Pertuzumab, trastuzumab and taxane-based treatment for visceral organ metastatic, trastuzumab-naïve breast cancer: real-life practice outcomes.

PURPOSE: In this study, we aimed to describe the real-life practice outcomes of pertuzumab-trastuzumab-taxane (PTT) combination in visceral organ metastatic, trastuzumab-naive breast cancer (BC) patients. METHODS: This study was conducted by Turkish Oncology Group and included 317 patients' data from 36 centers. RESULTS: Median age was 51 (22-82). Median PFS was 28.5 months, while median OS was 40.3 months. Patients with brain metastases (n: 13, 4.1%) had worse PFS (16.8 m vs. 28.5 m; p = 0.002) and OS (26.7 m vs. 40.3 m; p = 0.009). Patients older than 65 years of age (n: 42, 13.2%) had significantly lower OS results (19.8 m vs. 40.3 m; p = 0.01). Two hundred sixty-eight patients (86.7%) received docetaxel while 37 patients (11.7%) received paclitaxel. PFS and OS were similar between taxane groups. In eight patients (2.5%), 5-40% ejection fraction decrement from baseline was detected without any clinical sign of heart failure. CONCLUSIONS: Our RLP trial included only visceral metastatic, trastuzumab-naïve BC patients including cases with brain involvement who received PTT combination in the first-line treatment. Regardless of negative prognostic characteristics, our results are in parallel with pivotal trial. Further strategies for brain metastasis should be developed to improve outcomes despite encouraging results with PTT treatment. Taxane selection can be personalized and endocrine maintenance may further improve outcomes after taxanes were discontinued. To our knowledge, this is the largest scale real-life clinical practice study of pertuzumab-trastuzumab-taxane therapy to date.

GATA3 expression and its relationship with clinicopathological parameters in invasive breast carcinomas.

GATA3, as a transcription factor, is associated with estrogen receptor (ER) expression and necessary for luminal cell differentiation in mammary glands. Association of GATA3 expression with clinicopathological parameters, molecular subtypes of tumors, disease free survival (DFS) and overall survival (OS) for breast carcinoma patients were evaluated in this study. We immunohistochemically stained GATA3, CK5/6, EGFR, CK14 and vimentin on tissue microarray blocks of 457 invasive breast carcinomas. Tumors are sub-classified as luminal A, luminal B, HER2 expressing, basal-like and null type according to their hormonal status with cerbB2, CK 5/6 and EGFR expressions. Follow-up data for 254 cases were obtained. 215/457 (47%) tumors were GATA3 positive. GATA3 expression was inversely correlated with mitotic count (p<0.0001), nuclear grade (p=0.001), histological grade (p=0.001), tumor necrosis (p=0.001), stromal lymphocytic response (p<0.01), nipple invasion (p=0.01), metastasis (p=0.03), vimentin (p=0.0003), EGFR (p=0.015) and CK14 (p=0.001) expressions; and directly associated with ER (p<0.0001) and progesterone receptor (PR) (p<0.0001) expressions. Luminal A carcinomas had the highest frequency for GATA-3 (140/245), however basal-like carcinomas had the lowest (1/42) (p<0.0001). None of the medullary and metaplastic carcinomas expressed GATA3. GATA3 was associated with good DFS and OS (p=0.001 and p=0.0009) and was an independent prognostic factor for OS. GATA3 expression, regardless of the subtype, may have a prognostic significance for breast carcinomas through its ability to promote the differentiation of luminal progenitor cells.

The course of spinal tuberculosis (Pott disease): results of the multinational, multicentre Backbone-2 study.

