Παρασκευή 15 Ιουνίου 2018

Histological changes of superficial esophageal squamous cell carcinoma after preoperative chemotherapy

Abstract

Introduction

We aimed to analyze the clinical and histological effects of chemotherapy in superficial esophageal squamous cell carcinoma (SESCC).

Methods

We analyzed tumor samples from five patients with cT1bN1M0 who underwent subtotal esophagectomy following two courses of a new triplet chemotherapy regimen including docetaxel, cisplatin, and 5-fluorouracil (DCF). To assess the histological effects of chemotherapy, resected specimens were analyzed by macroscopic examination, hematoxylin & eosin (HE) staining, immunohistochemical (IHC) staining (p53, Ki-67 and cytokeratin) and periodic acid-Schiff (PAS) staining.

Results

All five patients had a pathological T stage of T0/1a-LPM/1a-MM/1b (1/2/1/1) and histological grade of grade1a/1b/2/3 (1/1/2/1). Endoscopic examination revealed substantial shrinkage of lugol-voiding lesions (LVLs) in all cases. One case showed complete LVL disappearance, and resected specimen examination confirmed pathological complete response (pCR). IHC and PAS staining revealed that most initial LVLs were PAS-negative. Obvious viable cells were confirmed in two cases. The other three cases exhibited nuclear atypia and strong expression of p53 and Ki-67 in the basal layer of mucosa or lamina propria mucosae, even though the superficial layer of mucosa showed no obvious LVLs with PAS-positive. p53-positive lesions were also observed in Ki-67-positive. This indicated discordance between the endoscopic findings and histopathological evaluation.

Conclusion

DCF chemotherapy alone had a substantial therapeutic effect on SESCC in all cases. However, despite the normal appearance of the mucosal surface, viable cancer cells remained below the basal layer of mucosa. Careful attention should be paid when diagnosing clinical CR, or securing a resection margin of SESCC after DCF chemotherapy.



https://ift.tt/2JOv5lT

Atypical chest pain in a patient with hydatid cyst of the interventricular septum

We report a 57-year-old man presenting with symptoms of sharp pricking, exertional retrosternal chest pain multiple times, each episode lasting for a few seconds. On evaluation, the ECG of the patient showed normal sinus rhythm with T wave inversions in leads V1–V3. Troponin T test was negative. Transthoracic echocardiography showed a globular mass in the interventricular septum. Cardiac MRI was suspicious of the lesion to be a hydatid cyst. Surgical excision of the lesion followed by histopathology was confirmatory of hydatid cyst.



https://ift.tt/2LTh4UI

Dengue fever with encephalitis: a rare phenomenon

The clinical profile and presentation of patients with dengue fever may differ from asymptomatic infection to the dreadful complications like dengue shock syndrome. However, neurological complications are very rare. Dengue encephalitis occurs by a direct involvement of central nervous system by the dengue virus which is an extremely rare complication. A 33-year-old man presented with fever, vomiting and severe headache. He had one episode of generalised tonic-clonic seizure followed by an altered sensorium on the day of admission to the hospital. The diagnosis of dengue fever was confirmed by dengue serology (IgM) and (NS1) antigen assay. MRI brain was suggestive of encephalitis. Thus, the patient was treated symptomatically and discharged in stable condition with minimal neurological deficit.



https://ift.tt/2t1hfXb

Rotator cuff tear following long-standing axillary neuropathy in a female motocross racer

A 'terrible triad' of anterior shoulder dislocation, axillary nerve damage and rotator cuff tear has been previously described. However, we are unaware of any report of anterior shoulder dislocation, humeral fracture, axillary neuropathy and subsequent rotator cuff tear requiring surgery when the axillary neuropathy was deemed permanent. We report the case of a 20-year-old woman who fell in a motocross accident and had an anterior shoulder dislocation, humeral fracture and axillary neuropathy. The fracture was treated surgically with open reduction and internal fixation. The axillary nerve injury was ultimately permanent. Thirteen months after the motocross accident, the patient sustained a rotator cuff tear from seemingly minor trauma. However, several months of aggressive physical therapy preceded the rotator cuff tear. The tear was repaired and the patient was followed for 5 years after the initial injury. She returned to competing in motocross, even though the axillary neuropathy remained complete and permanent.



https://ift.tt/2LVOBxG

Thiazide diuretics-associated skin rash

Description 

A 50-year-old man with a history of hypertension and dyslipidaemia, both controlled with oral medications, was admitted to the emergency department due to a sudden onset of pruritus 2 days before, which would not improve with the application of topic antihistamines prescribed by his family doctor. A maculopapular, symmetric rash with plaques located on sun-exposed areas (hands, forearms, face and upper torso, sparing the abdomen, lower limbs and arm flexures) had appeared a few hours before coming to the emergency department (figures 1 and 2). The patient denied any sort of respiratory distress, as well as prolonged exposure to sunlight, history of drug allergies or having seen anyone in his family with the same problem before. The only recent change had been to his hypertension medication in the last 13 days, when hydrochlorothiazide was combined with his usual medication (losartan), which he had been taking for the...



https://ift.tt/2t0O0Uk

Transdermal rotigotine patch in Parkinsons disease with a history of intestinal operation

A 42-year-old Japanese man with a history of small intestine resection and familial Mediterranean fever was referred to our hospital for a second opinion on parkinsonism. At the age of 35, the patient attended a hospital due to impaired left-hand movement and resting tremor. He was previously diagnosed with multiple system atrophy based on the lack of effectiveness of levodopa treatment. With suspicion of malabsorption due to his history of ileostomy, a levodopa challenge test with levodopa intravenous infusion was conducted, and revealed a 65% improvement in Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale part III. Therefore, diagnosis of Parkinson's disease was made and a transdermal rotigotine patch was selected as a treatment. This treatment dose-dependently improved the patient's symptoms. The transdermal drug delivery should be considered when patients show dose failure due to malabsorption.



https://ift.tt/2LUyuAf

Delayed presentation of iatrogenic splenic injury 21 days after laparoscopic donor left nephrectomy

