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

https://www.journal-of-hepatology.eu/article/S0168-8278(05)00684-7/pdf

Natural history and prognostic indicators of survival in cirrhosis: a systematic review of 118 studies.

Macrophages are prominent in the stromal compartment of virtually all types of malignancy. These highly versatile cells respond to the presence of stimuli in different parts of tumors with the release of a distinct repertoire of growth factors, cytokines, chemokines, and enzymes that regulate tumor growth, angiogenesis, invasion, and/or metastasis. The distinct microenvironments where tumor-associated macrophages (TAM) act include areas of invasion where TAMs promote cancer cell motility, stromal and perivascular areas where TAMs promote metastasis, and avascular and perinecrotic areas where hypoxic TAMs stimulate angiogenesis. This review will discuss the evidence for differential regulation of TAMs in these microenvironments and provide an overview of current attempts to target or use TAMs for therapeutic purposes. (Cancer Res 2006; 66(2): 605-12)

https://cancerres.aacrjournals.org/content/canres/66/2/605.full.pdf

Distinct Role of Macrophages in Different Tumor Microenvironments

It has been established that cancer can be promoted and/or exacerbated by inflammation and infections. Indeed, chronic inflammation orchestrates a tumor-supporting microenvironment that is an indispensable participant in the neoplastic process. The mechanisms that link infection, innate immunity, inflammation, and cancer are being unraveled at a fast pace. Important components in this linkage are the cytokines produced by activated innate immune cells that stimulate tumor growth and progression. In addition, soluble mediators produced by cancer cells recruit and activate inflammatory cells, which further stimulate tumor progression. However, inflammatory cells also produce cytokines that can limit tumor growth. Here we provide an overview of the current understanding of the role of inflammation-induced cytokines in tumor initiation, promotion, and progression.

/pdf/a-cytokine-mediated-link-between-innate-immunity-415d505u7x.pdf

A cytokine-mediated link between innate immunity, inflammation, and cancer

These guidelines were developed jointly by the American Society of Health-System Pharmacists (ASHP), the Infectious Diseases Society of America (IDSA), the Surgical Infection Society (SIS), and the Society for Healthcare Epidemiology of America (SHEA). This work represents an update to the

/pdf/clinical-practice-guidelines-for-antimicrobial-prophylaxis-1gq1adk8ux.pdf

Clinical practice guidelines for antimicrobial prophylaxis in surgery

Thirty-four consecutive patients with liver cirrhosis and esophageal varices were included in a prospective randomized trial done to investigate the efficacy and safety of two sclerosants 5% ethanolamine oleate (EO) and polidocanol (1% Aethoxysklerol [AS]) for use in endoscopic injection sclerotherapy (EIS). Eighteen patients were randomly allocated to the group given EO and 16 to the AS group. These two groups were comparable with regard to age, sex, etiology and severity of the liver disease. The bleeding rate from esophageal ulcers which developed during the course of repeated EIS was significantly (P less than 0.05) higher in the AS group (31.3%, 5/16) than in the EO group (0%, 0/18). In 4 occasions bleeding from the esophageal ulcer could not be controlled with AS. In 3 of these 4 bleeding episodes, EO successfully halted bleeding from esophageal ulcer. In the other patient, a Sengstaken-Blakemore tube was inserted to stop the hemorrhage. The period and number of sessions of EIS for eradication of esophageal varices were significantly (P less than 0.05) shorter in the EO group than the AS group (EO: 4.0 +/- 0.8 [means +/- SD] sessions during 4.7 +/- 1.5 weeks versus AS: 4.8 +/- 1.2 sessions during 5.4 +/- 1.6 weeks). The rate of early mortality did not differ between the two groups. We conclude that 5% ethanolamine oleate seems to be superior to 1% Aethoxysklerol when used for sclerosing esophageal varices.

Ethanolamine oleate is superior to polidocanol (aethoxysklerol) for endoscopic injection sclerotherapy of esophageal varices: a prospective randomized trial.

Searching for a marker of graft viability, adenosine triphosphate (ATP) content in the graft tissue was measured sequentially during orthotopic liver transplantation (OLT) in 24 adult mongrel dogs. According to the survival period, 12 recipients were divided into two groups: group I - early-death group (n = 6), death within 3 days after OLT and group II - survival group (n = 6), survived more than 7 days after OLT (average 12 days). Serum biochemical findings showed no differences between the two groups except that the prothrombin time on the first postoperative day in group I was significantly longer (p less than 0.05). The ATP content ratio (% of initial value) was significantly higher in group II, compared to that of group I (p less than 0.05), 94 versus 53% at 10 min after perfusion, 31 versus 17% at just before recirculation, respectively. The ATP content ratio recovered significantly to more than 80% at 10 min after recirculation in group II but only to less than 50% in group I. These results suggest that restoration of ATP content in the liver after graft recirculation reflects the viability of the graft and can serve as an appropriate prognostic marker in cases of OLT.

