Valor predictivo de los índices 18F-FDG PET/TC sobre la carga tumoral residual en pacientes con cáncer de mama extenso tratadas con quimioterapia neoadyuvante / Predictive value of 18F-FDG PET/CT indices on extensive residual cancer burden in breast cancer patients treated with neoadjuvant chemotherapy

Objetivo: Investigamos la correlación entre los índices de PET/TC con 18F-FDG y la respuesta patológica en el cáncer de mama tratado con quimioterapia neoadyuvante (QNA), que se puntuó con el sistema de carga de cáncer residual (RCB) después de la cirugía. Nuestro objetivo es detectar antes una carga extensa de cáncer residual mediante el uso de los índices de PET/TC. Métodos: Se recuperaron las características de las pacientes de forma retrospectiva. Se calculó el valor máximo de captación estándar (SUVmáx), el volumen metabólico del tumor (MTV) y los índices de glucólisis total de la lesión (TLG), así como la tasa de reducción (RR) entre la línea de base y la evaluación intermedia, con la exploración FDG PET/TC. Todos los pacientes fueron evaluados según las puntuaciones RCB después de la cirugía. Las respuestas patológicas y los resultados de las mediciones de PET/TC se analizaron con parámetros demográficos y clínicos. Resultados: Un total de 95 pacientes fueron incluidos en el estudio. Según las respuestas patológicas, la distribución de RCB-0, -1, -2, -3 fue de 13 (13,7%), 11 (11,6%), 30 (31,6%) y 41 (43,2%), respectivamente. La supervivencia libre de enfermedad fue significativamente menor en el grupo RCB-3 en comparación con el grupo de respuesta patológica (p=0,01). Según el análisis multivariante, se determinó que el RR del SUVmáx era una variable independiente que predecía la RCB extensa con un valor de corte óptimo del 86% (p<0,05). Conclusiones: Determinamos el RR de SUVmáx como un factor independiente para predecir la carga tumoral residual extensa. Creemos que el RR de SUVmáx es suficiente para predecir la respuesta patológica en la práctica diaria. Además, las mediciones de MTV y TLG no contribuyen adicionalmente al SUVmáx por sí solas y pueden causar una pérdida de trabajo innecesaria (AU)

Aim: We investigated the correlation between 18F-FDG PET/CT indices and pathological response in breast cancer treated with neoadjuvant chemotherapy (NACT) which was scored with Residual Cancer Burden (RCB) system after surgery. Our aim is to detect extensive residual cancer burden earlier by using PET/CT indices. Methods: Characteristics of patients were retrieved retrospectively. Baseline maximum Standart Uptake Value (SUVmax), Metabolic Tumor Volume (MTV) and Total Lesion Glycolysis (TLG) indices and reduction rate (RR) between baseline and interim evaluation were calculated with FDG PET/CT scan. All patients were evaluated according to RCB scores after surgery. Pathological responses and PET/CT measurement results were analyzed with demographic and clinical parameters. Results: A total of 95 patients were included in the study. According to pathological responses, the distribution of RCB-0, -1, -2, -3 were 13 (13.7%), 11 (11.6%), 30 (31.6%), 41 (43.2%), respectively. Disease-free survival was significantly lower in the RCB-3 group compared to the pathological responder group (P=.01). According to multivariate analysis, RR of SUVmax was determined as an independent variable predicting extensive residual cancer burden with an optimal cut-off value of 86% (P<.05). Conclusions: We determined RR of SUVmax as an independent factor for predicting extensive residual tumor burden. We believe that RR of SUVmax is sufficient to predict pathological response in daily practice. In addition, MTV and TLG measurements do not contribute additionally to SUVmax alone and can cause unnecessary labor loss (AU)

Relation between sarcopenia and dose-limiting toxicity in patients with metastatic colorectal cancer who received regorafenib.

