoma of parathyroid glands. Intraoperatively, right thyroid hemiagenesis was confirmed and left loboistmectomy was performed with removal of left inferior hyperplastic parathyroid gland. Postoperative PTH (parathyroid hormone) levels were within normal range. Five months after the operation PTH level was elevated again with calcium values at the upper limit. MIBI scintigraphy was performed again which showed increased accumulation of MIBI in the projection of the right parathyroid gland. Surgical reexploration of the neck and excision of the right upper parathyroid adenoma was performed which was located behind cricoid laryngeal cartilage. After surgery a normalization of calcium and PTH occured. CONCLUSION: From available literature we have not found the case that described parathyroid adenoma on the side of thyroid hemiagenesis,with parathyroid hyperplasia on the contralateral side.

Surgical management of primary thyroid carcinoma arising in thyroglossal duct cyst: an experience of a single institution in Serbia.

Thyroglossal duct cyst (TDC) carcinoma is a comparable rare entity and treatment strategies have not been standardized. Here, we report a favorable outcome of TDC carcinoma patients based on our therapeutic strategy. Twelve patients with TDC carcinoma treated in our department from 1986 to 2012 were enrolled. Ten patients underwent Sistrunk's procedure in other institutions and referred to our institution for re-operation after the diagnosis of TDC carcinoma and the remaining two underwent initial surgery in our institution. Eleven patients were diagnosed as papillary and one as follicular carcinoma originating from TDC. We performed total thyroidectomy for 11, and limited thyroidectomy for one patient. Three patients (25%) had carcinoma lesions in the thyroid. We routinely dissected level I bilaterally and 6 of 11 patients (55%) with papillary carcinoma-type TDC carcinoma had metastasis. Level II/III nodes were biopsied and if positive, we performed level II-IV dissection. Of the 5 patients positive for level II/III, 2 were also positive for level IV. For the 3 patients with synchronous carcinoma in the thyroid, we performed level VI dissection and two had metastasis in this level. To date, 1 patient showed a recurrence to the lung, but none of the patients in our series died of carcinoma. For surgery of TDC carcinoma, Sistrunk's procedure, total thyroidectomy with level I dissection is mandatory. Whether level II-IV dissection is performed depends on pathology of biopsied level II/III nodes. Level VI dissection is also recommended especially when carcinoma lesions are pre/intra operatively detected in the thyroid.

Mutational and clinico-pathological analysis of papillary thyroid carcinoma in Serbia.

Molecular pathogenesis of papillary thyroid carcinoma (PTC) is largely associated with mutational changes in the BRAF, RAS family and RET genes. Our aim was to assess clinico-pathological and prognostic correlations of these PTC-specific gene alterations, with a particular emphasis on the BRAF mutation, in a group of 266 Serbian PTC patients, for the first time. The reference center-based retrospective cohort included 201 (75.6%) females and 65 (24.4%) males aged 48.0±16.1 years (8-83 years old, range) diagnosed and treated for PTC during 1993-2008. Follow-up period was 53.1±41.6 months (7-187 months, range). BRAF and RAS mutations were determined by direct sequencing of genomic DNA. RET/PTC rearrangements were analyzed by RT-PCR/Southern blotting. Genetic alterations were detected in 150/266 tumors (56.4%). One tumor displayed two genetic alterations. The BRAF(V600E) was found in 84/266 (31.6%) cases, RAS mutations in 11/266 (4.1%) and RET/PTC in 55/266 (20.7%; 42/266 (15.8%) RET/PTC1 and 13/266 (4.9%) RET/PTC3). On multivariate analysis BRAF(V600E) was associated with the classical papillary morphology (P = 0.05), the higher pT category (P = 0.05) and advanced clinical stage (P = 0.03). In a proportional hazard model, BRAF(V600E) did not appear to be an independent risk factor for the faster recurrence (P = 0.784). We conclude that under the extensive thyroid surgery and limited application of radioiodine ablation BRAF(V600E) may not be an indicator of poorer disease-free survival during the short to middle follow-up period. However, it has a potential to contribute to patients stratification into high- and low-risk groups.

Usefulness of Sentinel Lymph Node Biopsy of Contralateral Neck Region in Papillary Thyroid Carcinoma.