We aimed to describe clinical, laboratory, diagnostic and therapeutic features of spinal tuberculosis (ST), also known as Pott disease. A total of 314 patients with ST from 35 centres in Turkey, Egypt, Albania and Greece were included. Median duration from initial symptoms to the time of diagnosis was 78 days. The most common complications presented before diagnosis were abscesses (69%), neurologic deficits (40%), spinal instability (21%) and spinal deformity (16%). Lumbar (56%), thoracic (49%) and thoracolumbar (13%) vertebrae were the most commonly involved sites of infection. Although 51% of the patients had multiple levels of vertebral involvement, 8% had noncontiguous involvement of multiple vertebral bodies. The causative agent was identified in 41% of cases. Histopathologic examination was performed in 200 patients (64%), and 74% were consistent with tuberculosis. Medical treatment alone was implemented in 103 patients (33%), while 211 patients (67%) underwent diagnostic and/or therapeutic surgical intervention. Ten percent of the patients required more than one surgical intervention. Mortality occurred in 7 patients (2%), and 77 (25%) developed sequelae. The distribution of the posttreatment sequelae were as follows: 11% kyphosis, 6% Gibbus deformity, 5% scoliosis, 5% paraparesis, 5% paraplegia and 4% loss of sensation. Older age, presence of neurologic deficit and spinal deformity were predictors of unfavourable outcome. ST results in significant morbidity as a result of its insidious course and delayed diagnosis because of diagnostic and therapeutic challenges. ST should be considered in the differential diagnosis of patients with vertebral osteomyelitis, especially in tuberculosis-endemic regions. Early establishment of definitive aetiologic diagnosis and appropriate treatment are of paramount importance to prevent development of sequelae.

Genitourinary brucellosis: results of a multicentric study.

This study reviewed the clinical, laboratory, therapeutic and prognostic data on genitourinary involvement of brucellosis in this largest case series reported. This multicentre study pooled adult patients with genitourinary brucellar involvement from 34 centres treated between 2000 and 2013. Diagnosis of the disease was established by conventional methods. Overall 390 patients with genitourinary brucellosis (352 male, 90.2%) were pooled. In male patients, the most frequent involved site was the scrotal area (n=327, 83.8%), as epididymo-orchitis (n=204, 58%), orchitis (n=112, 31.8%) and epididymitis (n=11, 3.1%). In female patients, pyelonephritis (n=33/38, 86.8%) was significantly higher than in male patients (n=11/352, 3.1%; p<0.0001). The mean blood leukocyte count was 7530±3115/mm3. Routine laboratory analysis revealed mild to moderate increases for erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). The mean treatment duration and length of hospital stay were significantly higher when there were additional brucellar foci (p<0.05). Surgical operations including orchiectomy and abscess drainage were performed in nine (2.3%) patients. Therapeutic failure was detected in six (1.5%), relapse occurred in four (1%), and persistent infertility related to brucellosis occurred in one patient. A localized scrotal infection in men or pyelonephritis in women in the absence of leucocytosis and with mild to moderate increases in inflammatory markers should signal the possibility of brucellar genitourinary disease.

Phase II study of lapatinib in combination with vinorelbine in patients with HER2 positive recurrent or metastatic breast cancer: a multicentric Turkish Oncology Group (TOG) trial.

BACKGROUND: The aim of this explorative phase II study was to evaluate the activity and safety of lapatinib in combination with intravenous vinorelbine in women with HER2 positive metastatic or recurrent breast cancer. METHODS: Twenty-nine patients were enrolled. The primary objectives were response and clinical benefit (CB) rates, secondary objectives were toxicity, response duration and progression free survival. Patients received 1250 mg oral lapatinib continuously once daily and intravenous vinorelbine 20-25 mg/m(2) on days 1 and 8, every 3 weeks. RESULTS: Although 25 patients were evaluable for response, according to intend to treat analysis of 28 patients; 14% had confirmed partial response (PR) and 36% had stable disease more than 24 weeks with a CB rate of 50%. Sixty four percent of the patients suffered from grade 3-4 hematologic and 18% from grade 3 extra-hematologic toxicities. CONCLUSION: The results of this trial provide evidence to further investigate the potential of this combination for patients unsuitable for trastuzumab or who become refractory to trastuzumab.

Prognostic analysis of patients with operable gastric cancer and tolerability to adjuvant radio-chemo-therapy.

