Surgery

Acute pancreatitis is a single-organ disorder that has multi-organ sequelae. As a result, it can have varied presentations. Acute pancreatitis presenting as acute limb ischemia is rare. We present a patient with acute pancreatitis presenting with bilateral lower limb ischemia. The episode of acute pancreatitis resolved but the acute lower limb ischemia precipitated as the pancreatitis progressed, and necessitated bilateral above-knee amputations. We review the literature and discuss the pathogenesis of such a phenomenon.

A 64-year-old man with no signifi cant past history presented with fever of two days duration associated with right sided chest pain radiating to the back. Physical examination revealed decreased air entry in the base of the right lung with stony dullness. A chest X-Ray confi rmed a right pleural effusion with right lower lobe consolidation. Thoracentesis produced an exudative blood-stained fl uid. Laboratory investigations revealed leucocytosis (18.2 x 10 9. L -1 ) and raised C-reactive protein (411 mg . L -

Giant fibrovascular polyps of the esophagus and hypopharynx are rare benign esophageal tumors. They arise most commonly in the upper esophagus and may, rarely, originate in the hypopharynx. They can vary significantly in size. Even though they are benign, they may be lethal due to either bleeding or, rarely, asphyxiation if a large polyp is regurgitated. Patients commonly present with dysphagia or hematemesis. The polyps may not be well visualized on endoscopy and imaging plays a vital role in aiding diagnosis as well as providing important information for preoperative planning, such as the location of the pedicle, the vascularity of the polyp and the tissue elements of the mass. They can also be recurrent in rare cases, especially if the resection margins of the base are involved. We review the recent literature and report a case of a 61-year-old man with a recurrent giant esophageal fibrovascular polyp with illustrative contrast barium swallow, CT and intra-operative images, who required several surgeries via a combination of endoscopic, trans-oral, trans-cervical, trans-thoracic and trans-abdominal approaches.

Methods: An Institutional Review Board approved retrospective review of 890 patients that had thyroid surgery for DTC between 2009 and 2010 was performed at our institution. Patients with palpable neck disease, distant metastases, less than total thyroidectomy, no postoperative thyroglobulin (Tg) determinations, and positive Tg antibodies were excluded leaving 465 patients available for analysis. Patients were divided into those who had a preoperative neck US to evaluate lateral neck nodes (nϭ234) and those that did not (nϭ231). Patient and tumor characteristics were compared using the Chi square test. The primary endpoint was Response to Therapy, defined by postoperative US and Tg levels.

Background. Therapeutic central neck dissection (CND) is an accepted part of the management of papillary thyroid carcinoma (PTC), while prophylactic CND remains controversial. Regardless of the indication for CND, the lower anatomic border of the central compartment, specifically the inclusion or otherwise of level VII, is not always clearly defined in the literature. This study aimed to determine if the routine inclusion of level VII lymph node dissection as part of CND confers increased utility in the detection of macrometastatic lymph nodes compared with level VI dissection alone.

Immune cells of the liver must be able to recognize and react to pathogens yet remain tolerant to food molecules and other nonpathogens. Dendritic cells (DCs) are believed to contribute to hepatic tolerance. Lipids have been implicated in dysfunction of DCs in cancer. Therefore, we investigated whether high lipid content in liver DCs affects induction of tolerance. METHODS: Mouse and human hepatic nonparenchymal cells were isolated by mechanical and enzymatic digestion. DCs were purified by fluorescence-activated cell sorting or with immunomagnetic beads. DC lipid content was assessed by flow cytometry, immune fluorescence, and electron microscopy and by measuring intracellular component lipids. DC activation was determined from surface phenotype and cytokine profile. DC function was assessed in T-cell, natural killer (NK) cell, and NKT cell coculture assays as well as in vivo. RESULTS: We observed 2 distinct populations of hepatic DCs in mice and humans based on their lipid content and expression of markers associated with adipogenesis and lipid metabolism. This lipid-based dichotomy in DCs was unique to the liver and specific to DCs compared with other hepatic immune cells. However, rather than mediate tolerance, the liver DC population with high concentrations of lipid was immunogenic in multiple models; they activated T cells, NK cells, and NKT cells. Conversely, liver DCs with low levels of lipid induced regulatory T cells, anergy to cancer, and oral tolerance. The immunogenicity of lipid-rich liver DCs required their secretion of tumor necrosis factor ␣ and was directly related to their high lipid content; blocking DC synthesis of fatty acids or inhibiting adipogenesis (by reducing endoplasmic reticular stress) reduced DC immunogenicity. CONCLUSIONS: Human and mouse hepatic DCs are composed of distinct populations that contain different concentrations of lipid, which regulates immunogenic versus tolerogenic responses in the liver.

Nonalcoholic steatohepatitis (NASH) is the most common etiology of chronic liver dysfunction in the United States and can progress to cirrhosis and liver failure. Inflammatory insult resulting from fatty infiltration of the liver is central to disease pathogenesis. Dendritic cells (DCs) are antigen-presenting cells with an emerging role in hepatic inflammation. We postulated that DCs are important in the progression of NASH. We found that intrahepatic DCs expand and mature in NASH liver and assume an activated immune phenotype. However, rather than mitigating the severity of NASH, DC depletion markedly exacerbated intrahepatic fibroinflammation. Our mechanistic studies support a regulatory role for DCs in NASH by limiting sterile inflammation through their role in the clearance of apoptotic cells and necrotic debris. We found that DCs limit CD8 1 T-cell expansion and restrict Toll-like receptor expression and cytokine production in innate immune effector cells in NASH, including Kupffer cells, neutrophils, and inflammatory monocytes. Consistent with their regulatory role in NASH, during the recovery phase of disease, ablation of DC populations results in delayed resolution of intrahepatic inflammation and fibroplasia. Conclusion: Our findings support a role for DCs in modulating NASH. Targeting DC functional properties may hold promise for therapeutic intervention in NASH.

Pancreatic ductal adenocarcinoma is an aggressive cancer that interacts with stromal cells to produce a highly inflammatory tumor microenvironment that promotes tumor growth and invasiveness. The precise interplay between tumor and stroma remains poorly understood. TLRs mediate interactions between environmental stimuli and innate immunity and trigger proinflammatory signaling cascades. Our finding that TLR7 expression is upregulated in both epithelial and stromal compartments in human and murine pancreatic cancer led us to postulate that carcinogenesis is dependent on TLR7 signaling. In a mouse model of pancreatic cancer, TLR7 ligation vigorously accelerated tumor progression and induced loss of expression of PTEN, p16, and cyclin D1 and upregulation of p21, p27, p53, c-Myc, SHPTP1, TGF-β, PPARγ, and cyclin B1. Furthermore, TLR7 ligation induced STAT3 activation and interfaced with Notch as well as canonical NF-κB and MAP kinase pathways, but downregulated expression of Notch target genes. Moreover, blockade of TLR7 protected against carcinogenesis. Since pancreatic tumorigenesis requires stromal expansion, we proposed that TLR7 ligation modulates pancreatic cancer by driving stromal inflammation. Accordingly, we found that mice lacking TLR7 exclusively within their inflammatory cells were protected from neoplasia. These data suggest that targeting TLR7 holds promise for treatment of human pancreatic cancer.