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 impact of the multifocality and subtypes of papillary thyroid carcinoma on central compartment lymph node metastasis.

OBJECTIVE: Papillary thyroid carcinoma (PTC) may often appear as multifocal disease. Few studies demonstrated a higher rate of central compartment lymph node metastasis (CCLNM) in multifocal PTC patients. Therefore, the effect of different histological subtypes of multifocal PTC on CCLNM is another subject for further examination. The aim of the present study is to evaluate the rate of central lymph node positivity in multifocal PTC as compared to unifocal disease, and to identify the role of different histologic subtypes of PTC on central neck lymph node positivity. PATIENTS AND METHODS: Patients with PTC who underwent total thyroidectomy (TT) + central cervical lymph node dissection (CCLND) at authors' institution between January 2012 and June 2016 were included (n=274). Independent Samples t-test, Mann-Whitney U test and Chi-square tests were used to determine univariate associations, and multivariate analysis was conducted by logistic regression. RESULTS: The rate of CCLND positivity in multifocal PTC is higher than unifocal tumors and the difference is significant (p < 0.05). The univariate analysis demonstrated significant relation with male sex, lymphovascular invasion and size of dominant nodule > 10 mm regarding of CCLND positivity in multifocal PTC patients. The comparison between solitary and mixed histologic subtype of multifocal PTC is also significant (p < 0.05). CONCLUSIONS: Multifocality is an important risk factor for CCLNM. Male sex, dominant tumor size >10 mm and mixed histological subtype in multifocal PTC may play an important role in CCLND positivity.

The risk of hypoparathyroidism after central compartment lymph node dissection in the surgical treatment of pT1, N0 thyroid papillary carcinoma.

OBJECTIVE: The role of central compartment lymph node dissection (CCLND) in the treatment of papillary thyroid carcinoma (PTC) is still controversial. The benefits of CCLND should be weighed against its potential risks. We aim to evaluate the positivity of central lymph nodes in pT1, N0 PTC and to establish the complication rates of total thyroidectomy (TT)+CCLND. PATIENTS AND METHODS: This is a retrospective study on prospectively collected data over a 45-month period. A total of 329 patients were included. Total thyroidectomy was performed in 130 (39.5%) of these patients due to benign thyroid pathologies, and 199 (60.5%) pT1, N0 PTC patients had TT+CCLND. Our TT technique was applied in the same way in both groups. Central lymph node positivity, the number of lymph nodes removed during CCLND and the operative complications were evaluated. T-test and chi-square analysis were conducted in independent groups for statistical evaluation. RESULTS: The rate of central lymph node positivity in TT+CCLND group was 38%. The average number of lymph nodes removed by CCLND is 10.2 (1-36). Complication rates between TT and TT+CCLND groups were statistically significant (3.8% vs. 11.1%, respectively) (p<0.05). The difference was found to be particularly more pronounced for transient hypocalcemia. Although there was no significant relation between the number of lymph nodes removed during CCLND and the number of parathyroid glands detected in the pathology specimens (p>0.05), the relation between the development of symptomatic hypocalcemia and the number of the parathyroid glands removed during surgery was significant (p <0.05). CONCLUSIONS: Central compartment lymph node metastasis in PTC is common. CCLND may increase the rate of transient hypocalcemia.

Is hemithyroidectomy a rational management for benign nodular goitre? A Multicentre Retrospective Single Group Study.

