Incidence and Impact of Documented Eradication of Breast Cancer Axillary Lymph Node Metastases Before Surgery in Patients Treated With Neoadjuvant Chemotherapy

OBJECTIVE: To determine the incidence and prognostic significance of documented eradication of breast cancer axillary lymph node (ALN) metastases after neoadjuvant chemotherapy. SUMMARY BACKGROUND DATA: Neoadjuvant chemotherapy is the standard of care for patients with locally advanced breast cancer and is being evaluated in patients with earlier-stage operable disease. METHODS: One hundred ninety-one patients with locally advanced breast cancer and cytologically documented ALN metastases were treated in two prospective trials of doxorubicin-based neoadjuvant chemotherapy. Patients had breast surgery with level I and II axillary dissection followed by additional chemotherapy and radiation treatment. Nodal sections from 43 patients who were originally identified as having negative ALNs at surgery were reevaluated and histologically confirmed to be without metastases. An additional 1112 sections from these lymph node blocks were obtained; half were stained with an anticytokeratin antibody cocktail and analyzed. Survival was calculated using the Kaplan-Meier method. RESULTS: Of 191 patients with positive ALNs at diagnosis, 23% (43 patients) were converted to a negative axillary nodal status on histologic examination (median number of nodes removed = 16). Of the 43 patients with complete axillary conversion, 26% (n = 11) had N1 disease and 74% (n = 32) had N2 disease. On univariate analysis, patients with complete versus incomplete histologic axillary conversion were more likely to have initial estrogen-receptor-negative tumors, smaller primary tumors, and a complete pathologic response in the primary tumor. The 5-year disease-free survival rates were 87% in patients with preoperative eradication of axillary metastases and 51% for patients with residual nodal disease after neoadjuvant chemotherapy. Of the 39 patients with complete histologic conversion for whom nodal blocks were available, occult nodal metastases were found in additional nodal sections in 4 patients (10%). At a median follow-up of 61 months, the 5-year disease-free survival rates were 87% in patients without occult nodal metastases and 75% in patients with occult nodal metastases. CONCLUSIONS: Neoadjuvant chemotherapy can completely clear the axilla of microscopic disease before surgery, and occult metastases are found in only 10% of patients with a histologically negative axilla. The results of this study have implications for the potential use of sentinel lymph node biopsy as an alternative to axillary dissection in patients treated with neoadjuvant chemotherapy.     

Risk stratification in patients with remote prior myocardial infarction using rest-stress myocardial perfusion spect: prognostic value and impact on referral to early catheterization

BACKGROUND: Little is known about the prognostic value of myocardial perfusion single photon emission computed tomography (SPECT) in patients with remote prior myocardial infarction (MI). METHODS AND RESULTS: We identified 1413 consecutive patients with remote prior MI who underwent rest-stress myocardial perfusion SPECT. Semiquantitative visual analysis of 20 SPECT segments was used to define the summed stress, rest, and difference scores. The number of non-reversible segments was used as an index of infarct size. During follow-up (>or=1 year), 118 hard events occurred: 64 cardiac deaths (CDs) and 54 recurrent MIs. Annual CD and hard event rates increased significantly as a function of SPECT abnormality. For summed stress scores less than 4, 4 to 8, 9 to 13, and more than 13, the annual CD rates were 0.4%, 0.9%, 1.7%, and 3.5%, respectively (P =.002). Patients with small MI (<4 non-reversible segments) and no or mild ischemia (summed difference score or=4 non-reversible segments) had moderate to high annual CD rates (3.7%-6.6%) regardless of the extent of ischemia. Nuclear testing added incremental prognostic information to pre-scan information. Compared with a strategy in which all patients are referred to catheterization, a strategy that referred only those patients with a risk for CD of greater than 1% by myocardial perfusion SPECT resulted in a 41.6% cost savings. CONCLUSIONS: Myocardial perfusion SPECT adds incremental value to pre-scan information and is highly predictive and cost-efficient in the risk stratification of patients with remote prior MI. Patients with normal or mildly abnormal scan results or small MI in combination with absent or mild ischemia have a low risk for CD.     

