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Cauda equina syndrome (CES) is a constellation of symptoms which consist of low back pain, sciatica, saddlearea paraesthesia, urinary or faecal incontinence, with or without motor weakness, and sensory deficit. Surgical decompression is indicated as soon as possible, as decompression within 48 hours from onset allows maximum improvement of symptoms. Recovery usually occurs months or years postoperatively. We report a case of a patient with cauda equina syndrome secondary to massive lumbar disc herniation who had undergone urgent decompression one week after onset of urinary and bowel dysfunction. The clinical outcome post surgery was also discussed.

Cellular identity is ultimately controlled by transcription factors (TFs), which bind to specific regulatory elements (REs) within the genome to regulate gene expression and cell fate changes. While recent advances in genome-wide epigenetic profiling techniques have significantly increased our understanding of which REs are utilized in which cell type, it remains largely unknown which TFs and cofactors interact with these REs to modulate gene expression. A major hurdle in dissecting the whole composition of a multi-protein complex formed at a specific RE is the shortage of appropriate techniques. We have developed a novel method termed TALE-mediated Isolation of Nuclear Chromatin (TINC). TINC utilizes epitope-tagged TALEs to isolate a specific genomic region from the mammalian genome and includes a nuclei isolation and chromatin enrichment step for increased specificity. Upon cross-linking of the cells and isolation of the chromatin, the target region is purified based on affinity purification of the TALE and associated nucleic acid and protein molecules can be subjected to further analyses. A key TF in the pluripotency network and therefore in embryonic stem cells (ESCs) is NANOG. It is currently not fully understood how Nanog expression is regulated and consequently it remains unclear how the ESC state is maintained. Using TINC we dissected the protein complex formed at the Nanog promoter in mouse ESCs and identified many known and numerous novel factors.

The brachial artery is rarely injured in closed posterior dislocation of the elbow, unlike the high rate of vascular injury seen after dislocation of the knee. Despite the anatomical proximity of the brachial artery to the elbow joint, most cases of brachial artery injury after dislocation of the elbow are related to an associated fracture, an open injury or high-energy trauma. A high index of suspicion should be maintained as well as a thorough neurovascular examination with regards this potentially disastrous complication. We describe an unusual case of complete thrombosis of the brachial artery presenting with a posterior elbow dislocation following a fall (low energy trauma) that was treated non- operatively. At three months follow-up, patient had good circulation over the affected limb, no complaints of ischemic pain or cold intolerance, no signs of Volkmann's ischemic contracture, and a range of motion that was comparable to the contralateral limb.

Many, if not all, tumours contain a sub-population of self-renewing and expanding stem cells known as cancer stem cells (CSCs). The symmetric division of CSCs is one mechanism enabling expansion in their numbers as tumours grow, while epithelial-mesenchymal transition (EMT) is an increasingly recognized mechanism to generate further CSCs endowed with a more invasive and metastatic phenotype. Putative CSCs are prospectively isolated using methods based on either a surface marker or an intracellular enzyme activity and then assessed by a 'sphere-forming' assay in non-adherent culture and/or by their ability to initiate new tumour growth when xenotransplanted into immunocompromised mice-hence, these cells are often referred to as tumour-propagating cells (TPCs). Cell sub-populations enriched for tumour-initiating ability have also been found in murine tumours, countering the argument that xenografting human cells merely select human cells with an ability to grow in mice. Cancer progression can be viewed as an evolutionary process that generates new/multiple clones with a fresh identity; this may be a major obstacle to successful cancer stem cell eradication if treatment targets only a single type of stem cell. In this review, we first briefly discuss evidence that cancer can originate from normal stem cells or closely related descendants. We then outline the attributes of CSCs and review studies in which they have been identified in various cancers. Finally, we discuss the implications of these findings for successful cancer therapies, concentrating on the self-renewal pathways (Wnt, Notch, and Hedgehog), aldehyde dehydrogenase activity, EMT, miRNAs, and other epigenetic modifiers as potential targets for therapeutic manipulation.

Despite many years of intensive effort, there is surprisingly little consensus on the most suitable markers with which to locate and isolate stem cells from adult tissues. By comparison, the study of cancer stem cells is still in its infancy; so, unsurprisingly, there is great uncertainty as to the identity of these cells. Stem cell markers can be broadly categorized into molecular determinants of self-renewal, clonogenicity, multipotentiality, adherence to the niche, and longevity. This review assesses the utility of recognizing cancer stem cells by virtue of high expression of aldehyde dehydrogenases (ALDHs), probably significant determinants of cell survival through their ability to detoxify many potentially cytotoxic molecules, and contributing to drug resistance. Antibodies are available against the ALDH enzyme family, but the vast majority of studies have used cell sorting techniques to enrich for cells expressing these enzymes. Live cells expressing high ALDH activity are usually identified by the ALDEFLUOR kit and sorted by fluorescence activated cell sorting (FACS). For many human tumours, but notably breast cancer, cell selection based upon ALDH activity appears to be a useful marker for enriching for cells with tumour-initiating activity (presumed cancer stem cells) in immunodeficient mice, and indeed the frequency of so-called ALDH(bri) cells in many tumours can be an independent prognostic indicator.

