Evaluation of an Early Individualized Integrated Rehabilitation Program versus Standard Rehabilitation Program for Smoking Cessation in 115 Smokers Among 467 Female Breast Cancer Patients 2019-2021 in Slovenia.

BACKGROUND Cigarette smoking affects cancer risk and cardiovascular risk. Smoking cessation is very beneficial for health. This study aimed to evaluate an early individualized integrated rehabilitation program and standard rehabilitation program for smoking cessation in breast cancer patients. MATERIAL AND METHODS This prospective study included 467 breast cancer patients (29-65 (mean 52) years of age) treated at the Institute of Oncology Ljubljana from 2019 to 2021 and were followed longer than 1 year. The control group and intervention group included 282 and 185 patients, respectively. Three questionnaires were completed by patients before and 1 year after the beginning of oncological treatment. The intervention group received interventions according to the patient's needs, while the control group underwent standard rehabilitation. The data obtained from the survey were analyzed using the chi-square test and analysis of variance. RESULTS In total, 115 patients were tobacco smokers before the beginning of cancer treatment. There were no differences between the intervention and control group in the prevalence of smoking before the treatment. Before the cancer treatment, smoking was present in the intervention group in 22% and in control group in 27% (P=0.27). One year after the beginning of cancer treatment, smoking was present in the intervention group in only 10% of cases, while it was present in control group in 20% of cases. Smoking was significantly less common in the intervention group than in the control group (P=0.004). CONCLUSIONS Smoking cessation was more common after early integrated rehabilitation than after standard rehabilitation.

Bilateral Disease Common Among Slovenian CHEK2-Positive Breast Cancer Patients.

BACKGROUND: Currently, data on pathogenic variants in the CHEK2 gene and their impact on cancer risk are lacking. This study aimed to explore the characteristics of breast cancer (BC) patients from families with CHEK2 pathogenic variants in Slovenia. METHODS: In the years 2014 to 2019, CHEK2 pathogenic variants/likely pathogenic variants (PV/LPVs) were found in probands from 50 different families who underwent genetic counseling and testing using a multigene panel at the authors' institution. Altogether, the study enrolled 75 individuals from 50 CHEK2 families who were carriers of a CHEK2 PV/LPV. The clinical data on 41 BC patients with CHEK2 PV/LPV and other carriers of CHEK2 PV/LPV from Slovenia were collected and analyzed. RESULTS: Breast cancer was diagnosed in 41 of 75 CHEK2 PV/LPV carriers (40 females, 1 male). The mean age at BC diagnosis was 42.8 years (range, 21-63 years), and 27 (65.8%) of the 41 of patients with BC had a positive family history for BC. Contralateral BC (CBC) was observed in 8 (19.5%) of the 41 patients (mean age, 55.6 years). Of 12 patients with human epidermal growth factor receptor 2 (HER2)-positive tumor type, a c.444+1G > A PV/LPV was detected in 4 patients, c.349A > G in 3 patients, deletion of exons 9-10 in 3 patients, deletion of exon 8 in 1 patient, and c.1427C > T PV/LPV in 1 patient. CONCLUSION: Bilateral BC was diagnosed in as many as 19.5% of the Slovenian BC patients with CHEK2 PV/LPVs. Breast cancer associated with a germline CHEK2 PV/LPV occurs in younger patients compared with sporadic BC.

Chronic adverse effects after an axillary lymphadenectomy in breast cancer patients after administering weaker and stronger postoperative analgesia: results of a prospective double-blind randomized study.

PURPOSE: The aim of this study was to compare the rate of chronic adverse effects after a weaker and stronger postoperative analgesia. METHODS: A prospective double-blind randomized study included 117 breast cancer patients receiving tramadol for pain relief for 4 weeks after an axillary lymphadenectomy from 2015 to 2018. Patients with a larger dose received 75/650 mg of tramadol with paracetamol every 8 h and a group with a lower dose received 37.5/325 mg of tramadol with paracetamol every 8 h from the 2nd to the 29th postoperative day. 1 year after surgery, patients were evaluated for the presence of neuropathic pain, chronic pain, arm symptoms and lymphedema. RESULTS: There was a trend for a lower rate of neuropathic pain after stronger analgesia in comparison to weaker analgesia (p = 0.059). Chronic pain was present in 18% of patients 1 year after the lymphadenectomy. There was no difference in the rate of chronic pain after stronger and weaker postoperative analgesia. Patients had less arm symptoms after a stronger analgesia than after a weaker analgesia (p = 0.02). Furthermore, there was a trend for a lower rate of lymphedema of the forearm after a stronger analgesia than after a lower analgesia (p = 0.078). CONCLUSIONS: The patients who received a stronger postoperative analgesia had less arm symptoms and a better quality of life in comparison to patients who received a weaker analgesia. The patients who received a stronger postoperative analgesia had a statistical trend for less neuropathic pain in comparison to patients who received a weaker analgesia.

