Sentinel node biopsy after neoadjuvant chemotherapy for breast cancer

BACKGROUND: After neoadjuvant chemotherapy, while results of sentinel node biopsy (SNB) are encouraging, conditions that may affect sentinel node (SN) detection and false negative rates with respect to clinical and pathological tumor response after neoadjuvant therapy require investigation. METHODS: Thirty-four patients with clinical stage I, II and IIIA invasive breast cancer underwent neoadjuvant chemotherapy with doxorubicin/cyclophosphamide or doxorubicin/cyclophosphamide and docetaxel/segmental resection, SNB, and axillary node dissection (AND). RESULTS: SNs were found in 31 of 34 patients (91.2%). SNs were found in 20 of 21 patients (95.2%) with complete clinical tumor response, it was positive in 40% and no false negatives occurred. SNs were found in 11 of 13 patients (84.6%) with partial or no clinical tumor response; in four patients (33%) the SN was positive and no false negative nodes were found. Seven patients had complete pathological tumor response. SNs were found in six of these patients (85.7%). The SN was positive in 1 of 6 patients (16.7%) with no false negative. In 25 of 27 patients (92%) with partial or no pathological tumor response, the SN was identified. Eleven of these patients (44%) had positive nodes with no false negatives. CONCLUSIONS: SN identification rate and accuracy after neoadjuvant chemotherapy for breast carcinoma were extremely good however there is potential for inaccuracy after less than complete pathological tumor response. Further evaluation of SNB in larger clinical trial is warranted prior to accepting this approach as a standard care.     

Evaluating the porcine dermis graft InteXen® in three-compartment transvaginal pelvic organ prolapse repair

Introduction and hypothesis

The aim was to assess the efficacy of three-compartment pelvic organ prolapse (POP) vaginal repair using the InteXen® biocompatible porcine dermal graft as compared to traditional colporrhaphy with sacrospinous ligament suspension.

Methods

Preoperative, operative, postoperative and follow-up data were collected retrospectively. Objective recurrence was defined as POP quantification ≥ stage II and subjective recurrence as a symptomatic bulge.

Results

Each group consisted of 63 patients. Surgery time was longer using InteXen® (72?±?24.5 vs 55?±?23.5 min, p?=?0.0002). Length of hospital stay (4.6?±?1.6 vs 4.9?±?2.1 days, p?=?0.34) as well as duration of follow-up (37.1 vs 35.7 months, p?=?0.45) were equivalent between the two groups. No case of mesh erosion or infection was noted. The objective (17% vs 8%, p?=?0.12) and subjective recurrence rates (13% vs 5%, p?=?0.12) between the two groups were not statistically different.

Conclusions

InteXen® was well tolerated but had similar efficacy to traditional colporrhaphy and sacrospinous ligament suspension.     

Remodeling of the plasma membrane in preparation for sperm–egg recognition: roles of acrosomal proteins

The interaction of sperm with the egg''s extracellular matrix, the zona pellucida (ZP) is the first step of the union between male and female gametes. The molecular mechanisms of this process have been studied for the past six decades with the results obtained being both interesting and confusing. In this article, we describe our recent work, which attempts to address two lines of questions from previous studies. First, because there are numerous ZP binding proteins reported by various researchers, how do these proteins act together in sperm–ZP interaction? Second, why do a number of acrosomal proteins have ZP affinity? Are they involved mainly in the initial sperm–ZP binding or rather in anchoring acrosome reacting/reacted spermatozoa to the ZP? Our studies reveal that a number of ZP binding proteins and chaperones, extracted from the anterior sperm head plasma membrane, coexist as high molecular weight (HMW) complexes, and that these complexes in capacitated spermatozoa have preferential ability to bind to the ZP. Zonadhesin (ZAN), known as an acrosomal protein with ZP affinity, is one of these proteins in the HMW complexes. Immunoprecipitation indicates that ZAN interacts with other acrosomal proteins, proacrosin/acrosin and sp32 (ACRBP), also present in the HMW complexes. Immunodetection of ZAN and proacrosin/acrosin on spermatozoa further indicates that both proteins traffic to the sperm head surface during capacitation where the sperm acrosomal matrix is still intact, and therefore they are likely involved in the initial sperm–ZP binding step.     

解脲支原体感染患者精浆中细胞因子对精子活力的影响

目的 观察解脲脲原体(Ureaplasma urealyticum,Uu)感染患者精浆中细胞因子的变化对精子活力的影响.探讨Uu对精子活力影响的免疫机制.方法 采用ELISA方法对Uu阳性组(44例)、治疗后转阴组(30例)和正常对照组(14例)精浆中的IL-8、IL-10、TNF-α,抗精子抗体(AsAb)进行检测.使用全自动精子分析仪对精子活力(路径速度、前向速度和活动率)进行分析.结果 Uu阳性组的IL-8、IL-10和TNF-α分别为(157.2±74.6)pg/ml、(315.4±112.5)pg/ml和(223.6±89.7)pg/ml,明显高于正常对照组IL-8、IL-10和TNF-α的(78.7±28.6)pg/ml、(158.2±56.3)pg/ml和(84.3±47.9)pg/ml,两组差异比较具有统计学意义(P<0.01).治疗转阴后该组IL-8、IL-10和TNF-α分别为(114.3±61.5)pg/ml、(237.2±86.1)pg/ml和(152.6±83.5)pg/ml,也显著下降(P<0.05).同时精子活力亦随三种细胞因子的下降而明显提高.结论 Uu可引起精浆中细胞因子紊乱,AsAb阳性率增高,使精子凝集、活力下降,从而生育能力下降.Uu转阴后细胞因子趋于正常,精子的活力也得以提高.     

