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.

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.

Treatment and outcome of patients with Graves' disease and metastatic differentiated thyroid cancer.

BACKGROUND: The aim of the study was to report on the experience in a single tertiary cancer center about the treatment and outcome of patients with Graves' disease (GD) and metastatic thyroid cancer as compared with patients without GD in our country. PATIENTS AND METHODS: Altogether, 28 patients (8 males, 20 females; 49-85 years of age; median 74 years) were treated because of differentiated thyroid cancer and distant metastasis at the time of diagnosis during a 10-year period (from 2010 to 2019) in the Republic of Slovenia. The subject of our retrospective study were four patients (three men, one female; 64-76 years of age, median 73 years) who had Graves' disease and metastatic thyroid cancer. RESULTS: The mean age of patients without GD and with GD was 74 years and 71 years, respectively (p = 0.36). There was a trend for male predominance in patients with GD (p = 0.06). There was no statistical difference in size of primary tumors, pT stage or pN stage between the group of patients without GD and with GD. The median length of follow-up was 3.33 years (range 0.04-7.83) and 5-year disease-specific survival was 51%. One of four patients with GD and 14 of 24 patients without GD died of thyroid cancer. There was no statistical difference in disease-specific survival between patients' group of without GD and with GD (p = 0.59). CONCLUSIONS: In our country Slovenia, 14% of patients with metastatic differentiated thyroid carcinoma at the time of diagnosis had Graves' disease. There was no difference in the treatment, outcome or survival of patients with GD in comparison to those without GD.

Association of OPRM1, MIR23B, and MIR107 genetic variability with acute pain, chronic pain and adverse effects after postoperative tramadol and paracetamol treatment in breast cancer.

BACKGROUND: Tramadol is an opioid analgesic often used for pain management after breast cancer surgery. Its analgesic activity is due to the activation of the µ-opioid receptor, encoded by the OPRM1 gene. This study investigated the association of genetic variability in OPRM1 and its regulatory miRNA genes with outcomes of tramadol/paracetamol treatment after breast cancer surgery with axillary lymphadenectomy. PATIENTS AND METHODS: The study included 113 breast cancer patients after breast cancer surgery with axillary lymphadenectomy treated with either 75/650 mg or 37.5/325 mg of tramadol with paracetamol for pain relief within the randomized clinical trial KCT 04/2015-DORETAonko/si at the Institute of Oncology Ljubljana. All patients were genotyped for OPRM1 rs1799971 and rs677830, MIR23B rs1011784, and MIR107 rs2296616 using competitive allele-specific PCR. The association of genetic factors with acute and chronic pain as well as adverse effects of tramadol treatment was evaluated using logistic regression, Fisher's exact test, and Mann-Whitney test. RESULTS: The investigated OPRM1 related polymorphisms were not associated with acute pain assessed with the VAS scale within four weeks after surgery (all P > 0.05). Carriers of at least one polymorphic OPRM1 rs1799971 allele had a higher risk of constipation in the first four weeks after surgery compared to non-carriers (OR = 4.5, 95% CI = 1.6-12.64, P = 0.004). Carriers of at least one polymorphic OPRM1 rs677830 allele had a higher risk of constipation after third week of tramadol treatment (OR = 3.11, 95% CI = 1.08-8.89, P = 0.035). Furthermore, carriers of two polymorphic MIR23B rs1011784 alleles had a higher risk of nausea after 28 days of tramadol treatment (OR = 7.35, 95% CI = 1.27-42.6, P = 0.026), while heterozygotes for MIR107 rs2296616 allele had a lower risk of nausea after 21 days of tramadol treatment (OR = 0.21, 95% CI = 0.05-0.87, P = 0.031). In carriers of two polymorphic MIR107 rs2296616 alleles, chronic pain was significantly more common than in carriers of two wild-type alleles (P = 0.004). Carriers of at least one polymorphic MIR23B rs1011784 allele experienced more neuropathic pain after adjustment for tramadol dose (OR = 2.85, 95% CI = 1.07-7.59, P = 0.036), while carriers of at least one polymorphic OPRM1 rs677830 allele experienced less neuropathic pain compared to carriers of two wild-type alleles (OR = 0.38, 95% CI = 0.15-0.99, P = 0.047). CONCLUSIONS: Genetic variability of OPRM1 and genes coding for miRNAs that could affect OPRM1 expression may be associated with adverse effects of tramadol/paracetamol treatment as well as with chronic and neuropathic pain after breast cancer surgery with axillary lymphadenectomy.