Pre-operative and intra-operative detection of axillary lymph node metastases in 108 patients with invasive lobular breast cancer undergoing mastectomy.

BACKGROUND: Despite the recent changes in the treatment of the axilla in selected breast cancer patient, positive sentinel lymph node (SLN) in patients undergoing mastectomy still necessitates axillary lymph node dissection (ALND). In invasive lobular carcinoma (ILC), pre-operative detection of the lymph node metastasis may be demanding due to its unique morphology. The aim of this study was to examine the benefit of preoperative axillary ultrasound (AUS), ultrasound-guided fine-needle aspiration biopsy (US-FNAB), and intra-operative imprint cytology (IIC), in order to avoid two-stage axillary surgery in patients with ILC undergoing mastectomy. METHODS: The object of this study were 102 patients (median age 52, range 34-73 years) with clinically non-suspicious axilla in whom 108 mastectomies were performed after a pre-operative AUS investigation. Whenever a metastasis was detected in a sentinel lymph node, ALND was done. Reports of the pre-operative AUS investigation, US-FNAB, and IIC were compared with definitive histopathological reports of surgical specimens. RESULTS: In 46 cases lymph node metastases were diagnosed. AUS suspicious lymph nodes were found in 29/108 cases and histopathology confirmed metastases in 22/30 cases. US-FNAB was performed in 29 cases with AUS suspicious lymph nodes. Cytology proved metastases in 11/29 cases. Histopathology confirmed metastases in 10/11 cases with only isolated tumor cells found in one case. IIC investigation was performed in 63 cases and in 10/27 cases metastases were confirmed by histopathology. Pre-operative AUS, US-FNAB, and/or IIC investigation enabled ALND during a single surgical procedure in 20/46 patients with metastases in lymph nodes. CONCLUSION: Pre-operative AUS, US-FNAB, and/or IIC are/is beneficial in patients with ILC planned for mastectomy in order to decrease the number of two stage axillary procedures.

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.

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.

Treatment and outcome of 32 patients with distant metastases of Hürthle cell thyroid carcinoma: a single-institution experience.

BACKGROUND: It is generally believed that patients with Hürthle cell thyroid carcinoma (HCTC) have a poor prognosis. Furthermore, distant metastases represent the most frequent cause of thyroid cancer-related death of patients with HCTC. The aim of this study was to report the treatment and outcomes of patients with distant metastases. METHODS: Altogether 108 patients were treated for HCTC from 1972 to 2011 in our tertiary center and 32 patients (19 females, 13 males; median age 64.5 years) had either initially proven metastatic disease (N = 12) or distant progression of HCTC after initial treatment (N = 20). Patients with metastases were followed for 1-226 (median 77) months. Data were collected on the patients' gender and age, extent of their disease, morphologic characteristics, therapy, outcome, and survival rate. Statistical correlation between possible prognostic factors and cause-specific survival from time of detection of metastases was analyzed by univariate analysis and log-rank test. RESULTS: The most common were lung metastases, followed by bone, mediastinum, kidney, and liver in 24, 8, 2, 1, and 1 case, respectively. Total thyroidectomy, lobectomy, subtotal thyroidectomy and neck dissection were performed in 19, 10, 3, and 7 patients, respectively. Radioiodine (RAI) ablation of thyroid remnant was performed in 30 patients, while 20 of them had RAI therapy (median 4 times). RAI uptake in metastases was present in 16 patients and ranged from 0.05 % to 12 %. Chemotherapy was used in 13 patients and external beam radiotherapy in 19 patients. Locoregional control of disease was achieved in 19/21 (90 %) cases who succumbed due to HCTC. Estimated 10-year disease-specific survival for all patients was 60 %. 10-year disease-specific survival for patients with pulmonary metastases and other sites metastases was 60 % and 62 %, respectively. 10-year disease-specific survival for patients with single organ and multiple organ metastases was 52 %, and 100 %, respectively. Estimated median disease-specific survival after the diagnosis of metastatic disease for all patients was 77 months. The median disease-specific survival after the diagnosis of metastatic disease for patients with pulmonary metastases and other sites metastases was 72 and 138 months, respectively. CONCLUSIONS: Ten-year disease-specific survival for all patients with metastatic Hürthle cell thyroid carcinoma, patients with pulmonary metastases and bone metastases was 60 %, 60 % and 68 %, respectively.

