Novel uterine lavage system for recovery of human embryos fertilized and matured in vivo.

Purpose: In this paper we describe a novel uterine lavage system for the recovery of in vivo preimplantation embryos. Currently, no other method exists to retrieve preimplantation embryos except for in vitro fertilization (IVF). Methods: A single center, prospective feasibility study was conducted to test a novel uterine lavage system for the recovery of in vivo preimplantation embryos in egg donors and patients seeking pregnancy. Subjects were placed on controlled ovarian hyperstimulation followed by intrauterine insemination (IUI) and uterine lavage performed approximately 4-6 days after IUI. Subjects were followed up for 30 days after the procedure to monitor for safety events. Results: A total of 134 uterine lavage cycles were performed on 81 subjects (average: 1.7 cycles/subject). Ova (oocytes or embryos) were collected in 53% (71/134) of the cycles with steady improvement of recovery efficiency over the course of the study, and embryos collected in 42% (56/134) of cycles. Embryos of many stages were collected, but 71% (96/136) of embryos collected were blastocyst stage embryos which are at the most advanced stage of embryogenesis. Embryos recovered were of good quality based on blastocyst gradings in which 74% (70/95, 1 blastocyst not graded) of the blastocysts were good quality as determined by the Gardner Scale of Morphology. The procedure was well tolerated with minor side effects. In 8% of cycles a positive hCG was observed after the lavage indicating some embryos were not recovered by the lavage system. Conclusion: Through this work the system has been shown to recover embryos from the uterus in a safe and effective manner, thus opening the possibility that uterine lavage may serve as an alternative to IVF where patient indications allow.

Branchial cysts within the parotid salivary gland.

Cystic lesions within the parotid gland are uncommon and clinically they are frequently misdiagnosed as tumours. Many theories have been proposed as to their embryological origin. A 20-year retrospective review was undertaken of all pathological codes (SNOMED) of all of patients presenting with any parotid lesions requiring surgery. After analysis seven subjects were found to have histopathologically proven parotid branchial cysts in the absence of HIV infection and those patients are the aim of this review. Four of the most common embryological theories are also discussed with regard to these cases, as are their management.

Video-assisted thoracic surgery systematic mediastinal nodal dissection and stage migration: impact on clinical pathway.

OBJECTIVES: The aim of this study is to investigate the role of routine systematic mediastinal nodal dissection (SND) performed during video-assisted thoracic surgery (VATS) major pulmonary resections (VMPRs) as a staging strategy for non-small-cell lung cancer (NSCLC), compared with preoperative staging by conventional positron emission tomography (PET) and computed tomography (CT) imaging. METHODS: All patients suspected of having early lung cancer (T1-2, N0-1 and M0) were staged preoperatively by CT/PET. During VMPR, all lymph nodes on the right side at stations 2-4, 7, 8, 9, 10 and 11 and on the left stations 4-6, 7, 8, 9, 10, 11 and 3 when indicated were dissected en bloc. Histology was provided on the paraffin-embedded nodes, and patients staged accordingly. Preoperative and postoperative stagings were compared. Stage migration and impact on clinical pathway were noted. Stage IIa and higher were referred for adjuvant chemotherapy. RESULTS: Between April 2007 and January 2011, 106 consecutive patients with suspected primary NSCLC proceeded to VMPR+SND. Histology confirmed NSCLC in 96 patients. Forty-five were men and 51 women. Median age was 68.6 (range 42.8-84.7) years. As many as 91 (94.8%) patients underwent lobectomy, three (3.1%) bilobectomy and two (2.1%) pneumonectomy. PET accurately correlated with SND histological diagnosis in 42 (43.8%) patients. The unexpected N2 disease in cN0-1 was 9/86 (10.5%). SND resulted in 25 stage migrations, upstaged 16 (16.6%) and down-staged nine (9.4%) patients. All upstagings were adenocarcinoma. Four (4.2%) PET-negative patients had multi-station N2 disease. SND resulted in changing the clinical pathway for 19 (20%) patients. Fourteen (14.6%) patients upstaged to qualify for chemotherapy, and 5/9 (5.2%) down-staged patients were saved the chemotherapy. There was no morbidity or mortality attributable to this added procedure. CONCLUSIONS: SND during VMPR is safe and should be routinely performed even when nodal metastases is considered unlikely. VATS-SND is more accurate than PET in staging the mediastinum for NSCLC. PET sensitivity is significantly reduced in adenocarcinoma and might result in stage migration. Adjuvant multidisciplinary treatment should be based on SND staging.

Resistance gene expression determines the in vitro chemosensitivity of non-small cell lung cancer (NSCLC).

BACKGROUND: NSCLC exhibits considerable heterogeneity in its sensitivity to chemotherapy and similar heterogeneity is noted in vitro in a variety of model systems. This study has tested the hypothesis that the molecular basis of the observed in vitro chemosensitivity of NSCLC lies within the known resistance mechanisms inherent to these patients' tumors. METHODS: The chemosensitivity of a series of 49 NSCLC tumors was assessed using the ATP-based tumor chemosensitivity assay (ATP-TCA) and compared with quantitative expression of resistance genes measured by RT-PCR in a Taqman Array following extraction of RNA from formalin-fixed paraffin-embedded (FFPE) tissue. RESULTS: There was considerable heterogeneity between tumors within the ATP-TCA, and while this showed no direct correlation with individual gene expression, there was strong correlation of multi-gene signatures for many of the single agents and combinations tested. For instance, docetaxel activity showed some dependence on the expression of drug pumps, while cisplatin activity showed some dependence on DNA repair enzyme expression. Activity of both drugs was influenced more strongly still by the expression of anti- and pro-apoptotic genes by the tumor for both docetaxel and cisplatin. The doublet combinations of cisplatin with gemcitabine and cisplatin with docetaxel showed gene expression signatures incorporating resistance mechanisms for both agents. CONCLUSION: Genes predicted to be involved in known mechanisms drug sensitivity and resistance correlate well with in vitro chemosensitivity and may allow the definition of predictive signatures to guide individualized chemotherapy in lung cancer.

Problems in mesothelioma diagnosis.

Many centres are now seeing increasing numbers of patients with malignant mesothelioma. This presents pathologists involved in making the diagnosis with a number of problems, which can be divided into those encountered in making the distinction between mesothelioma and benign changes and those experienced in separating mesotheliomas from other types of epithelial and connective tissue tumours. Immunohistochemistry plays a major role in helping to make the diagnosis, but it should be interpreted with due regard to the clinical setting and radiological features, and with a knowledge of the wide morphological variations seen in mesothelioma. This review identifies some of these problems and addresses the uses and limitations of immunohistochemistry in different situations. It includes a discussion of some of the less common variants of mesothelioma and other pleural-based tumours that enter into the differential diagnosis.

Thoracic intrathymic thyroid and cervical goiter: single-stage resection.

Ectopic thyroid tissue in the chest is rare. We report a case of a euthyroid patient with benign ectopic thyroid tissue presenting as a thymic mass in association with a multinodular goiter. Both disorders were managed successfully by surgical intervention.