Factors associated with a high level of unmet needs and their prevalence in the breast cancer survivors 1-5 years after post local treatment and (neo)adjuvant chemotherapy during the COVID-19: A cross-sectional study.

Objective: To assess the prevalence of unmet needs in post-treatment breast cancer survivors and identify sociodemographic, clinical, and psychosocial variables associated with reported unmet needs during the COVID-19 pandemic. Materials and methods: In this cross-sectional study, 430 post-treatment breast cancer survivors, ranging between 1 and 5 years after the procedure, completed the Cancer Survivors' Unmet Needs (CaSUN) questionnaire from September 2021 and January 2022. The multivariate logistic analysis identified factors associated with at least one reported unmet need in the total CaSUN scale and specific domains. Results: A total of 67% of survivors reported at least one unmet need. The most frequently reported unmet needs were the lack of accessible hospital parking (43%) and recurrence concerns (39.5%). The majority of reported unmet needs relate to comprehensive care (44%), followed by the psychological and emotional support domain (35.3%). Younger age (OR = 0.95, 95% CI = 0.92-0.99; p < 0.001), three or more comorbidities (OR = 0.27, 95% CI = 0.11-0.71, p < 0.01), a lower quality of life (OR = 0.06, 95% CI = 0.01-0.47, p < 0.01) and low resilience (OR = 0.95, 95% CI = 0.93-0.99) were associated with a high level of unmet needs in the multivariate regression model. Results are presented for factors associated with a high level of unmet needs for comprehensive cancer care and psychological and emotional support domain. Conclusion: A high prevalence found in our study could be attributed to the COVID-19 pandemic, where patients may have missed adequate follow-up care, although comparing to studies done in non-pandemic time is difficult. Family physicians should be more attentive toward younger cancer survivors and those with more comorbidities as both characteristics can be easily recognized in the family practice.

Outcome of Patients with Locally Advanced Metastatic Medullary Thyroid Cancer and Induction Therapy with Tyrosine Kinase Inhibitors in Slovenia.

BACKGROUND: The aim of our retrospective study was to evaluate the outcome of patients with metastatic medullary thyroid cancer (MTC) treated with tyrosine kinase inhibitors (TKIs) and/or chemotherapy with the emphasis on analysis on the cohort treated by induction TKI because of locally advanced metastatic MTC. METHODS: We analyzed the outcome of 30 patients (21 males, 9 females; median age 63.8 years) with metastatic MTC treated between 2000-2020. Sunitinib was used in 20 patients. RESULTS: Median progression-free survival on TKI and on chemotherapy was 10.6 (95% CI 7.1-14) months and 3.5 (95% CI 1.4-5.5) months, respectively. Median overall survival from diagnosis and from metastasis presentation was 38.2 (95% CI 4.7-71.7) months and 20.9 (95% CI 13.8-27.9) months, respectively. Eight patients (five females, three males; 58-86 years of age, median age 70 years) were treated with induction TKI because of inoperable locally advanced and metastatic MTC. The response rate to induction TKI was 50%; two patients (25%) had stable disease, and two patients (25%) had progressive disease. CONCLUSION: Our data support a new paradigm that TKIs may be the first treatment option in selected patients with locally advanced metastatic MTC, followed by locoregional treatment with surgery and/or external beam radiotherapy. Further studies are required to consolidate the presented data.