We report the case of a 46-year-old woman who had presented with left-sided abdominal pain 21 days after undergoing a left-sided laparoscopic nephrectomy for donation. Initial haemoglobin and haematocrit levels were within normal range, and vital signs on admission were unremarkable. Significant intra-abdominal pathology was not suspected; however, inpatient CT scan of the abdomen showed a posterolateral subcapsular splenic haematoma with free abdominal fluid. Initial trial of conservative management was not successful as the patient became hypotensive on the third day of admission with a sudden decrease in haemoglobin and haematocrit. The patient was immediately taken to theatre for laparotomy and splenectomy. Recovery was uneventful and was discharged home on the fifth postoperative day. In this article, we aim to discuss several important clinical lessons involving iatrogenic injury of the spleen, its management, and diagnosis of acute and severe haemorrhage.



https://ift.tt/2JHrWbP

Paraneoplastic cerebellar degeneration in a patient with anaplastic non-Hodgkins lymphoma

A 31-year-old man presented with a subacute cerebellar syndrome of unknown aetiology. Investigations including a paraneoplastic antibody screen were negative and a working diagnosis of possible vasculitis was concluded. After 1 month, he re-presented with worsening of his symptoms and a neck lump. He was diagnosed with anaplastic lymphoma kinase, negative non-Hodgkin's lymphoma and paraneoplastic cerebellar syndrome. A more extensive paraneoplastic antibody screen found patient to be Tr (delta/notch-like epidermal growth factor-related receptor) antibody positive. After a period of chemotherapy and steroid treatments, his symptoms are now stable in terms of cerebellar function. This case report summarises a very rare diagnosis of paraneoplastic cerebellar degeneration with a positive onconeuronal antibody associated with anaplastic non-Hodgkin's lymphoma.



https://ift.tt/2LXgVjh

Ectopic varices: a potential cause of gastrointestinal bleeding in patients with portal hypertension

A newly diagnosed 53-year-old woman with cirrhosis has repeated gastrointestinal bleeding with resulting symptomatic anaemia. She underwent routine diagnostic endoscopic evaluation without localisation of the aetiology of her bleed. Ultimately, she was found to have ectopic varices in the small bowel as a result of underlying high portal pressures. She underwent transjugular intrahepatic portosystemic shunt for portal system decompression with resolution in her bleeding.



https://ift.tt/2JDRHcO

Lymphedema secondary to limited cutaneous systemic sclerosis

Systemic sclerosis (SSc) is an autoimmune connective tissue disease characterised by vascular abnormalities, immune system activation and fibrosis. Lymphatic involvement in SSc was described more recently and starts in early stages. This report describes a 46-year-old patient who developed over the last 2 years asymmetric lymphedema in lower extremities. Compromise in lymphatic drainage was confirmed by lymphoscintigraphy. She also presented Raynaud's phenomenon, a scleroderma pattern in nailfold capillaroscopy, cutaneous thickening and anticentromere antibodies, which together resulted in a new diagnosis of limited cutaneous SSc. Treatment with methotrexate, prednisolone and lymphatic drainage resulted in lymphedema improvement. To our knowledge, this is the first case of grade 2 lymphedema in the setting of anticentromere-positive limited cutaneous SSc. We highlight the importance of considering rheumatic diseases in the differential diagnosis of lymphedema.



https://ift.tt/2LRgXcj

Graves disease presenting as severe postpartum pruritus

A 39-year-old multigravida woman presented 3 weeks postpartum with worsening generalised pruritus without primary rash. Workup was significant for cholestasis and undiagnosed Graves' disease. She began to have symptomatic relief after starting methimazole, and liver function tests normalised as she became euthyroid.



https://ift.tt/2t0NOV6

Closed-loop small bowel obstruction from lateral trocar site hernia following robotic sigmoid resection

Description

A 67-year-old man with medical history significant for hypertension and hyperlipidaemia was found on screening colonoscopy to have a large, polypoid adenomatous polyp of the distal descending colon not amenable to colonoscopic resection. He underwent a robotic sigmoid colon resection with primary anastomosis. Postoperatively the patient developed persistent abdominal distention, nausea and had no passage of flatus or bowel movements after 7 days which was initially attributed to ileus. Cross-sectional CT revealed a closed-loop small bowel obstruction secondary to an incarcerated hernia at the right lateral 8 mm robotic trocar site with surrounding subcutaneous emphysema (figure 1). On physical examination, there was no palpable bulge or overlying erythema along the previous incision. The patient was brought back to the operating room and underwent a diagnostic laparoscopy utilising the prior robotic incisions. On exploration, the incarcerated small bowel loop was easily reduced with gentle traction and appeared...



https://ift.tt/2LWCqR0

Common femoral artery aneurysm repair using bifurcated graft

Common femoral artery aneurysms are rare, and surgical repair is indicated if they are significantly large, or if they are symptomatic (thrombosis causing limb ischaemia and compression of surrounding structures). Synthetic grafts are preferred, especially in cases involving large aneurysms, or the bifurcation of the common femoral artery. We present a case of bilateral common femoral artery aneurysms extending into the bifurcation repaired using a synthetic graft which is traditionally used for an axillobifemoral bypass. This technique was employed due to the specific anatomical relationship between the profunda femoris and the superficial femoral artery in our patient. We will also review the current literature on the operative approaches to repair of common femoral artery aneurysms.



https://ift.tt/2t0NHZG

Discontinuation of hormone therapy for elderly breast cancer patients after hypofractionated whole-breast radiotherapy

Abstract

The purpose of the study was to examine adherence to hormone therapy (HT) in elderly breast cancer patients (≥ 65 years old) treated with hypofractionated radiotherapy. We analyzed data on 550 ER-positive breast cancer patients given hypofractionated whole-breast radiotherapy from June 2009 to September 2016. Baseline comorbidities considered in the hypertension-augmented Charlson Comorbidity Index (hCCI) were retrospectively retrieved. Total hCCI scores were classified as no comorbidity (hCCI = 0), low burden of comorbidity (hCCI = 1), and high burden of comorbidity (hCCI ≥ 2). Competing risk analysis was used to estimate the 5-year cumulative incidence of HT discontinuation. Fine and Gray models were used to estimate the adjusted subhazard ratio (SHR) of HT discontinuation by hCCI score. HT was initially prescribed for 85.6% of patients and almost all of them (468/471) took it for at least one month. It was subsequently discontinued by 45 patients (9.6%), for an overall 5-year cumulative incidence of 11.7%. The 5-year cumulative incidence of HT discontinuation rose from 3.9% in the youngest age group (65–69 years) to 23.3% in the oldest (≥ 80 years) (p = 0.005). Baseline comorbidity had some effect on the likelihood of discontinuing HT, but only among patients with a low burden of comorbidity (hCCI = 1, SHR 2.00, 95%CI 0.95–4.20). Adherence to HT was better in our sample than in the literature, probably because patients were selected and motivated to continue HT. This confirms the importance of communication with patients to improve adherence to HT. We confirmed the association between HT discontinuation and older age, while comorbidity had a limited influence.



