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.

Assessment of Palliative Care in Lung Cancer in Turkey.

OBJECTIVE: To investigate the symptoms of lung cancer in Turkey and to evaluate approaches to alleviate these symptoms. SUBJECTS AND METHODS: This study included 1,245 lung cancer patients from 26 centers in Turkey. Demographic characteristics as well as information regarding the disease and treatments were obtained from medical records and patient interviews. Symptoms were evaluated using the Edmonton Symptom Assessment Scale (ESAS) and were graded on a scale between 0 and 10 points. Data were compared using the χ2, Student t, and Mann-Whitney U tests. Potential predictors of symptoms were analyzed using logistic regression analysis. RESULTS: The most common symptom was tiredness (n = 1,002; 82.1%), followed by dyspnea (n = 845; 69.3%), appetite loss (n = 801; 65.7%), pain (n = 798; 65.4%), drowsiness (n = 742; 60.8%), anxiety (n = 704; 57.7%), depression (n = 623; 51.1%), and nausea (n = 557; 45.5%). Of the 1,245 patients, 590 (48.4%) had difficulty in initiating or maintaining sleep. The symptoms were more severe in stages III and IV. Logistic regression analysis indicated a clear association between demographic characteristics and symptom distress, as well as between symptom distress (except nausea) and well-being. Overall, 804 (65.4%) patients used analgesics, 630 (51.5%) received treatment for dyspnea, 242 (19.8%) used enteral/parenteral nutrition, 132 (10.8%) used appetite stimulants, and 129 (10.6%) used anxiolytics/antidepressants. Of the 799 patients who received analgesics, 173 (21.7%) reported that their symptoms were under control, and also those on other various treatment modalities (dyspnea: 78/627 [12.4%], appetite stimulant: 25/132 [18.9%], and anxiolytics/antidepressants: 25/129 [19.4%]) reported that their symptoms were controlled. CONCLUSION: In this study, the symptoms progressed and became more severe in the advanced stages of lung cancer, and palliative treatment was insufficient in most of the patients in Turkey.

Gastroprotective effects of CoQ10 on ethanol-induced acute gastric lesions.

INTRODUCTION: Alcohol consumption is frequently associated with gastric mucosal lesions. The purpose of this study was to determine the effect of Coenzyme-Q10 (CoQ10) supplementation on the ethanol-induced gastric mucosal damage in a rat model. MATERIAL AND METHOD: Sixty-four female wistar albino rats were randomly divided into 8 groups (n = 8). Studies were performed in ethanol induced gastric ulcer model in Wistar albino rats. Famotidine at a dose of 5 mg/kg or 20 mg/kg and CoQ10 at a single dose of 10 mg/kg or 20 mg/kg and 30 mg/kg for 7 days were administered as pretreatment. All the rats in study groups received 2 ml/kg ethanol 95 % intragastrically, 30 minutes after pretreatment. Four hour after ethanol administration, all rats were sacrificed and their stomachs were removed under ketamin anaesthesia. Gastric protection was evaluated by measuring the ulcer index, MDA concentrations, and histopathological studies. RESULTS AND DISCUSSION: Rats pretreated either with famotidine or CoQ10 had significantly diminished gastric mucosal damage which was assessed with gross and microscopic analysis (p < 0.00625). MDA levels were significantly lower in famotidine 20 mg/kg and CoQ10 pretreatment for 7 days group (p < 0.00625).

A stereological study of the renal and adrenal glandular structure of red-legged partridge (Alectoris chukar).

BACKGROUND: Partridge is a major bird species that has recently gained an increasing importance as an alternative food source and a game animal in hunting tourism. Herein, we aimed to examine the histological structure and stereological properties of the renal and adrenal glands of red-legged partridge. MATERIALS AND METHODS: Seven healthy adult red-legged partridges (Alectoris chukar) of both genders were used in this study. The Alectoris chukars were perfused with the intracardiac method and were kept in 10% formaldehyde for 72 h for optimal fixation. The tissues were embedded in paraffin after routine light microscopic processes. Then, 5-µm thick sections were taken, which were stained with haematoxylin and eosin, photographed, and examined in light microscope. Modified Cavalieri principle was used for volume calculation as stereological analysis. Total tissue volume ratios were calculated with the help of a point grid provided by the Shtereom 1.5 packaged programme. Mann Whitney-U test was used for inter-group comparisons. The significance level was set at 5% SPSS (ver: 13) statistical software was used for all statistical analyses. RESULTS: Renal histological structure was found to resemble those of other bird species and contained a mixed type (mammalian, reptilian) glomerular structure. It was also found that the adrenal histology was not in the form of separate layers but composed of cell groups with different properties. Stereological renal volume assessment revealed statistically similar right and left renal size (p > 0.05). In adrenal gland volume assessment, the right and left adrenal volumes were also statistically similar (p > 0.05). CONCLUSIONS: The obtained data in the present study is thought to contribute to the understanding of the stereological, morphological and histological structure of the red-legged partridge (Alectoris chukar) kidney and adrenal gland.