A new paradigm of surgery after neoadjuvant/induction tyrosine kinase inhibitors is not accepted as a standard of care in patients with medullary thyroid cancer. The aim of our retrospective study was to evaluate the outcome of all patients with metastatic medullary cancer treated in a 20-year period in Slovenia and, among these, the cohort treated with induction tyrosine kinase inhibitors because of locally advanced metastatic medullary thyroid cancer. Our first hypothesis was that the outcome of metastatic medullary cancer treated with tyrosine kinase inhibitors is better than in those treated with chemotherapy. Our second hypothesis was that induction therapy with tyrosine kinase inhibitors was effective in the treatment of initially inoperable primary tumors. In the treatment of metastatic medullary cancer a systemic therapy was used in 83.4% (25/30) patients. Patients on targeted treatment with tyrosine kinase inhibitors had more often a partial remission than on chemotherapy (65% vs. 17%, respectively). Eight patients were treated with induction tyrosine kinase inhibitors because of locally advanced metastatic disease. The computer tomography evaluation of the primary tumor during tyrosine kinase inhibitor therapy revealed partial response in four cases and stable disease in four cases, but surgery was performed in two cases only. Our data support a new paradigm that tyrosine kinase inhibitors may be the first treatment option in patients with locally advanced metastatic medullary thyroid carcinoma followed by locoregional treatment with surgery and/or external beam radiotherapy. However, further studies are required to consolidate the presented data.

Graves disease and metastatic hormonal-active Hürthle cell thyroid cancer: A case report.

RATIONALE: A hormone-active metastatic Hürthle cell thyroid carcinoma (HCTC) and Graves disease (GD) present a therapeutic challenge and is rarely reported. PATIENT CONCERNS: We present a 64-year-old male patient, who had dyspnea and left hip pain lasting 4 months. He had clinical signs of hyperthyroidism and a tumor measuring 9 cm in diameter of the left thyroid lobe, metastatic neck lymph node and metastases in the lungs, mediastinum, and bones. DIAGNOSIS: Laboratory findings confirmed hyperthyroidism and GD. Fine-needle aspiration biopsy and cytological investigation revealed metastases of HCTC in the skull and in the 8th right rib. A CT examination showed a thyroid tumor, metastatic neck lymph node, metastases in the lungs, mediastinum and in the 8th right rib measuring 20 × 5.6 × 4.5 cm, in the left acetabulum measuring 9 × 9 × 3 cm and parietooccipitally in the skull measuring 5 × 4 × 2 cm. Histology after total thyroidectomy and resection of the 8th right rib confirmed metastatic HCTC. INTERVENTIONS: The region of the left hip had been irradiated with concomitant doxorubicin 20 mg once weekly. When hyperthyroidism was controlled with thiamazole, a total thyroidectomy was performed. Persistent T3 hyperthyroidism, most likely caused by TSH-R-stimulated T3 production in large metastasis in the 8th right rib, was eliminated by rib resection. Thereafter, the patient was treated with 3 radioactive iodine-131 (RAI) therapies (cumulative dose of 515 mCi). Unfortunately, the tumor rapidly progressed after treatment with RAI and progressed 10 months after therapy with sorafenib. OUTCOMES: Despite treatment, the disease rapidly progressed and patient died due to distant metastases. He survived for 28 months from diagnosis. LESSONS: Simultaneous hormone-active HCTC and GD is extremely rare and prognosis is dismal. Concomitant external beam radiotherapy and doxorubicin chemotherapy, followed by RAI therapy, prevented the growth of a large metastasis in the left hip in our patient. However, a large metastasis in the 8th right rib presented an unresolved problem. Treatment with rib resection and RAI did not prevent tumor recurrence. External beam radiotherapy and sorafenib treatment failed to prevent tumor growth.

Machine learning algorithm improved automated droplet classification of ddPCR for detection of BRAF V600E in paraffin-embedded samples.

