Impact of Relative Dose Intensity (RDI) on Survival in Non-Metastatic Breast Cancer: Nigerian Experience

Background: This study was initiated to determine practices patterns in adjuvant chemotherapy for non-metastatic breast cancer and to examine the relationship between received dose intensity (RDI) and survival in patients with breast cancer Nigeria. Methods: Our study was a retrospective analysis of patients with breast cancer recruited from 2012 and 2015. A total of 204 patients were initially entered into the study, 102 were lost to follow-up leaving 102 patients who were suitable for the survival analysis. Survival time was calculated from 106 days, the scheduled end of chemotherapy. Results: The total average RDI for patients was 74%. Over the 204 patients that were reviewed, 144 (70.6%) had some reduction of RDI. This subgroup had an average RDI of 63%. On average, 79% of the intended dose of chemotherapy was given. The time to completion of chemotherapy was 1.33 times that specified by the protocol. Dose delays an overall reduction was mainly attributed to intolerability and financial constraints. Survival by RDI showed a significant decrease in survival rate for patients with RDI of >49% (Hazard Ratio = 3.473, 95% CI 1.21 - 9.91, P = 0.020);RDI of 50% - 59% (Hazard Ratio = 3.916, 95% CI 1.01 - 15.18, P = 0.048);RDI of 60% - 69% (Hazard Ratio = 4.462, 95% CI 1.65 - 12.03, P = 0.003) compared with patients who received an RDI of 100%. Although associated with poorer prognosis, there were no significant changes in the survival rate for patients with RDI of 70% - 79% (Hazard Ratio = 1.667, 95% CI 0.56 - 4.96, P = 0.359);RDI of 80% - 89% (Hazard Ratio = 1.620, 95% CI 0.47 - 5.53, P = 0.441);RDI 90% - 99% (Hazard Ratio = 1.590, 95% CI 0.53 - 4.73, P = 0.405) compared with patients who received an RDI of 100%. Conclusion: This study provides evidence that decreased RDI of <70% in non-metastatic breast cancer patients is strongly associated with decreased overall survival.

p53 gene in treatment of hepatic carcinoma:Status quo

Hepatocellular carcinoma (HCC) is one of the 10 most common cancers worldwide. There is no ideal treatment for HCC yet and many researchers are trying to improve the effects of treatment by changing therapeutic strategies. As the majority of human cancers seem to exhibit either abnormal p53 gene or disrupted p53 gene activation pathways, intervention to restore wild-type p53 (wt-p53) activities is an attractive anti-cancer therapy including HCC. Abnormalities of p53 are also considered a predisposition factor for hepatocarcinogenesis. p53 is frequently mutated in HCC. Most HCCs have defects in the p53-mediated apoptotic pathway although they carry wt-p53. High expression of p53 in vivo may exert therapeutic effects on HCC in two aspects: (1) High expression of exogenous p53 protein induces apoptosis of tumor cells by inhibiting proliferation of cells through several biologic pathways and (2) Exogenous p53 renders HCC more sensitive to some chemotherapeutic agents. Several approaches have been designed for the treatment of HCC via the p53 pathway by restoring the tumor suppression function from inactivation, rescuing the mutated p53 gene from instability, or delivering therapeutic exogenous p53. Products with p53 status as the target have been studied extensively in vitro and in vivo . This review elaborates some therapeutic mechanisms and advances in using recombinant human adenovirus p53 and oncolytic virus products for the treatment of HCC.

