Open liver resection for colorectal metastases: better short- and long-term outcomes in patients potentially suitable for laparoscopic liver resection

Background:

There is no prospective randomized data comparing laparoscopic to open hepatectomy. This study compared short- and long-term outcomes in patients undergoing hepatectomy for colorectal metastases (CRM), who were suitable for either laparoscopic or open surgery.

Methods:

Data were prospectively collected from consecutive patients undergoing hepatic resection of CRM at a single centre (1987–2007). Patients who were suitable for laparoscopic resection (Group 1) were compared with patients whose tumour characteristics would best be considered for open resection (Group 2).

Results:

Out of 1152 hepatectomies, 266 (23.1%) were deemed suitable for a laparoscopic approach. The median (IQR) number of metastases was greater in Group 2 [2(1–20) vs. 1(1–10), P < 0.001], as was the mean (SD) tumour size [5.3(3.6) cm vs. 3.3(1.2) cm, P < 0.001]. The median (IQR) operation time [210 (70) min vs. 240 (90) min, P < 0.001] and blood loss [270 (265) ml vs. 355 (320) ml, P < 0.001] were less in Group 1. There was no difference in length of stay, morbidity or mortality. Patients in Group 2 had a higher R1 resection rate (14.9%) compared with Group 1 (4.5%, P < 0.001) and lower 5-year survival (37.8% vs. 44.2%, P= 0.005).

Discussion:

Current criteria for laparoscopic hepatectomy selects patients who have more straight-forward surgery, with less risk of an involved resection margin and better long-term survival, compared with patients unsuited to a laparoscopic approach. Clearly defined criteria for laparoscopic hepatectomy are essential to allow meaningful analysis of outcomes and the results of unrandomized series of laparoscopic hepatectomies must be interpreted with caution.     

A crucial role for TNF-α in mediating neutrophil influx induced by endogenously generated or exogenous chemokines,KC/CXCL1 and LIX/CXCL5

Background and purpose:

Chemokines orchestrate neutrophil recruitment to inflammatory foci. In the present study, we evaluated the participation of three chemokines, KC/CXCL1, MIP-2/CXCL2 and LIX/CXCL5, which are ligands for chemokine receptor 2 (CXCR2), in mediating neutrophil recruitment in immune inflammation induced by antigen in immunized mice.

Experimental approach:

Neutrophil recruitment was assessed in immunized mice challenged with methylated bovine serum albumin, KC/CXCL1, LIX/CXCL5 or tumour necrosis factor (TNF)-α. Cytokine and chemokine levels were determined in peritoneal exudates and in supernatants of macrophages and mast cells by elisa. CXCR2 and intercellular adhesion molecule 1 (ICAM-1) expression was determined using immunohistochemistry and confocal microscopy.

Key results:

Antigen challenge induced dose- and time-dependent neutrophil recruitment and production of KC/CXCL1, LIX/CXCL5 and TNF-α, but not MIP-2/CXCL2, in peritoneal exudates. Neutrophil recruitment was inhibited by treatment with reparixin (CXCR1/2 antagonist), anti-KC/CXCL1, anti-LIX/CXCL5 or anti-TNF-α antibodies and in tumour necrosis factor receptor 1-deficient mice. Intraperitoneal injection of KC/CXCL1 and LIX/CXCL5 induced dose- and time-dependent neutrophil recruitment and TNF-α production, which were inhibited by reparixin or anti-TNF-α treatment. Macrophages and mast cells expressed CXCR2 receptors. Increased macrophage numbers enhanced, while cromolyn sodium (mast cell stabilizer) diminished, LIX/CXCL5-induced neutrophil recruitment. Macrophages and mast cells from immunized mice produced TNF-α upon LIX/CXCL5 stimulation. Methylated bovine serum albumin induced expression of ICAM-1 on mesenteric vascular endothelium, which was inhibited by anti-TNF-α or anti-LIX/CXCL5.

Conclusion and implications:

Following antigen challenge, CXCR2 ligands are produced and act on macrophages and mast cells triggering the production of TNF-α, which synergistically contribute to neutrophil recruitment through induction of the expression of ICAM-1.     