https://ift.tt/2ldLea5

The relationship between anticipated response and subsequent experience of cancer treatment-related side effects: A meta-analysis comparing effects before and after treatment exposure

S03057372.gif

Publication date: Available online 15 June 2018
Source:Cancer Treatment Reviews
Author(s): Chloe Fletcher, Carlene Wilson, Amanda D. Hutchinson, Elizabeth Alice Grunfeld
ObjectiveTo review the evidence for a systematic relationship between cancer patients' pre-treatment expectations (anticipated side effects) and subsequent experience of treatment-related side effects, and to compare this relationship in patients with no prior treatment experience (cognitive expectations) and with some prior treatment experience (conditioned response).MethodsA total of 12,952 citations were identified through a comprehensive search of the literature published on or before November 2016 and screened against inclusion criteria. Studies were eligible if they included participants undergoing curative treatment for cancer, measured a treatment side effect, examined the relationship between anticipation and experience of side effects, and reported quantitative data.ResultsThirty-one studies were included in the review and meta-analysis (total N = 5,069). The side effects examined were nausea (anticipatory and post-treatment), vomiting, fatigue, pain, problems with concentration, and skin reactions. Meta-analyses indicated significant and positive associations between anticipation and subsequent experience for all included side effects in patients with no prior treatment exposure (r = 0.153 – 0.431). Stronger associations were found for all included conditioned side effects in patients with previous treatment experience (r = 0.211 – 0.476). No significant differences were found when overall effect sizes for patients with and without prior treatment exposure were compared for each side effect, except for anticipatory nausea (p = 0.012).ConclusionThese results may have implications for future interventions that target patients' expectations of cancer treatment-related side effects. Future research could explore patient reports of messages received about likely treatment effects both before and during treatment.



https://ift.tt/2t2y6bU

Narrative medicine in metastatic prostate cancer reveals ways to improve patient awareness & quality of care

Future Oncology, Ahead of Print.


https://ift.tt/2LWD6WN

Unexpected benefits of aging for favorable responses to PD-1 blockade in melanoma?

Immunosenescence might be expected to reduce the efficacy of checkpoint blockade, which depends on a functionally intact immune system. However, it seems that older melanoma patients may respond better to anti-PD1 treatment than younger patients, possibly due to their having fewer regulatory T-cells relative to CD8+ T-cells within tumour deposits.



https://ift.tt/2laFs93

Repositioning Dopamine D2 Receptor Agonist Bromocriptine to Enhance Docetaxel Chemotherapy and Treat Bone Metastatic Prostate Cancer

Docetaxel resistance remains a major obstacle in the treatment of prostate cancer (PCa) bone metastasis. In this study, we demonstrate that the dopamine D2 receptor (DRD2) agonist bromocriptine effectively enhances docetaxel efficacy and suppresses skeletal growth of PCa in preclinical models. DRD2 is ubiquitously expressed in PCa cell lines, and DRD2 is significantly reduced in PCa tissues with high Gleason score. Bromocriptine has weak to moderate cytotoxicity in PCa cells, but effectively induces cell cycle arrest. At the molecular level, bromocriptine inhibits the expression of c-Myc, E2F-1 and survivin, and increases the expression of p53, p21 and p27. Intriguingly, bromocriptine markedly reduces androgen receptor (AR) levels, partially through heat-shock protein 90 (Hsp90)-mediated protein degradation. The combination of bromocriptine and docetaxel demonstrates enhanced in vitro cytotoxicity in PCa cells and significantly retards the skeletal growth of C4-2-Luc tumors in mice. Collectively, these results provide the first experimental evidence for repurposing bromocriptine as an effective adjunct therapy to enhance docetaxel efficacy in PCa.



https://ift.tt/2JFBx2K

The Role of Pyruvate Dehydrogenase Kinase-4 (PDK4) in Bladder Cancer and Chemoresistance

Advanced bladder cancer (BCa) remains a major source of mortality, with poor treatment options. Cisplatin based chemotherapy is the standard treatment, however many patients are or become resistant. One potential cause of chemoresistance is the Warburg Effect, a metabolic switch to aerobic glycolysis that occurs in many cancers. Upregulation of the pyruvate dehydrogenase kinase family (PDK1-4) is associated with aerobic glycolysis and chemoresistance through inhibition of the pyruvate dehydrogenase complex (PDH). We have previously observed upregulation of PDK4 in high grade compared to low grade bladder cancers. We initiated this study to determine if inhibition of PDK4 could reduce tumor growth rates or sensitize BCa cells to cisplatin. Upregulation of PDK4 in malignant BCa cell lines as compared to benign transformed urothelial cells was confirmed using qPCR. Inhibition of PDK4 with dichloroacetate (DCA) resulted in increased PDH activity, reduced cell growth, and G0/G1 phase arrest in BCa cells. Similarly, siRNA knockdown of PDK4 inhibited BCa cell proliferation. Co-treatment of BCa cells with cisplatin and DCA did not increase caspase-3 activity but did enhance overall cell death in vitro. While daily treatment with 200mg/kg DCA alone did not reduce tumor volumes in a xenograft model, combination treatment with cisplatin resulted in dramatically reduced tumor volumes as compared to either DCA or cisplatin alone. This was attributed to substantial intra-tumoral necrosis. These findings indicate inhibition of PDK4 may potentiate cisplatin induced cell death and warrant further studies investigating the mechanism through which this occurs.



https://ift.tt/2ym3jw6

Treatment of giant cervico-mediastinal lymphatic malformations: a case series

Lymphatic malformations are histologically benign vascular structures that vary in anatomic lesion and size. Extensive head and neck lymphatic malformations may be life-threatening. In the present study, we de...

https://ift.tt/2JVCGlT

Philadelphia chromosome-positive lymphoblastic lymphoma—Is it rare or underdiagnosed?