Axillary recurrences following positive sentinel lymph node biopsy with individual tumor cells or micrometastases and no axillary dissection

The increased use of sentinel lymph node (SLN) excision for staging the axilla in women with breast cancer has benefited women by lowering morbidity and at the same time has raised issues related to the extent of treatment needed to the nodal basin. This is of particular concern when micrometastases or isolated tumor cells are found in the sentinel nodes on the final pathology. The probability of finding metastatic disease in non-sentinel lymph nodes (NSLN) ranges from 0 to 20% with only micrometastatic deposits in the SLN. Very low rates (0-3.7%) of axillary recurrence have been reported in selected patients with micrometastases tumor in sentinel nodes who have not had a completion axillary node dissection (ALND). Risk factors for additional positive NSLN include primary tumor size, the presence of lymphovascular invasion and the size of the SN metastatic deposit. Currently, the decision to not complete the ALND when micrometastic disease is found in the SLN should be made on a case-by-case basis. One should consider the tumor characteristics, findings within the SLN, and a multidisciplinary treatment plan. Clinical trial results may help to resolve the dilemma. There appears to be a low risk for axillary recurrence.     

Primary localized cutaneous nodular amyloidosis successfully treated with cyclophosphamide

Primary localized cutaneous nodular amyloidosis (PLCNA) is a rare subtype of localized cutaneous amyloidosis and can be associated with various connective tissue disorders. It can be difficult to treat and past therapies include surgical excision, dermabrasion, electrodessication and curettage, cryotherapy and laser therapy. We present a case of a middle‐aged woman with PLCNA associated with CREST (calcinosis, Raynaud phenomenon, oesophageal motility disorders, sclerodactyly and telangiectasia) syndrome and Sjögren's syndrome responding to cyclophosphamide with no new amyloid deposits and resolution of skin ulceration after many years of resistance to drug therapy. It is important to monitor these patients for progression into systemic amyloidosis.     

Rapamycin for treatment of refractory dysthyroid compressive optic neuropathy

We report a patient with dysthyroid optic neuropathy refractory to steroids and orbital decompression treated with rapamycin, a fibroblast and T cell inhibitor. Symptoms, visual acuity, color plate testing, and visual fields improved. Aside from hypercholesterolemia, no complication related to this therapy was observed. By addressing the pathogenesis of thyroid eye disease, rapamycin may represent an alternative when standard treatments fail. Further investigation of rapamycin for treatment of dysthyroid orbitopathy is warranted.     

Fibroblasts in Dermal Tissue Repair

ABSTRACT: The cellular dynamics of dermal regeneration were studied in nonsutured cutaneous wounds of female pigs and monkeys with electron microscopy and immunohistochemistry to demonstrate the origin and the development of fibroblasts forming granulation tissue. The results indicate that fibroblasts do not originate from histiocytes but from resting fibroblasts in the wound margins. These resting fibroblasts first become undifferentiated mesenchymal cells termed “X” cells. The “X” cells then multiply, migrate, and invade the wound defect in approximately 3 days, transforming into highly active fibroblasts. The active fibroblasts are endowed with the capacity of further transformation to fibroclasts and myofibroblasts. The latter two cell populations then effectively cause remodeling of newly formed tissue and contraction of wound margins.     

Chondromyxoid fibroma of the mastoid facial nerve canal mimicking a facial nerve schwannoma

Chondromyxoid fibroma of the skull base is a rare entity. Involvement of the temporal bone is particularly rare. We present an unusual case of progressive facial nerve paralysis with imaging and clinical findings most suggestive of a facial nerve schwannoma. The lesion was tubular in appearance, expanded the mastoid facial nerve canal, protruded out of the stylomastoid foramen, and enhanced homogeneously. The only unusual imaging feature was minor calcification within the tumor. Surgery revealed an irregular, cystic lesion. Pathology diagnosed a chondromyxoid fibroma involving the mastoid portion of the facial nerve canal, destroying the facial nerve. Laryngoscope, 2009     

locStra: Fast analysis of regional/global stratification in whole‐genome sequencing studies

locStra is an ‐package for the analysis of regional and global population stratification in whole‐genome sequencing (WGS) studies, where regional stratification refers to the substructure defined by the loci in a particular region on the genome. Population substructure can be assessed based on the genetic covariance matrix, the genomic relationship matrix, and the unweighted/weighted genetic Jaccard similarity matrix. Using a sliding window approach, the regional similarity matrices are compared with the global ones, based on user‐defined window sizes and metrics, for example, the correlation between regional and global eigenvectors. An algorithm for the specification of the window size is provided. As the implementation fully exploits sparse matrix algebra and is written in C++, the analysis is highly efficient. Even on single cores, for realistic study sizes (several thousand subjects, several million rare variants per subject), the runtime for the genome‐wide computation of all regional similarity matrices does typically not exceed one hour, enabling an unprecedented investigation of regional stratification across the entire genome. The package is applied to three WGS studies, illustrating the varying patterns of regional substructure across the genome and its beneficial effects on association testing.