The aim of this study is to evaluate the tolerability and toxicity of adjuvant chemoradiotherapy (CRT) and to analyze the prognosis in patients with operable gastric cancer. The retrospective analysis included 723 patients with operable gastric cancer; stage IB-IV (M0), received adjuvant CRT from 8 Medical Centers in Turkey between 2003 and 2010. The patients' age, sex, tumor localization, Lauren classification, grade and stage of the disease, type of dissection, the toxicity and tolerability status and survival rate were analyzed. All patients were divided into two groups as tolerable group to adjuvant CRT and intolerable group to adjuvant CRT .Among the patient, 73.9% had stage III-IVM0 disease; 61.0% had the intestinal type of gastric cancer, 51.1% had the distal type, and 61.4% had undergone D2 dissections. The number of patients who completed the entire course of the adjuvant CRT was 545 (75.4%).The median follow-up period was 20.8 months (range: 1.5-107 months). Overall Survival (OS) rates were 80% and 52%, while the relapse free survival (RFS) rates were 75% and 48% at 1 and 3 years, respectively.In the univariate analysis of the groups based on the the age defined as <65 or ≥ 65 (p=0.16 / p=0.003), Lauren classification (p=0.004 / p<0.001), localization of tumor (p=0.02 / p=0.04), tumor grade (p=0.06 / p=0.003), disease stage (p<0.001 / p<0.001), type of dissection (p=0.445 / p=0.043), presence or absence of toxicity (p=0.062 / p=0.077) and tolerability of the therapy (p=0.002 / p=0.001). In the cox regression analysis, tumor stage (Hazard Ratio (HR): 0.332; 95% confidence interval (CI): 0.195-0.566; p<0.001), and tolerability (HR: 0.516; 95% CI: 0.305-0.872; p=0.014), were found to be related with the OS. Tumor stage (HR: 0.318; 95% CI: 0.190-0.533; p=<0.001) and tolerability (HR: 0.604; 95% CI: 0.367-0.995; p=0.048) were observed to be statistically significant in terms of the RFS.We have observed that whether a patient can or cannot tolerate adjuvant CRT due to its toxicity is an independent prognostic factor besides the known prognostic factors like tumor stage and Lauren classification. We are of the opinion that the treatment of patients who cannot tolerate adjuvant CRT should be replaced with less toxic adjuvant therapies.

Serum copper levels in benign and malignant thyroid diseases.

OBJECTIVE: To examine the changes in serum copper (Cu) levels in benign and malignant thyroid disease in humans. BACKGROUND: Thyroid hormones influence the metabolism of trace elements including copper. METHODS: 47 papillary thyroid cancer and 43 benign multinodular goitre patients who underwent total thyroidectomy and 37 healthy control subjects were included into this study. All of the patients and controls were females. Serum Cu levels were detected with atomic absorption spectrophotometer. RESULTS: In the papillary thyroid cancer group serum level of Cu was 131.61 ± 33.9 µg/dL before surgery and 120.81 ± 30.4 µg/dL after 20 days from surgery. In the benign group serum Cu level was 84.75 ± 12.1 µg/dL and 68.01 ± 9.4 µg/dL postoperatively.These results were compared to healthy control's value of 105.87 ± 10.68 µg/dL. In the papillary thyroid cancer group pre- and postoperative serum Cu level was significantly higher when compared to control group (p<0.05). Postoperative serum Cu level significantly decreased when compared to pre-operative level(p<0.05), in which, it was still higher than the control(p<0.05). In the benign group pre- and postoperative serum Cu level was significantly lower than in the control group (p<0.05).Postoperative serum Cu level significantly decreased when compared to pre-operative level in the benign group (p<0.05). CONCLUSION: This is a pioneer study to examine serum Cu level in benign and malignant thyroid patients compared to controls. In our small groups serum Cu levels increased in malignant thyroid patients and decreased in the benign group (Tab. 1, Ref. 18).

Combination of culture-dependent and culture-independent molecular methods for the determination of lactic microbiota in sucuk.