胆管癌组织中MMP-9的表达及其意义

目的　探讨基质金属蛋白酶 9(matrixmetalloproteinase 9,MMP 9)在胆管癌发展中的作用及与胆管癌浸润、转移和预后的关系。方法　应用免疫组织化学法 (S P法 )对 5 2例经手术和病理证实的胆管癌及 10例经手术切除的正常胆管壁标本进行MMP 9蛋白检测。结果　 (1)MMP 9表达在胆管癌组织、癌旁组织及正常胆管上皮组织阳性率分别为 84 6 % (4 4 /5 2 )、2 2 6 % (7/31)和 0 %(0 /10 ) ,有显著性差异 (P <0 0 1)。 (2 )在 5 2例胆管癌组织中 ,MMP 9表达分别与肿瘤的病理分级、TNM分期、浸润和转移及手术方式有关 (P <0 0 5 ) ,而与性别、年龄、肿瘤部位及大小无关 (P >0 0 5 )。 (3)MMP 9表达阳性患者一年生存率明显低于阴性者 (P <0 0 1)。结论　MMP 9表达与胆管癌发展、浸润和转移密切相关 ,检测MMP 9的表达有助于对胆管癌转移潜能和预后的判断。     

High Precision DNA Modification Analysis of HCG9 in Major Psychosis

New epigenetic technologies may uncover etiopathogenic mechanisms of major psychosis. In this study, we applied padlock probe-based ultra-deep bisulfite sequencing for fine mapping of modified cytosines of the HLA complex group 9 (nonprotein coding) gene in the postmortem brains of individuals affected with schizophrenia or bipolar disorder and unaffected controls. Significant differences between patients and controls were detected in both CpG and CpH modifications. In addition, we identified epigenetic age effects, DNA modification differences between sense and anti-sense strands, and demonstrated how DNA modification data can be used in clustering of patient populations. Our findings revealed new epigenetic complexities but also highlighted the potential of DNA modification approaches in the search of heterogeneous causes of major psychiatric disease.Key words: epigenetics, brain, schizophrenia, bipolar disorder, bisulfite sequencing, padlock probes     

Sporadic and familial myoclonic dystonia: Report of three cases and review of literature

Myoclonic dystonia refers to a clinical syndrome characterized by rapid jerky movements along with dystonic posturing of the limbs. Clinically, it is characterized by sudden, brief, electric shock-like movements, mostly involving the upper extremities, shoulders, neck and trunk. Characteristically, the movements wane with consumption of small dose of alcohol in about 50% of cases. Additionally, dystonic contractions are observed in most of the patients in the affected body parts and some patients may exhibit cervical dystonia or graphospasm as well. It may manifest as an autosomal dominant condition or sometimes, as a sporadic entity, though there are doubts whether these represent cases with reduced penetrance. The condition is usually treated with a combination of an anticholinergic agent like, benztropine, pimozide and tetrabenazine. We report one sporadic case and one familial case where the father and the son are affected. The cases were collected from the Movement Disorders Clinic of Bangur Institute of Neurosciences, Kolkata, West Bengal in a period of ten months. Myoclonic dystonia is a rare condition and to the best of our knowledge, this series is the first one reported from our country. Videos of the patients are also provided with the article.     

Novel insights on the bottom–up rise strength transfer: investigating massed vs. distributed exercise training

Sport Sciences for Health - The purpose of this study is to investigate the Bottom–Up Rise Strength Transfer (BURST) induced by massed vs. distributed-rehabilitative exercise training....     

Neglected floating fifth metacarpal: a case report

Simultaneous dislocation of the metacarpophalangeal and carpometacarpal joint has been previously reported. Floating metacarpals occur when the metacarpal head displaces volarly and the base displaces towards the dorsal side. A closed dislocation at both ends of the fifth ray is unusual. In this study, we report a neglected case of floating fifth ray and its management along with a review of the literature.     

Complications and reintervention following elective open abdominal aortic aneurysm repair: a 10-year retrospective analysis

INTRODUCTION

Recent data have shown higher rates of graft related complication or reintervention in patients undergoing endovascular aneurysm repair compared with open aneurysm surgery (OAS). However, there are fewer data available regarding procedure related reinterventions following OAS. The aim of this study was to investigate the incidence of procedure related complications and reintervention following elective open abdominal aortic aneurysm repair.

METHODS

This was a retrospective analysis of prospectively collected data from the dedicated Portsmouth POSSUM database. Data from 361 patients (median age: 72 years, 91.4% male) who underwent elective OAS between 1993 and 2004 were analysed. The incidences of early and late complications and subsequent reintervention were investigated.

RESULTS

The median follow-up duration was 10 years 4 months (range: 5 years - 16 years 4 months). There were 52 reinterventions in the follow-up period. Of these, 34.6% were for incisional hernias or small bowel obstruction with the majority of the remaining laparotomies performed for bleeding or distal ischaemic complications. Almost two-thirds (63.5%) of reinterventions occurred in the first 30 days. There were 30 emergency readmissions to the acute surgical wards that did not require reintervention.