Comparison of different magnetic resonance imaging sequences for assessment of fistula-in-ano

AIM: To assess agreement between different forms of T2 weighted imaging(T2WI), and post-contrast T1WI in the depiction of fistula tracts, inflammation, and internal openings with that of a reference test. METHODS: Thirty-nine consecutive prospective cases were enrolled. The following sequences were used for T2WI: 2D turbo-spin-echo(2D T2 TSE); 3D T2 TSE; short tau inversion recovery(STIR); 2D T2 TSE with fat saturation performed in all patients. T1WI were either a 3D T1-weighted prepared gradient echo sequence with fat saturation or a 2D T1 fat saturation [Spectral presaturation with inversion(SPIR)]. Agreement for each sequence for determination of fistula extension, internal openings, and the presence of active inflammation was assessed separately and blindly against a reference test comprised of follow-up, surgery, endoscopic ultrasound, and assessment by an independent experienced radiologist with access to all images.RESULTS: Fifty-six fistula tracts were found: 2 intersphincteric, 13 trans-sphincteric, and 24 with additional tracts. The best T2 weighted sequence for depiction of fistula tracts was 2D T2 TSE(Cohen's kappa = 1.0), followed by 3D T2 TSE(0.88), T2 with fat saturation(0.54), and STIR(0.19). Internal openings were best seen on 2D T2 TSE(Cohen's kappa = 0.88), followed by 3D T2 TSE(0.70), T2 with fat saturation(0.54), and STIR(0.31). Detection of inflammation showed Cohen's kappa of 0.88 with 2D T2 TSE, 0.62 with 3D T2 TSE, 0.63 with STIR, and 0.54 with T2 with fat saturation. STIR, 3D T2 TSE, and T2 with fat saturation did not make any contributions compared to 2D T2 TSE. Post-contrast 3D T1 weighted prepared gradient echo sequence with fat saturation showed better agreement in the depiction of fistulae(Cohen's kappa = 0.94), finding internal openings(Cohen's kappa = 0.97), and evaluating inflammation(Cohen's kappa = 0.94) compared to post-contrast 2D T1 fat saturation or SPIR where the corresponding figures were 0.71, 0.66, and 0.87, respectively. Comparing the best T1 and T2 sequences showed that, for best results, both sequences were necessary. CONCLUSION: 3D T1 weighted sequences were best for the depiction of internal openings and active inflammatory components, while 2D T2 TSE provided the best assessment of fistula extension.

A rare case of pregnancy complicated by mesenteric mass:What does chylous ascites tell us?

Mesenteric fibromatosis is a rare benign nonmetastatic neoplasm that appears as a sporadic lesion or occurs in patients with familial polyposis, while chylous ascites associated with aggressive mesenteric fibromatosis during pregnancy has never been reported thus far. Here we present the case of a 28-year old pregnant woman, in whom an aggressive mesenteric fibromatosis with chylous ascites was detected, involving the jejunum, superior rnesenteric artery （SMA） and superior rnesenteric vein （SMV） and pancreas. One year after a successful surgical excision, the patient had no signs of recurrence. The authors report the case for its rarity and emphasize on combining clinicopathological, radiological and immunohistochemistry analysis for management of the disease.

The Pyramidal Lobe of the Thyroid

Anatomy of the thyroid has been extensively studied but the presence of pyramidal lobe varies in percentages from 15% to 75% of cases according to different authors. We therefore investigated systematically this peculiar anatomical aspect. From January 2001 to December 2011, 1002 patients underwent total thyroidectomy in our Division of General Surgery. We analyzed the data collected on the latest 200 thyroidectomies: for all patients pyramidal lobe was measured at removal of the specimen then dimension of the pyramidal lobe after fixation was checked. We found the pyramidal lobe in all cases. In most cases, it was approximately 2 cm (range 1 - 8 cm on fresh specimen). At histology it was described in 72% of cases, after fixation size decreased by a third approximatively. This is the first systematic intraoperative study to verify the prevalence of the thyroid pyramidal lobe. In our experience, the pyramidal lobe is always present and the thyroglossal duct is identifiable.

