Predictors of Complications Occurrence Associated With Emergency Surgical Tracheotomy.

OBJECTIVE: In emergency airway management, the occurrence of surgical tracheotomy complications is increased and may be fatal for the patient. However, the factors that play a role in complication occurrence and lead to lethal outcome are not known. The objective of this study was to determine predictors associated with the occurrence of complications and mortality after emergency surgical tracheostomy. STUDY DESIGN: Retrospective study with a systematic review of the literature. SETTING: Tertiary medical academic center. SUBJECTS AND METHODS: We included 402 adult patients who underwent emergency surgical tracheostomy under local anesthesia due to upper airway obstruction. Demographic, clinical, complication occurrence, and mortality data were collected. For statistical analysis, univariable and multivariable logistic regression methods were used. RESULTS: In multivariable analysis, significant positive predictors of complication occurrence were previously performed tracheotomy (odds ratio [OR] 3.67, 95% confidence interval [CI], 0.75-17.88), neck pathology (OR 2.05, 95% CI 1.1-1.77), and tracheotomy performed outside the operating room (OR 5.88, 95% CI, 1.58-20). General in-hospital mortality was 4%, but lethal outcome as a direct result of tracheotomy complications occurred in only 4 patients (1%) because of intraoperative and postoperative complications. CONCLUSION: The existence of neck pathology and situations in which tracheotomy was performed outside the operating room in uncontrolled conditions were significant prognostic factors for complication occurrence. Tracheotomy-related mortality was greater in patients with intraoperative and early postoperative complications. Clinicians should be aware of the increased risk in specific cases, to prepare, prevent, or manage unwanted outcomes in further treatment and care.

Sentinel lymph node biopsy in clinically node negative patients with papillary thyroid carcinoma.

PURPOSE: The incidence of histologically proven lymph node metastases (LNM) in papillary thyroid carcinoma (PTC) reaches 80%. According to different guidelines surgical management in clinically N0 (cN0) patients with PTC remains controversial. The purpose of this study was to investigate if sentinel lymph node biopsy (SLNb) using methylene blue dye is accurate in the detection of LNM in the lateral neck compartment in cN0 patients with PTC. METHODS: Enrolled were 153 cN0 patients with PTC. All underwent total thyroidectomy with central neck dissection and SLNb in the lateral neck compartment, using methylene blue dye as marker. Selective modified radical neck dissection was performed in cases of metastatic SLNs. RESULTS: Neck LNMs were histologically verified in 40.9% of the cases. Predictive factors for LNM were: males, younger than 45 years, tumors greater than 1cm, capsular and vascular invasion. The central neck compartment of LNM was predictive for lateral LNM in 80.5% of the cases. LNM were confirmed in 24% of SLNs in the lateral neck compartment, which were over 56% predictive of LNM to other dissected lateral LN. SLN identification rate (IR) was 91.8%. Sensitivity, specificity, positive value (PPV) and negative predictive value (NPV) were 85.7, 96.7, 88.3 and 95.9%, respectively. The overall accuracy of the method was 94.3%, with probability of 91.2% (ROC AUC, 95% CI; 84.2-98.3). CONCLUSION: The proposed method of SLN biopsy using methylene blue dye is feasible, safe and accurate in the detection of LNM in the lateral neck compartment and may help in the decision to perform selective modified radical neck dissection in cN0 patients with PTC.

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.

The influence of papillary thyroid microcarcinomas size on the occurrence of lymph node metastases.

