Intervention for Hepatic and Pulmonary Metastases in Breast Cancer Patients: Prospective, Multi-institutional Registry Study-IMET, Protocol MF 14-02.

BACKGROUND: One fourth of early-stage breast cancer cases become metastatic during the follow-up period. Limited metastasis is a metastatic disease condition in which the number of metastatic sites and the extent of the disease both are limited, and the disease is amenable to metastatic intervention. This prospective study aimed to evaluate intervention for limited metastases in the lung, liver, or both. METHODS: The study enrolled luminal A/B and/or human epidermal growth factor receptor 2 (HER2)-neu+ patients with operable lung and/or liver metastases in the follow-up assessment after completion of primary breast cancer treatment and patients with a diagnosis of metastasis after 2014. Demographic, clinical, tumor-specific, and metastasis detection-free interval (MDFI) data were collected. Bone metastasis in addition to lung and liver metastases also was included in the analysis. The patients were divided into two groups according to the method of treatment for metastases: systemic therapy alone (ST) group or intervention (IT) group. RESULTS: Until June 2020, 200 patients were enrolled in the study. The demographic data were similar between the two groups. The median follow-up time was 77 months (range 55-107 months) in the IT group (n = 119; 59.5%) and 57 months (range 39-84) in the ST-only group (n = 81; 40.5%). The median MDFI was 40 months (range 23-70 months) in the IT group, and 35 months (range 13-61 months) in the ST-only group (p = 0.47). The groups had similar surgeries for the primary tumor and axilla. Most of the patients had liver metastases (49.5%, n = 99), and 42% (n = 84) of the patients had lung metastases. Both lung and liver metastases were found in 8.5% (n = 17) of the patients. The primary tumor was estrogen receptor/progesterone receptor-positive in 75% (n = 150) of the patients, and 32% (n = 64) of the patients had HER2-neu+ tumors. Metastatic-site resection was performed for 32% (n = 64) of the patients, and 27.5% (n = 55) of the patients underwent metastatic ablative interventions. In the Kaplan-Meier survival analysis, the hazard of death (HoD) was 56% lower in the IT group than in the ST-only group (hazard ratio [HR], 0.44; 95% confidence interval [CI] 0.26-0.72; p = 0.001). The HoD was lower in the IT group than in the ST-only group for the patients younger than 55 years (HR, 0.32; 95% CI 0.17-0.62; p = 0.0007). In the multivariable Cox regression model, HoD was significantly lower for the patients who underwent intervention for metastases and had an MDFI longer than 24 months, but their liver metastases doubled the risk of death compared with lung metastases. CONCLUSION: Metastasis-directed interventions have reduced the risk of death for patients with limited lung/liver metastases who are amenable to interventions after completion of primary cancer treatment. For a select group of patients, such as those with luminal A/B or HER2-neu+ breast cancer who are younger than 55 years with limited metastases to the lung and liver or an MDFI longer than 24 months, surgical or ablative therapy for metastases should be considered and discussed on tumor boards.

The opinions of adults about the ban on cigarette sales to minors.

BACKGROUND: Selling of tobacco products to minors has been banned since 1996 by the tobacco control law in Turkey. However, it is also important for the public to support practices that prevent the access of tobacco products to minors. In addition, every individual has the responsibility of carrying out society based programs that restrict access to tobacco products especially to children and the youths. Social sensitivity is considered an important factor in the prevention of tobacco use. This study aims to learn about the opinions and attitudes of adults with regards to minors access to tobacco products. METHODS: The study was a descriptive study conducted in nine city centers in Turkey. The total number of participants reached was 3241. The questionnaire was developed by the research team and consisted of 22 questions concerning knowledge and behaviors of adults on restriction of tobacco sales to minors and their observations with regards tobacco sales to minors. Data was collected through face to face interview. Pearson chi-square test was used for the bivariate analysis whereas logistic regression was investigate the relationship between "the participant's response against tobacco sales to minors" and the following explanatory variables; "age", "educational status", "income level", "working status", "minors access to cigarettes", "smoking ratio in high school" and "sales of tobacco to minors". RESULTS: More than half of the participants (60.5%) belonged to the age group 25-44 years, 61.3% graduated from high school or university. Most of the participants were smoker (39.2%) or ex-smoker (19.1%), and 41.7% of the participants was non-smoker. A greater proportion of the participants (76.2%) believed that smoking prevalence was greater than 40% among high school students. One in four (27.8%) adults did not know that tobacco control law bans sell of tobacco products to minors in Turkey. More than half of the participants (57.1%) ever witnessed tobacco sales to minors and 63.6% of them did not act when confronted with the event. Almost all (96.8%) of the respondents thought that access of minors to tobacco products was not difficult. The results of logistic regression of participant's response against tobacco sales to minor and related factors for current smokers showed that respondents who believed smoking ratio in high school was 4-5 adolescent out of 10 (aOR: 1.59; 95% CI: 1.09-2.34) were more likely to give a warning or informing the police or other people as compared to respondents whose perception on the smoking ratio among high school students was 6-7 adolescents out of 10. The results of logistic regression of non-smokers' response against tobacco sales to minor were who are from higher educational level, higher economic status, working status and who believed smoking ratio in high school was 4-5 adolescent out of 10 and 2-3 adolescent out of 10 were more likely to give a warning or informing the police or other people as compared to the others. CONCLUSIONS: Although laws prohibiting the sale of tobacco products to the under age group is very important with regards to accessibility of minors to tobacco products, most of the study participants believed that minors can still easily access tobacco products, and more than half of the participants did not act when confronted with the event. The education, information and monitoring program most especially as it concerns salesman, should be reviewed and strengthened to obey the rules on sales of tobacco products to minors. Education program should be carried out to increase the knowledge and awareness of the community for sale of tobacco to minors. Social sensitivity is important for the prevention of tobacco use and every individual have a responsibility in carrying out this society based program, most especially as it related to prevention of tobacco usage among children and youths.