BACKGROUND: The incidence and potential risk factors for the recurrence of benign nodular goitre after unilateral thyroidectomy are not clearly defined. The aim of this study was to assess the rate of progression of nodular goitre in the contralateral thyroid lobe and of hypothyroidism requiring replacement therapy after unilateral thyroid lobectomy for benign nodular goitre. PATIENTS AND METHODS: Patients who underwent hemithyroidectomy for benign nodular goitre between 2000 and 2009 were included in the study. The primary outcome of this study was the reoperation rate for recurrent goitre, the rate of progression of nodular goitre and the rate of hypothyroidism requiring L-T4 replacement therapy. Clinical factors that have an effect on progression were further analysed. RESULTS: 259 patients were included for study. Progression of the nodular goitre in the remnant lobe was observed in 32% (n = 83) of the patients. However, over time, only 2% of these 83 patients underwent contralateral hemithyroidectomy due to this progression. Fifty-six (22%) patients required L-thyroxin replacement due to persistent hypothyroidism after hemithyroidectomy. The factors shown to affect progression of nodular goitre were advanced age, preoperative hyperthyroidism, preoperative diagnosis of toxic nodular goitre and the presence of surgical indication for a toxic goitre causing hyperthyroidism and a definitive pathological diagnosis of nodular hyperplasia. CONCLUSION: There was a progression of the nodular goitre in the remnant lobe in about one-third of the patients who underwent hemithyroidectomy. However, only 2% of these patients underwent complementary contralateral hemithyroidectomy due to clinical progression in 31 months of follow-up.

The predictive value of the clinical features of malignancy in cases of preoperative follicular thyroid neoplasia.

AIM: It is generally impossible to make a distinction between benign and malign with a cytopathological examination using a fine needle aspiration biopsy (FNAB) in follicular lesions of the thyroid gland. This is the reason why lesions are frequently reported as follicular neoplasia (FN). Our study aims to examine the predictive value of carcinoma detection of different clinical features in cases with determined FN with FNAB. METHODS: Clinical and histopathological data of a total of 116 patients (26 male, 90 female) subjected to surgery because of thyroid gland pathology with FN between March 1997 and December 2011 were retrospectively examined in two different centers. RESULTS: Results of the histopathological examinations were reported as: carcinoma in 33 (28.4%) cases (18 [54.5%] cases with papillary thyroid cancer, 11 [33.3%] cases with follicular thyroid cancer and 4 [12.1%] cases with papillary thyroid cancer follicular variant), as follicular adenoma (FA) in 32 (27.6%) patients and as a benign colloidal nodule in 51 (43.9%) patients. No statistical significance was determined between advanced age, male sex, solid single nodule, increased nodule diameter, hypoactive nodule existence and malignancy (P>0.05). CONCLUSION: Malignancy was found in 28.4% cases with FN detected as a result of FNAB in our study series, a ratio which is significantly higher than that reported in the literature. We think that the characteristics of the patient and the tumor are not effective in diagnosing cancer. In the case of the existence of bilateral thyroid pathology, the surgical therapy option should be bilateral total thyroidectomy due to such a high ratio of cancer occurrence.

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.

Current iodine status in Turkey.

OBJECTIVES: To evaluate the current nationwide iodine status in Turkey by determining urinary iodine concentrations (UIC) and household salt iodine content. A follow- up monitoring study was also conducted in 30 urban areas. METHODS: A school-based survey was conducted in 2007 by using multistage 'proportionate to population size' (PPS) cluster sampling method. The study population was composed of 900 school-age children (SAC) from different urban, suburban, and rural areas. UIC and iodine content of the table salt used at home were analyzed. RESULTS: Median UIC was 107 microg/l (147 in urban, 42 in suburban and rural areas, p<0.001). There were severe iodine deficiency (ID) in 7.2%, moderate and mild ID in 20.6% and 19.3%, of the SAC, respectively. UIC was sufficient (>100 microg/l) in 50% of the study population, whereas it was excessive (>300 microg/l) in 10.5% of them. Of the 900 salt samples, 662 (73.5%) were iodized and 508 samples (56.5%) contained adequately iodized salt (iodine content >15 ppm). UIC of the study population and salt iodine levels correlated well (r=0.42, p<0.001). CONCLUSIONS: Moderate to severe ID still exists in 27.8% of the Turkish population, which is much better compared to 1997 and 2002 surveys (i.e. 58%, 38.9%, respectively). The follow-up monitoring study (in 2007) demonstrated that ID has been eliminated in 20 of 30 cities surveyed, and median UIC was 130 microg/l. ID has been eliminated in most of the urban population, however, it is still an important problem in rural areas and in particular geographical regions, which should be the target of future programs.

Mothers' knowledge of young child development in a developing country.