PURPOSE: Lymph node metastases (LNM) in papillary thyroid microcarcinomas (PTMC) are common. PTMC greater than 5 mm are considered to be more aggressive. Tumor greater than 5 mm is predictive factor for occurrence of LNM in PTMC, although there are insufficient data regarding this fact. The purpose of this study was to explore the relation between LNM and patients with small (≤5mm) and large (>5mm) PTMC. The second target was to determine the frequency of multifocality, bilaterality and capsular invasion in small and large PTMC, and their relation with LNM occurrence. METHODS: This study included 257 patients with PTMC. In all patients total thyroidectomy was performed, and lymph node checking of central and lateral neck region using sentinel lymph node (SLN) biopsy in clinically N0 patients, or modified radical neck dissection in clinically N1b patients or in case with positive SLN. RESULTS: LNM were detected in 33% of the patients, 27% in the central neck region and 20% in the lateral neck region with 6.23% of skip metastases. LNM were significantly frequent in large PTMC compared with small (46 vs 24%), in the central region (38 vs 19%) and the lateral region (28 vs 14%), with skip metastases 7.62% and 5.26%, respectively. Bilaterality and capsular invasion were frequent in large PTMC. Multifocality and male gander were predictive factors for LNM in small PTMC, while capsular invasion was the only predictive factor in large PTMC. CONCLUSIONS: Although LNM are frequent in large PTMC, the percentage of LNM is not negligible in small PTMC, especially if they are multifocal.

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.

Serbian consensus of neoadjuvant therapy for breast cancer: NeoPULSE.

Even though surgery is the primary treatment of operable breast cancer, it has been known for decades that the administration of postoperative adjuvant or preoperative neoadjuvant therapy is extremely important. Indications for neodjuvant therapy administration have been expanded over the years, and nowadays this kind of treatment represents an inevitable option in early breast cancer treatment. The NeoPULSE project, which gathered a group of experts in the field of breast cancer from five Serbian university centres, was formed with the aim to define optimal breast cancer diagnosis, indications for neoadjuvant therapy, therapeutic combinations in relation to molecular/biological parameters of breast cancer, as well as the treatment after neoadjuvant therapy. During two separate expert meetings involving surgeons, medical oncologists, radiation oncologists, a pathologist, and a "Blueprint" workshop, the project participants answered questions over the indications for neoadjuvant therapy. The first part covered local practice and referred to the existence and work of a multidisciplinary team, as well as commonly applied therapeutic regimens in the neoadjuvant setting. Experts analysed personal views regarding indications for the administration and benefits of neoadjuvant therapy, their perception on the correlation between achieving a pathological complete response (pCR) and the outcome of treatment, as well as the attitude towards controversies about this type of treatment, primarily regarding a possible change in the receptor status after therapy and therapeutic options after a suboptimal response. The analysis of the answers pointed to problems and deviations from recommendations in everyday clinical practice, based on which appropriate solutions were proposed. The establishment of such a panel and consensus is an attempt to modernize multidisciplinary teams in Serbia, achieve reaching uniform decisions of all subjects dealing with breast cancer, and therefore, at least in one segment, improve breast cancer treatment in Serbia.

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.

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.

Potential clinical relevance of uPA and PAI-1 levels in node-negative, postmenopausal breast cancer patients bearing histological grade II tumors with ER/PR expression, during an early follow-up.

We evaluated urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) prognostic value in postmenopausal, node-negative breast cancer patients bearing tumors with estrogen receptor (ER)/progesterone receptor (PR) expression, treated with locoregional therapy alone, within an early follow-up. We focused our analysis on tumors of histological grade II in order to improve its prognostic value and, consequently, to improve a decision-making process. The cytosol extracts of 73 tumor samples were used for assessing several biomarkers. ER and PR levels were measured by classical biochemical method. Cathepsin D was assayed by a radiometric immunoassay while both uPA and PAI-1 level determinations were performed by enzyme-linked immunosorbent assays. HER-2 gene amplification was determined by chromogenic in situ hybridization (CISH) in primary tumor tissue. Patients bearing tumors smaller than or equal to 2 cm (pT1) or those with low PAI-1 levels (PAI-1 < 6.35 pg/mg) showed favorable outcome compared to patients bearing tumors greater than 2 cm (pT2,3) or those with high PAI-1 levels, respectively. Analyses of 4 phenotypes, defined by tumor size and PAI-1 status, revealed that patients bearing either pT1 tumors, irrespective of PAI-1 levels, or pT2,3 tumors with low PAI-1 levels, had similar disease-free interval probabilities and showed favorable outcome compared to those bearing pT2,3 tumors with high PAI-1 levels. Our findings suggest that tumor size and PAI-1, used in combination as phenotypes are not only prognostic but might also be predictive in node-negative, postmenopausal breast cancer patients bearing histological grade II tumors with ER/PR expression, during an early follow-up period.