Association of PALB2 sequence variants with the risk of early-onset breast cancer in patients from Turkey.

The PALB2 gene, has been accepted as a moderate-penetrance gene associated with breast cancer susceptibility and this gene product is involved in the DNA damage repair pathway via co-localization with BRCA2. Germline PALB2 mutations are associated with an increased breast cancer risk. However, the prevalence of the diverse types of PALB2 variants depend on the population. Thus, the aim of the present study was to determine, for the first time, the prevalence of PALB2 variants in a Turkish population of BRCA1/BRCA2-negative early-onset patients with breast cancer. In total, 223 Turkish patients with BRCA1/BRCA2 negative early-onset breast cancer and 60 unaffected women were included in the study. All the coding exons and intron/exon boundaries of PALB2 were subjected to mutational analysis by heteroduplex analysis (HDA)and DNA sequencing. Eighteen PALB2 variants were found in breast cancer patients within the Turkish population. Three variants (c.271G>A, c.404C>A and c.2981T>A) have not been previously reported. In addition, nine intronic variants were described, and this study is the first to describe the c.1685-44T>A intronic variant. The prevalence of possible pathogenic PALB2 variants was found to be 4.03 % in BRCA1/2-negative Turkish patients with early-onset breast cancer. Different variants of PALB2 have been reported in the literature, and the prevalence of these variants could different for each population. This is the first study to investigate the prevalence of PALB2 variants in Turkish patients with early-onset breast cancer.

Prognostic significance of estrogen receptor, progesterone receptor, HER2/neu, Ki-67, and nm23 expression in patients with invasive breast cancer.

PURPOSE: To determine the prognostic significance of estrogen receptor (ER), progesterone receptor (PR), HER2/neu, Ki-67, and nm23 immunohistochemical expression with respect to progression free survival (PFS) and overall survival (OS) in Turkish patients with invasive breast cancer (IBC). METHODS: Patients with IBC (n = 81; mean age = 51.9 ± 11.1 years) were prospectively enrolled at the Department of Oncology, Uludag University Medical Center, Bursa, Turkey. Immunohistochemistry was performed on formalin- fixed, paraffin-embedded tissue sections. RESULTS: We did not find any significant association between immunohistochemical expression of ER, PR, HER2/ neu, Ki-67, and nm23 and the baseline characteristics of IBC patients. The median patient PFS was 30 months (range 22-45), and the median OS was 32 months (range 23-46). Stratification of the patient population according to nm23 immunohistochemical expression revealed a statistically significant difference in terms of both OS (p < 0.05) and DFS (p < 0.05). Multivariate Cox regression analysis indicated that tumor grade, axillary lymph node status, and nm23 immunohistochemical expression were the 3 main independent prognostic factors for PFS and OS in IBC patients. CONCLUSION: Reduced nm23 immunohistochemical expression is an independent negative prognostic factor for OS and PFS. Patients with negative nm23 expression may require a more intensive follow-up.

Validation of breast cancer nomograms for predicting the non-sentinel lymph node metastases after a positive sentinel lymph node biopsy in a multi-center study.