BACKGROUND: Although interventions on child development target supporting mothers' relationships with their children, little is known about maternal knowledge of child development in developing countries. The purpose of this study was to determine maternal knowledge about child development in Turkey. METHODS: The Caregiver Knowledge of Child Development Inventory (CKCDI) developed for this study consisted of questions on when children begin to demonstrate developmental skills and when caregivers should provide opportunities for developmental stimulation. RESULTS: In total, 1200 mothers of children aged

Surgical management of primary hyperparathyroidism - results of a national survey.

BACKGROUND: During the last decade, the surgical management of primary hyperparathyroidism has been limited to those patients with symptoms or complications of the disease and most surgeons have advocated routine bilateral neck exploration. Several recent articles, however, have supported the role of early surgical intervention and minimally invasive surgery for these patients. The aim of this study was to define the current surgical management of primary hyperparathyroidism in the UK and Ireland. METHODS: A postal questionnaire was sent to all consultant members of the British Association of Endocrine Surgeons in November 2000. The surgeons were asked about their current criteria for patient selection, methods of pre-operative localisation, imaging technique before re-exploration, operative technique and follow-up. RESULTS: Questionnaires were returned from 66 of 92 surgeons (response rate 71.7%) currently performing parathyroid surgery in the UK and Ireland, at an average of 23.1 parathyroidectomies performed per annum (range, 5-120). The majority of patients referred for surgery were either asymptomatic (12.1%) or minimally symptomatic (53%). There was marked variability among surgeons in the use of pre-operative imaging techniques before the initial operation (sestamibi used by 39.4% [26/66] and ultrasound by 39.4% [26/66] also, alone or in combination with other imaging techniques, while 39.4% (26/66) of surgeons used no imaging) and re-exploration. CONCLUSIONS: This survey demonstrates marked variation in pre-operative localisation and surgical management of patients with primary hyperparathyroidism. The majority of surgeons in the UK and Ireland currently perform bilateral neck exploration with or without pre-operative localisation.

Bone marrow micrometastasis in breast cancer.

BACKGROUND: Several studies have demonstrated that bone marrow micrometastasis in patients with breast cancer is an independent prognostic factor for systemic recurrence and poorer survival. METHODS: This review describes the detection and clinical significance of micrometastatic cells in bone marrow, and examines the correlation between such micrometastasis and established clinicopathological prognostic factors. The relevant English language literature on bone marrow micrometastasis in breast cancer was searched via Medline (1975-2002), cross-referencing with key articles on the subject. RESULTS AND CONCLUSION: The balance of evidence favours the hypothesis that bone marrow micrometastasis impacts on disease-free and overall survival. Further prospective studies are required to examine this in greater detail, with particular reference to early node-negative breast cancer and the value of adjuvant systemic therapy in patients with bone marrow micrometastasis.

Laparoscopic hepatic wedge resection of hemangioma: report of two cases.

INTRODUCTION: Cavernous hemangiomas are the most frequent type of benign liver tumor. A large proportion are discovered unexpectedly. The widespread use of ultrasound (US) and computerized tomography (CT) scanning has made diagnosis more common. Laparoscopic liver surgery has, however, developed more slowly. There have been only a few anecdotal reports of hepatic laparoscopic resections, most of which are limited to wedge resections. Laparoscopic anatomical liver resections are still at an early stage of development. DISCUSSION: This paper describes two cases of hepatic cavernous hemangiomas, both of which were removed laparoscopically. No blood transfusion was necessary. No surgical complications occurred and the patients were discharged on the second postoperative day. We conclude that, depending on the size and location of the tumor, laparoscopic resection of liver hemangiomas can be performed safely.

Coeliac artery aneurysm: aorto-hepatic artery reconstruction.

Aneurysms of the coeliac axis are rare. Up to 1997, 137 cases had been reported. Here we present a coeliac aneurysm which involved the origin of the splenic, left gastric, and common hepatic arteries. After making a midline incision, infra-diaphragmatic control of the aorta was obtained. The aorta was clamped for 25 minutes to resect the aneurysm. The defect at the origin of the coeliac axis was closed with 1.5 cm PTFE patch. The distal segments of the splenic and left gastric arteries were ligated. A 6-mm ringed PTFE graft was interposed between the infra-renal aorta and the proper hepatic artery. The control arteriogram showed a good arterial flow. The patient recovered uneventfully after surgery with normalisation of hepatic function.

