The acute elevation in IAP during laparoscopy significantly increased the optic nerve sheath diameter. The changes in the ONSD reflect a temporary and reversible increase in the ICP due to the acute elevation of IAP.

The portal venous circulation provides a conduit for pancreatic ductal adenocarcinoma (PDAC) tumor cells to the liver parenchyma sinusoids, a frequent site of metastasis. Turbulent flow in the portal circulation promotes retention of PDAC shed circulating tumor cells (CTC) and myeloid-derived immunosuppressor cells (MDSC). Excessive colony stimulating factor-1 receptor (CSF1R) signaling can induce myeloid differentiation to MDSC and transformation of MDSC to myeloid-derived fibroblasts (M-FB). Interactions between PDAC CTC and M-FB in the portal blood promotes the formation of immunoresistant clusters that enhance CTC proliferation, migration, and survival. Analysis of portal and peripheral blood samples collected intraoperatively from 30 PDAC patients undergoing pancreatico-duodenectomy showed that PDAC patient plasma contained high levels of macrophage colony stimulating factor (M-CSF/CSF1), granulocyte-macrophage colony stimulating factor (GM-CSF/CSF2), interleukin-8 (IL-8), and interleukin-34 (IL-34) compared to healthy control levels. Moreover, the level of M-CSF in portal blood was significantly higher than that detected in the peripheral blood of PDAC patients. PDAC CTC aseptically isolated by fluorescence activated cell sorting (FACS) out of freshly collected patient portal blood mononuclear cells (PortalBMC) had elevated RNA expression of IL34 (IL-34 gene) and CSF1 (M-CSF/CSF1 gene) which both signal through CSF1R. PDAC CTC also had high levels of RNA expression for CXCL8, the gene encoding chemokine interleukin-8 (IL-8) which can attract myeloid cells through their CXCR2 receptors. FACS-isolated portal PDAC CTC and M-FB co-cultured ex vivo had increased CTC proliferation, motility, and cluster formation compared to CTC cultured alone. CSF1R and CXCR2 cell surface expression were found on PDAC portal blood CTC and M-FB, suggesting that both cell types may respond to M-CSF, IL-34, and IL-8-mediated signaling. Portal PDAC CTC displayed enhanced RNA expression of CSF1 and IL34, while CTC+M-FB+ clusters formed in vivo had increased RNA expression of CSF2 and IL34. Portal M-FB were found to have high CSF1R RNA expression. CTC isolated from ex vivo 7-day cultures of PDAC patient portal blood mononuclear cells (PortalBMC) expressed elevated CSF1, IL34, and IL8 RNA, and CSF1 expression was elevated in M-FB. Treatment with rabbit anti-CSF1R antibodies decreased CTC proliferation. Treatment of PortalBMC cultures with humanized anti-CSF1R, humanized anti-IL-8, or anti-IL-34 antibodies disrupted CTC cluster formation and increased CTC apoptosis. U937 myeloid precursor cell line cultures treated with conditioned media from PortalBMC ex vivo cultures without treatment or treated with anti-IL-8 and/or anti-CSF1R did not prevent myeloid differentiation in the myeloid precursor cell line U937 to macrophage, dendritic cell, MDSC, and M-FB phenotypes; whereas, U937 cultures treated with conditioned media from PortalBMC ex vivo cultures exposed to anti-IL-34 were significantly inhibited in their myeloid differentiation to all but the M-FB phenotype. PDAC patient T cells that were found phenotypically anergic (CD3+CD25+CTLA4+PD1L1+) in PortalBMC could be re-activated (CD3+CD25+CTLA4-PD1L1-), and displayed increased interferon gamma (IFNγ) production when PortalBMC ex vivo cultures were treated with anti-CSF1R, anti-IL-8, and anti-IL-34 antibodies alone or in combination. These findings suggest that PDAC CTC have the potential to influence myeloid differentiation and/or antigen presenting cell activation in the PDAC portal blood microenvironment, and that disruption of CTC/M-FB interactions may be potential targets for reversing the immunosuppression supporting CTC survival in the portal blood.

Spontaneous hemorrhage from hepatic tumors is an uncommon but serious complication. Recently, interventional radiologic (IR) techniques are being used increasingly in the management of these patients. We report our 16-year experience in managing spontaneous hemorrhage from liver tumors. Twenty-six consecutive patients were diagnosed with spontaneous liver hemorrhage between 1995 and 2011. Initial management was operative in eight, IR in six, and supportive in 12 patients. Of those managed operatively, five were segmentectomies; one hemihepatectomy; one wedge resection; and one packing who later died from coagulopathy. In the IR patients, seven had an angiographic embolization; two required reembolization; one underwent resection of a hepatic adenoma 21 days after angiographic embolization. The malignant lesions included hepatocellular carcinoma (n = 6), angiosarcoma (n = 1), metastatic squamous cell carcinoma (n = 1), metastatic leiomyosarcoma (n = 1), nonsquamous cell carcinoma (n = 1), or metastatic angiosarcoma (n = 1). Benign diseases included hepatic adenoma (n = 5), end-stage liver disease (n = 1), and polycystic liver (n = 1). Spontaneous hemorrhage from the liver occurs evenly from benign or malignant causes, one-third of which are primary liver disease. If the patients presents emergently, angiographic embolization may control the bleeding and allow for elective resection once the sequelae of bleeding have resolved.

Goals The aim of this study was to characterize current trends in the use of endoscopic retrograde cholangiopancreatography (ERCP) in the United States for patients hospitalized with chronic pancreatitis. Background Historically, ERCP was the primary tool for diagnostic and therapeutic management of chronic pancreatitis. With increased availability of magnetic resonance imaging (MRI) and endoscopic ultrasound (EUS), indications for ERCP are being redefined. Study We performed a retrospective cohort study using the Nationwide Inpatient Sample from 1998-2010. We identified patients with a primary discharge diagnosis of chronic pancreatitis who underwent ERCP. We excluded patients diagnosed with biliary, gallbladder, or pancreatic neoplasm and patients who underwent gallbladder or pancreatic operation during the same admission. We analyzed patient and hospital characteristics, length of stay, and in-hospital mortality, and adjusted for weighted sample schema. Results During the study period, 29,318 patients with chronic pancreatitis (mean age 52, 57.2% female) underwent ERCP during their hospitalization. The majority of patients were white (56.1%). The majority of procedures were performed at large (72.4%), urban (95.2%), academic (69.0%) hospitals. Mean hospital charges were $32,929 (S.E. $1,605). Mean length of stay was six days (S.E. 0.3), with in-hospital mortality of 0.76%. Over the study period, the number of procedures has decreased significantly (p<0.001). Conclusions In the United States, ERCP has been an important diagnostic and therapeutic tool for chronic pancreatitis. Over the last decade, ERCP has become an uncommon inpatient procedure for chronic pancreatitis.