A morphological and stereological study on calculating volume values of thoracic segments of geese.

BACKGROUND: In this study, the total volume of the thoracic segments of the spinal cord and volume densities of grey matter and white matter were examined by using stereological methods in adult geese having a weight of 3-4 kg. MATERIALS AND METHODS: Ten geese were used as material without sex discrimi- nation. All animals were perfused with 10% formaldehyde. In addition, after perfusion, the geese were kept in 10% formaldehyde for 1 week. Afterwards, thoracic spine was removed and thoracic part of spinal cord was excised. 5 µm thick sections were taken from these tissue samples by microtome. The cross- sectional series were obtained by sampling from each segment at 250th section. Twelve sections were taken from tissue specimens of every segment. The sections were stained by using haematoxylin-eosin and photographed on a microscope. RESULTS: By using the Cavalieri's Principle, the volume densities (volume fractions) of thoracic segments of spinal cord, volume of white matter, and volume of grey matter in segments were calculated. CONCLUSIONS: In the study, total volume of the thoracic segment, volume of white matter, and the volume of grey matter, and the ratio of these volume values to each other were calculated. The SHTEREOM 1.0 software was used for calculating the volume of section specimens.

Genetic damage of operating and recovery room personnel occupationally exposed to waste anaesthetic gases.

Occupational exposure to the waste anaesthetic gases (WAGs) is a crucial problem for healthcare personnel. Cancer is among the potential long-term adverse effects of WAGs. The present occupational molecular epidemiology study was conducted in healthcare personnel (anaesthetists, nurses and technicians; n = 46), working in operating rooms (ORs; n = 34) and recovery units (RUs; n = 12) of the same hospital, to assess the genotoxicity risk of WAGs exposure. Twenty-one healthy available hospital staff allocated to other wards, without the history of working in ORs and RUs were the control group. A micronucleus test was carried out for peripheral blood lymphocytes (PBLs) and buccal epithelial cells (BECs). Exposure to the anaesthetics was assessed with sevoflurane concentrations and inorganic fluoride levels in post-shift urine samples of the healthcare staff. As an exposure marker, sevoflurane concentrations in ORs and RUs were measured using passive samplers. The micronuclei frequencies were increased in both PBLs (approximately two times) and BECs (approximately three times) of the healthcare personnel. Urinary sevoflurane concentrations exceeded the biological equivalent level in 23 personnel. Air sevoflurane levels in the breathing zone in three ORs and one RU did not exceed the established occupational exposure limits. Both in surrogate tissue (PBLs) and in target tissue (BECs) of the personnel of RUs and ORs of the same hospital, the genotoxicity risk was evident and similar. Originality of this study, in addition to the WAGs exposure confirmation of the healthcare personnel, was the involvement of the RU personnel for the genotoxicity assessment, which was the first time in the scientific literature.

Experimental obstructive jaundice results in oxidized low-density-lipoprotein accumulation in surgical wound of rats.

INTRODUCTION: Mounting evidence suggests that impaired wound healing is a well-defined consequence in obstructive jaundice and, as redox-regulated processes are relevant to wound healing, it is not unreasonable to suppose that oxidative stress associated with lipid peroxidation in cholestasis might be a systemic phenomenon probably comprising all tissues and organs, including wounds. The aim of the present investigation was to analyse the lipid peroxidation status of surgical wounds, in terms of oxidized low-density-lipoprotein (oxLDL) accumulation in experimental obstructive jaundice. METHODS: Sixteen Wistar-Albino rats weighing 200-230 gr were randomly divided into two groups. Group I (n = 8) was designed as the prolonged obstructive jaundice group and was subjected to bile duct ligation. Group II (Sham-control, n = 8) rats underwent laparotomy alone and bile duct was just dissected from the surrounding tissue. Histopathological evaluation, immunohistochemical screening and immunoflourescent staining of the surgical wound was conducted to the bile-duct ligated rats and control group on the 21st postoperative day. RESULTS: Wound healing was found to be impaired in jaundiced rats histopathologically. When compared with the control group, significant positive oxLDL staining and intracellular accumulation of TNF-alpha, IL-2 and IL-6 was detected in the wound sections of the prolonged obstructive jaundice group. CONCLUSION: Our present data is the first in the literature, indicating significant oxLDL accumulation in surgical wounds of cholestatic rats, which might be one of the results of systemic oxidative stress leading to deficient healing capacity as a consequence of persistent inflammation.