Recurrence rate in regional lymph nodes in 737 patients with follicular or Hürthle cell neoplasms.

BACKGROUND: Preoperative ultrasound (US) evaluation of central and lateral neck compartments is recommended for all patients undergoing a thyroidectomy for malignant or suspicious for malignancy cytologic or molecular findings. Our aim was to find out how frequent was recurrence in regional lymph nodes in patients with follicular or Hürthle cell neoplasm and usefulness of preoperative neck US investigation in patients with neoplasm. PATIENTS AND METHODS: Altogether 737 patients were surgically treated because of follicular or Hürthle cell neoplasms from 1995 to 2014 at our cancer comprehensive center, among them 207 patients (163 females, 44 males; mean age 52 years) had thyroid carcinoma. RESULTS: Carcinoma was diagnosed in follicular and Hürthle cell neoplasm in 143/428 and 64/309 of cases, respectively. A recurrence in regional lymph nodes occurred in 12/207 patients (6%) during a median follow-up of 55 months. Among patients with carcinoma a recurrence in regional lymph nodes was diagnosed in follicular and Hürthle cell neoplasms in 2% and 14%, respectively (p = 0.002). Recurrence in regional lymph nodes was diagnosed in 3/428 of all patients with follicular neoplasm and 9/309 of all patients with Hürthle cell neoplasm. CONCLUSIONS: Recurrence in lymph nodes was diagnosed in 0.7% of patients with a preoperative diagnosis of follicular neoplasm and 3% of patients with a Hürthle cell neoplasm. A recurrence in regional lymph nodes is rare in patients with carcinoma and preoperative diagnosis of follicular neoplasm. Preoperative neck ultrasound examination in patients with a follicular neoplasm is probably not useful, but in patients with Hurtle cell neoplasm it may be useful.

Functional polymorphisms in antioxidant genes in Hurthle cell thyroid neoplasm - an association of GPX1 polymorphism and recurrent Hurthle cell thyroid carcinoma.

BACKGROUND: Hurthle cells of the thyroid gland are very rich in mitochondria and oxidative enzymes. As a high level oxidative metabolism may lead to higher level of oxidative stress and can be associated with an increased risk for cancer, we investigated whether common functional polymorphisms in antioxidant genes (SOD2, CAT, GPX, GSTP1, GSTM1 and GSTT1) are associated with the development or clinical course of Hurthle cell thyroid carcinoma (HCTC). METHODS: A retrospective study was performed in 139 patients treated by thyroid surgery for a Hurthle cell neoplasm. HCTC, Hurthle cell thyroid adenoma (HCTA) or Hurthle cell thyroid nodule (HCTN) were diagnosed by pathomorphology. DNA was extracted from cores of histologically confirmed normal tissue obtained from formalin-fixed paraffin-embedded specimens and genotyped for investigated polymorphisms. Logistic regression was used to compare genotype distributions between patient groups. RESULTS: HCTC, HCTA and HCTN were diagnosed in 53, 47 and 21 patients, respectively. Metastatic disease and recurrence of HCTC were diagnosed in 20 and 16 HCTC patients, respectively. Genotypes and allele frequencies of investigated polymorphisms did not deviate from Hardy-Weinberg equilibrium in patients with HCTC, HCTA and HCTN. Under the dominant genetic model we observed no differences in the genotype frequency distribution of the investigated polymorphisms when the HCTA and HCTN group was compared to the HCTC group for diagnosis of HCTC or for the presence of metastatic disease. However, GPX1 polymorphism was associated with the occurrence of recurrent disease (p = 0.040). CONCLUSIONS: GPX1 polymorphism may influence the risk for recurrent disease in HCTC.

Neoadjuvant chemotherapy in 13 patients with locally advanced poorly differentiated thyroid carcinoma based on Turin proposal - a single institution experience.