grey_pxl.gif

Publication date: Available online 15 June 2018
Source:Hematology/Oncology and Stem Cell Therapy
Author(s): Ahmad Alshomar, Riad El Fakih
Lymphoblastic lymphomas (LBLs) are neoplasms of precursor B and T cells; they are considered in the same spectrum as precursor B and T cell acute lymphoblastic leukemia (ALL). The World Health Organization classification classifies both LBL and ALL as one disease entity. While chromosome abnormalities are well defined with all of their therapeutic and prognostic implications in ALL, these are not well studied in LBL. Here, we describe a case of Philadelphia chromosome-positive LBL and review the available literature regarding this entity.



https://ift.tt/2t0UliC

Rosai-Dorfman disease masquerading as Uveal Melanoma: Case report and review of literature

alertIcon.gif

Publication date: Available online 15 June 2018
Source:Hematology/Oncology and Stem Cell Therapy
Author(s): Yacoub A. Yousef, Maysa Al-Hussaini, Rashed Nazzal, Ghadeer Abdeen, Ibrahim Alnawaiseh, Khaleel Alrawashdeh
Objective/BackgroundIntra ocular Rosai-Dorfman disease (RDD) is an extremely rare disease. We are reporting the first case of RDD presenting as ciliary body mass mimicking ciliary body melanoma, and we are reviewing the English literature reporting on cases of RDD presented with intraocular disease.MethodsAn 18-year-old lady presented with loss of vision in the right eye, and was found to have intraocular mass lesion. She was diagnosed clinically and radiologically as a case of ciliary body melanoma associated with total retinal detachment.ResultsHistopathological sections and stains proved to be intraocular RDD. Review of the literature revealed three cases of intraocular RDD; two of them had choroid thickening associated with serous retinal detachment, and one presented with intraocular mass mimicking choroid melanoma. Two of the three cases were enucleated. Our case is the first case in English literature of intraocular ciliary body RDD, mimicking ciliary body melanoma.ConclusionRDD can present as an intraocular mass that mimics ciliary body melanoma. This case emphasizes the importance of diagnostic biopsy before considering the final therapy in unclear cases, mainly when associated with unusual systemic features like lymphadenopathy.



https://ift.tt/2LVTCGx

Granulocytic sarcoma and mediastinal germ cell tumor: A common cell of origin?

alertIcon.gif

Publication date: Available online 15 June 2018
Source:Hematology/Oncology and Stem Cell Therapy
Author(s): Sarbajit Mukherjee, Sami Ibrahimi, Teresa Scordino, Mohamad Cherry




https://ift.tt/2t74iez

Parvovırus-induced thrombocytopenıa

alertIcon.gif

Publication date: Available online 15 June 2018
Source:Hematology/Oncology and Stem Cell Therapy
Author(s): Burak Furkan Demir, Aysenur Karahan Meteris, Gokhan Yirgin, Mustafa Comoglu, Bilal Katipoglu, Nisbet Yılmaz, Ihsan Ates




https://ift.tt/2LQuT6n

Regional Anesthesia: What We Need to Know in the Era of Enhanced Recovery After Surgery Protocols and the Opioid Epidemic

alertIcon.gif

Publication date: Available online 15 June 2018
Source:Anesthesiology Clinics
Author(s): Lee A. Fleisher




https://ift.tt/2lekK8k

Long-term risks of secondary cancer for various whole and partial breast irradiation techniques

For early stage breast cancer patients, non-breast cancer mortality including secondary cancers and cardiac events can overshadow the benefit of adjuvant radiotherapy. This study evaluates the excess risk of secondary cancer for various breast radiotherapy techniques including accelerated partial breast irradiation (APBI).

https://ift.tt/2MrUDHc

Circulating miR-215-5p and miR-642a-5p as potential biomarker for diagnosis of osteosarcoma in Mexican population

Abstract

Osteosarcoma is the most common malignant bone neoplasia affecting individuals in the second decade of life. The survival rate has not been improved during the last 25 years, in part because of the lack of specific markers. The microRNAs have been identified as important regulators of gene expression, experimental evidence suggests these molecules as key players in cancer development and progression. To identify miRNAs differentially expressed in serum from patients with osteosarcoma compared to healthy donors in Mexican population. Fifteen osteosarcoma patients and fifteen age and sex matched healthy individuals were recruited. Two pools of total RNA extracted from serum per study group were prepared and the miRNA expression profiles were analyzed through TaqMan Low Density Arrays. Validation was carried out through RT-qPCR using individual TaqMan assays for those miRNAs differentially expressed. Fifteen miRNAs were differentially expressed in osteosarcoma patients compared to healthy controls. Overexpression of miR-215-5p and miR-642a-5p was confirmed by validation through RT-qPCR. The expression analysis of miRNAs from serum in osteosarcoma patients revealed differential expression of miR-215-5p and miR-642a-5p. Both microRNAs are potential markers for osteosarcoma diagnosis.



https://ift.tt/2MudB03

To propose adding index of achievement (IOA) to IMRT QA process

In intensity modulated radiation therapy (IMRT) quality assurance (QA), evaluation of QA result using a pass/non-pass strategy under an acceptance criterion often suffers from lack of information on how good t...

https://ift.tt/2yfBHsn

Triple thrombophilic simultaneous mutations in patients after bariatric surgery: is there a role for screening in the Eastern Mediterranean?

m_rjy135f01.png?Expires=2147483647&Signa

Abstract
Background and purpose: Thrombophilia is a hypercoagulable state that predisposes to thrombosis. Several genetic risk factors have been shown to predispose to thromboembolic events. Homozygosity to a thrombophilic mutation certainly predisposes the affected patient to more serious symptoms. Materials and methods: Here we present a case of a 56-year-old male patient who underwent sleeve gastrectomy for morbid obesity, presenting to our institution with abdominal pain. Investigations revealed thrombosis of the splenic, axillary vein as well as the right pulmonary artery. The patient was found to have triple thrombophilic mutations. Results: To our knowledge, this is the first reported case of three specific simultaneous thrombophilic mutations in a patient from the Eastern Middle East. Conclusion: We suggest a role for screening for thrombophilic mutations in the Eastern Mediterranean patients undergoing bariatric surgeries for morbid obesity due to the increased risk of thrombosis in this group of patients

https://ift.tt/2ye6Z2R

Diagnosis of human immunodeficiency virus following femoral head harvest post-total hip arthroplasty

m_rjy130f01.png?Expires=2147483647&Signa

Abstract
Elective total hip arthroplasty (THA) is a routine procedure. Intraoperative harvesting of excised femoral heads for the purpose of donation during this procedure has become standard practice, in response to increasing bone allograft demand. Robust patient screening and femoral head analysis typically occurs, to minimize the risk of disease transmission to any potential recipient. Screening for human immunodeficiency virus (HIV), a virus normally first diagnosed through serological testing, makes up part of this process. This case describes a 43-year-old male who underwent elective THA, with subsequent analysis of the excised femoral head at time of screening revealing a diagnosis of HIV, a condition previously never detected in the donor. First diagnosis of HIV from bone is exceedingly rare, with this case illustrating an unusual diagnostic pathway of a well-understood condition, as well as representing an unfamiliar outcome following a common surgical intervention.