A Morphological and Stereological Study on Cervical Segment of Spinal Cord of Quails.

In this study, volume densities of white and grey matters of cervical segments of spinal cords of quail were investigated stereologically. In both sexes, mature, six quails were used as material of this study. All animals were fixed by perfusing in 10% buffered formalin. Tissue specimens were obtained from cervical spinal cords. These tissue specimens were cut every fiftieth section at 5 µm thickness by a microtome. And mean six or seven sections were examined from every block by this method at microscope. After that, these sections were stained by haematoxylin eosin and photographed. Densities of volumes of all tissues of cervical segments of whole spinal cords and white and grey matters were calculated with principle of Cavalieri. As a result, total volume of spinal cord, volumes of white and grey matters of cervical segment and volume rates of white and grey matters were calculated.

Fade or fate. Seroma in laparoscopic inguinal hernia repair.

BACKGROUND: Postoperative fluid collection in the space left behind the dissected hernia sac in laparoscopic herniorraphy puts the surgeon in a dilemma as to whether it is a recurrence or a seroma, and it is not always easily judged only by physical examination (PE). Another important issue is what kind of seroma can be accepted as a complication of surgery. METHODS: Thirty patients with unilateral inguinal hernia who had a hernia sac of >4 cm were operated on with transabdominal preperitoneal hernia repair (TAPP) technique and the collection at the hernia site was followed by PE and superficial ultrasonography (USG) postoperatively on the first day, first week, first month, and third month. RESULTS: USG detected seroma in 20 patients, while 17 could be noticed by PE on the first postoperative day. At the end of the third month, seromas resolved by 90%, and could only be detected by USG in two patients. Pain or complication rates attributable to seroma in patients were not determined (p > 0.05) in the statistical analyses between the groups. CONCLUSIONS: Superficial USG is a beneficial tool in differentiating early recurrence or seroma in patients. It should not be intervened with as a complication until the patient has complaints attributable to seroma.

Micronuclei frequencies in exfoliated nasal mucosa cells from pathology and anatomy laboratory workers exposed to formaldehyde.

Formaldehyde (FA) is a widely used industrial chemical. Sufficient evidence exists to consider FA as an animal carcinogen. A possible causal role for FA may be considered likely for cancer of the nasopharynx and the nasal cavities in humans. The frequency of micronuclei (MN) in cells of the nasal mucosa was evaluated for 23 individuals in pathology and anatomy laboratories exposed to FA. Twenty-five healthy subjects were selected from the university and hospital staff as a control group. The measured air concentrations of FA in the breathing zone of the laboratory workers were between 2 and 4 ppm. The mean +/- SD values of nasal mucosa MN (per 1000) frequency from exposed and controls were 1.01 +/- 0.62 and 0.61 +/- 0.27, respectively (p < 0.01). Effect of smoking, age, sex and duration of exposure on the genotoxicity parameters analyzed were also evaluated. Our data suggest that low level exposure to FA is associated with cytogenetic changes in epithelial cells of the nasal region and that nasal mucosa cells exposed through respiration is an important target of FA-induced genotoxic effects.

Intestinal obstruction due to bezoars: a retrospective clinical study.

PURPOSE: The purpose of this study was to compare the results of surgical procedures applied to rare intestinal obstruction cases due to bezoars and to identify effective factors for determining the type of surgical procedure to be applied. METHODS: The records of 62 patients who had received gastrointestinal surgical treatment due to bezoars were assessed retrospectively. The preoperative characteristics, perioperative findings and postoperative results of cases that had and had not undergone an enterotomy were compared RESULTS: The average patient age was 57.7 years (range, 26-84 years), and all patients had phytobezoars, except one. The most common location for bezoars was the jejunum (28 cases, 45.1 %). Sixteen cases (25.8 %) had multiple bezoars located in different parts of the gastrointestinal tract. While milking was applied to 26 cases (41.9 %) with small intestinal bezoars, an enterotomy was used to remove bezoars in 23 cases (37 %). More complications tended to be identified in patients who underwent an enterotomy; however, the difference was not significant (p = 0.553). CONCLUSIONS: The frequency of previous abdominal surgery in patients suffering from an intestinal obstruction due to bezoars causes diagnostic conflict. The location of bezoars in the small intestine should also be considered when deciding the surgical procedure, as well as the physical properties of the bezoars. Our opinion is that conducting the milking procedure should not be insisted on, and that an enterotomy should be conducted when necessary.