In this study, the culture-dependent and culture-independent molecular methods were used for the identification of lactic acid bacteria (LAB) in sucuk a Turkish fermented dry sausage. On the one hand, the PCR-DGGE method targetting the V1 and V3 regions of 16S DNA was applied to DNA that was directly extracted from sucuk samples. On the other hand, rep-PCR fingerprinting was performed for the primary differentiation and grouping of the isolates, and the results were confirmed by sequencing of the 16S rDNA and 16S-23S rDNA intergenic spacer region. As a result of the PCR-DGGE analysis of all the samples, total 8 different lactic acid bacteria were identified, and Lactobacillus sakei, Lactobacillus curvatus and Weissella viridescens were the dominant microbiota among these bacteria. The culture-dependent approach indicated that the majority of the strains belonged to the Lactobacillus genera including Lb. sakei, Lactobacillus plantarum, Lb. curvatus, Lactobacillus brevis, Lactobacillus farciminis and Lactobacillus alimentarius. However, Leuconostoc and Weisella were also detected as minor genera. Again, Lactococcus piscium, Weissella halotolerans, Staphylococcus succinus and the comigrated Staphylococcus piscifermentans/Staphylococcus condimenti/Staphylococcus carnosus group were detected only with the culture-independent method while Lb. plantarum, Leuconostoc mesenteroides and Leuconostoc citreum were identified only by using the culture-dependent method. In the results, it was concluded that the combination of culture-dependent and culture-independent methods was necessary for reliable and detailed investigation of LAB communities in fermented food products.

Multiple primary malignant neoplasms: multi-center results from Turkey.

PURPOSE: Multiple primary malignant neoplasms (MPMNs) are defined as a diagnosis of two or more indepen-dent primary malignancies of different histologies/origins in an individual. The frequency of MPMN is being increasing. In this study we aimed to determine the frequency and clinical features of second primary cancers (SPCs). METHODS: From January 1990 to December 2010, patients with MPMNs were screened in 5 centers. Data were obtained retrospectively from hospital charts. RESULTS: Three hundred seventy-seven patients with MPMNs were evaluated. The median age at initial cancer diagnosis was 61 years (range 18-88). The median age at second cancer was 64 years (range 20-89). The median time between two cancer diagnoses was 15 months (range 0-504). Male to female ratio was 1.44 (M/F 223/154). The most frequent initial cancer types were head and neck (54 patients, 14.3%), breast (54 patients, 14.3%), and colorectal (43 patients, 11.4%). The most frequent second cancer types were lung (76 patients, 20.2%), colorectal (39 patients, 10.3%) and breast (33 patients, 8.8%). The most common cancer pairs in females were breast-gynecologic cancers (15 patients, 9.7%), colorectal-breast cancers (9 patients, 5.8%) and breast-colorectal cancers (7 patients, 4.5%). The most common cancer pairs in males were head and neck-lung cancers (29 patients, 13%), bladder-lung cancers (9 patients, 4%), and bladder-prostate cancers (7 patients, 3%). The median follow up was 36 months (range 17horbar;595). CONCLUSION: Physicians should be aware of SPCs probabilities. Newly developed suspicious lesions should be evaluated rigorously. Histopathologic evaluations of suspicious lesions for second tumors should be used extensively if needed. In our series, the most common pairs were breast-gynecologic cancers in females and head and neck-lung cancers in males.

Postoperative changes related to intraoperative blood transfusions.

OBJECTIVE: Wound infection, flap necrosis rates and peripheral complete blood cell count changes related to intraoperative whole-blood transfusions were investigated. BACKGROUND: Evidence is growing that whole-blood cell transfusions are immunosuppressive and predispose patients to postoperative infections. METHODS: 102 female breast carcinoma patients with hemoglobin levels = 10 g/dl before modified radical mastectomy and < 10 g/dl intraoperatively but with no signs of oxygen debt were included. Group I included patients who had received two units of whole-blood transfusions intraoperatively. Patients who had received no transfusion were in group II. Peripheral complete blood cell count, wound infection rates and flap necrosis were compared. RESULTS: Perioperative neutrophile and monocyte count increased in both groups. This increase was especially significant in the transfused group (p < 0.05). In both groups, these changes returned to normal levels on the tenth postoperative day. The decreased perioperative basophile count did not return to the baseline even on the tenth postoperative day in group I (p < 0.05). Lymphocyte count, and flap necrosis did not differ between the groups (p > 0.05). Wound infection seemed to take place and increase in the transfused group (p < 0.05). CONCLUSION: Two units of whole-blood transfusions seem to increase wound infection and decrease basophile count in this series (Tab. 3, Ref. 30).