BACKGROUND: There is a paradigm that chemotherapy is ineffective in thyroid carcinoma. The aim of our study was to find out whether neoadjuvant chemotherapy before thyroid surgery had an effect on the size of primary tumour in patients with poorly differentiated thyroid carcinoma (PDTC) based on Turin proposal. PATIENTS AND METHODS: Altogether, 13 patients (8 women, 5 men; median age 61 years) with PDTC based on Turin proposal were treated with neoadjuvant chemotherapy between 1986 and 2005. Tumour diameter was from 4.5 to 18 cm (median 9 cm). Regional and distant metastases were detected in 6 and 9 patients, respectively. Eight patients had pT4 tumour. RESULTS: Altogether, 29 (range 1-5) cycles of chemotherapy were given. Tumour diameter decreased in all the patients and by more than 30% in 5 patients (= 38%). Two of these five patients had also preoperative external beam irradiation (EBRT). Total thyroidectomy, lobectomy and neck dissection were performed in 10, 3 and 5 cases, respectively. R0 and R1 resection was done in 5 and 8 cases, respectively. Eight patients had postoperative EBRT of the neck and upper mediastinum. The 5-year and 10-year cause-specific survival rates of patients were 66% and 20%, respectively. CONCLUSIONS: After neoadjuvant chemotherapy a partial tumour regression was observed in 38% of patients with PDTC based on Turin proposal.

Prognostic factors for disease-specific survival in 108 patients with Hürthle cell thyroid carcinoma: a single-institution experience.

BACKGROUND: Hürthle cell thyroid carcinoma (HCTC) is a rare disease. It is believed that it is more aggressive than follicular thyroid carcinoma. The aim of our study was to identify factors associated with disease-specific and disease-free survival. METHODS: Altogether, 108 patients with HCTC (26 male, 82 female; median age 62 years; range 19-87 years) treated at our Institute from 1972 to 2011 were included in the present retrospective study. Data on age, clinical and histopathological factors, tumor stage, recurrence, disease-free and disease-specific survival were collected. Univariate analysis was used to identify factors associated with disease-specific survival. Cox's multivariate regression model was used to identify independent prognostic factors for disease-specific survival. RESULTS: The follow-up period was 1 to 337 (median 105) months. Of 108 patients, 12 (11%) had distant and 8 (7%) had locoregional metastases before primary treatment. Recurrence was diagnosed in 26 cases (24%): locoregional, distant, and both locoregional and distant in 12, 11, and 3 cases, respectively. The 5-year, 10-year, and 20-year disease-specific survival were 96%, 88%, and 67%, respectively. Independent prognostic factors for disease-specific survival were: age of patients at diagnosis, distant metastases and residual tumor after surgery. CONCLUSION: Long disease-specific survival was found in patients with HCTC younger than 45 years of age without distant metastases and without residual tumor after surgery.

Surgical treatment of breast cancer in patients aged 80 years or older--how much is enough?

BACKGROUND: The population of elderly people is increasing and so is the population of breast cancer patients aged ≥80 years. The aim of our retrospective study was to identify independent prognostic factors for the duration of breast cancer-specific survival of surgically treated patients aged ≥80 years. The secondary aim was to determine the appropriate surgical treatment of breast cancer in patients aged ≥80 years. METHODS: We reviewed the medical records of 154 patients aged ≥80 years with early-stage breast cancer (mean age 83 years) who underwent surgery at the tertiary cancer center in the period from 2000 to 2008. Tumor stage was pT1/pT2 and pT3/pT4 in 75% and 25%, respectively. Surgical treatment comprised: quadrantectomy (in 27%), mastectomy (in 73%), axillary dissection (in 57%), and sentinel lymph node biopsy (in 18%), while 25% of patients had no axillary surgery. RESULTS: During a median follow-up of 5.3 years, 31% of patients died of breast cancer, while 28% of patients died of other causes. Half of our patients with poorly differentiated breast cancer or estrogen receptor-negative tumor died of breast cancer. Multivariate statistical analysis showed that the pathological T-stage, pathological N-stage and estrogen receptors were independent prognostic factors for the duration of breast cancer-specific survival of patients. CONCLUSION: Short breast cancer-specific survival indicates that, in patients aged ≥80 years, breast cancer with metastases in axillary lymph nodes can be an aggressive disease.

Long-term use of metformin and the molecular subtype in invasive breast carcinoma patients - a retrospective study of clinical and tumor characteristics.