Here, we present a 9-year-old male boy admitted at the Institute for Oncology and Radiology of Serbia due to enlarged lymph node in the left lateral neck region and palpable tumor in the upper pole of the left thyroid lobe. Clinically and sonographically, there were no metastases in the right jugulo-carotid chain, but the lymph nodes in the central pretracheal neck compartment and left jugulo-carotid chain were metastatic. Chest X ray, abdominal ultrasound, and laryngoscopy findings were normal. After injection of 2 mL of methylene blue dye in the normal right lobe, we accessed the right lateral neck region and the colored sentinel lymph node was removed, which was proven to be metastatic on frozen section analysis. Then, we explored entire thyroid gland and there were no nodules in the right lobe. The left lobe was explored and tumor was verified, which was in close contact to the infrahyoid muscles. We performed left loboisthmectomy by shaving off left lobe from trachea. Three foci of papillary carcinoma were found in the upper pole of left lobe 11 mm, just below 6 mm, and in isthmic region focus of 6 mm. We proceeded with the removal of the right lobe and central lymph nodes, including Delphian, which was metastatic, pretracheal, right paratracheal, and the lymph nodes behind the right recurrent laryngeal nerve down to the aortic arch. Upper mediastinal lymph nodes were removed. In the central neck region and upper mediastinal compartment, 15 lymph nodes were removed and 11 were metastatic. Right modified radical neck dissection from region two to four was performed. Twenty-one lymph nodes were examined, 5 were metastatic, including the sentinel lymph node. Left modified radical neck dissection, from level IIB to V, was performed on two incisions, which enabled reaching left level II and common carotid artery bifurcation. Left lateral lymph nodes were removed in one piece, berry picking must be avoided. Of 21 removed lymph nodes, 5 were metastatic in the left lateral region. A total of 57 lymph nodes were removed and 21 were metastatic. We showed the necessity and usefulness of sentinel lymph node biopsy of contralateral neck region by injecting vital dye in the normal right lobe. We confirmed the presence of metastases in a patient with clinically and sonographically negative lymph nodes. All authors declare no conflict of interest. Runtime of video: 10 mins.

Difference between Luminal A and Luminal B Subtypes According to Ki-67, Tumor Size, and Progesterone Receptor Negativity Providing Prognostic Information.

BACKGROUND: The St. Gallen International Expert Consensus of 2011 proposes a new classification system for breast cancer based on its division into five subgroups. The criteria to identify these subtypes were recently refined at the 2013 Conference. In this respect, the authors of this paper have conducted a retrospective analysis of breast cancer subtypes, related to Ki-67 and involvement of the axillary lymph nodes (ALNs). The analysis was performed only in the cases of invasive breast cancer in the pT2 stages. The research and results of the paper have shown that investigating the value of these parameters could be of great benefit in future treatment strategies of invasive breast cancer. METHODS: A retrospective analysis of breast cancer subtypes, tumor nodal metastatic staging, and histopathological grading of 108 cases has been performed according to the methods recommended and provided by the St. Gallen International Expert Consensus Report, 2011. The estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER2), and Ki-67 of 108 tumor samples were all investigated by immunohistochemistry according to the methods used to classify breast cancer subtypes as proposed in the St. Gallen Consensus Report, 2011. Invasive breast cancers (n = 108) were immunohistochemically classified as follows: 28 (25.92%) as Luminal A, 51 (47.22%) as Luminal B (HER2 negative), 21 (19.44%) as Luminal B-like (HER2 negative), 2 (1.85%) as HER2 positive, and 6 (5.55%) as being a triple-negative subtype. RESULTS: The conclusion was made that when Ki-67 was found to be higher, patients also showed a higher involvement in their ALNs. The chi-square test shows the difference to be significant (chi-square = 4.757; P = 0.029). Luminal B subtypes had the highest percentage (54.9%) of involvement of lymph nodes when compared to the other four subtypes. The Luminal B subtype had a higher percentage (51.4%) of involvement of lymph nodes than did Luminal A (10.7%). The chi-square test also shows the difference to be significant (P < 0.05). CONCLUSION: A combination of the Ki-67 index, HER negative tumors, PR negativity, and a low value that can be used to segregate ER positive pT2 tumors into prognostically significantly different clinical outcomes may be utilized clinically to guide patient management in accordance with these tumor characteristics.

