Deciphering osteoarthritis genetics across 826,690 individuals from 9 populations.

Osteoarthritis affects over 300 million people worldwide. Here, we conduct a genome-wide association study meta-analysis across 826,690 individuals (177,517 with osteoarthritis) and identify 100 independently associated risk variants across 11 osteoarthritis phenotypes, 52 of which have not been associated with the disease before. We report thumb and spine osteoarthritis risk variants and identify differences in genetic effects between weight-bearing and non-weight-bearing joints. We identify sex-specific and early age-at-onset osteoarthritis risk loci. We integrate functional genomics data from primary patient tissues (including articular cartilage, subchondral bone, and osteophytic cartilage) and identify high-confidence effector genes. We provide evidence for genetic correlation with phenotypes related to pain, the main disease symptom, and identify likely causal genes linked to neuronal processes. Our results provide insights into key molecular players in disease processes and highlight attractive drug targets to accelerate translation.

Posterior subdeltoid and external rotators preserving approach for reduction and fixation of displaced extra-articular fractures of the scapula.

BACKGROUND: Operative management of scapular body fractures, when indicated, typically involves extensive exposure through a posterior approach. We present our experience with a deltoid preserving approach that allows excellent exposure of the fracture lines for reduction and fixation while minimizing muscle detachment and overall tissue trauma. TECHNIQUE: Exposure of the scapula was obtained through a posterior incision. The posterior deltoid was exposed and retracted superiorly while the arm was abducted in accordance with Brodsky et al. The scapula was exposed in the interval between infraspinatus and teres minor. PATIENTS AND METHODS: Six patients were treated using this approach and were retrospectively reviewed. All were men with a mean age of 34 years (range 24-45 ± 6.7 years). The injuries involved two 14-A3.1 and four 14-A3.2 AO/OTA types of fractures. The mean follow-up after surgery was 28 months (range 21-36 ± 4.93 months). RESULTS: All fractures could be anatomically reduced and healed without compromise. The mean Constant score was 93.8 (range 91-97 ± 2.13), while range of motion and strength returned to levels equal to the uninjured shoulder. All patients returned to their previous level of activity. We did not observe atrophy of the posterior muscles or hardware complications, and none required hardware removal. CONCLUSION: The deltoid and external rotators preserving posterior approach permitted good visualization of the fractures while allowing reduction and fixation without extensive muscular dissection and provided excellent functional outcomes. We consider that it offers obvious advantages over more aggressive muscle detaching approaches. LEVEL OF EVIDENCE: Therapeutic study, IV.

Latissimus Dorsi Transfer in Posterior Irreparable Rotator Cuff Tears.

BACKGROUND: Massive rotator cuff tears pose a difficult and complex challenge even for the experienced surgeon; inability to repair these tears by conventional means designates them as irreparable, while management becomes quite taxing. Several operative options have been suggested for the management of such lesions with varying degrees of success, while it is imperative to match patient demands and expectations to the predicted outcome. METHODS: Research articles are examined and key concepts are discussed, in order to provide an evidence based review of the available literature. The anatomy and pathomechanics along with the indications, contraindications and surgical techniques are reported. RESULTS: Transfer of the Latissimus dorsi has been used with success to restore shoulder function in deficits of the posterior rotator cuff. Although it can be used in a variety of settings, the ideal patient for a Latissimus dorsi tendon transfer is a young and active individual, with no glenohumeral osteoarthritis that has a severe disability and weakness related to an irreparable posterior cuff tear. CONCLUSION: Tendon transfers have proved to be a successful treatment option in salvaging this difficult problem, providing pain relief and restoring shoulder function. Despite the excellent functional outcomes and pain suppression following operation, a variety of factors may affect the outcome; thus making indications and preoperative assessment a valuable component.

Co-expression of survivin, c-erbB2, and cyclooxygenase-2 (COX-2): prognostic value and survival of endometrial cancer patients.

AIM: The purpose of this study was to investigate the co-expression of survivin, c-erbB2, and COX-2 in endometrial cancer tissues and evaluate its prognostic significance in endometrial cancer METHODS: Tumor tissue biopsies from 110 patients with primary untreated endometrial carcinomas were studied by immunohistochemistry. Statistical analysis evaluated correlation of antigen expression with tumor stage, grade, myometrial invasion, and histologic type. Association with disease outcome was also investigated RESULTS: The results showed that expression of the three antigens was independently associated with histological grade, disease stage, and myometrial invasion. Clinicopathological parameters were also associated with the number of antigens expressed by each tumor, the expression of more antigens correlating with advanced stage disease and deep myometrial invasion. In a 10-year follow-up, patients with tumors expressing more of these three antigens had significantly lower survival rate that those with smaller expression score CONCLUSIONS: Our results indicate that the co-expression score has independent prognostic value for endometrial cancer.

Jaw bone metastases: four cases.