Diabetes is a degenerative disease that results from the selective destruction of pancreatic beta-cells. These cells are responsible for insulin production and secretion in response to increases in circulating concentrations of nutrients, such as glucose, fatty acids and amino acids. This degenerative disease can be treated by the transplantation of differentiated islets obtained from cadaveric donors, according to a new surgical intervention developed as Edmonton protocol. Compared to the classical double transplant kidney-pancreas, this new protocol presents several advantages, concerning to the nature of the implant, immunosuppressive drug regime and the surgical procedure itself. However, the main problem to face in any islet transplantation program is the scarcity of donor pancreases and the low yield of islets isolated (very often around 50%) from each pancreas. Nevertheless, transplanted patients presented no adverse effects and no progression of diabetic complications. In the search of new cell sources for replacement trials, stem cells from embryonic and adult origins represent a key alternative. In order to become a realistic clinical issue transplantation of insulin-producing cells derived from stem cells, it needs to overcome multiple experimental obstacles. The first one is to develop a protocol that may allow obtaining a pure population of functional insulin-secreting cells as close as possible to the pancreatic beta-cell. The second problem should concern to the transplantation itself, considering issues related to immune rejection, tumour formation, site for implant, implant survival, and biosafety mechanisms. Although transplantation of bioengineered cells is still far in time, experience accumulated in islet transplantation protocols and in experiments with appropriate animal models will give more likely the clues to address this question in the future.

This is an initial report of a new method of axillary dissection via a periareolar incision and an 8 mm incision in the axilla with the da Vinci Surgical System. The 10x magnification and three-dimensional image, together with the versatility and precision of the robotic telemanipulators, has enabled us to perform nerve-sparing axillary dissection in four patients with invasive ductal carcinoma of the breast undergoing segmental (conservative) excision and level II axillary dissection. The time for the robotic axillary dissection ranged from 30 to 105 minutes (average 70.5 minutes). The average number of lymph nodes retrieved was 13 (11, 11, 13, and 17, respectively). Postoperatively all four patients recovered well and were discharged the next day. The robotic system can enhance the surgeon's ability by providing a high-definition, magnified, three-dimensional view of the operative field, intuitively controlled articulating instruments, and elimination of tremors; and it has potential benefits for the patient.

Hungry bone syndrome (HBS) is a postoperative condition of severe hypocalcemia that can be seen in patients who have undergone parathyroidectomy (PTX) for secondary hyperparathyroidism (2HPT) of renal origin. This study examines HBS in patients after PTX for 2HPT.Prospectively collected data was retrospectively reviewed in patients who underwent PTX for 2HPT of renal origin at a single institution. HBS was defined as the need for additional days of hospitalization or readmission for intravenous calcium supplementation due to clinical symptoms of hypocalcemia, including tingling, muscle spasms, and bone pain and/or immediate postoperative low serum calcium ≤7.5 mg/dl.Of 79 patients who underwent PTX for 2HPT, 27.8% (n = 22) experienced HBS. Young age (≤45 years, p = 0.02) was the only preoperative variable that predicted HBS. Most patients developed HBS within 18 h after surgery and required a prolonged hospital stay (19/22) compared to those requiring hospital readmission within the first 7 days (3/22). Initial postoperative serum calcium levels within 18 h of surgery were significantly lower in those patients who developed HBS (7.1 vs. 8.3 mg/dl, p = 0.001), and those patients also had a greater absolute decrease in serum calcium (2.8 vs. 3.5 mg/dl, p = 0.04).HBS develops in a significant proportion of patients generally within the first 18 h after subtotal PTX for 2HPT. The only identifiable preoperative risk factor for HBS was young age. Additionally, low initial calcium levels and greater absolute decrease in serum calcium may help identify those patients that will develop HBS requiring judicious calcium supplementation.

Most tumours appear to contain a sub-population (s) of self-renewing and expanding stem cells known as cancer stem cells (CSCs). The CSC model proposes that CSCs are at the apex of a hierarchically organized cell population, somewhat akin to normal tissue organization. Selection pressures may also facilitate the stochastic clonal expansion of sub-sets of cancer cells that may co-exist with CSCs and their progeny, moreover the trait of stemness may be more fluid than hitherto expected, and cells may switch between the stem and non-stem cell state. A large body of evidence points to the fact that CSCs are particularly resistant to radiotherapy and chemotherapy. In this review we discuss the basis of such resistance that highlights the roles of ABC transporters, aldehyde dehydrogenase (ALDH) activity, intracellular signalling pathways, the DNA damage response, hypoxia and proliferative quiescence as being significant determinants. In the light of such observations, we outline strategies for the successful eradication of CSCs, including targeting the self-renewal controlling pathways (Wnt, Notch and Hedgehog), ALDH activity and ABC transporters, blocking epithelial mesenchymal transition (EMT), differentiation therapy and niche targeting.