Primary mucinous eccrine adenocarcinoma of the skin in a 69-year-old man.

The authors report a rare case of primary mucinous eccrine adenocarcinoma of the skin initially diagnosed as metastatic adenocarcinoma and treated with local excision and adjuvant radiotherapy in another center. The tumor reoccurred in the left axilla 2.5 years later after the initial treatment. Diagnosis in our center was primary cutaneous eccrine mucinous adenocarcinoma. We present the clinical, histological, and immunohistochemical features of this rare tumor in the light of the searched literature.

Factors affecting seroma formation after mastectomy with full axillary dissection.

BACKGROUND AND OBJECTIVES: Seroma formation is the most common complication after breast cancer surgery, especially when axillary dissection is performed. This clinical research was undertaken to identify factors that predict the development of seroma after modified radical mastectomy for breast cancer. METHODS: 40 patients with primary breast cancer were included. Modified radical mastectomy with full axillary dissection was performed without electrocautery dissection. The seroma was diagnosed clinically by detection of the collection beneath the skin flaps. Drains were retained until the 24 h total output was < or = 40 ml. RESULTS: A total of 40 patients with a mean = age of 53 +/- 11 years were included in this study. Nine patients (27.5%) developed seroma after mastectomy. Patients with hypertension were more likely to develop seroma after mastectomy (50% versus 11% in patients without hypertension), but no such difference was found with age, tumour size, total number of lymph nodes or metastatic lymph nodes. When a drain was required for > 7 days, seroma formed more often (36.4%) as compared to when the drain stayed for a shorter time (6%). CONCLUSIONS: It is concluded that hypertension and a drainage flow rate greater than 40 mL/day for more than 7 days predict seroma formation following breast cancer surgery.

Acupuncture and immunomodulation.

Acupuncture is a well-known form of Asian medical treatment and it is used not only as an effective curative method but also to prevent illness and maintain health. It is used for the production of analgesic effect; stress related physical-mental disorders and homeostasis. Electroacupuncture (EA) stimulation, an application of electrical current on acupuncture needles, is one of the most popular types of this traditional therapy. In recent years, intensive studies have been carried out to explain the underlying mechanisms of the efficacy of acupuncture. An increase in the release of endogen opioid peptides is generally accepted to be a keystone pathway that affects the immune system after the acupuncture application. To understand the huge gap between specific skin point applications and immune responses, a vast number of accumulating data of experimental and clinical studies in the literature have been collected. This paper reviews the data to explain the updated mechanisms related to immune modulation via acupuncture therapy.

Epidemiology and etiology of catheter-related nosocomial infections in a Turkish hospital.

In this study a total of 219 patients who developed nosocomial infections and were treated in Sisli Etfal Training and Research Hospital between January 2001 and March 2003 were evaluated retrospectively. In all, 337 bacterial strains were isolated in these patients. The aim of our study was to assess the causative agents of catheter-related nosocomial infections, the distribution rate of causative agents due to hospital units, infection sites and catheter types, and determine the risk factors which facilitate such nosocomial infections. The most frequently isolated causative agents in catheter infections were Pseudomonas spp. (17%), Klebsiella spp. (16%), E. coli (13%), Acinetobacter spp. (12%), Coagulase Negative Staphylococci (CNS) (11%) and Methicillin-Resistant S. aureus (MRSA) (9%). In 136 (59%) patients infections were due to urinary catheterization and in 52 patients (23%) due to tracheal aspiration catheters. Of the 229 catheters applied, the polymicrobial infection rate was found to be 24% (55 patients). Multiple drug resistant strains were more frequently isolated in Intensive Care Units (ICU). It was emphasized that as ICUs are important risk factors for the development of catheter infections, the resistance patterns of the isolated microorganisms from the unit should be taken into consideration for the selection of appropriate antibiotics. We also conclude that it is important to avoid unnecessary catheterization and that preventive measures should be properly applied.

Acute renal failure: a common manifestation of leptospirosis.