Somatic mutations in cancer driver genes can help diagnosis, prognosis and treatment decisions. Formalin-fixed paraffin-embedded (FFPE) specimen is the main source of DNA for somatic mutation detection. To overcome constraints of DNA isolated from FFPE, we compared pyrosequencing and ddPCR analysis for absolute quantification of BRAF V600E mutation in the DNA extracted from FFPE specimens and compared the results to the qualitative detection information obtained by Sanger Sequencing. Sanger sequencing was able to detect BRAF V600E mutation only when it was present in more than 15% total alleles. Although the sensitivity of ddPCR is higher than that observed for Sanger, it was less consistent than pyrosequencing, likely due to droplet classification bias of FFPE-derived DNA. To address the droplet allocation bias in ddPCR analysis, we have compared different algorithms for automated droplet classification and next correlated these findings with those obtained from pyrosequencing. By examining the addition of non-classifiable droplets (rain) in ddPCR, it was possible to obtain better qualitative classification of droplets and better quantitative classification compared to no rain droplets, when considering pyrosequencing results. Notable, only the Machine learning k-NN algorithm was able to automatically classify the samples, surpassing manual classification based on no-template controls, which shows promise in clinical practice.

Preoperative serum CA-125 level as a predictor for the extent of cytoreduction in patients with advanced stage epithelial ovarian cancer.

BACKGROUND: Ovarian cancer is the seventh most common cancer in women worldwide and the eighth most common cause of cancer death. Due to the lack of effective early detection strategies and the unspecific onset of symptoms, it is diagnosed at an advanced stage in 75% of cases. The cancer antigen (CA) 125 is used as a prognostic marker and its level is elevated in more than 85% of women with advanced stages of epithelial ovarian cancer (EOC). The standard treatment is primary debulking surgery (PDS) followed by adjuvant chemotherapy (ACT), but the later approach is neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS). Several studies have been conducted to find out whether preoperative CA-125 serum levels influence treatment choice, surgical resection and survival outcome. The aim of our study was to analyse experience of single institution as Cancer comprehensive center with preoperative usefulness of CA-125. PATIENTS AND METHODS: At the Institute of Oncology Ljubljana a retrospective analysis of 253 women with stage FIGO IIIC and IV ovarian cancer was conducted. Women were divided into two groups based on their primary treatment. The first group was the NACT group (215 women) and the second the PDS group (38 women). The differences in patient characteristics were compared using the Chi-square test and ANOVA and the Kaplan-Meier method was used for calculating progression-free survival (PFS) and overall survival (OS). RESULTS: The median serum CA-125 level was higher in the NACT group than in the PDS group, 972 IU/ml and 499 IU/ ml, respectively. The PFS in the NACT group was 8 months (95% CI 6.4-9.5) and 18 months (95% CI 12.5-23.4) in the PDS group. The median OS was lower in the NACT group than in the PDS group, 25 months (95% CI 20.6-29.5) and 46 months (95% CI 32.9-62.1), respectively. CONCLUSIONS: Preoperative CA-125 cut off value of 500 IU/ml is a promising threshold to predict a successful PDS.

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.

Acute pain and side effects after tramadol in breast cancer patients: results of a prospective double-blind randomized study.

The objective of this study was to evaluate the severity of acute pain and side effects in breast cancer patients postoperatively treated with two regimens of tramadol with paracetamol in a prospective double-blind study. Altogether 117 breast cancer patients who had axillary lymphadenectomy were randomized into two analgesic study groups and the analgesic treatment lasted 4 weeks. Stronger analgesia group received every 8 h 75/650 mg of tramadol with paracetamol, while weaker analgesia group received every 8 h 37.5/325 mg of tramadol with paracetamol. Patients with the higher dose of tramadol had less pain during the 1st and 4th week than patients with the lower dose. Frequency of nausea, vomiting, lymphedema or range of shoulder movement was not significantly different between the two groups of patients. Constipation was significantly more common in the group with stronger analgesia during the 2nd week in comparison to patients with weaker analgesia. The patients who were on 75/650 mg of tramadol with paracetamol had less pain in comparison to patients who were on 37.5/325 mg. Side effects were mild, but common in both groups of patients.

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.

Dietary iodine intake, therapy with radioiodine, and anaplastic thyroid carcinoma.