BACKGROUND: Sarcopenia is related to poor prognosis and drug toxicities in solid tumors. The aim of our study is to investigate the predisposition of patients with metastatic colorectal carcinoma who started regorafenib treatment to sarcopenia and prolonged survival. METHODS: Patients with metastatic colorectal carcinoma who receives regorafenib were search retrospectively. Dose-limiting toxicity was defined as dose reduction or toxicity requiring drug withdrawal. Sarcopenia evaluation was made with computed tomography performed within a month before treatment. Progression-free survival and overall survival were estimated. RESULTS: Thirty-six patients were found as suitable for the study. 63.9% of patients were found as basally sarcopenic. Dose-limiting toxicity occured 13 of 23 patients (56.5%) with basal sarcopenia, whereas only 1 of 13 patients (7.6%) with no sarcopenia exhibited dose-limiting toxicity (p = 0.005). Three patients suffered from grade 3-4 toxicity. Hand-foot syndrome, hypertension, and mucosal rash were the most seen side effects. Mean regorafenib treatment duration was 3.36 months. There was no significant difference in the progression-free survival (PFS) and the overall survival (OS) between sarcopenic patients and patients with no sarcopenia. Durations were as OS 24.2 weeks in patients with sarcopenia (95% CI 16.7-31.7), 28.1 weeks in patients with no sarcopenia (95% CI 20.5-35.7) (p = 0.36), and as PFS 14.2 weeks in patients with sarcopenia (95% CI 12.1-16.4), 14.8 weeks in patients with no sarcopenia (95% CI 9.7-20.1) (p = 0.65). CONCLUSION: Dose-limiting toxicity was significantly higher in basally sarcopenic patients who were started regorafenib as treatment of metastatic colorectal carcinoma. There was no significant relationship between overall survival and progression-free survival with sarcopenia.

Skeletal muscle loss during anti-EGFR combined chemotherapy regimens predicts poor prognosis in patients with RAS wild metastatic colorectal cancer.

PURPOSE: We aimed to assess whether anti-EGFR combined chemotherapy regimens are related with loss of skeletal muscle mass and to compare cetuximab and panitumumab therapies in the aspect of skeletal muscle area change as well as to assess whether skeletal muscle mass loss has prognostic significance in the RAS wild mCRC patients. MATERIALS AND METHODS: A total of 56 patients (30 patients in cetuximab arm and 26 patients in panitumumab) who had computed tomography images were retrospectively evaluated at the diagnosis and follow up during the treatment period before progression. RESULTS: During treatment period 24 patients (42.8%) had muscle loss. Of these, 7 (29.2%) patients were treated at first-line and 17 (70.8%) patients were treated at second-line setting. There was no significant difference in the aspect of skeletal muscle loss among cetuximab and panitumumab combined treatment regimens. Median PFS was 9.1 (8.6-9.6) months in muscle loss group and 13.9 (7.2-20.6) months in muscle stable group (p = 0.001). Median OS was 23.4 (95% CI 15.8-31.0) months in muscle stable group and 19.1 (95% CI 17.0-21.3) months in muscle loss group (p = 0.57) at first-line setting. For second-line, median OS was 21.2 (14.7-27.7) months in muscle stable group and 14.4 (6.0-22.4) months in muscle loss group (p = 0.003). CONCLUSIONS: Decrease in skeletal muscle mass before progression on CT imaging is an independent indicator for shorter PFS value in RAS WT mCRC patients who received anti-EGFR combined chemotherapy regimens at both the first and second-line settings. Beside that shorter overall survival values also were significantly seen in patients who had muscle loss during anti-EGFR therapy in the second-line setting.

Assessment of left ventricular systolic and diastolic dyssynchrony with tissue Doppler echocardiography in patients with heart failure and narrow QRS complex.

AIM: Cardiac dyssynchrony is a well known entity in patients with wide QRS complex (>120 ms). Dyssynchrony may also cause ventricular dysfunction in heart failure patients with narrow QRS complexes. In the study, the presence and extent of cardiac dyssynchrony were investigated in patients with heart failure both with narrow and wide QRS complexes using tissue Doppler echocardiography (TDE). METHODS: Forty-nine patients with heart failure, were included to the study. The first group of 30 patients with a QRS duration of <120 ms (23M; mean age, 64±10.1 years) and the second group consisted of 19 patients with a QRS duration of >120 ms (12M; mean age, 65±11.6 years). In order to examine cardiac synchronization, TDE was performed. Systolic and diastolic intraventricular dyssynchrony and interventricular dyssynchrony were calculated. In order to define systolic and diastolic dyssynchrony, intraventricular delay was accepted as >60 ms, and interventricular delay was accepted as >40 ms. RESULTS: Left ventricular systolic dyssynchrony was detected in 18 patients (60%) within the narrow QRS group and in 18 patients (94%) within the wide QRS group. Interventricular dyssynchrony was detected in 17 patients (56%) within the narrow QRS group and in 18 patients (94%) within the wide QRS group. For systolic dyssynchrony, correlations existed between intraventricular delay and QRS duration (r=0.48), left ventricular end diastolic diameter (r=0.62), left ventricular end systolic diameter (r=0.61), and EF (r=-0.63). Similarly, correlations existed between interventricular delay and QRS duration (r=0.58), left ventricular end diastolic diameter (r=0.65), left ventricle end systolic diameter (r=0.64), and EF (r=-0.64). CONCLUSION: The present study suggested that systolic or diastolic dyssynchrony exists despite normal levels of QRS duration.