OBJECTIVE: Metastatic tumors make up approximately one percent of all oral malignancies. Such tumors may present in the jaw bones and oral soft tissues. The commonest oral site is the mandible. PATIENTS AND METHODS: This is a retrospective study of four cases of metastatic tumors of the jaws seen at the Oral-Maxillofacial Department, General University Hospital of Alexandroupolis, Thrace, Greece from 1989 to 2005, representing 1% of all histologically confirmed malignant tumors at the hospital. RESULTS: Two cases originated from the thyroid gland, one was from the esophagus, and one from the liver. Three metastases occurred in the mandible and one in the maxilla. The oral symptoms were similar to odontogenic infections or to benign neoplasms. CONCLUSIONS: In view of the resemblance in the presentation of metastases and other tumors affecting the jaws, a high index of clinical suspicion is advocated to ensure early, multidisciplinary care of hosts.

Cytoplasmic expression of c-erb-B2 in endometrial carcinomas.

BACKGROUND: The aim of this study was to investigate the expression of c-erb-B2 in endometrial cancer with attention to both membranous and cytoplasmic staining, and to elucidate the significance of cytoplasmic signaling. MATERIALS AND METHODS: c-erb-B2 reactivity was assessed by immunohistochemistry in 110 patients using a polyclonal antibody, and evaluated semiquantitatively according to the percentage of cells demonstrating membranous or diffuse cytoplasmic staining. Correlation was made with tumor stage, grade, myometrial invasion, histologic type, and disease outcome. RESULTS: c-erb-B2 overexpression, indicated by membranous and cytoplasmic staining of at least 10% of the tumor cells, was found in 47 (42.7%) cases. Cytoplasmic expression of c-erb-B2 was observed more frequently than membranous (69.1 vs. 5.5%). Synchronous cytoplasmic and membranous signaling was noticed in 7.9% of cases. Interestingly, patients with cytoplasmic c-erb-B2-positive tumors had a significantly shorter survival (p = 0.047). CONCLUSIONS: These results indicate that c-erb-B2 is a specific marker of endometrial cancer. It is also an independent prognostic indicator of poor outcome. Cytoplasmic staining is as important as membranous staining, and is also a specific finding.

Papillary thyroid carcinoma metastasis most probably due to fine needle aspiration biopsy. A case report.

Implantation of cancer cells from needle biopsy has been reported in a wide range of malignancies. Fine needle aspiration biopsy has become an accepted method for assessment of thyroid nodules. Local reappearance of thyroid cancer from needle track dissemination is a rare complication of thyroid aspiration. A 45-year-old female developed local recurrence of papillary thyroid carcinoma four years after aspiration biopsy and thyroidectomy. Metastatic deposits appeared in the skin and the sternocleidomastoid muscle. The linear array and the site of metastases implied that seeding most probably resulted from the needle biopsy.

Does neoplastic cholecystokinin expression reflect the embryonal pattern of the protein? A study in human pancreas.

AIM: To determine the immunoreactivity of cholecystokinin (CCK) during the development of the human fetal pancreas and pancreatic adenocarcinoma, given that, CCK positive cells were demonstrated either in its embryonic anlage or in pancreatic cancer. In order to obtain possible parallels in the expression pattern of neoplastic cells in adults (well--moderately--poorly differentiated), we investigated the pattern of CCK expression in the pancreatic tissue during the various stages of development and compared these with the proliferation of tissue assessed by proliferating cell nuclear antigen (PCNA) immunohistochemistry. EXPERIMENTAL DESIGN: Tissue sections from 15 pancreatic fetal specimens, and equal number of ductal adenocarcinoma specimens, were assessed using immunohistochemical methods for CCK. RESULTS: The density of positive cells in the primitive exocrine ductal walls and outgrowing buds was significantly higher than the relevant density in the neoplastic pancreatic tissue of mixed (ductal-endocrine) and pure ductal type (p1=0.004, p2 < 0.0005, p3 < 0.0005 and p4=0.023 respectively). The above values were estimated from 20th to 22nd weeks of gestation. There was no significant difference in the density of positive cells in the islet cell epithelium from 25-30 weeks, and the neoplastic tissue of mixed (p5=0.10) and pure ductal type (p6=0.15). CONCLUSIONS: The immunostaining for CCK identifies a sub-group of pancreatic ductal adenocarcinomas with a neuroendocrine component (initially considered as pure ductal tumors), and mixed ductal-endocrine tumors. This pattern of expression in neoplasms recapitulates the normal pattern during the embryonal development of the organ, and may be important for the development of new therapeutic approaches with eventual clinical utility.

Brooke-Spiegler syndrome with parotid gland involvement.

Salivary gland involvement in Brooke-Spiegler syndrome (BSS), an autosomal dominantly inherited disease, is known though not frequent. A case of familial cylindromatosis with parotid gland adenoma is herein reported. A 67-year-old lady presented with multiple scalp nodules and papular coalescent lesions over the nasolabial folds and the forehead. The clinical examination also revealed a left preauricular lump. Multiple biopsies of the scalp lesions and the nasolabial papules revealed cylindromas and trichoepitheliomas respectively. CT scan and FNA of the preauricular lump were suggestive of parotid gland adenoma. The patient underwent excision of the scalp cylindromas and total left parotidectomy. There is no evidence of recurrence after 4 years. The association of BSS with salivary gland tumours, emphasizes the necessity of thorough salivary gland examination in all patients with skin lesions. Knowledge of the genetic background of BSS allows for genetic counseling of patients.