https://ift.tt/2Mr4zki

Benign inverted papilloma at bladder neck causing acute urinary retention

m_rjy125f01.png?Expires=2147483647&Signa

Abstract
Inverted papilloma of the urinary tract is a rare benign lesion. A 59-year-old male who presented with the chief complaint of gross hematuria and acute urinary retention is described. Cystoscopy revealed a solitary, papillary tumor at the bladder neck. Transurethral resection was performed, and histological examination revealed a pathological diagnosis of inverted papilloma. Following resection, the patient was able to void without difficulty. This is an interesting case of acute urinary retention secondary to an inverted papilloma at the bladder neck causing intermittent outlet obstruction, and we review the literature on inverted papilloma of the bladder.

https://ift.tt/2JNeMpo

Management of dermatofibrosarcoma protuberans of the face using lower trapezius musculocutaneous pedicle flap reconstruction: a case report

m_rjy089f01.png?Expires=2147483647&Signa

Abstract
Dermatofibrosarcoma protuberans (DFSP) is a rare neoplasm which represents <0.1% of all tumors but it is considered the most common skin sarcoma. It is a slow-growing tumor that arises from the dermis and invades deeper tissues. The precise origin of DFSP is not well known. It is most frequently seen on the trunk, extremities, and head and neck. The standard treatment of the localized huge DFSP consists of a wide local surgical resection with recommended surgical margins of 2–3 cm. Local recurrence after incomplete excision is common. We present a case of 35-year-old man with enormous bulky mass on the face. Upon histological examination, the diagnosis of DFSP was made, and the patient underwent en bloc wide local excision of the mass followed by the use of Trapezius musculocutaneous pedicle flap reconstruction. On 32 months follow-up, no recurrence has been reported.

https://ift.tt/2MuzbSc

Unique surgical approach to a twisted ileal-anal pouch

m_rjy133f01.png?Expires=2147483647&Signa

Abstract
Total proctocolectomy with ileal pouch-anal anastomosis can restore gastrointestinal continuity in patients requiring colectomy for ulcerative colitis, however, it can be associated with high morbidity. Reoperation for pouch-related complications is technically challenging and often leads to deterioration of pouch function or need for permanent stoma. We report a case of acute on chronic small bowel obstruction secondary to a 360-degree twist in the small bowel introduced during creation of the ileal-anal pouch. Our novel approach at repair has not been reported in past literature which included resection and re-anastomosis of the small bowel proximal to the pouch allowing for pouch salvage with return to function.

https://ift.tt/2JOjRy1

Reply to the Letter to the Editor: "The hard road to patient-centered care: 3 or 6 months of adjuvant chemotherapy for patients with stage III colon cancer?" By P. Trendsz et al.



https://ift.tt/2JCZ1pb

Enhanced anticancer effect of MAP30–S3 by cyclosproin A through endosomal escape

Cyclosporin A (CsA) is a calcium antagonist and can enhance the efficacy of some protein drugs, but its mechanism remains unknown. In this study, MAP30, a ribosome-inactivating protein reported to have apoptotic effects on cancer cells, was fused with S3, an epidermal growth factor receptor (EGFR)-targeting peptide. In addition, CsA was used to investigate whether it can further promote the apoptotic effects of S3 fused MAP30 (MAP30–S3). Our result showed that the internalization of FITC-labeled MAP30–S3 was increased significantly by S3 in HeLa cells. Unexpectedly, MAP30–S3 only showed a minor decrease in the viability of EGFR-overexpressing cancer cells, including HeLa, SMMC-7721, and MGC803 (IC50>5 μmol/l). However, 2 μmol/l CsA significantly increased the cytotoxicity of MAP30–S3, especially for HeLa cells (IC50=40.3 nmol/l). In comparison, CsA did not further decrease the cytotoxicity of MAP30–S3 on MRC-5, an EGFR low-expressing cell line from normal lung tissue, indicating that CsA did not affect the cancer-targeting specificity of MAP30–S3. Our results also showed that CsA further increased the apoptotic activity of MAP30–S3 in HeLa cells. CsA could promote the endosomal escape of FITC-MAP30–S3 with a diffused pattern in the cytoplasm. Five endocytic inhibitors were used to investigate the cellular uptake mechanism of MAP30–S3, and the results showed that the endosomal escape-enhancing effect of CsA on MAP30–S3 may be associated with the clathrin-dependent endocytic pathways. Our study suggested that CsA could be a novel endosomal escape enhancer to potentiate the intracellular release of anticancer protein drugs, resulting in their improved therapeutic efficacy. Correspondence to Jian Zhao, PhD, Department of Applied Biology, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, China Tel: +86 216 425 2256; fax: +86 216 425 2255; e-mail: zhaojian@ecust.edu.cn or Correspondence to Fu-Jun Wang, MSc, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai 201203, China Tel: +86 215 132 2515; fax: +86 215 132 2508; e-mail: wfj@shutcm.edu.cn Received January 10, 2018 Accepted April 27, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2yb5IcU

ERCC1 assessment in upfront treatment with and without cisplatin-based chemotherapy in stage IIIB/IV non-squamous non-small cell lung cancer

