Breast-conserving surgery: quadrantectomy

The surgical techniques and clinical results of quadrantectomy as a form of breast-conserving surgery are described. A quadrantectomy is a breast-conserving technique including wide resection and tumorectomy. A quadrantectomy is designed to remove an anatomic segment of breast tissue (duct-lobular system). It has the advantage of greater surgical curability than other conserving techniques in cases with ductal spread, because breast cancer arising in the terminal duct often spreads in the duct-lobular system. However, quadrantectomy poses some cosmetic problems due to the large volume of breast tissue excised. Additionally, quadrantectomy has failed to show better results in local recurrence rates compared with wide resection. Therefore quadrantectomy should be limited to breast cancer with segmental and wide ductal spread. It is important to determine the surgical technique that compromises between local curability and cosmetic results for each patient with breast cancer.     

Randomized controlled trial of bipolar diathermy vs ultrasonic scalpel for closed hemorrhoidectomy

AIM:To compare hemorrhoidectomy with a bipolar electrothermal device or hemorrhoidectomy using an ultrasonically activated scalpel.METHODS:Sixty patients with grade Ⅲ or Ⅳ hemorrhoids were prospectively randomized to undergo closed hemorrhoidectomy assisted by bipolar diathermy(group 1) or hemorrhoidectomy with the ultrasonic scalpel(group 2).Operative data were recorded,and patients were followed at 1,3,and 6 wk to evaluate complications.Independent assessors were assigned to obtain postoperative pain scores,oral analgesic requirement and satisfaction scores.RESULTS:Reduced intraoperative blood loss median 0.9 mL(95% CI:0.8-3.7) vs 4.6 mL(95% CI:3.8-7.0),P = 0.001 and a short operating time median 16(95% CI:14.6-18.2) min vs 31(95% CI:28.1-35.3) min,P < 0.0001 was observed in group 1 compared with group 2.There was a trend towards lower postoperative pain scores on day 1 group 1 median 2(95% CI:1.8-3.5) vs group 2 median 3(95% CI:2.6-4.2),P = 0.135.Reduced oral analgesic requirement during postoperative 24 h after operation median 1(95% CI:0.4-0.9) tablet vs 1(95% CI:0.9-1.3) tablet,P = 0.006 was observed in group 1 compared with group 2.There was no difference between the two groups in the degree of patient satisfaction or number of postoperative complications.CONCLUSION:Bipolar diathermy hemorrhoidectomy is quick and bloodless and,although as painful as closed hemorrhoidectomy with the ultrasonic scalpel,is associated with a reduced analgesic requirement immediately after operation.     

CXCR4 blockade augments bone marrow progenitor cell recruitment to the neovasculature and reduces mortality after myocardial infarction

We hypothesized that a small molecule CXCR4 antagonist, AMD3100 (AMD), could augment the mobilization of bone marrow (BM)-derived endothelial progenitor cells (EPCs), thereby enhancing neovascularization and functional recovery after myocardial infarction. Single-dose AMD injection administered after the onset of myocardial infarction increased circulating EPC counts and myocardial vascularity, reduced fibrosis, and improved cardiac function and survival. In mice transplanted with traceable BM cells, AMD increased BM-derived cell incorporation in the ischemic border zone. In contrast, continuous infusion of AMD, although increasing EPCs in the circulation, worsened outcome by blocking EPC incorporation. In addition to its effects as a CXCR4 antagonist, AMD also up-regulated VEGF and matrix metalloproteinase 9 (MMP-9) expression, and the benefits of AMD were not observed in the absence of MMP-9 expression in the BM. These findings suggest that AMD3100 preserves cardiac function after myocardial infarction by enhancing BM-EPC–mediated neovascularization, and that these benefits require MMP-9 expression in the BM, but not in the ischemic region. Our results indicate that AMD3100 could be a potentially useful therapy for the treatment of myocardial infarction.     