N-acetyl cysteine promotes angiogenesis and clearance of free oxygen radicals, thus improving wound healing in an alloxan-induced diabetic mouse model of incisional wound.

BACKGROUND: This study investigated whether N-acetyl cysteine induces any favourable effects on cutaneous incisional wound healing in diabetic and nondiabetic mice. The wounds were assessed using detection of vascular endothelial growth factor (VEGF) and inducible nitric oxide synthase (iNOS) expression, and wound-breaking strength (WBS) measurements. METHODS: In total, 48 BALB/c mice were used. These were divided into four groups, each consisting of 12 mice. Incisional wounds were made on the back of each mouse. Two of the groups consisted of healthy animals and the other two groups consisted of mice with alloxan-induced diabetes. One group of healthy mice and one group of diabetic mice received intraperitoneal N-acetyl cysteine (NAC) 150 mg/kg for 5 consecutive days, while the other two groups were untreated. On the fifth day all animals were killed, and the WBS, oxidative stress parameters, histopathological and immunohisotchemical results were assessed. RESULTS: Both diabetic and nondiabetic mice receiving NAC had lower levels of oxidative stress markers and higher WBS measurements than untreated counterparts. CONCLUSIONS: A mouse model of incisional wound treated with NAC resulted in lower levels of tissue oxidative stress, higher levels of tissue glutathione, and downregulation of iNOS expression coupled with upregulation of VEGF expression, producing an overall favourable clinical outcome of higher WBS and a shorter wound-healing period both in diabetic and nondiabetic mice. Both antioxidant and anti-inflammatory properties of NAC may be involved in this improved healing process for incisional wounds.

Determination of vitreous interleukin-1 (IL-1) and tumour necrosis factor (TNF) levels in proliferative diabetic retinopathy.

We measured interleukin-1 beta (IL-1beta) and tumour necrosis factor-alpha (TNF-alpha) in the vitreous humour and serum of patients with proliferative diabetic retinopathy (PDR), in order to determine the role of these cytokines in the pathogenesis of the disease. Vitreous and serum samples were collected from 21 patients with PDR who were undergoing pars plana vitrectomy. Control vitreous samples were obtained from cadavers and control serum samples from healthy subjects. The cytokines were measured by enzyme-linked immunosorbent assay. Vitreous IL-1beta and TNF-alpha concentrations in patients with PDR exceeded those of controls (P<0.05), as did serum IL-1beta and TNF-alpha. We suggest that increased vitreous IL-1beta and TNF-alpha levels may play a significant role in the pathogenesis of PDR, which features abnormal cell proliferation and neovascularisation.

Effect of hyperthyroidism and propylthiouracil treatment on liver biochemical tests.

Liver biochemical test (LBT) changes can be commonly observed in hyperthyroid patients. Those kinds of changes could also be observed because of propylthiouracil (PTU) therapy. We prospectively evaluated LBT changes because of PTU use for 1 year in patients who had been diagnosed with hyperthyroidism first. We studied 64 patients who had been diagnosed with hyperthyroidism. These patients took at least 1-year PTU treatment. We analysed LBT at diagnosis and after 2 and 12 months of treatment with PTU. Prior to PTU treatment, 30 (46.8%) of the 64 patients had at least one LBT abnormality. We observed at least one LBT abnormality in 11 (32%) patients after 2 months and nine (26%) patients after 12 months of treatment with PTU in 34 patients whose CBT were normal before treatment. We did not observe any deterioration in clinical picture and bilirubin levels. Elevated serum LBT during the pretreatment and PTU treatment period is common and usually transient and asymptomatic. PTU could be used for long times by lowering the dose and close follow-up in patients who have elevated LBT during the pretreatment and after PTU treatment period.

Pars plana vitrectomy in ocular Behçet's disease.