Restoration of ATP contents in the transplanted liver closely relates to graft viability in dogs.

Background
Recent experimental studies have shown that Bcl-2, which has been established as a key player in the control of apoptosis, plays a role in regulating the cell cycle and proliferation. The aim of this study was to investigate the relationship between Bcl-2 and p27 protein expression, p53 protein expression and the proliferation activity as defined by the MIB-1 counts. The prognostic implication of Bcl-2 protein expression in relation to p27 and p53 protein expressions and MIB-1 counts for breast cancer was also evaluated.

/pdf/bcl-2-protein-expression-is-associated-with-p27-and-p53-qta63mpu8e.pdf

Bcl-2 protein expression is associated with p27 and p53 protein expressions and MIB-1 counts in breast cancer.

Using an ex vivo liver sanguinous perfusion system, hemodynamic and biochemical changes of the porcine livers were studied, which were preserved cold (4 degrees C) for 24 hr in University of Wisconsin solution and reperfused with normothermic (37 degrees C) (n = 8) or hypothermic (32 degrees C) (n = 8) blood for 3 hr. Six more livers were reperfused with normothermic blood (37 degrees C) immediately after procurement as controls. The total hepatic blood flow was adjusted to 1 ml/min/g liver weight, in which hepatic artery and portal vein flows were administered at a 1:2 ratio. In livers stored cold for 24 hr in UW solution and perfused normothermically, a statistically higher hepatic artery resistance was exhibited at 30 and 60 min after reperfusion (P less than 0.05), and there was lower bile output (P less than 0.05) at 90 and 120 min as compared to the controls. In livers stored cold for 24 hr in UW solution and perfused hypothermically, as compared to ones perfused normothermically, statistically higher hepatic-artery and portal-vein resistances (P less than 0.05) were observed throughout the perfusion period and 60 min after reperfusion, respectively. In addition, bile output and oxygen consumption of these livers were statistically lower than those of ones perfused normothermically (P less than 0.05). In contrast, chemistries of the perfusate of livers perfused hypothermically were comparable to ones perfused normothermically. Histologic examination of the liver perfused hypothermically demonstrated hepatic arterial and/or portal venous congestion and mild-to-moderate hemorrhage in the portal triads. This study suggests that livers preserved for a prolonged period of time demonstrate a high hepatic arterial resistance shortly after revascularization, and that recipient hypothermia after revascularization may be a risk factor for the development of hepatic arterial thrombosis following liver transplantation.

/pdf/hemodynamic-and-biochemical-changes-during-normothermic-and-56396hcvhw.pdf

Hemodynamic and biochemical changes during normothermic and hypothermic sanguinous perfusion of the porcine hepatic graft.

Plasma levels and gastric mucosal contents of prostaglandin (PG) E2 and prostacyclin were determined in cirrhotic patients with portal hypertensive gastropathy (PHG), in cirrhotic patients without PHG and in healthy controls. PGE2 and 6-keto-PGF1 alpha (a stable metabolite of prostacyclin) levels were measured in 30 cirrhotic patients and 10 controls, using radioimmunoassay. Of 30 cirrhotics, 13 had PHG of the fundus and the corpus. Plasma concentrations of 6-keto-PGF1 alpha in the cirrhotic patients were significantly higher than in the controls (p < 0.01), but there was no significant difference between cirrhotics and controls with regard to plasma levels of PGE2. The gastric mucosal contents of 6-keto-PGF1 alpha in the fundus was significantly higher in cirrhotics with PHG than those without PHG (p < 0.05) and controls (p < 0.01). However, the gastric mucosal contents of PGE2 in the fundus were not significantly different in cirrhotics with and without PHG. The gastric mucosal contents of 6-keto-PGF1 alpha significantly correlated to the plasma levels (r = 0.37, p < 0.05), but there was no significant correlation between plasma levels and gastric mucosal contents of PGE2. Since prostacyclin has vasodilator and gastric acid inhibitory effects, we speculate that high contents of prostacyclin in the gastric mucosa may have some role in the pathogenesis of PHG.

Hidefumi Higashi

Papers

Ethanolamine oleate is superior to polidocanol (aethoxysklerol) for endoscopic injection sclerotherapy of esophageal varices: a prospective randomized trial.

Restoration of ATP contents in the transplanted liver closely relates to graft viability in dogs.

Bcl-2 protein expression is associated with p27 and p53 protein expressions and MIB-1 counts in breast cancer.

Hemodynamic and biochemical changes during normothermic and hypothermic sanguinous perfusion of the porcine hepatic graft.

Increased prostacyclin content in gastric mucosa of cirrhotic patients with portal hypertensive gastropathy