Abstract

Prior studies have demonstrated an association between excision repair cross-complementation group 1 (ERCC1) expression level and outcomes in patients with advanced non-small cell lung cancer (NSCLC) treated with platinum-based chemotherapy. The aim of this study was to assess the impact of ERCC1 on survival for patients with stage IIIB/IV non-squamous NSCLC (NS-NSCLC) enrolled in the INNOVATIONS trial, thus receiving as treatment either erlotinib/bevacizumab (EB) or cisplatin/gemcitabine/bevacizumab (PGB). We retrospectively analyzed tumor tissue of 72 patients using immunohistochemistry to assess the expression of ERCC1. The distribution between treatment arms was equal (36 patients each). Two different H scores were calculated and correlated with survival. In ERCC1-positive patients, no significant difference in terms of progression-free survival (PFS) between treatment arms has been detected. ERCC1-negative patients benefited from PGB compared to EB arm (H score: HR = 0.377, 95% CI [0.167–0.849], p = 0.0151; modified H score: HR = 0.484, 95% CI [0.234–1.004], p = 0.0468). With respect to the scoring system, in the EB-arm, a significant superior PFS turned out in ERCC1-positive patients when employing the H-score (HR = 0.430, 95% CI [0.188–0.981], p = 0.0397; median 4.9 vs. 3.9 months), but not with the modified H-score. Our findings support the hypothesis that NS-NSCLC displaying a low ERCC1 expression might benefit from cisplatin-based chemotherapy. High expression indicated better PFS in the EB arm supporting the prognostic impact. However, as impact of ERCC1-assessment even might depend on scoring systems differences, the need in standardization of assessment methodology is emphasized.



https://ift.tt/2JTslah

α-Viniferin activates autophagic apoptosis and cell death by reducing glucocorticoid receptor expression in castration-resistant prostate cancer cells

Abstract

Prostate cancer (PCa) is one of the most commonly diagnosed urological malignancies. However, there are limited therapies for PCa patients who develop biochemical recurrence after androgen deprivation therapy (ADT). In the present study, we investigated the therapeutic efficacy and mechanism of α-Viniferin (KCV), an oligostilbene of trimeric resveratrol, against human PCa cells and found that it markedly inhibited the proliferation of LNCaP, DU145, and PC-3 cancer cells in a time- and dose-dependent manner, and had a strong cytotoxicity in non-androgen-dependent PCa cells. In addition, KCV inhibited AR downstream expression in LNCaP cells, and inhibited activation of GR signaling pathway in DU145 and PC-3. Further investigation indicated that KCV could induce cancer cell apoptosis through AMPK-mediated activation of autophagy, and inhibited GR expression in castration-resistant prostate cancer(CRPC). These findings suggest that KCV may prove to be a novel and effective therapeutic agent for the treatment of CRPC.



https://ift.tt/2LTmNd4

Changes in programmed death ligand 1 expression in non-small cell lung cancer patients who received anticancer treatments

Abstract

Background

The expression of programmed death ligand 1 (PD-L1) is considered a predictive biomarker of anti-programmed death 1 (PD-1)/PD-L1 cancer therapies. However, changes in PD-L1 expression of tumor cells during clinical courses have not been fully evaluated. We evaluated changes in PD-L1 expression for non-small cell lung cancer (NSCLC) patients who received anticancer treatments during clinical courses.

Methods

In 76 NSCLC patients, PD-L1 expression was evaluated before and after anticancer treatment by immunohistochemical (IHC) analysis using an anti-PD-L1 antibody. We defined two cut-off points of PD-L1 expression (1 and 50%) and three corresponding IHC groups (A: 0%, B: 1–49%, and C: ≥50%). IHC group B and C were considered to be positive expression, and we defined the difference of IHC group between pre- and post-treatment as 'major change' in PD-L1 expression.

Results

Before anticancer treatment, PD-L1 expression was observed in 38/76 (50%) patients, and was significantly less common in patients harboring mutations in the epidermal growth factor receptor gene (EGFR) than in those without (P = 0.039). After anticancer treatment, PD-L1 expression was observed in 36/76 (47%) patients. Major increases in PD-L1 expression were seen in 11 (14%), and major decreases in 18 (24%) patients. Among 13 patients harboring EGFR mutations treated with EGFR tyrosine-kinase inhibitor (EGFR-TKI), five (38%) showed major increases.

Conclusion

Major changes of PD-L1 expression in tumor cells were observed in 38% of NSCLC patients who received anticancer treatments. And, treatments with EGFR-TKI may increase PD-L1 expression in NSCLC patients harboring EGFR mutations.



https://ift.tt/2l9eRZQ

Colorectal obstruction is a potential prognostic factor for stage II colorectal cancer

Abstract

Background

Obstructive colorectal cancer (CRC) is an emergency situation with high morbidity and mortality, but long-term outcomes of stage II/III obstructive CRC remain unclear. The aim of this study was to evaluate prognostic factors, including colorectal obstruction.

Methods

Data were retrospectively reviewed from consecutive patients with stage II/III CRC who underwent curative surgery between January 2007 and December 2011 at two Japanese institutions. We analyzed overall survival (OS) and relapse-free survival (RFS), according to various prognostic factors including colorectal obstruction.

Results

In total, 979 patients with stage II/III CRC were identified for this study. Among these 979 patients, 94 patients showed colorectal obstruction (9.6%). In both stage II and stage III CRCs, colorectal obstruction showed significantly poorer OS and RFS compared to non-obstruction (5-year OS, obstruction vs. non-obstruction, stage II: 65.9 vs. 86.5%, P = 0.002; stage III: 55.9 vs. 73.6%, P = 0.007) (5-year RFS, obstruction vs. non-obstruction, stage II: 59.2 vs. 77.8%, P = 0.008; stage III 31.3 vs. 56.3%, P = 0.001). Multivariate analysis demonstrated colorectal obstruction as a significant independent and poor prognostic factor in terms of both OS (hazard ratio (HR) 2.469; 95% CI 1.339–4.545; P = 0.004) and RFS (HR 1.992; 95% CI 1.160–3.425; P = 0.012) for stage II CRC, as well as pT4 stage. On multivariate analysis for stage III CRC, colorectal obstruction was a significant predictor of poor RFS (HR 1.626; 95% CI 1.070–2.469; P = 0.023), but not poor OS.

