EASL-EORTC clinical practice guidelines : management of hepatocellular carcinoma

Bevacizumab plus Irinotecan,Fluorouracil,and Leucovorin for Metastatic Colorectal Cancer

Posthepatectomy liver failure: A definition and grading by the International Study Group of Liver Surgery (ISGLS)

There is still an unresolved paradox with respect to the immunomodulating role of estrogens. On one side, we recognize inhibition of bone resorption and suppression of inflammation in several animal models of chronic inflammatory diseases. On the other hand, we realize the immunosupportive role of estrogens in trauma/sepsis and the proinflammatory effects in some chronic autoimmune diseases in humans. This review examines possible causes for this paradox. This review delineates how the effects of estrogens are dependent on criteria such as: 1) the immune stimulus (foreign antigens or autoantigens) and subsequent antigen-specific immune responses (e.g., T cell inhibited by estrogens vs. activation of B cell); 2) the cell types involved during different phases of the disease; 3) the target organ with its specific microenvironment; 4) timing of 17beta-estradiol administration in relation to the disease course (and the reproductive status of a woman); 5) the concentration of estrogens; 6) the variability in expression of estrogen receptor alpha and beta depending on the microenvironment and the cell type; and 7) intracellular metabolism of estrogens leading to important biologically active metabolites with quite different anti- and proinflammatory function. Also mentioned are systemic supersystems such as the hypothalamic-pituitary-adrenal axis, the sensory nervous system, and the sympathetic nervous system and how they are influenced by estrogens. This review reinforces the concept that estrogens have antiinflammatory but also proinflammatory roles depending on above-mentioned criteria. It also explains that a uniform concept as to the action of estrogens cannot be found for all inflammatory diseases due to the enormous variable responses of immune and repair systems.

/pdf/the-complex-role-of-estrogens-in-inflammation-29aw75ptuv.pdf

The complex role of estrogens in inflammation

This review is intended to stimulate interest in the effect of increased expression of heme oxygenase-1 (HO-1) protein and increased levels of HO activity on normal and pathological states. The HO system includes the heme catabolic pathway, comprising HO and biliverdin reductase, and the products of heme degradation, carbon monoxide (CO), iron, and biliverdin/bilirubin. The role of the HO system in diabetes, inflammation, heart disease, hypertension, neurological disorders, transplantation, endotoxemia and other pathologies is a burgeoning area of research. This review focuses on the clinical potential of increased levels of HO-1 protein and HO activity to ameliorate tissue injury. The use of pharmacological and genetic probes to manipulate HO, leading to new insights into the complex relationship of the HO system with biological and pathological phenomena under investigation, is reviewed. This information is critical in both drug development and the implementation of clinical approaches to moderate and to alleviate the numerous chronic disorders in humans affected by perturbations in the HO system.

Pharmacological and Clinical Aspects of Heme Oxygenase

We report a case of small pancreatic carcinoma misdiagnosed as superficially spreading cholangiocarcinoma using percutaneous transhepatic cholangioscopy (PTCS). The patient was a 72-year-old man admitted to a local hospital with obstructive jaundice. The patient underwent percutaneous transhepatic biliary drainage and PTCS. He was referred to our hospital with a diagnosis of superficially spreading cholangiocarcinoma. Cholangiography revealed a stenosis of the common bile duct, and also revealed some irregularities from the common hepatic duct to the left hepatic duct, suggesting a superficial spread of cancer. No pancreatic tumor was identified by endoscopic retrograde pancreatography or by enhanced computed tomography. Cholangioscopy disclosed an elevated tumor with torsional vessels and granular mucosal lesions, which were extended to the left hepatic duct. Repeated cholangioscopic biopsies of the bile duct mucosa revealed adenocarcinoma. The patient was diagnosed with superficially spreading cholangiocarcinoma extending to the left hepatic duct and the right anterior hepatic duct. Left trisectionectomy combined with pancreatoduodenectomy was performed. The cut surface of the resected specimen showed a pancreatic head tumor that was 8 mm in diameter. Histological findings of the resected specimen revealed adenocarcinoma arising from the pancreatic head with invasion in the common bile duct. Additionally, extensive inflammatory granulation tissue was observed along the surface of the bile duct, without any evidence of carcinoma. This case implies to us that the results of PTCS, even after repeated biopsies, should be interpreted with great caution.

Small pancreatic carcinoma misdiagnosed as superficially spreading cholangiocarcinoma

Surgical Treatment of Distal Cholangiocarcinoma

Perihilar cholangiocarcinoma (PCC) is a devastating disease with poor prognosis. Surgical resection remains a first-line therapy in patients with PCC, and the primary goal is to gain a tumor-free surgical margin. However, surgical margins are sometimes involved after curative intent surgery even now, which is plausibly explained by the fact that there is a potential gap between the extent of radiologic tumor staging and that of histologic cancer invasion. It is known that cancer cells of cholangiocarcinoma invade the surrounding area beyond the gross tumor border. The length is limited within 1 cm for invasive cancer and 2 cm for carcinoma in situ (CIS) in most cases of cholangiocarcinoma. Although this finding guides the ductal margin length, it is often difficult to obtain a satisfactory length, especially in the proximal direction for PCC. Therefore, pathological assessment with frozen sections of the ductal stump is widely used to confirm the ductal margin status. A positive ductal margin with CIS, unlike one with invasive cancer, is a mild prognostic factor, so it works negatively only in patients with an early-staged tumor who are expecting a prolonged survival. The present review article provides an overview on the growing knowledge about the surgical pathology of cholangiocarcinoma.

/pdf/basic-surgical-pathology-of-perihilar-cholangiocarcinoma-3ecsp3rr2d.pdf

Basic Surgical Pathology of Perihilar Cholangiocarcinoma: Bridging Knowledge for Surgical Practice

https://www.jstage.jst.go.jp/article/jjgs/43/2/43_43.160/_pdf

Two Cases of Non-specific Chronic Cholangitis at the Hepatic Hilum Masquerading Hilar Cholangiocarcinoma

Although severely compromised humoral and cell-mediated immune functions have been observed after the induction of sepsis in male animals, these immune changes are not evident in proestrus females, who have high levels of circulating female sex hormones. Furthermore, when trauma hemorrhage was preceded by the induction of sepsis by cecal ligation and puncture, the subsequent mortality rate was significantly lower in proestrus females compared with males. These results suggest an important role for female sex hormones in protecting animals from severe stresses such as trauma hemorrhage and sepsis. In this regard, estradiol, prolactin, and dehydroepiandrosterone have been shown to restore immune functions and increase the survival rate in sepsis models. In contrast to controlled animal models, human sepsis studies show highly variable results. One of the major reasons for this discrepancy might be due to the lack of information concerning sex hormone levels in human sepsis patients. Experimental animal studies suggest that a careful estimation and correlation between sex hormone levels and outcome from sepsis in humans is needed. Such a study is likely to improve therapeutic treatments for such patients.

Yukihiro Yokoyama

Papers

Small pancreatic carcinoma misdiagnosed as superficially spreading cholangiocarcinoma

Surgical Treatment of Distal Cholangiocarcinoma

Basic Surgical Pathology of Perihilar Cholangiocarcinoma: Bridging Knowledge for Surgical Practice

Two Cases of Non-specific Chronic Cholangitis at the Hepatic Hilum Masquerading Hilar Cholangiocarcinoma

The Role of Female Sex Hormones in Preventing Mortality in Sepsis