Fascioliasis observed during laparoscopic cholecystectomy.

Fascioliasis is an uncommon zoonotic disease caused by Fasciola hepatica, a liver fluke, for which humans act as an accidental host, infected by the ingestion of water or raw aquatic vegetables contaminated with the metacercaria. We report the case of a patient who presented to our clinic with right upper abdominal pain and nausea. Physical examination and abdominal ultrasonography revealed cholelithiasis. Peripheral blood eosinophilia was the only positive sign observed during routine laboratory tests. We therefore decided to perform laparoscopic cholecystectomy. During laparoscopy peritoneal implants approximately 0.5-1 cm diameter were detected which gave an impression of peritoneal carcinomatosa. Laparoscopic cholecystectomy was performed, and biopsies were taken from the peritoneal implants which were examined histopathologically, and fascioliasis was determined.

Evaluation of vocal cord function after thyroid surgery.

OBJECTIVE: To compare clinical evaluation and indirect laryngoscopy with videolaryngostroboscopy (VLS), which is a new method of diagnosing abnormalities and dysfunction of the vocal folds. DESIGN: Prospective study. SETTING: Teaching hospital, Turkey. SUBJECTS: 218 patients who required thyroidectomy and who had no vocal abnormality preoperatively. INTERVENTIONS: Clinical evaluation, indirect laryngoscopy, and VLS before operation and on the second postoperative day. MAIN OUTCOME MEASURES: Sensitivity and specificity. RESULTS: The specificity of all three investigations was 100%. The sensitivity of VLS was 100%, of clinical evaluation 81%, and of indirect laryngoscopy 67%. CONCLUSIONS: Clinical evaluation and indirect laryngoscopy are safe ways of evaluating abnormalities of the vocal cords postoperatively. It would probably not be cost-effective to use VLS routinely, but for differential diagnosis and evaluation of prognosis of vocal abnormalities after thyroidectomy it is more accurate.

Does pneumoperitoneum cause bacterial translocation?

Although extensive research has been carried out on the respiratory and renal effects of intra-abdominal pressure increase, there is limited research with regard to its effects on bacterial translocation. The objective of this study was to discuss whether the high intra-abdominal pressure due to carbon dioxide (CO2) insufflation during laparoscopy leads to bacterial translocation. Eighteen male dogs, 7 of which constituted the control group, were used in the study. Two study groups, in which the intra-abdominal pressure was raised to 15 mm Hg and kept at that level for 30 and 120 minutes, respectively, were set. Blood gases and blood pressure values were observed throughout the experiments. Samples of peritoneal smear, portal vein blood, mesenteric lymph node, liver, spleen, and cecum were examined to detect bacterial translocation. Histopathological examinations of all samples were also carried out. No translocation was detected in the samples of peritoneal smear, portal blood, mesenteric lymph node, liver, or spleen, but in the samples of cecum, bacterial colonization for the second group (p<0.05) and for the third group (p<0.05) was significantly higher compared with the control group. There was a considerable difference between the second and third groups (p<0.05). The changes in the mesenteric lymph nodes were interpreted to be a result of bacterial drainage. Histopathological examination disclosed active changes in the mesenteric lymph nodes in all groups, but there was considerable sinus histiocytosis only in the third group. We conclude that the intraabdominal pressure of 15 mm Hg created by carbon dioxide insufflation does not lead to bacterial translocation but causes intraluminal bacterial colonization in the cecum after 30 minutes and after 2 hours.

The importance of lifelong follow-up for patients with pheochromocytoma: report of a case.

We report herein the case of a patient who developed a malignant recurrence of pheochromocytoma 13 years after undergoing complete resection of a histologically benign, unilateral, sporadic tumor. A discussion on the importance of lifelong follow-up for patients undergoing surgery for pheochromocytoma follows this case report.