BACKGROUND: Metformin may exhibit inhibitory effects on cancer cells by inhibiting mTOR signaling pathway. The aim of our retrospective study was to examine if patients with breast carcinoma (BC) and diabetes mellitus (DM) receiving metformin have a lower stage of carcinoma in comparison to patients not receiving metformin, and if the use of metformin correlates with the molecular subtype of BC. METHODS: A chart review of 253 patients with invasive BC and DM (128 on metformin and 125 not on metformin) was performed. Control group consisted of 320 consecutive patients with invasive BC without DM. BC subtypes were classified by immunohistochemical surrogates as luminal A (estrogen receptor [ER] + and/or progesterone receptor [PR]+, HER-2-), luminal B (ER + and/or PR+, HER-2+), HER-2 (ER-, PR-, HER-2+), triple-negative/basal (ER-, PR-, HER-2-). RESULTS: Patients on metformin had a lower proportion of T3 or T4 tumors than patients who were not receiving metformin (16% vs. 26%; p = 0.035). No statistical difference was found between the two study groups in N stage. Patients with DM on metformin, with DM not on metformin and the control group had different molecular subtypes of BC (p = 0.01): the luminal A subtype was found in 78%, 83% and 71%, the luminal B in 12.6%, 9% and 11%, HER-2 in 0.8%, 1.6% and 8%, and the triple-negative/basal-like subtype in 8.6%, 6.4% and 10%, respectively. CONCLUSION: Our data indicate that long-term use of metformin use correlates with molecular subtype of BC in diabetics on metformin in comparison to diabetics not on metformin and patients without DM. However, most likely, different distribution of the molecular subtypes of BC in these three groups of patients was caused by other risk factors for breast carcinoma, such as age of patients or obesity.

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.

Preoperative serum thyroglobulin concentration as a predictive factor of malignancy in small follicular and Hürthle cell neoplasms of the thyroid gland.

BACKGROUND: Cytologic examination of a fine-needle aspiration biopsy specimen cannot distinguish between benign and malignant follicular or Hürthle cell neoplasms. Serum thyroglobulin (Tg) concentrations are higher in follicular and Hürthle cell carcinomas than in benign follicular or Hürthle cell tumors, but preoperative measurement of Tg is not recommended for initial evaluation of thyroid nodules. The aim of this study was to find out whether preoperative serum Tg concentration is a predictive factor of malignant disease in patients with a follicular or Hürthle cell neoplasm with a diameter of 2 cm or less. METHODS: From 1988 to 2013, a total of 244 patients (214 female, 30 male, age range 9 to 82 years, median age 52 years) had a surgical procedure at our institute because of follicular or Hürthle cell neoplasms with a tumor diameter of 2 cm or less. In these patients a preoperative concentration of Tg was determined and Tg-autoantibodies were negative. The risk factors for malignancy were identified by a chi-square test and multivariate logistic regression. RESULTS: The histopathologic diagnoses were carcinoma, adenoma, and benign goiter in 62 (25.5%), 115 (47%), and 67 (27.5%) patients, respectively. The median preoperative Tg concentration in benign tumors, papillary carcinomas, follicular carcinomas, and Hürthle cell carcinomas was 41, 87, 72, and 106 ng/ml (P = 0.05), respectively. The predictive factors for carcinoma shown by the chi-square test were: sex, thyroid volume, and preoperative Tg concentration. The independent predictors of malignancy as shown by multivariate logistic regression were: male sex (odds ratio, 2.57; P = 0.02), and a Tg concentration of more than 80 ng/ml (odds ratio, 2.35; P = 0.005). CONCLUSION: The independent predictors of malignancy in follicular or Hürthle cell neoplasms are sex and preoperative Tg concentration.

Does a continuous local anaesthetic pain treatment after immediate tissue expander reconstruction in breast carcinoma patients more efficiently reduce acute postoperative pain--a prospective randomised study.

BACKGROUND: Immediate breast reconstruction with an expander is a reasonable option for properly selected patients. After reconstruction, patients have severe postoperative pain, which responds poorly to opioids. Our aim was to evaluate if continuous wound infusion of a local anaesthetic into the surgical wound reduces postoperative pain, consumption of opioids and incidence of chronic pain compared to standard intravenous piritramide after primary breast reconstruction in breast carcinoma patients. METHODS: Altogether, 60 patients were enrolled in our study; one half in the group with wound infusion of a local anaesthetic, and the other half in the standard (piritramide) group. Parameters measured included: pain intensity (visual analogue scale), drug requirements, alertness, hospitalisation, side-effects and late complications. A p-value of < 0.05 was considered statistically significant. RESULTS: In the recovery room, the test group reported less acute pain at rest (P = 0.03) and at activity (P = 0.01), and on the day of the surgical procedure they reported less pain at activity (P = 0.003). Consumption of piritramide and metoclopramide was lower in this group (P < 0.0001), but their alertness after the surgical procedure was higher compared to the standard group (P < 0.001). After three months, the test group reported less chronic pain (P = 0.01). CONCLUSIONS: After primary tissue expander breast reconstruction, wound infusion of a local anaesthetic significantly reduces acute pain and enables reduced opioid consumption, resulting in less postoperative sedation and reduced need for antiemetic drugs. Wound infusion of a local anaesthetic reduces chronic pain.