CONCLUSIONS

OAS carries a significant reintervention rate. In this study, 54% of reinterventions were directly related to laparotomy.     

The role of a standardized 36 core template-assisted transperineal prostate biopsy technique in patients with previously negative transrectal ultrasonography-guided prostate biopsies

Study Type – Diagnostic (exploratory cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Template assisted transperineal biopsy of the prostate has become increasingly popular over the past decade. Several studies have demonstrated that transperineal prostate biopsy (TPB) is associated with an increased rate of cancer detection, increased histological concordance with final prostatectomy samples and an increase in anterior and apical prostate cancers than standard TRUS biopsy. However, interpretation of the literature is difficult due to considerable variation between studies in terms of technique and equipment. We examined a small cohort (n= 40) of patients using a standardized 36 core template assisted TPB technique. We show that utilising this technique is associated with high cancer (68%) detection rate in patients with two previous negative TRUS biopsies. Of patients were found to have anterior gland tumours which would not have been detected by standard TRUS guided biopsy.

OBJECTIVE

? To determine the efficacy and safety of a standardized 36 core template‐assisted transperineal biopsy technique for detecting prostate cancer in patients with previously negative transrectal ultrasonography‐guided prostate biopsies and elevated prostate‐specific antigen (PSA) levels.

PATIENTS AND METHODS

? Between April 2008 to September 2010, a total of 40 patients with a mean (range) age of 63 (49–73) years, a mean (range) elevated PSA level of 21.9 (4.7–87) ng/mL and two previous sets of negative TRUS‐guided prostate biopsies underwent standardized 36 core template‐assisted transperineal prostate biopsies under general anaesthetic as a day case procedure. ? The cancer detection rate and complications for all cases were evaluated.

RESULTS

? In total, 27 of 40 (68%) patients were found to have adenocarcinoma of the prostate, two patients (5.0%) had atypical small acinar proliferation, one had high‐grade prostatic intraepithelial neoplasia (2.5%), four (10%) had chronic active inflammation and six (15%) had benign histology. ? Gleason scores were in the range 6–9, with a median Gleason score of 7. ? There were no cases of urosepsis, urinary tract infections or haematuria. A single patient experienced acute urinary retention, with a subsequent succesful trial without a catheter, and haematospermia was common, although minor.

CONCLUSIONS

? Our standardized 36 core template‐assisted transperineal prostate biopsy technique is safe and associated with a high detection rate of prostate cancer. ? This technique should be considered in patients with elevated PSA levels and previously negative TRUS‐guided prostate biopsies.     

Steroid withdrawal at 3 months after kidney transplantation: a comparison of two tacrolimus-based regimens

The 6 month prospective, randomized study compared the steroid-sparing potential of two tacrolimus-based regimens after renal transplantation. A total of 489 patients were randomized (1:1) to receive tacrolimus/mycophenolate mofetil (MMF)/steroids (n = 243; group Tac/MMF/S) or tacrolimus/azathioprine/steroids (n = 246; group Tac/Aza/S). At 3 months, steroids were tapered off in 267 (54.6%) patients free from steroid-resistant acute rejection and with serum creatinine concentrations <160 micromol/l. The incidence of biopsy-confirmed acute rejection at month 3 was lower in group Tac/MMF/S compared with group Tac/Aza/S (18.1% vs. 26.0%,P = 0.035). Moreover, more patients in the Tac/MMF/S group met the criteria for steroid withdrawal than in the Tac/Aza/S group (60.5% vs. 48.8%; P < 0.01). The incidence of acute rejection during months 4-6 was low in all groups, both for patients on steroid-free dual therapy (Tac/MMF: 2.7%, Tac/Aza: 0.8%) and for patients who continued steroid maintenance therapy (Tac/MMF/S: 3.5%, Tac/Aza/S: 7.1%). Moreover, kidney function was well preserved in steroid-free patients with month 6 median serum creatinine levels of 119.5 micromol/l (Tac/MMF), and 115.1 micromol/l (Tac/Aza). For patients who continued to receive steroids, month 6 median creatinine levels were 130.5 micromol/l (Tac/MMF/S) and 132.8 micromol/l (Tac/Aza/S). The criteria for the selection of patients to discontinue steroids were adequate. Both tacrolimus-based regimens allowed the safe discontinuation of steroids in low-risk patients at month 3. The Tac/MMF combination was superior in the prevention of acute rejections and more patients met the chosen criteria for steroid withdrawal.