Socioeconomic inequalities in prognostic markers of non-Hodgkin lymphoma: analysis of a national clinical database

The survival of non-Hodgkin lymphoma patients strongly depends on a range of prognostic factors. This registry-based clinical cohort study investigates the relation between socioeconomic position and prognostic markers in 6234 persons included in a national clinical database in 2000-2008, Denmark. Several measures of individual socioeconomic position were achieved from Statistics Denmark. The risk of being diagnosed with advanced disease, as expressed by the six prognostic markers (Ann Arbor stage III or IV, more than one extranodal lesion, elevated serum lactate dehydrogenase (LDH), performance status of two or more, presence of B symptoms and International Prognostic Index (IPI) of two or more), increased with decreasing level of education, in patients living alone, and in men. For instance, a significant decrease in the odds of being diagnosed with elevated LDH (p = 0.02), high performance status (p = 0.004), high IPI score (p = 0.004) and B symptoms (p = 0.02) was seen with higher level of education, whereas high stage of disease was significantly less likely in the higher educated (odds ratio [OR] = 0.85 (0.74-0.99)). The difference in risk seemed not to be mediated by differences in histological subgroups reflecting aggressiveness of disease among the social groups. One of the most likely mechanisms of the social difference is longer delay in those with low socioeconomic position. The findings of social inequality in prognostic markers in non-Hodgkin lymphoma (NHL) patients could already be implemented in the clinical practice if general practitioners (GP’s) and physicians on hospitals paid special attention to patients with low educational level and unspecific symptoms.     

Cerebral Glutamine Concentration and Lactate–Pyruvate Ratio in Patients with Acute Liver Failure

Aim  Hyperammonemia causes brain edema and high intracranial pressure (ICP) in acute liver failure (ALF) by accumulation of glutamine in brain. Since a high-level glutamine may compromise mitochondrial function, the aim of this study was to determine if the lactate–pyruvate ratio is associated with a rise in the glutamine concentration and ICP. Patients and Methods  In 13 patients with ALF (8F/5M; median age 46 (range 18–66) years) the cerebral extracellular concentrations of glutamine, lactate, and pyruvate were measured by in vivo brain microdialysis together with ICP and cerebral perfusion pressure (CPP). Results  The cerebral glutamine concentration was 4,396 (1,011–9,712) μM, lactate 2.15 (1.1–4.45) mM, and pyruvate 101 (43–255) μM. The lactate–pyruvate ratio was 21 (16–40), ICP 20 (2–28) mmHg, and CPP 72 (56–115) mmHg. Cerebral glutamine concentration correlated with the lactate–pyruvate ratio (r = 0.89, P < 0.05). Also the ICP, but not CPP, correlated to the lactate–pyruvate ratio (r = 0.64, P < 0.05). Conclusion  ICP and the cerebral glutamine concentration in patients with ALF correlate to the lactate–pyruvate ratio. Since CPP was sufficient in all patients the rise in lactate–pyruvate ratio indicates that accumulation of glutamine compromises mitochondrial function and causes intracranial hypertension.     

Survival,surveillance, and genetics in patients with Peutz–Jeghers syndrome: A nationwide study

Peutz–Jeghers syndrome (PJS) is an autosomal dominant hereditary polyposis syndrome causing increased morbidity and mortality due to complications of polyposis and the development of cancer. STK11 is the only gene known to be associated with PJS, although in 10%–15% of patients fulfilling the diagnostic criteria no pathogenic variant (PV) is identified. The primary aim of this study was to identify the genetic etiology in all known PJS patients in Denmark and to estimate the risk of cancer, effect of surveillance and overall survival. We identified 56 patients (2–83 years old) with PJS. The detection rate of PVs was 96%, including three cases of mosaicism (6%). In two patients a variant was not detected. At the age of 40 years, the probabilities of cancer and death were 21% and 16%, respectively; at the age of 70 years these probabilities were 71% and 69%. Most cases of cancer (92%) were identified between the scheduled examinations in the surveillance program. These observations emphasize that PJS should be regarded as a general cancer predisposition syndrome, where improvement of clinical care is needed.     

Endocardial activation mapping and endocardial pace-mapping using a balloon apparatus

The relation between endocardial activation mapping and endocardial pace-mapping was evaluated in 8 dogs while they were on cardiopulmonary bypass. Pacing or recording was accomplished by using a balloon apparatus (with 32 bipolar electrodes) inserted through a left apical ventriculotomy. Ventricular tachycardia (VT) was produced by occlusion followed by reperfusion of the left anterior descending coronary artery. During each VT, activation mapping was performed and early sites determined. Pace-map correlates (sites at which endocardial pacing produced a similar QRS morphology to that of the VT) were also determined. Isochronous maps were constructed for activation mapping and pace-mapping. There was a total of 29 morphologically distinct VTs. Groups were delineated according to correlations between activation mapping and pace-mapping. In 14 episodes of VT (group 1), pace-mapping confirmed the findings of activation mapping with all early sites being pace-map correlates (total number of early sites (tES) = 19; total number of pace-map correlates (tPMC) = 88; tES same as tPMC = 19). In 9 episodes of VT (group 2), there was a partial correlation between pace-mapping and activation mapping, such that pace-mapping when used with activation mapping appeared to further delineate the region of arrhythmogenesis (tES = 31; tPMC = 59; tES same as tPMC = 14). In 6 episodes of VT (group 3), there was no correlation between pace-mapping and activation mapping (tES = 15; tPMC = 0). With the balloon apparatus, endocardial activation mapping can be performed without the need for sustained monomorphic VT, and endocardial pace-maps may be generated easily.(ABSTRACT TRUNCATED AT 250 WORDS)     