Conclusions

Colorectal obstruction is an independent poor prognostic factor for stage II CRC. Adjuvant chemotherapy might be feasible for stage II CRC with colorectal obstruction.



https://ift.tt/2tcrqqY

Effectiveness of lomustine and bevacizumab in progressive glioblastoma: a meta-analysis

88x31.png



https://ift.tt/2Mo0ygr

Acute Macular Neuroretinopathy following Oral Intake of Adrenergic Flu Treatments

Purpose: The purpose of this study was to report a case series of patients with acute macular neureretinopathy in which patients concomitantly used ephedrine or pseudo-ephedrine. Methods: This is a retrospective case review. Results: Two patients with retinal findings consistent with acute macular neuroretinopathy are presented. Conclusion: Acute macular neuroretinopathy should be considered in any young patient with unexplained loss of vision and exposed to direct or indirect adrenergic stimulation.
Case Rep Ophthalmol 2018;9:322–326

https://ift.tt/2sZN6Hz

Cancers, Vol. 10, Pages 205: Oncolytic Reovirus and Immune Checkpoint Inhibition as a Novel Immunotherapeutic Strategy for Breast Cancer

Cancers, Vol. 10, Pages 205: Oncolytic Reovirus and Immune Checkpoint Inhibition as a Novel Immunotherapeutic Strategy for Breast Cancer

Cancers doi: 10.3390/cancers10060205

Authors: Ahmed A. Mostafa Daniel E. Meyers Chandini M. Thirukkumaran Peter J. Liu Kathy Gratton Jason Spurrell Qiao Shi Satbir Thakur Don G. Morris

As the current efficacy of oncolytic viruses (OVs) as monotherapy is limited, exploration of OVs as part of a broader immunotherapeutic treatment strategy for cancer is necessary. Here, we investigated the ability for immune checkpoint blockade to enhance the efficacy of oncolytic reovirus (RV) for the treatment of breast cancer (BrCa). In vitro, oncolysis and cytokine production were assessed in human and murine BrCa cell lines following RV exposure. Furthermore, RV-induced upregulation of tumor cell PD-L1 was evaluated. In vivo, the immunocompetent, syngeneic EMT6 murine model of BrCa was employed to determine therapeutic and tumor-specific immune responses following treatment with RV, anti-PD-1 antibodies or in combination. RV-mediated oncolysis and cytokine production were observed following BrCa cell infection and RV upregulated tumor cell expression of PD-L1. In vivo, RV monotherapy significantly reduced disease burden and enhanced survival in treated mice, and was further enhanced by PD-1 blockade. RV therapy increased the number of intratumoral regulatory T cells, which was reversed by the addition of PD-1 blockade. Finally, dual treatment led to the generation of a systemic adaptive anti-tumor immune response evidenced by an increase in tumor-specific IFN-&gamma; producing CD8+ T cells, and immunity from tumor re-challenge. The combination of PD-1 blockade and RV appears to be an efficacious immunotherapeutic strategy for the treatment of BrCa, and warrants further investigation in early-phase clinical trials.



https://ift.tt/2JZosRn

Clinical and Molecular Recursive Partitioning Analysis of High-grade Glioma Treated With IMRT

Introduction: Despite multimodal treatment for high-grade gliomas, prognosis remains grim. Prior Radiation Therapy Oncology Group-Recursive Partitioning Analysis (RTOG-RPA) reports indicate based on pretreatment and treatment-related factors, a subset of patients experience a significantly improved survival. Since the development of the RTOG-RPA, high-grade gliomas have seen the widespread introduction of temozolomide and tumor oncogenetics. Here we aimed to determine whether the RTOG-RPA retained prognostic significance in the context of modern treatment, as well as generate an updated RPA incorporating both clinical and genetic variables. Methods: Patients with histologically proven glioblastoma, gliosarcoma, anaplastic astrocytoma, and anaplastic oligodendroglioma treated with intensity-modulated radiation therapy (IMRT) between 2004 and 2017 were reviewed. The primary endpoint was overall survival from date of diagnosis. Primary analysis compared actual survival rates to that expected of corresponding RTOG-RPA class. Secondary analysis utilized the rpart function to recursively partition overall survival by numerous clinical and genetic pretreatment and treatment-related variables. A tertiary analysis recursively partitioned a subset of patients in which the status of all genetic markers were known. Results: We identified 878 patients with histologically proven high-grade glioma treated with IMRT and 291 patients in our genetic subset. Median overall survival for the entire cohort was 14.2 months (95% confidence interval, 13.1-15.3). Applying the RTOG-RPA to our cohort validated the relative prognostic ordering of the survival classes except class II. Generating our new RPA created 7 significantly different survival classes (P

https://ift.tt/2JRZOBP

Primary prophylactic granulocyte colony-stimulating factor according to ASCO guidelines has no preventive effect on febrile neutropenia in patients treated with docetaxel, cisplatin, and 5-fluorouracil chemotherapy

Abstract

Background

The efficacy of primary prophylactic granulocyte colony-stimulating factor (G-CSF) in preventing febrile neutropenia (FN) in patients treated with docetaxel, cisplatin, and 5-fluorouracil (TPF) chemotherapy remains controversial. We compared the incidence of FN in patients treated with and without primary prophylactic G-CSF.

Methods

We performed a retrospective analysis of 142 patients with locally advanced head and neck or esophageal cancer treated with TPF between January 2009 and March 2017. Among them, 116 patients started TPF without primary prophylactic G-CSF (control group) while 26 patients were given primary prophylactic G-CSF from day 7 of the first cycle of TPF (prophylactic group).

Results

The incidence of grade 4 neutropenia during the first cycle of TPF was significantly higher in the control group than in the prophylactic group [58.6% (n = 68) vs. 30.8% (n = 8), p = 0.02]. However, the incidence of FN in the first cycle was not significantly different between the two groups [32 patients (27.5%) in the control group and 8 patients (30.8%) in the prophylactic group (p = 0.62)]. In addition, the mean relative dose intensity throughout all cycles of TPF, as well as the survival time and response after TPF, were also not significantly different between the two groups.