OBJECTIVE: In the study, our aim was to evaluate the predictability of four different nomograms on non-sentinel lymph node metastases (NSLNM) in breast cancer (BC) patients with positive sentinel lymph node (SLN) biopsy in a multi-center study. METHODS: We identified 607 patients who had a positive SLN biopsy and completion axillary lymph node dissection (CALND) at seven different BC treatment centers in Turkey. The BC nomograms developed by the Memorial Sloan Kettering Cancer Center (MSKCC), Tenon Hospital, Cambridge University, and Stanford University were used to calculate the probability of NSLNM. Area under (AUC) Receiver Operating Characteristics Curve (ROC) was calculated for each nomogram and values greater than 0.70 were accepted as demonstrating good discrimination. RESULTS: Two hundred and eighty-seven patients (287) of 607 patients (47.2%) had a positive axillary NSLNM. The AUC values were 0.705, 0.711, 0.730, and 0.582 for the MSKCC, Cambridge, Stanford, and Tenon models, respectively. On the multivariate analysis; overall metastasis size (OMS), lymphovascular invasion (LVI), and proportion of positive SLN to total SLN were found statistically significant. We created a formula to predict the NSLNM in our patient population and the AUC value of this formula was 0.8023. CONCLUSIONS: The MSKCC, Cambridge, and Stanford nomograms were good discriminators of NSLNM in SLN positive BC patients in this study. A newly created formula in this study needs to be validated in prospective studies in different patient populations. A nomogram to predict NSLNM in patients with positive SLN biopsy developed at one institution should be used with caution.

The effect of distance on the postoperative follow-up of patients with breast carcinoma.

PURPOSE: To assess the effect of in or out of city residence of patients with breast carcinoma, where breast surgery unit treatment and follow-up is made postoperatively. METHOD: 234 patients operated on for breast carcinoma at the Breast Surgery Unit were retrospectively studied. Patients were divided into two groups; patients living in the major city where the Breast Surgery Centre is located and patients living in smaller cities, districts, towns and villages out of the city. The distance of patients' residences from the Breast Centre has also been determined in kilometres. The number of patients and the frequency of check-up visits were compared in both groups. RESULTS: The number of patients residing in the city centre where the Breast Unit is located was 156 (66.7%). Comparing the frequency of patients' visits for check-up during the postoperative period, there were no differences between the two groups during the first four years. However, the patients living out of the city did not visit the Breast Unit for check-ups during the fifth postoperative year. Moreover, when the patients were classified into two groups with known and unknown outcomes, it was observed that those patients with unknown outcomes lived further away from the city where the Breast Surgery Unit was located compared to those with known outcomes (p = 0.002). DISCUSSION: Living within or out of the major city centre where the Breast Surgery Unit is located does not have any effect on the frequency of follow-up visits or the number of patients applying for check ups during the first four years postoperatively. However, there were gradual decreases over the course of time in both groups and these differences became apparent during the 5th year. In addition to this, the distance was also found to be an important factor for patients with unknown outcomes in the present study. The combination of living outside the city where The Breast Unit was located and the distance may have a negative effect on follow-ups. There is a need for new, larger scale, studies with longer follow-ups to show how this difference will change over a longer time period.

Hydatid cyst of diaphragm--a case of hydatid cyst with rare localisation.

Hydatid cyst (H.C.) disease, frequently seen in our country, has been known since ancient times. It can localise in each part of the body but more frequently in the liver. However, diaphragmatic localization is known to be rare. In this article, we report a case of hydatid cyst with diaphragmatic localization.

Postoperative retention of urine in general surgical patients.

OBJECTIVE: To find out the incidence of retention of urine after various general surgical operations, and to assess the effects of applying a bag filled with warm water (40-45 degrees C), and encouraging early mobilisation onreducing the necessity for catheterisation. DESIGN: Open study. SETTING: Cumhuriyet University Hospital, Sivas, Turkey. SUBJECTS: 577 consecutive patients who had no history of urinary problems and had not already been catheterised, and who underwent general surgical operations between April 1989 and December 1991. MAIN OUTCOME MEASURE: Ability to pass urine spontaneously. RESULTS: 64 of 272 men (24%) and 47 of 305 women (15%) developed retention of urine (p = 0.02), and 15 and 11, respectively, required catheterisation. Patients were most likely to develop retention after repair of incisional hernia (13/32, 38%), midline laparotomy (19/82, 23%), and subcostal incisions (30/142, 21%), but there were no significant differences among these. Significantly more patients whose operations had lasted 60 minutes or more, and who had opiate analgesia, required catheterisation (5/232 compared with 21/345, p = 0.04, and 11/120 compared with 15 out of 457, p = 0.01, respectively). 85 of the 111 patients who went into retention (77%) were able to pass urine spontaneously after application of a bag containing warm water to the suprapubic region, and walking about. The mean period of catheterisation was 12 hours (range 4-76), and all patients but one passed urine spontaneously when the catheter was removed. Only two of the 26 patients who were catheterised developed microbiologically confirmed urinary tract infections. CONCLUSION: Retention of urine is a common complication after general surgical operations, but the necessity for catheterisation can be kept to a minimum by simple and inexpensive measures.