Systemic T-cell activation in acute clinically isolated optic neuritis

We examined untreated 60 patients with acute monosymptomatic optic neuritis (ON). Patients examined early after onset showed increased expression of HLA-DR and CD45R0 on CD4 and CD8 T cells. Expression of HLA-DR on CD4 T cells was higher in patients without IgG oligoclonal bands. Expression of HLA-DR on CD4 and CD8 T cells correlated negatively with measures of disease activity and positively with measures of good visual function, and expression of CD45R0 on CD4 T cells correlated negatively with measures of disease activity. We hypothesize that HLA-DR expression may characterize a protective T-cell subset in ON.     

Human papillomavirus mRNA and DNA testing in women with atypical squamous cells of undetermined significance: A prospective cohort study

In this prospective cohort study, we compared the performance of human papillomavirus (HPV) mRNA and DNA testing of women with atypical squamous cells of undetermined significance (ASC‐US) during cervical cancer screening. Using a nationwide Danish pathology register, we identified women aged 30–65 years with ASC‐US during 2005–2011 who were tested for HPV16/18/31/33/45 mRNA using PreTect HPV‐Proofer (n = 3,226) or for high‐risk HPV (hrHPV) DNA using Hybrid Capture 2 (HC2) (n = 9,405) or Linear Array HPV‐Genotyping test (LA) (n = 1,533). Women with ≥1 subsequent examination in the register (n = 13,729) were followed for up to 9.5 years for high‐grade cervical intraepithelial neoplasia (CIN) or cancer. After 3 years' follow‐up, mRNA testing had higher specificity for CIN3 or worse (CIN3+) than HC2 testing (88.1% [95% confidence interval (CI): 86.8–89.6%] versus 59.3% [95% CI: 58.1–60.4%]) and higher positive predictive value (PPV) (38.2% [95% CI: 33.8%–43.1%] versus 19.5% [95% CI: 17.8–20.9%]). However, the sensitivity of mRNA testing was lower than that of HC2 testing (66.7% [95% CI: 59.3–74.5%] versus 97.0% [95% CI: 95.5–98.4%]), and women testing mRNA negative had higher 3‐year risk for CIN3+ than those testing HC2 negative (3.2% [95% CI: 2.2–4.2%] versus 0.5% [95% CI: 0.3–0.7%]). Patterns were similar after 18 months and 5 years'; follow‐up; for CIN2+ and cancer as outcomes; across all age groups; and when comparing mRNA testing to hrHPV DNA testing using LA. In conclusion, the HPV16/18/31/33/45 mRNA test is not optimal for ASC‐US triage due to its low sensitivity and the substantial risk for precancer following a negative test.     

Use of a counterpulsation balloon as a substitute for the pulmonic valve: a new application

An inflatable, 3-ml balloon positioned within the distal right ventricular outflow tract was used to restore pulmonic valve function in 8 dogs that had undergone open-chest valvectomy. Balloon inflation and deflation were accomplished with a counterpulsation console. Valvectomy produced loss of the pulmonic incisura, a decrease in pulmonary artery diastolic pressure (PADP; mean +/- standard error) (9.5 +/- 1.3 versus 4.4 +/- 0.6 mm Hg, p less than 0.01), and an increase in pulmonary artery pulse pressure (PAPP) (8.6 +/- 0.7 versus 19.1 +/- 1.9 mm Hg, p less than 0.01) without significantly affecting forward cardiac output (CO) (1,750 +/- 110 versus 1,880 +/- 230 ml/min, p is not significant). Properly timed counterpulsation restored the pulmonic incisura, raised the PADP from 6.1 +/- 0.8 to 9.5 +/- 0.8 mm Hg (p less than 0.01), lowered the PAPP from 15.1 +/- 1.4 to 10.6 +/- 1.0 mm Hg (p less than 0.01), and raised the forward CO from 1,850 +/- 260 to 1,920 +/- 260 ml/min (p less than 0.01). The injection of glass beads, 40 to 150 microns in diameter, into the right ventricular outflow tract increased pulmonary vascular resistance from 383 +/- 87 to 730 +/- 150 dyne . sec cm-5 (p less than 0.05) and decreased forward CO from 1,850 +/- 260 to 1,570 +/- 230 ml/min (p less than 0.05). Following this injection, counterpulsation again restored the pulmonic incisura, raised the PADP from 9.3 +/- 1.4 to 16.0 +/- 1.8 mm Hg (p less than 0.01), lowered the PAPP from 25.0 +/- 2.5 to 18.2 +/- 2.5 mm Hg (p less than 0.01), and raised the forward CO from 1,570 +/- 230 to 1,720 +/- 220 ml/min (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)