Liver metastases:Contrast-enhanced ultrasound compared with computed tomography and magnetic resonance

The development of ultrasound contrast agents with excellent tolerance and safety profiles has notably improved liver evaluation with ultrasound(US)for several applications,especially for the detection of metastases.In particular,contrast enhanced ultrasonography(CEUS)allows the display of the parenchymal microvasculature,enabling the study and visualization of the enhancement patterns of liver lesions in real time and in a continuous manner in all vascular phases,which is similar to contrast-enhanced computed tomography(CT)and contrast-enhanced magnetic resonance imaging.Clinical studies have reported that the use of a contrast agent enables the visualization of more metastases with significantly improved sensitivity and specificity compared to baseline-US.Furthermore,studies have shown that CEUS yields sensitivities comparable to CT.In this review,we describe the state of the art of CEUS for detecting colorectal liver metastases,the imaging features,the literature reports of metastases in CEUS as well as its technique,its clinical role and its potential applications.Additionally,the updated international consensus panel guidelines are reported in this review with the inherent limitations of this technique and best practice experiences.

Neo-adjuvant radiotherapy in rectal cancer

In rectal cancer treatment,attention has focused on the local primary tumour and the regional tumour cell deposits to diminish the risk of a loco-regional recurrence.Several large randomized trials have also shown that combinations of surgery,radiotherapy and chemotherapy have markedly reduced the risk of a locoregional recurrence,but this has not yet had any major influence on overall survival.The best results have been achieved when the radiotherapy has been given preoperatively.Preoperative radiotherapy improves loco-regional control even when surgery has been optimized to improve lateral clearance,i.e.,when a total mesorectal excision has been performed.The relative reduction is then 50%-70%.The value of radiotherapy has not been tested in combination with more extensive surgery including lateral lymph node clearance,as practised in some Asian countries.Many details about how the radiotherapy is performed are still open for discussion,and practice varies between countries.A highly fractionated radiation schedule(5 Gy×5),proven efficacious in many trials,has gained much popularity in some countries,whereas a conventionally fractionated regimen(1.8-2.0 Gy×25-28),often combined with chemotherapy,is used in other countries.The additional therapy adds morbidity to the morbidity that surgery causes,and should therefore be administered only when the risk of loco-regional recurrence is sufficiently high.The best integration of the weakest modality,to date the drugs(conventional cytotoxics and biologicals)is not known.A new generation of trials exploring the best sequence of treatments is required.Furthermore,there is a great need to develop predictors of response,so that treatment can be further individualized and not solely based upon clinical factors and anatomic imaging.

Giant myxoinflammatory fibroblastic sarcoma with bone invasion:a very rare clinical entity and literature review

Myxoinflammatory fibroblastic sarcoma(MIFS) is a rare low-grade, malignant soft tissue tumor that is usually observed in the extremities of adult patients. Magnetic resonance imaging findings for this tumor type have rarely been reported. We report a case involving the distal left femur of a middle-aged man and tumoral invasion of the bone, which, to our knowledge, has been previously described only once. He was treated with distal femoral tumor resection and reconstruction with a modular prosthesis. Histopathologic diagnosis confirmed MIFS. We reviewed literature of the diagnostic imaging and bone invasion findings associated with this tumor type.

^(11)C-PK11195 plasma metabolization has the same rate in multiple sclerosis patients and healthy controls:a cross-sectional study

^(11)C-PK11195 is a positron emitter tracer used for Positron Emission Tomography(PET)imaging of innate immune cell activation in studies of neuroinflammatory diseases.For the image quantitative analysis,it is necessary to quantify the intact fraction of this tracer in the arterial plasma during imaging acquisition(plasma intact fraction).Due to the complexity and costs involved in this analysis it is important to evaluate the real necessity of individual analysis in each 11C-PK11195 PET imaging acquisition.The purpose of this study is to compare 11CPK11195 plasma metabolization rate between healthy controls and multiple sclerosis(MS)patients and evaluate the interference of sex,age,treatment,and disease phenotype in the tracer intact fraction measured in arterial plasma samples.11C-PK11195 metabolization rate in arterial plasma was quantified by high performance liquid chromatography in samples from MS patients(n=50)and healthy controls(n=23)at 20,45,and 60 minutes after 11C-PK11195 injection.Analyses were also stratified by sex,age,treatment type,and MS phenotype.The results showed no significant differences in the metabolization rate of healthy controls and MS patients,or in the stratified samples.In conclusion,11C-PK11195 metabolization has the same rate in patients with MS and healthy controls,which is not affected by sex,age,treatment,and disease phenotype.Thus,these findings could contribute to exempting the necessity for tracer metabolization determination in all 11C-PK11195 PET imaging acquisition,by using a population metabolization rate average.The study procedures were approved by the Ethics Committee for Research Projects Analysis of the Hospital das Clinicas of the University of Sao Paulo Medical School(approval No.624.065)on April 23,2014.