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.

Genetic alterations in quadruple malignancies of a patient with multiple sclerosis: their role in malignancy development and response to therapy.

Multiple cancers represent 2.42% of all human cancers and are mainly double or triple cancers. Many possible causes of multiple malignancies have been reported such as genetic alterations, exposure to anti-cancer chemotherapy, radiotherapy, immunosuppressive therapy and reduced immunologic response. We report a female patient with multiple sclerosis and quadruple cancers of different embryological origin. Patient was diagnosed with stage III (T3, N1a, MO) medullary thyroid carcinoma (MTC), multicentric micropapillary thyroid carcinoma, scapular and lumbar melanomas (Clark II, Breslow II), and lobular invasive breast carcinoma (T1a, NO, MO). All tumors present in our patient except micropapillary thyroid carcinomas were investigated for gene alterations known to have a key role in cancer promotion and progression. Tumor samples were screened for the p16 alterations (loss of heterozygosity and homozygous deletions), loss of heterozygosity of PTEN, p53 alterations (mutational status and loss of heterozygosity) and mutational status of RET, HRAS and KRAS. Each type of tumor investigated had specific pattern of analyzed genetic alterations. The most prominent genetic changes were mutual alterations in PTEN and p53 tumor suppressors present in breast cancer and two melanomas. These co-alterations could be crucial for promoting development of multiple malignancies. Moreover the insertion in 4(th) codon of HRAS gene was common for all tumor types investigated. It represents frameshift mutation introducing stop codon at position 5 which prevents synthesis of a full-length protein. Since the inactivated RAS enhances sensitivity to tamoxifen and radiotherapy this genetic alteration could be considered as a good prognostic factor for this patient.

Trefoil factor 1 in early breast carcinoma: a potential indicator of clinical outcome during the first 3 years of follow-up.

BACKGROUND: A role of an estrogen-regulated, autocrine motogenic factor was assumed to be a major biological role of trefoil factor 1 (TFF1) in breast cancer. TFF1 is regarded as a predictive factor for positive response to endocrine therapy in breast cancer patients. The aim of our study was to examine TFF1 level distribution in breast carcinomas in order to distinguish estrogen-independent from estrogen-dependent TFF1 expression and to evaluate clinical usefulness of TFF1 status in early breast cancer during the first 3 years of follow-up. METHODS: The study included 226 patients with primary operable invasive early breast carcinomas for whom an equal, a 3-year follow-up was conducted. TFF1 levels as well as estrogen receptor (ER) and progesterone receptor (PR) levels were measured in cytosolic extracts of tumor samples by immunoradiometric assay or by use of classical biochemical method, respectively. Non-parametric statistical tests were applied for data analyses. RESULTS: Statistical analysis revealed that TFF1 levels were significantly higher in premenopausal patients (p=0.02), or in tumors with: lower histological grade (p<0.001), positive ER or PR status (p<0.001, in both cases). On the basis of TFF1 level distribution between ER-negative and ER-positive postmenopausal patients with tumors of different histological grade, 14 ng/mg was set as the cut-off value to distinguish estrogen-independent from estrogen-dependent TFF1 expression in breast cancer. Depending on menopausal and PR status, positive TFF1 status identified patients at opposite risk for relapse among ER-positive patients with grade II tumors. Among ER- and PR-positive premenopausal patients with grade II tumors, TFF1 status alone identified patients at opposite risk for relapse. CONCLUSIONS: Determination of TFF1 status might identify patients at different risk for relapse and help in making decision on administering adjuvant therapy for early breast cancer patients during the first 3 years of follow-up.

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.

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.

Cathepsin D as an indicator of clinical outcome in early breast carcinoma during the first 3 years of follow-up.