Impact of early integrated rehabilitation on fatigue in 600 patients with breast cancer - a prospective study.

BACKGROUND: Fatigue after breast cancer treatment is a common burden that is challenging to treat. The aim of this study was to explore if such integrated rehabilitation program reduces the prevalence of chronic fatigue compared to simple, non-integrated rehabilitation. PATIENTS AND METHODS: The subjects of our prospective study were 600 female breast cancer patients (29-65 [mean 52 years] of age), who participated in the pilot study on the individualized integrated rehabilitation of breast cancer patients in 2019-2021 and were monitored for one year. The control group included 301 patients and the intervention group numbered 299 patients. The patients completed three questionnaires (EORTC QLQ-C30, -BR23 and NCCN): before cancer treatment, and then six and twelve months after the beginning of cancer treatment. The control group obtained the standard rehabilitation program, while the intervention group was part of the early, individualized multidisciplinary and integrated approach of rehabilitation. The rehabilitation coordinator referred patients for additional interventions (e.g., psychologist, gynecologist, pain management team, physiotherapy, clinical nutrition team, kinesiologist-guided online training, vocational rehabilitation, general practitioner). Data on the patients' demographics, disease extent, cancer treatment and complaints reported in questionnaires were collected and analyzed. RESULTS: There were no differences between the control and the intervention group of patients in terms of age, education, disease extent, surgical procedures, systemic cancer treatment, or radiotherapy, and also no differences in the fatigue before the beginning of treatment. However, patients from the control group had a greater level of constant fatigue than patients from the intervention group half a year (p = 0.018) and a year (p = 0.001) after the beginning of treatment. Furthermore, a greater proportion of patients from the control group experienced significant interference with their usual activities from fatigue than from the intervention group, half a year (p = 0.042) and a year (p = 0.001) after the beginning of treatment. A multivariate logistic regression showed that one year after the beginning of treatment, the only independent factor correlated to fatigue was inclusion into the intervention group (p = 0.044). Inclusion in the intervention group was beneficial-patients from the control group were 1.5 times more likely to be fatigued. CONCLUSIONS: Early individualized integrated rehabilitation is associated with a lower prevalence of chronic fatigue or fatigue interfering with usual activities in breast cancer patients in comparison to the control group of patients.

Symptoms of Anxiety and Depression Among Slovenian Breast Cancer Survivors Post-Treatment During the COVID-19 Pandemic: A Cross-Sectional Study.

Background: Although anxiety and depression are important determinants of mental health, the literature in this area is sparse as most studies focus on the period during treatment. Mental health problems can affect cancer recovery as well as quality of life and survival. In this cross-sectional study, we investigated the prevalence of anxiety and depression in Slovenian cancer survivors after treatment and assessed the associated correlates during the COVID-19 pandemic. Methods: From September 2021 to January 2022, we collected data from 430 breast cancer survivors one to five years after receiving post-local treatment and (neo)adjuvant chemotherapy. We used the Hospital Anxiety and Depression Scale (HADS) to measure anxiety and depression levels. Multivariate linear regression was used to identify factors associated with higher levels of anxiety and depression. Results: Key findings from this study are increased levels of psychological distress and identification of relevant factors associated with those elevated levels. Approximately one-third of breast cancer survivors exhibited symptoms of elevated anxiety and depression, with one in eight meeting clinical thresholds. Multivariate linear regression revealed that age, lower quality of life, heightened fear of cancer recurrence (FCR), reduced resilience, limited social support, and unmet psychosocial and emotional needs correlated with increased anxiety symptoms. Additionally, lower quality of life, higher FCR, diminished resilience, and limited social support were associated with higher depression symptomatology. Conclusions: Our study of Slovenian breast cancer survivors one to five years post-treatment observed a significant increase in anxiety and depression symptoms, possibly exacerbated by the COVID-19 pandemic. The demographic and psychosocial factors identified in this study offer valuable insights for future research. The study emphasises the importance of recognising and addressing the psychological needs of breast cancer survivors and the need to follow them throughout their cancer journey.