Background Anaplastic thyroid cancer (ATC) is one of the most aggressive tumors. The aim of the study was to determine the correlation between a higher dietary intake of iodine, frequency of ATC and the characteristics of ATC, and to find out how often patients with ATC had a history of radioiodine (RAI) therapy. Patients and methods This retrospective study included 220 patients (152 females, 68 males; mean age 68 years) with ATC who were treated in our country from 1972 to 2017. The salt was iodinated with 10 mg of potassium iodide/ kg before 1999, and with 25 mg of potassium iodide/kg thereafter. The patients were assorted into 15-year periods: 1972-1986, 1987-2001, and 2002-2017. Results The incidence of ATC decreased after a higher iodination of salt (p = 0.04). Patients are nowadays older (p = 0.013) and have less frequent lymph node metastases (p = 0.012). The frequency of distant metastases did not change over time. The median survival of patients in the first, second, and third periods was 3, 4, and 3 months, respectively (p < 0.05). The history of RAI therapy was present in 7.7% of patients. Conclusions The number of patients with a history of RAI therapy did not change statistically over time. The incidence of ATC in Slovenia decreased probably because of higher salt iodination.

Long term survival in 200 patients with advanced stage of colorectal carcinoma and diabetes mellitus - a single institution experience.

Background Diabetes mellitus (DM) and DM related comorbidities may initiate difficulties during cancer specific treatment and may have an impact on cancer management and outcome. The aim of our study was to find out if DM in patients with advanced colorectal carcinoma (CRC) is associated with cancer-specific or overall survival. Patients and methods This study included 200 consecutive patients (131 males, 69 females, mean age 63 years) with elective CRC surgery at the Institute of Oncology Ljubljana and DM was found in 39 (19.5%) of them. Even 64% of patients had Stage 3 or 4 disease, so neo-adjuvant chemotherapy (CTX) and/or radiotherapy (RT) were carried out in 59% of cases. Data about gender, age, body mass index, presence of DM, American Society of Anesthesiologists (ASA) physical status score, stage of disease and postoperative complications were collected prospectively. Cancer-specific survival and overall survival were compared by log-rank test. Results Patients with DM had a higher ASA score, BMI, the illness marker, rate of massive bleeding, blood transfusion and longer hospital stay than those without DM. The mean follow-up period was 4.75 years. All causes mortality in patients with DM and without DM was 23% and 27%, respectively. Three-year cancer-specific survival in patients with DM and without DM was 85% and 89%, respectively (p = 0.68). Three-year overall survival in patients with DM and without DM was 82% and 84%, respectively (p = 0.63). Conclusions The presence of DM was not associated with tumor stage, disease-specific survival or overall survival in patients with advanced CRC.

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.

Locoregional disease control after external beam radiotherapy in 91 patients with differentiated thyroid carcinoma and pT4 tumor stage - a single institution experience.

Background Locoregional recurrence is common in patients with locally advanced differentiated thyroid carcinoma (DTC). Our aim was to find out the rate of locoregional control of the disease after external beam radiotherapy (EBRT) of the neck and mediastinum in patients with DTC and pT4 tumor. Patients and methods Altogether 91 patients (47 males, 44 females, median age 61 years) with DTC had EBRT of the neck and mediastinum as part of the multimodal treatment of pT4 tumor (63 cases pT4a, 28 cases pT4b) from the year 1973 to 2015. Data on clinical factors, histopathology and recurrence were collected. Disease-free, disease-specific and overall survival was calculated. Results Median tumor size was 5 cm (range 1-30 cm). Out of 91 patients, 23 had distant and 38 regional metastases. A total or near-total thyroidectomy, lobectomy, subtotal thyroidectomy and lymph node dissection was performed in 70%, 14%, 2% and 30% of cases, respectively. Thirteen percent of patients were not treated with surgery. All patients had EBRT and 39 had chemotherapy. Radioiodine (RAI) ablation of thyroid remnant and RAI therapy was applied in 90% and 40% of cases, respectively. Recurrence was diagnosed in 29/64 patients without a persistent disease: locoregional and distant in 16 and 13 cases, respectively. Five-year and ten-year disease-free survival rate was 64% and 48%, respectively. Conclusions The majority of patients with DTC and pT4 tumors who were treated with EBRT of the neck and mediastinum region as part of multimodal treatment have long-lasting locoregional control of the disease.

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.