Leptospirosis is an infectious disease caused by pathogenic leptospires and may vary in degree from an asymptomatic infection to severe and fatal illness. Sixteen patients (all males; aged 40+/-17 years) with leptospirosis were admitted to Sisli Etfal Training and Research Hospital between July 1998 and August 2003 and were retrospectively reviewed. Age, gender, occupation, clinical presentation, laboratory features, seasonal distribution of the disease, diagnostical approach, and prognostic factors were evaluated. Eleven patients were cured with no complication; four patients died of hepatic and/or renal failure. Eight patients presented with acute renal failure; seven of them needed dialytic support. One patient developed chronic renal failure and had to undergo regular hemodialysis. All deceased patients (aged 61+/-7 years) were anuric at admission and their serum bilirubin changed between 39-44 mg/dL (mean 41.3+/-2.2 mg/dL). Cured patients ranged in age from 14-62 years (34+/-14 years) and their serum bilirubin levels ranged from 9-35 mg/dL (23.1+/-11.4 mg/dL). Crystalline penicillin G 12 million U/day was administered to all patients. Six patients also received hepatic coma treatment. This study emphasizes that leptospirosis presenting with renal failure is a severe disease, and mortality is frequently related to delays in diagnosis due to lack of clinical understanding. The association of acute renal failure and jaundice should lead the clinician to suspect leptospirosis. We concluded that old age, oliguria/anuria, high serum bilirubin levels (>36 mg/dL), and high serum potassium levels might be risk factors that increase mortality in leptospirosis.

Sublingual isosorbide dinitrate-stimulated tilt test for diagnosis of vasovagal syncope in children and adolescents.

Vasovagal syncope is the most likely cause of syncope in the young. Head-up tilt-table test (HUT) provides the ability to provoke vasovagal syncope under controlled laboratory settings. In adult populations, pharmacologic stimulation with intravenous/sublingual isosorbide dinitrate (ISDN) has been shown to be an alternative to isoproterenol for increasing the diagnostic yield of HUT. In this study, 40 patients aged 9-18 years with unexplained syncope and 12 healthy age-matched children were evaluated by HUT to 70 degrees for 45 minutes. If tilting alone did not induce symptoms (syncope and presyncope), 0.1 mg/kg ISDN was given while the patient lay supine. After 5 min, the table was tilted to 70 degrees for 15 min or until the symptoms occurred. The control group consisted of 12 healthy age-matched children studied in a similar manner. Six patients (15%) had a positive basal tilt test. Twenty-five patients (62.5%) lost consciousness following ISDN administration. In the control group, nobody had a syncopal episode during the basal tilt test. However, ISDN administration resulted in 1 positive response (8.3%). The sensitivity of the test was 77.5% and its specificity was 91.6%. It is concluded that sublingual nitroglycerin HUT is suitable for routine clinical practice in children and adolescents with unexplained syncope.

Whipple's disease confined to the central nervous system: case report and review of the literature.

Whipple's disease confined exclusively to the CNS without systemic involvement appears to be very rare, with only 8 cases reported in the literature. We present here a further case of primary cerebral Whipple's disease in which the neurological symptoms were seen in the absence of systemic involvement and emphasize the importance of diagnosing this treatable disease.

Conservative treatment of diabetic foot infections.

Foot infections commonly occur in diabetic patients, constituting a serious problem. 15% of diabetic have foot infections during their life-time. In previous years these life- threatening infections in 50-70% of patients resulted in limb amputation. Today, using an aggressive surgical approach, broad spectrum antimicrobial chemotherapy and intensive regulation of blood glucose level, the amputation rate has decreased to 5%. During the last 2 years, we evaluated 13 diabetic foot infections. 6 of the presented cases were grade 4 and 5, 3 of them grade 3 and 4 of them grade 2. All of the patients were managed by multidisciplinary approach consisting of plastic and reconstructive surgery, endocrinology and infectious diseases specialists. All of the patients were monitored with daily wound care, regulation of blood glucose levels and administration of broad spectrum antibiotics. Only one of them required amputation. For 12 of the cases after the infection was controlled, the defects were reconstructed by plastic surgical procedures. We retrospectively analysed them to review diabetic foot infections and factors affecting prognosis.