Like their normal counterparts, many tumours are thought to have a hierarchical organization, albeit a disorganized one. Accordingly, the concept of cancer stem cells has emerged, and that these cells are responsible for perpetuating tumour existence. Operationally, cancer stem cells are regarded as prospectively purified cells that are the most effective at tumour initiation in an in vivo assay, usually after xenotransplantation to NOD/SCID mice. The conventional wisdom is that such tumour-initiating cells are rare based upon having to xenotransplant large numbers of human tumour cells into immunodeficient mice to propagate the tumour, but new evidence indicates that perhaps these cells are not so rare, at least in malignant melanoma, if a supportive soil is provided for the transplanted cells along with further restriction of the murine host's immune response.

Cancer-associated fibroblasts/myofibroblasts and inflammatory cells produce a vast array of growth factors, chemokines and extracellular matrix (ECM) components that facilitate cancer progression, invasion/metastasis and neovascularization. This review highlights some surprisingly novel mechanisms of this paracrine relationship.Mesenchymal stem/stromal cells (MSCs) are known for their tropism towards certain tumours, but now we find that cross-talk between tumours and MSCs leads to greater tumour motility and metastasis. Two closely related populations of immature myeloid cells, so-called 'cap cells' and myeloid-derived suppressor cells (MDSCs) also cross-talk with tumour cells, promoting invasion and metastasis through matrix metalloproteinase (MMP) secretion, as well as contributing to neovascularization and T-cell tolerance. The contribution of bone marrow-derived cells (BMDCs) to tumour neovascularization is controversial, but BMD--endothelial progenitor cells (EPCs)--are strongly implicated in the angiogenic switch in a mouse model. BMDCs are also credited with the creation of premetastatic niches to which metastatic cells adhere via integrins.There is no doubt that BMDCs are not simply bystanders in the tumour battleground. The mechanisms through which they aid tumour progression are numerous; effective treatments that combat BMDC-tumour cross-talk are surely on the way.

The worldwide shortage of donor livers to transplant end stage liver disease patients has prompted the search for alternative cell therapies for intractable liver disease. Embryonic stem cells can be readily differentiated into hepatocytes, and their transplantation into animals has improved liver function in the absence of teratoma formation: their use in bioartificial liver support is an obvious application. In animal models of liver disease, adopting strategies to provide a selective advantage for transplanted foetal or adult hepatocytes have proved highly effective in repopulating recipient livers, but the poor success of today's hepatocyte transplants can be attributed to the lack of a clinically applicable procedure to force a similar repopulation of the human liver. The activation of bipotential hepatic progenitor cells is clearly vital for survival in many cases of acute liver failure, but surprisingly little progress has been made with these cells in terms of transplantation. Finally there is the controversial subject of autologous bone marrow, and while the contribution of these indigenous cells to liver turnover seems at best, trivial, results from a small number of phase 1 studies of transplantation of bone marrow to cirrhotic patients have been moderately encouraging.

Background Significant morbidity such as pain, paresthesia, and arm stiffness has often been associated with axillary dissection for breast cancer. We report our experience of 30 patients with stage I and II invasive ductal carcinoma of the breast who underwent laparoscopic-assisted axillary dissection together with segmental mastectomy. Methods Tumours were situated in the upper or lower lateral quadrants only. In all cases, initial exposure for axillary dissection was performed through the breast periareolar incision. A 10-mm 30° laparoscope was introduced through the breast incision to gain entry to the axilla. A separate stab incision in the lower aspect of the axilla was used for introduction of the 5-mm Harmonic shears (Ethicon Endo-Surgery, Inc, Cincinnati, OH). A grasping forceps was introduced through the main incision alongside the endoscope. Subsequent axillary dissection was performed laparoscopically, and the axillary content was removed through the breast incision. Results Average yield of lymph nodes was 15 (range 7 to 25). There were no intraoperative complications. Immediately postsurgery, all patients were able to fully mobilize the upper limb, facilitated by absence of an axillary scar. Patients also reported minimal pain, paresthesia, with no stiffness or frozen shoulder. Conclusion Laparoscopic-assisted axillary dissection offers a safe and improved approach to the axilla, which can be incorporated into breast cancer surgery.

Newborn pigs prevented from suckling colostrum were shown to have less than 0.05 micrograms/ml total immunoglobulin present in their serum. Rabbit heart xenografts transplanted heterotopically into the neck of such pigs were hyperacutely rejected, with a mean survival time of 92 +/- 14 min (mean +/- SD). Pigs which had been allowed to suckle and whose serum contained 10-15 mg/ml maternal immunoglobulin hyperacutely rejected rabbit heart xenografts in 109 +/- 62 min. Histological studies showed no Ig binding but complement component 3 (C3) binding to rabbit hearts placed in immunoglobulin-negative pigs. Prolongation of rabbit heart xenograft survival was achieved by administering cobra venom factor (1 mg/kg) to the pigs pretransplant. These data show hyperacute xenograft rejection in the absence of antibody and suggest that its cause is activation of complement by the alternative pathway.