High Protein Diet Feeding Aggravates Hyperaminoacidemia in Mice Deficient in Proglucagon-Derived Peptides

(1) Background: Protein stimulates the secretion of glucagon (GCG), which can affect glucose metabolism. This study aimed to analyze the metabolic effect of a high-protein diet (HPD) in the presence or absence of proglucagon-derived peptides, including GCG and GLP-1. (2) Methods: The response to HPD feeding for 7 days was analyzed in mice deficient in proglucagon-derived peptides (GCGKO). (3) Results: In both control and GCGKO mice, food intake and body weight decreased with HPD and intestinal expression of Pepck increased. HPD also decreased plasma FGF21 levels, regardless of the presence of proglucagon-derived peptides. In control mice, HPD increased the hepatic expression of enzymes involved in amino acid metabolism without the elevation of plasma amino acid levels, except branched-chain amino acids. On the other hand, HPD-induced changes in the hepatic gene expression were attenuated in GCGKO mice, resulting in marked hyperaminoacidemia with lower blood glucose levels; the plasma concentration of glutamine exceeded that of glucose in HPD-fed GCGKO mice. (4) Conclusions: Increased plasma amino acid levels are a common feature in animal models with blocked GCG activity, and our results underscore that GCG plays essential roles in the homeostasis of amino acid metabolism in response to altered protein intake.     

Cardiopulmonary exercise variables in diastolic versus systolic heart failure

The response to cardiopulmonary exercise (CPX) in patients with heart failure (HF) with normal left ventricular (LV) ejection fractions (EFs) is not well characterized. To determine if CPX testing could distinguish between patients with HF with normal EFs (>50%; i.e., diastolic HF) and those with decreased EFs (> or =50%; i.e., systolic HF), CPX responses were compared between 185 patients with systolic HF (79% men, mean age 62.6 +/- 10.9 years) and 43 with diastolic HF (54% men, mean age 67.4 +/- 9.8 years) enrolled in a phase II multicenter clinical trial. All patients were evaluated with echocardiography and a standardized CPX test as part of the trial. CPX variables, including oxygen uptake at peak exercise (peak VO(2)) and the slope of the ventilation/carbon dioxide production ratio (VE/VCO(2)), were determined and analyzed by core laboratory personnel. Echocardiographic measurements included the LV EF, the E/A ratio, filling time, cavity volumes, right ventricular function, and mitral regurgitation. Patients in the diastolic HF group tended to be older (p <0.08), with more women (p <0.006) and with greater body mass indexes (p <0.02), than those in the systolic HF group. There was no significant difference in the use of beta blockers or the incidence of coronary artery disease. Patients with diastolic HF had decreased E/A ratios (0.9 +/- 0.4 vs 1.4 +/- 1.1, p <0.02, diastolic HF vs systolic HF) and increased filling times (30.4 +/- 3.2 vs 26.5 +/- 4.7 ms, p <0.01, diastolic HF vs systolic HF). No significant differences in peak VO(2) (14.4 +/- 1.9 vs 15.6 +/- 3.2 ml/kg/min, p = 0.06, diastolic HF vs systolic HF) were observed. The VE/VCO(2) ratios for the 2 groups were abnormal and comparable (32 2 +/- 7.5 vs 34.0 +/- 8.3, p = 0.3, diastolic HF vs systolic HF). In conclusion, the CPX response in patients with diastolic HF and systolic HF is markedly abnormal and indistinguishable with regard to peak VO(2) and ventilation despite marked differences in the LV EF.     

Apoptosis of colorectal adenocarcinoma (COLO 201) by tumour necrosis factor-alpha (TNF-α) and/or interferon-gamma (IFN-γ), resulting from down-modulation of Bcl-2 expression

Fas antigen is constitutively expressed in the normal colon epithelium, but considerably diminished in most colorectal carcinomas. In the present study, we examine the relationship between Fas antigen expression and apoptosis using the colorectal carcinoma cell line COLO 201, on which a low grade of Fas antigen is expressed. Anti-Fas antibody had no effect on the induction of apoptosis of COLO 201. However, TNF-α and/or IFN-γ, independently and additively, up-regulated Fas antigen expression on COLO 201 and induced apoptosis in a dose-dependent manner. Both cytokines also increased the COLO 201 sensitivity to anti-Fas antibody, resulting from the down-modulation of Bcl-2 and the up-regulation of Bax. These findings indicate that cytokine(s) plus anti-Fas antibody (which mimics natural Fas ligand) are more effective in inducing apoptosis of COLO 201 than cytokine(s) alone. These findings suggest that immunotherapy in combination with cytokine(s) and lymphokine-activated killer (LAK) cells will become a more effective therapy for cancer than cytokine(s) or LAK cells alone, since the Fas ligand is expressed on activated T cells, natural killer cells and macrophages.     

c-Jun N-terminal kinase inhibition and alpha-tocopherol protect midbrain dopaminergic neurons from interferon-gamma/lipopolysaccharide-induced injury without affecting nitric oxide production