The effects of resveratrol on the healing of left colonic anastomosis.

INTRODUCTION: Resveratrol (RSV) is a natural polyphenolic compound found in grape skins and the red wine which improves histological reorganization of the regenerating tissue in dermal wound healing. Since anastomotic healing possesses paramount importance to prevent complications in colorectal surgery, the present study is aimed to evaluate the effect of RSV on the healing of experimental left colonic anastomoses. METHODS: Thirty-two male Wistar albino rats were randomized into two groups and subjected to colonic anastomosis. The study group was treated with RSV and the control group received tap water instead. The rats were sacrificed 3 and 7 days postoperatively. Wound complications, intra-abdominal abscesses, and anastomotic leaks and stenosis were recorded. Four types of assessment were performed: bursting pressure, hydroxyproline (OHP) content, histopathology, and biochemical analysis. RESULTS: Compared to the control group, the RSV-treated rats displayed a higher bursting pressure (p < .001) and anastomotic OHP content (p < .05)]. RSV treatment leads to significant increase in PON activity at both time points and decrease in malondialdehyde levels on postoperative day 3 (p < .001). Histopathological analysis revealed that RSV administration leads to a better anastomotic healing in terms of mucosal ischemia, neovascularization, reepithelialization, fibroblast, and lymphocyte infiltration. CONCLUSION: The study results suggest that exogenous RSV administration exerts a positive effect on experimental colonic wound healing in the rat. Although the precise cellular mechanisms by which RSV enhances anastomotic wound healing is not clear, stimulation of neovascularization, generation of collagen synthesis, inhibition of over inflammation, and restriction of oxidative injury seems to be of paramount importance.

Simvastatin improves wound strength after intestinal anastomosis in the rat.

BACKGROUND: Simvastatin is a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor commonly known as a cholesterol-lowering drug with additional pleiotropic effects. Also, it is demonstrated that it prevents postoperative peritoneal adhesions in rat. This study was designed to assess its effects on the healing process of colonic anastomosis. METHODS: Thirty-two male Wistar albino rats were randomized into two groups and subjected to colonic anastomosis. The study group was treated with simvastatin and the control group received only tap water instead. The rats were killed 3 and 7 days postoperatively. Wound complications, intra-abdominal abscesses, and anastomotic leaks and stenosis were recorded. Four types of assessment were performed: bursting pressure, hydroxyproline content, histopathology, and biochemical analysis. RESULTS: Compared to the control group, simvastatin-treated rats displayed a higher bursting pressure (p < 0.001) and anastomotic hydroxyproline content (p < 0.05). Simvastatin treatment leads to a significant decrease in malondealdehyde levels (p < 0.05) and increase in paraoxonase activity (p < 0.001) at both time points. Histopathological analysis revealed that simvastatin administration leads to a better anastomotic healing in terms of reepithelialization, decreased granuloma formation, reduced ischemic necrosis, and inflammatory infiltration to muscle layer. CONCLUSION: Clinically relevant doses of simvastatin do not have a negative impact on colonic anastomosis but improve intestinal wound healing in rats.

Inadvertent parathyroidectomy and temporary hypocalcemia: an adverse natural outcome or a true complication during thyroidectomy?

OBJECTIVE: The aim of this study was to assess the factors that might predict patients at increased risk for inadvertent parathyroidectomy and postoperative symptomatic hypocalcemia during thyroidectomy. METHODS: Demographic data as well as the data on preoperative diagnosis, preoperative ultrasonography reports, operation reports, histological findings, and postoperative symptomatic hypocalcemia were collected. A total of 273 (83 male and 190 female patients) thyroid operations were included in this study. RESULTS: Histopathological examination identified inadvertent parathyroidectomy in 10 (3.7%) cases. Statistical analysis identified the presence of cervical lymphadenopathy as detected by preoperative ultrasonography as a risk factor for inadvertent parathyroidectomy. In 57 patients (20.9%) clinically symptomatic postoperative hypocalcemia was observed. However, the difference in the frequency of such hypocalcemia between the patients with and without inadvertent parathyroidectomy was not significant. Statistical evaluation identified total thyroidectomy as a risk factor for postoperative hypocalcemia (p<0.005). CONCLUSION: Due to our experience, inadvertent parathyroidectomy is not a rare entity during thyroidectomy and the presence of cervical lymphadenopathy, as observed by preoperative ultrasonography, is the only risk factor for inadvertent parathyroidectomy. In contrast, no association between inadvertent parathyroidectomy and postoperative hypocalcemia was detected. Total thyroidectomy was found to be the sole risk factor for symptomatic temporary hypocalcemia.