Conclusions

Primary prophylactic G-CSF from day 7 of the first cycle of TPF did not reduce the incidence of FN. Our findings suggest that the timing of primary prophylactic G-CSF, as recommended by the American Society of Clinical Oncology guidelines, should be modified to reduce the incidence of FN in TPF.



https://ift.tt/2JF0Z8v

Cancers, Vol. 10, Pages 203: Biomarkers for Early Diagnosis and Prognosis of Malignant Pleural Mesothelioma: The Quest Goes on

Cancers, Vol. 10, Pages 203: Biomarkers for Early Diagnosis and Prognosis of Malignant Pleural Mesothelioma: The Quest Goes on

Cancers doi: 10.3390/cancers10060203

Authors: Caterina Ledda Paola Senia Venerando Rapisarda

Malignant pleural mesothelioma (MM) is a highly aggressive tumor characterized by a poor prognosis. Although its carcinogenesis mechanism has not been strictly understood, about 80% of MM can be attributed to occupational and/or environmental exposure to asbestos fibers. The identification of non-invasive molecular markers for an early diagnosis of MM has been the subject of several studies aimed at diagnosing the disease at an early stage. The most studied biomarker is mesothelin, characterized by a good specificity, but it has low sensitivity, especially for non-epithelioid MM. Other protein markers are Fibulin-3 and osteopontin which have not, however, showed a superior diagnostic performance. Recently, interesting results have been reported for the HMGB1 protein in a small but limited series. An increase in channel proteins involved in water transport, aquaporins, have been identified as positive prognostic factors in MM, high levels of expression of aquaporins in tumor cells predict an increase in survival. MicroRNAs and protein panels are among the new indicators of interest. None of the markers available today are sufficiently reliable to be used in the surveillance of subjects exposed to asbestos or in the early detection of MM. Our aim is to give a detailed account of biomarkers available for MM.



https://ift.tt/2l7XQiO

Cancers, Vol. 10, Pages 202: Loss of Cyclin-Dependent Kinase Inhibitor Alters Oncolytic Adenovirus Replication and Promotes More Efficient Virus Production

Cancers, Vol. 10, Pages 202: Loss of Cyclin-Dependent Kinase Inhibitor Alters Oncolytic Adenovirus Replication and Promotes More Efficient Virus Production

Cancers doi: 10.3390/cancers10060202

Authors: Naseruddin Höti Tamara Jane Johnson Wasim H. Chowdhury Ronald Rodriguez

We elucidate the role of p21/Waf-1, a cyclin-dependent kinase inhibitor, on the oncolytic infection and replication cycle of adenovirus by studying both mRNA and adenoviral proteins expression. We found that infection in the absence of p21 causes a significant increase in adenoviral genomes and late gene expression. Similarly, the oncolytic adenoviral infected p21&minus;/&minus; cells have earlier formation of replication foci and robust replication kinetics that were not observed in the wild type p21/Waf-1 intact cells. These findings suggest a culmination that the presence of intact p21 in host cells causes defects in the oncolytic viral life cycle which results in the production of immature and noninfectious particles.



https://ift.tt/2ycW7C6

Cancers, Vol. 10, Pages 204: The Role of Immune Checkpoint Inhibitors in Classical Hodgkin Lymphoma

Cancers, Vol. 10, Pages 204: The Role of Immune Checkpoint Inhibitors in Classical Hodgkin Lymphoma

Cancers doi: 10.3390/cancers10060204

Authors: Nicholas Meti Khashayar Esfahani Nathalie A. Johnson

Hodgkin Lymphoma (HL) is a unique disease entity both in its pathology and the young patient population that it primarily affects. Although cure rates are high, survivorship can be linked with significant recent long-term morbidity associated with both chemotherapy and radiotherapy. The most significant advances have been with the use of the anti-CD30-drug conjugated antibody brentuximab vedotin (BV) and inhibitors of program death 1 (PD-1). HL is genetically wired to up-regulate program death ligand 1 (PD-L1) in &gt;95% of cases, creating a state of so-called &ldquo;T cell exhaustion&rdquo;, which can be reversed with immune checkpoint-inhibitor blockade. The overall and complete response rates to PD-1 inhibitors in patients with relapsed or refractory HL are 70% and 20%, respectively, with a long median duration of response of ~16 months. In fact, PD-1 inhibitors can benefit a wide spectrum of relapsed HL patients, including some who have &ldquo;progressive disease&rdquo; by strict response criteria. We review the biology of HL, with a focus on the immune micro-environment and mechanisms of immune evasion. We also provide the rationale supporting the use of PD-1 inhibitors in HL and highlight some of the challenges of monitoring disease response in patients treated with this immunotherapy.



https://ift.tt/2l7XJDU

Adjuvant radiotherapy after curative surgery for oral cavity squamous cell carcinoma and treatment effect of timing and duration on outcome—A Taiwan Cancer Registry national database analysis

Cancer Medicine, EarlyView.


https://ift.tt/2yeqyYS

Targeting MCT4 to reduce lactic acid secretion and glycolysis for treatment of neuroendocrine prostate cancer

Cancer Medicine, EarlyView.


https://ift.tt/2l8IIl8

Chronic myelogenous leukemia on target

Cancer Medicine, EarlyView.


https://ift.tt/2yfac24

Phase II study of carboplatin, pemetrexed, and bevacizumab in advanced nonsquamous non–small‐cell lung cancer

Cancer Medicine, EarlyView.


https://ift.tt/2lbFxcJ

HOTAIRM1 competed endogenously with miR‐148a to regulate DLGAP1 in head and neck tumor cells

Cancer Medicine, EarlyView.


https://ift.tt/2tahpKR

Decreased oral Epstein‐Barr virus DNA loads in patients with nasopharyngeal carcinoma in Southern China: A case‐control and a family‐based study

Cancer Medicine, EarlyView.


https://ift.tt/2laoJmc

Neoadjuvant endocrine therapy with exemestane followed by response‐guided combination therapy with low‐dose cyclophosphamide in postmenopausal patients with estrogen receptor‐positive breast cancer: A multicenter, open‐label, phase II study

Cancer Medicine, EarlyView.


https://ift.tt/2ydt7dF

Low expression of WW domain‐containing oxidoreductase associates with hepatocellular carcinoma aggressiveness and recurrence after curative resection

Cancer Medicine, EarlyView.


https://ift.tt/2lbFrSp

Plasma cell‐free DNA quantification is highly correlated to tumor burden in children with neuroblastoma

Cancer Medicine, EarlyView.


https://ift.tt/2tbLCJy

Increased risk of bone tumors after growth hormone treatment in childhood: A population‐based cohort study in France

Cancer Medicine, EarlyView.


https://ift.tt/2l8XMzj

Electronic cigarette use patterns and reasons for use among smokers recently diagnosed with cancer

Cancer Medicine, EarlyView.


https://ift.tt/2tah8rj

Feasibility of using negative ultrasonography results of axillary lymph nodes to predict sentinel lymph node metastasis in breast cancer patients

Cancer Medicine, EarlyView.


https://ift.tt/2ldafCi