Interferon-gamma (IFN-gamma)/lipopolysaccharide (LPS) induces delayed dopaminergic neuron loss in midbrain slice cultures, because of nitric oxide production resulting from p38 mitogen-activated protein kinase (p38 MAPK)-dependent induction of inducible nitric oxide synthase (iNOS). In this study, we show that inhibition of c-Jun N-terminal kinase (JNK), but not of extracellular signal-regulated kinase, protects dopaminergic neurons from IFN-gamma/LPS-induced degeneration. In contrast to a p38 MAPK inhibitor, SB203580, however, a JNK inhibitor, anthra[1,9-cd]pyrazol-6(2H)-one (SP600125), did not suppress IFN-gamma/LPS-induced iNOS expression and nitric oxide production. Involvement of NADPH oxidase-derived superoxide production in dopaminergic neurodegeneration was not obvious, in that superoxide dismutase/catalase or manganese 3-methoxy-N,N'-bis(salicylidene)ethylenediamine chloride (EUK-134), a superoxide dismutase/catalase mimetic, did not afford neuroprotection. Moreover, the NADPH oxidase inhibitors apocynin and diphenylene iodonium were protective against IFN-gamma/LPS cytotoxicity only at concentrations that suppressed nitric oxide production. Notably, alpha-tocopherol effectively prevented IFN-gamma/LPS-induced dopaminergic neuron degeneration, without affecting iNOS induction and nitric oxide production. These results underscore the neuroprotective potential of JNK inhibitor and alpha-tocopherol, in the sense that both agents could rescue dopaminergic neurons under inflammatory conditions associated with robust increases in nitric oxide production.     

Squamous differentiation and prognosis in upper urinary tract urothelial carcinoma

Squamous differentiation is the most common histological variation in urothelial carcinoma (UC). However, the clinical significance of squamous differentiation in upper urinary tract UC is unclear. To investigate the significance of squamous differentiation, hematoxylin and eosin stained slides from 140 patients with upper urinary tract UC who underwent nephroureterectomy were reviewed by a single pathologist and the presence of squamous differentiation was recorded. Squamous differentiation was observed in 23 out of 140 studied cases (16%). Squamous differentiation significantly correlated with several adverse prognostic factors including histological grade 3 tumors, presence of lymphovascular invasion, concomitant carcinoma in situ, advanced tumor stage, and occurrence of lymph node metastasis. The Kaplan-Meier and univariate Cox regression analyses revealed that the presence of squamous differentiation was significantly associated with shorter metastasis-free survival [log-rank P = 0.030; univariate hazard ratio (HR), 2.30; 95% confidence interval (CI), 1.06-4.99], cancer-specific survival (log-rank P = 0.0024; univariate HR 3.34; 95% CI, 1.47-7.85), and overall survival (log-rank P = 0.018; univariate HR 2.39; 95% CI, 1.13-5.06) after nephroureterectomy. However, in multivariate analyses, squamous differentiation was not significantly associated with patient outcomes. These findings suggest that squamous differentiation is associated with disease progression, but is not an independent predictor of a worse prognosis in patients with upper urinary tract UC.     

Ciliates rapidly enhance the frequency of conjugation between Escherichia coli strains through bacterial accumulation in vesicles

The mechanism underlying bacterial conjugation through protozoa was investigated. Kanamycin-resistant Escherichia coli SM10λ⁺ carrying pRT733 with TnphoA was used as donor bacteria and introduced by conjugation into ciprofloxacin-resistant E. coli clinical isolate recipient bacteria. Equal amounts of donor and recipient bacteria were mixed together in the presence or absence of protozoa (ciliates, free-living amoebae, myxamoebae) in Page’s amoeba saline for 24 h. Transconjugants were selected with Luria broth agar containing kanamycin and ciprofloxacin. The frequency of conjugation was estimated as the number of transconjugants for each recipient. Conjugation frequency in the presence of ciliates was estimated to be approximately 10^?6, but in the absence of ciliates, or in the presence of other protozoa, it was approximately 10^?8. Conjugation also occurred in culture of ciliates at least 2 h after incubation. Successful conjugation was confirmed by the polymerase chain reaction. Addition of cycloheximide or latrunculin B resulted in suppression of conjugation. Heat killing the ciliates or bacteria had no effect on conjugation frequency. Co-localization of green fluorescent protein-expressing E. coli and PKH-67-vital-stained E. coli was observed in the same ciliate vesicles, suggesting that both donor and recipient bacteria had accumulated in the same vesicle. In this study, the conjugation frequency of bacteria was found to be significantly higher in vesicles purified from ciliates than those in culture suspension. We conclude that ciliates rapidly enhance the conjugation of E. coli strains through bacterial accumulation in vesicles.