Sentinel lymph node biopsy may be used to support the decision to perform modified radical neck dissection in differentiated thyroid carcinoma.

BACKGROUND: The prognostic significance of lymph node metastases (LNM) in follicle cell-derived differentiated thyroid carcinoma (DTC) is still controversial. The management of cervical lymph nodes varies from "berry picking" to modified radical neck dissection (MRND). The incidence of LNM in papillary thyroid carcinoma varies from 27% to 80%. The importance of sentinel lymph node (SLN) biopsy for decisions about the surgical management of lymph nodes in DTC has been the subject of several previous studies. PATIENTS AND METHODS: In 40 patients with DTC methylene blue dye was applied peritumorally. Both SLN and non-SLN in the lower third of the jugulo-carotid chain were dissected prior to total thyroidectomy and routine dissection of the central neck compartment and examined by frozen-section and standard histology. MRND was performed in 9 cases of LNM in the lateral neck compartment. RESULTS: The SLN identification rate was 92.5%. Metastases in SLNs were revealed by frozen-section histology in 7 cases, leading to immediate MRND. The findings were confirmed on standard HE examination. In 2 false-negative cases SLN metastases were revealed on standard histology and MRND was performed 1 week later. The specificity of the method was 100%, sensitivity 77.7%, negative predictive value 94%, positive predictive value 100%, with overall accuracy of 95%. CONCLUSION: Our results seem to imply that SLN biopsy in the jugulo-carotid chain using methylene blue dye mapping may be a feasible and valuable method for estimating lymph node status in the lateral neck compartment. It may be helpful in the detection of true-positive but nonpalpable lymph nodes, and in such cases may support the decision to perform MRND in patients with DTC.

[Treatment of postoperative pain in elderly oncology patients with intravenous administration of a 50% glucose solution]. / Lecenje postoperativnog bola u starih onkoloskih pacijenata intravenskom primenom 50% rastvora glikoze.

Postoperative pain is the most important factor od so called "tumor-promotive effect of surgery" i.e. of endocrine-metabolic changes having the consequence drop in immune, antiinfective and antitumor defense. Due to presence of organic involutive changes, old people (= 65 years), often have serious side effects during application of usual analgetics. Since hypertonic glucose (33%) given i.v. or per os, works analgesically in small children there is assumption that it can be used in treatment of postoperative pain in old oncology patients. We tested the hypothesis that postoperative pain in old oncology patients can be treated with i.v. application of 50% of glucose solution. 37 oncology patients over 65 years, 26 females and 11 males, operated for breast cancer and soft tissue cancer, were investigated. Average age of the patients was 72 +/- 4 years. 50% Glucose solution was given in two boluses of 20 ml each: the first bolus was given to all patients at the end of anesthesia, and the other bolus was given individually after appearance of post-operative pain. Pain intensity (in coefficients of the visual analogue scale VAK = 1-100) and its characteristics were tested by oral testing of operated patients; after weakening from anesthesia, after the first appearance of the pain and 15 minutes after giving of the second glucose bolus. None patient had pain weakening from anesthesia. All tested patients experienced pain during the first 70 minutes and it could be categorized as very strong pain (= 82 VAK). The pain was decreased with another glucose bolus by approximately (= 56% VAK) so it was classifies in category of bearable pains (= 36 VAK). In 9 patients (24.3%) the pain had neuropathic component (filing of "burning") which could not be eliminated by hypertonic glucose, but only with application of tramadol. Activation of the central cholinergic transmission is the most significant mechanism of analgesic glucose effect, but, probably there is another one: facilitation of entrance of formerly given analgesics in the brain cells. As energetic substrate, entering all organism cells, glucose could make easier intracell breakthrough of any other analgesic drug, of the peripheral or central action, and final antipain effect could be potential or additional one. It was concluded that 40 ml of 50% glucose solution given in two identical boluses, has good analgesic effect in treatment of postoperative pain in old oncology patient: the pain was not completely eliminated, but it was significantly decreased and became tolerable. Hypertonic glucose neither eliminates, nor decreases neuropathic component of the pain, so, when the pain appears the therapy should be supplemented with other drugs, which may completely eliminate all pain components.