PURPOSE: To evaluate the results of pars plana vitrectomy in Behçet patients with dense vitreous opacities, and its effect on intraocular inflammatory episodes and visual prognosis. METHODS: The study group consisted of nine patients (one eye in eight patients, both eyes in one) with Behçet's disease who underwent pars plana vitrectomy because of dense vitreous opacification. The indications for vitrectomy, the effect of vitrectomy on the frequency of severe intraocular inflammatory episodes, and visual prognosis were investigated in these patients. All the patients were male, and their ages ranged between 28-45 years. Combined lensectomy was performed on those with complicated cataracts. The postoperative follow-up was between 12-66 months. RESULTS: In all of the patients preoperative visual acuity was hand motions. Postoperatively there was no change in vision in five eyes, however visual acuity improved in five eyes, between counting fingers and 0.4. None of the patients showed any severe postoperative intraocular inflammatory episodes, and phthisis did not develop in any of the patients. CONCLUSION: In this study, pars plana vitrectomy was found to have a beneficial effect on the prognosis of vision. There was also a decrease in the frequency of severe intraocular inflammatory episodes in patients with Behçet's disease with severe vitreous opacities, who did not respond to maximum medical treatment. However, further studies on larger groups should be performed in order to confirm the findings of this study.

Effect of hyperbaric oxygen therapy on fetal spinal grafts: an experimental study.

In neural transplantation, lack of oxygen supply to the graft in acute stage is an important problem. This study was undertaken to evaluate the effects of hyperbaric oxygen (HBO2) on fetal spinal grafts. Spinal cord tissues obtained from 16-day fetal rats were transplanted into the spinal cord of adult Wistar rats (n = 30). After transplantation, they were randomly divided into two groups (n = 15 for each group); Group 1 received transplant alone, group 2 received transplant and HBO2 therapy consisting of 100% oxygen at 2.5 atm abs for 90 min twice a day for 7 days. Seven days after their surgery, all animals were killed for histologic examination. Degenerative changes, parenchymal integrity, host spinal cord edema, and vascularization of the graft were scored on a 3-point scale. Scores of these parameters were statistically analyzed. The graft survival rates in groups 1 and 2 were 54.5% and 71.4%, respectively. Animals treated with HBO2 showed statistically less spinal cord edema than the untreated groups (P < 0.05). Parenchymal integrity was also significantly better in this group (P < 0.05). The results indicate that edema reduction effect of HBO2 prevents the displacement of graft from the gap and contributes to the integration between the graft and host.

MR imaging for early complications of transpedicular screw fixation.

This series comprises ten patients treated with transpedicular screw fixation, who suffered early postoperative problems such as radicular pain or motor weakness. Besides plain radiographs, all patients were also evaluated with MR imaging. Three patients were reoperated for either repositioning or removal of the screws. MR images, especially T1-weighted ones, were very helpful for visualizing the problem and verifying the positions of the screws. In cases of wide areas of signal void around the screws, the neighboring axial MR images at either side, which have fewer artifacts, gave more information about the screws and the vertebrae.

Iatrogenic arachnoid cyst with distinct clinical picture as a result of bone defect in the floor of the middle cranial fossa: case report.

OBJECTIVE AND IMPORTANCE: This kind of arachnoid cyst has not previously been described as a complication of a cranial base bone defect. Recognition of this rare complication may be delayed, because clinicians are unaware of its possibility. CLINICAL PRESENTATION: A 22-year-old man presented with severe headache and increasing difficulty in breathing and swallowing. A physical examination revealed a pulsatile mass in the oral cavity, arising from the parapharyngeal area. A cystic mass that protruded into the oral cavity, through a dural and bony defect in the left middle fossa, was detected on neuroimages. INTERVENTION: A left frontotemporal craniotomy was made, and the cyst was decompressed. Duraplasty was performed with lyophilized dura. The bone defect was managed with a calvarial free bone graft and a pedicled myofacial flap. Serial neuroimaging studies performed postoperatively showed that the cyst had decreased in size. CONCLUSION: This report describes an unusual complication of a cranial base bone defect. Although not all bone defects in the cranial base require reconstruction, management of the large bone defect, particularly in the middle fossa, should preferably be accomplished with the help of a bone graft to support the dural graft.

Untreated growing cranial fractures detected in late stage.