Lessons learned from a young man with recurrent metastasis parathyroid carcinoma with failed combination treatment

Parathyroid carcinoma is an extremely rare malignant tumor,composed primarily of vacuolated principal cells,but may also be composed of eosinophils.The exact etiology and pathogenesis of parathyroid carcinoma is unknown,and head and neck radiation exposure,chronic stimulation from renal failure,and familial syndromes can lead to the development of parathyroid carcinoma.Most parathyroid carcinoma is difficult to distinguish from benign HPT and is often diagnosed only when there is a recurrence of hypercalcemia several years later,which can manifest as weight loss,extreme fatigue,anorexia,and muscle atrophy.At present,surgical resection remains the primary treatment.In this case,the patient underwent initial surgery for primary hyperparathyroidism and was subsequently diagnosed with parathyroid carcinoma.During the 8 years of follow-up,the patient underwent 7 surgeries in combination with radiation therapy,chemotherapy and targeted medications.Although the neck tumor was cured,the patient died of complications related to hypercalcemia.We will review the literature on the combination of surgery,radiotherapy,chemotherapy,and targeted drug therapy in order to improve the diagnosis and treatment of parathyroid carcinoma.

Detection sensitivity of ultrasound scanning vs.clinical examination for insulin injection-related lipohypertrophy

To the Editor:Lipohypertrophy(LH)is the most common local complication caused by multiple overlapping insulin injections.Clinically,LH manifests as prominent and/or thickened tissue at injection or infusion sites,sometimes resulting in lump formation under the skin.Histologically,LH is characterized by decreased vascularity,fibrosis,and adipocyte enlargement and proliferation in the subcutaneous tissue at insulin injection sites.Because of this,the existing screening methods for LH are mainly based on clinical examination and ultrasound scanning(USS).A recent systematic review revealed that only limited information is available for detection sensitivity among the different methods used to identify LH to date.Thus far,the gold standard examination for LH diagnosis remains debatable and there has been insufficient research on which patients require both kinds of examination.Currently,the detection sensitivity of USS vs.clinical examination for LH has not been reported in large sample-based studies.The present study aimed to compare the detection accuracy between USS and clinical examination using a large patient cohort and to determine the influencing factors for inconsistent detection results of LH between the two methods.

Molecular bases of Sorcin-dependent resistance to chemotherapeutic agents

Soluble resistance-related calcium binding protein(Sorcin)is a protein initially labelled“resistance-related”,since it is co-amplified with ABCB1 in multidrug(MD)-resistant cells.While for years Sorcin overproduction was believed to be a by-product of the co-amplification of its gene with the P-glycoprotein gene,many recent studies view Sorcin as an oncoprotein,playing an important role in MD resistance(MDR).Sorcin is one of the most highly expressed calciumbinding proteins,which is overexpressed in many human tumors and MD resistant cancers,and represents a novel MDR marker.Sorcin expression in tumors inversely correlates with patients’response to chemotherapies and overall prognosis.Sorcin is highly expressed in MDR cell lines over their parent cells.Sorcin overexpression by gene transfection increases drug resistance to a variety of chemotherapeutic drugs in many cancer lines.On the other hand,Sorcin silencing leads to reversal of drug resistance in many cell lines.This review describes:(1)the roles of Sorcin in the cell;(2)the studies showing Sorcin overexpression in tumors and cancer cells;(3)the studies showing the effects of Sorcin overexpression and silencing;(4)the molecular effects of Sorcin overexpression;and(5)the structural and genetic bases of Sorcin-dependent MDR.