AIM: The aim of this study was to evaluate clinical usefulness of cathepsin D status in early breast cancer during the first 3 years of follow-up. PATIENTS & METHODS: The study included 226 patients with histologically verified, primary operable invasive early breast carcinomas. Concentrations of estrogen receptor (ER) and progesterone receptor (PR) in breast tumor cytosols were measured by use of the classical biochemical method. The concentration of three cathepsin D forms (52-, 48- and 34-kDa proteins) was determined by a radioimmunoassay RESULTS: On the basis of differences in cathepsin D levels either within an ER(-)/PR(-) phenotype or between this and either ER(+)/PR(+) or ER(+)/PR(-) phenotypes, a concentration of 39 pmol/mg was determined as the cutoff value for distinguishing estrogen-regulated cathepsin D expression. Estrogen-regulated cathepsin D expression was recognized as a high-risk biomarker for low-risk (histological grade I) breast cancer patients and as a low-risk biomarker for high-risk patients (pN(+) pT2,3). CONCLUSION: Determination of cathepsin D status in breast cancer might identify patients at different risk for relapse and might facilitate the selection of more or less aggressive adjuvant therapy for early breast cancer patients during the first 3 years of follow-up.

Breast cancer metastasis to the conjunctiva.

INTRODUCTION: Conjunctival metastasis is exceedingly rare, and it is, as a rule, a sign of advanced malignant disease with poor prognosis. We presented a female patient with breast cancer metastasis to the conjunctiva. CASE REPORT: A 45-year-old premenopausal female patient was presented with a solitary, yellowish, thin, demarcated lesion in the superior nasal quadrant of the bulbar conjunctiva of the left eye noted by chance a week earlier. There was no sign of irritation, and no pain, and no other functional or morphological problem in either eye or orbit. Five years before the appearance of conjunctival metastasis, breast carcinoma was diagnosed and the patient underwent chemotherapy, preoperative radiotherapy and radical mastectomy. Three years later, computed tomography scan showed metastasis in the left hepatic lobe with ascites and the patient underwent chemotherapy again. But, four months prior to the appearance of conjunctival lesion body scintigraphy showed multifocal sceletal lesions and nuclear magnetic resonance revealed diffuse hepatic metastases and bilateral ovarial tumors. Paliative radiotherapy and hormonal therapy (megestrol, 160 mg) were carried out. An excisional biopsy of the observed conjunctival lesion was performed under topical anesthesia and the material was subjected to histopathological (HP) examination. HP and immunohistochemical examinations established the presence of breast infiltrating lobular carcinoma metastatic to the conjunctiva. The patient showed rapid deterioration after intervention, and died after three weeks. CONCLUSION: A survival period less than one month after the appearance of conjunctival metastasis deserves attention because it is unexpected and has never been reported previously. It is not a rule that HP presentation of a metastatic lesion is so characteristic that it is possible to determine a primary tumor.

Lactate dehydrogenase, catalase, and superoxide dismutase in tumor tissue of breast cancer patients in respect to mammographic findings.

Lactate dehydrogenase (LDH), marker of anaerobic metabolism, is associated with highly invasive and metastatic breast cancer. Novel studies show that increased anaerobic metabolism (LDH), as well as activity of antioxidative enzymes (superoxide dismutase (SOD) and catalase (CAT)), is correlated with higher mammographic density, as known predictor of breast cancer risk. In this study, we measured LDH, MDH, and SOD activity in tumor and adjacent tissues of breast cancer patients by spectrophotometric assay. Mammograms were evaluated according to the American College of Radiology Breast Imaging Reporting and Data system. Mammographically dense breast tissue is associated with higher activity of LDH in tumor tissue of breast cancer patients. Moreover, patients with masses have significantly higher activity of LDH compared to patients with focal asymmetries or architectural distortion. Patients with spiculated mass margin had higher activity of LDH compared to patients with focal asymmetries or architectural distortion. Activity of LDH in patients significantly increases, while activity of CAT significantly decreases with the increase of BIRADS category. These results suggest that the association of activity of LDH and CAT in tumor tissue with mammographic characteristics could help in defining aggressive breast cancers.