OBJECTIVE: Because the great majority of published cases of treated growing cranial fractures (GCFs) involved infants and children, the natural evolution of untreated GCFs is not well known. The question of whether untreated GCFs may cause progressive neurological deficits is controversial. METHODS: This retrospective study is of GCFs treated between 1989 and 1997. Nine patients (eight male patients and one female patient; median age, 20.5 yr) with GCFs who underwent surgical intervention during the late stage are presented. The dural and cranial defects were repaired, and additional decompressive surgical procedures (cyst fenestration, n = 6; cyst excision, n = 1; cyst excision with cystoperitoneal shunting, n = 2) were performed for all patients. This is the largest of the published series. RESULTS: All of the patients had histories of severe head trauma that occurred during childhood. The average age at the time of the onset of symptoms was approximately 13.1 years, and the interval between head injury and first symptom ranged from 8 to 13 years. All of the patients had lytic lesions in the cranium. Headache was the most common symptom, and of eight patients, seven improved completely and one improved partially. One of four epileptic patients was seizure-free postoperatively. None of the paresis improved, except in one patient. CONCLUSION: We conclude that untreated GCFs may cause delayed onset neurological manifestations in addition to cranial growth asymmetry. GCFs, discovered incidentally in adolescence or adulthood without any neurological deficits, should be operated on as soon as feasible to prevent further brain destruction. Cranioplasty with dural repair, in addition to cyst fenestration, should be considered as the essential procedure for the treatment of these lesions.

Etiology of pediatric perforating eye injuries in southern Turkey.

In the present study, the records of 242 children, aged 1-14 years, admitted with perforating ocular injury were reviewed retrospectively over a 5-year period. There were 175 boys and 67 girls in the study group. The patients were divided into 3 groups according to their ages. Perforating injuries occurred most frequently in the street in all groups. The second most common place of the injury was at home in the 1-9 year-olds and in the fields in the 10-14 year-olds. The cause of the perforation was a metallic substance in 32.6%, wood in 15.3%, stone in 12.0%, glass in 12.3%, pellets in 12%, and injection needles in 8.3%. Most of the perforations occurred during unsupervised play, while all perforations with glass occurred during traffic accidents. Surgery was performed in 234 patients, while 8 patients in whom spontaneous closure had already occurred during admission received only medical treatment. In 28.9% the visual acuity was undetermined, in 25.7% the visual acuity was 0.1 or more, in 22.7% the visual acuity was between 0.06 and light perception, and in 22.7% there was no light perception on final evaluation. It is emphasized that educative and legislative measures such as informing the parents, teachers and children about the causative factors and potential hazards of perforating ocular injuries and restricting the availability of dangerous items to children, should be taken into consideration in order to prevent perforating ocular injuries in children.

Clinical features of Bardet-Biedl syndrome.

Six patients with Bardet-Biedl syndrome who have been followed in our clinics for the last 5 years are reported in this study. Of the five classic features of this syndrome; obesity and mental retardation were present in all cases, retinal disturbances were present in five, polydactyly in three and hypogenitalism was observed in all four male patients. Renal involvement, often suggested as a cardinal feature of this syndrome, was described in two patients. Iron deficiency anemia occurred in three patients, two patients were of short stature, one patient presented with an empty sella, and in two patients clinodactyly was detected. The results are compared to previously published literature and discussed.

Early clinical and ultrastructural effects of diltiazem injection on rabbit extraocular muscles.

We injected diltiazem into the left lateral rectus muscles (LR) of 10 rabbits in order to examine the ultrastructural effects of diltiazem on rabbit extraocular muscles and estimate its advantages in clinical use as an alternative to the surgical therapy of strabismus. The animals were divided into two groups according to the time of evaluation following the injection. The LR muscles of both eyes of the first group were respected 60 min after the injection, for ultrastructural examination. The same procedure was done for the second group at the 24th hour. The right eyes were used as the control group. There was a medial shift 3-5 min following the injection in the left eyes of both groups. The ultrastructural examination revealed weakness in muscle contractility, probably as a result of inhibition of glycogen usage due to calcium accumulation. In this study, we examined the early clinical and ultrastructural effects of diltiazem.

PUVA treatment and choroidal malignant melanoma.

Choroidal malign melanoma showing rapid progression in a boy 17 years old is presented. The patient was under therapy with methoxy psoralen + Ultraviolet A (PUVA)* for psoriasis vulgaris. He had undergone complete ophthalmologic examinations with three-month intervals from the beginning of this therapy. The tumor was detected in the seventh month, rapidly enlarging within the next twenty days, and eventually leading to enucleation. PUVA is known to be a risk factor for cutaneous malign melanoma. However, there is no reported incidence of choroidal malign melanoma in PUVA treated patients. To our knowledge, this is the only case showing the possible role of PUVA therapy as a predisposing factor in the development of uveal malign melanoma.