Stephen R.T. Evans

Predicting in-hospital mortality during cardiopulmonary resuscitation

On the average, 10-15% of patients who undergo cardiopulmonary resuscitation (CPR) following a cardiopulmonary arrest in the hospital environment will survive to be discharged. The purpose of this study was to determine objective factors influencing patient outcome after CPR to determine who should be resuscitated and when to end CPR efforts. The records of 266 patients who underwent in-hospital CPR over a 3-year period were retrospectively analyzed with regard to age, gender, co-morbid conditions, setting of arrest, duration of resuscitation, initial pH and PO2 during resuscitation, and outcome of resuscitative efforts. Twenty-four (9%) patients survived to be discharged from hospital. Eighty-seven (33%) patients arrested in the intensive care unit, 77 (29%) on the ward, 91 (34%) in the emergency room, six (2%) in the cardiac catheterization laboratory and five (2%) in the operating room. There was no significant difference in survival based on location of arrest. Factors associated with a poor prognosis included age greater than 60, co-morbid disease (i.e. pneumonia, sepsis, renal failure, heart disease, etc.), an initial PO2 < 50 mmHg and CPR efforts extending beyond 10 min. Based on this data, guidelines regarding initiation and termination of CPR should be instituted in light of poor outcome in patients over 60 years of age with co-morbid conditions, specifically after 10 min of CPR.

Vitamin D receptors in breast cancer cells.

Summary1,25-(OH)2-Vitamin D3, the active metabolite of vitamin D, is a secosteroid hormone with known differentiating activity in leukemic cells. Studies have demonstrated the presence of vitamin D receptors (VDR) in a wide range of tissues and cell types. Antiproliferative activity of 1,25-(OH)2-vitamin D3 has been documented in osteosarcoma, melanoma, colon carcinoma, and breast carcinoma cells. This study was designed to analyze vitamin D receptor level in breast cancer cells as a marker of differentiation and as a predictor of growth inhibition by 1,25-(OH)2-vitamin D3.VDR messenger RNA was found to be present in relatively high levels in well-differentiated cells and in low levels in poorly differentiated cells. All cell lines had detectable VDR mRNA. Radiolabeled ligand binding assay showed a similar pattern. MCF-7 and T47D cells, which express VDR at moderate levels, showed significant growth inhibition by 10−9 M 1,25-(OH)2-vitamin D3 (p < 0.05). MDA-MB-231 cells, which have very low levels of VDR, demonstrated no growth inhibition by 1,25-(OH)2-vitamin D3 at concentrations up to 10−6 M. Based on these results it can be stated that VDR expression is lost with de-differentiation and that receptor is essential for the antiproliferative response to 1,25-(OH)2-vitamin D3.

Ectopic breast cancer: case report and literature review

Ectopic breast tissue includes both supernumerary and aberrant breast tissue. The incidence of supernumerary tissue has been reported as high as 6% depending on the ethnic group studied. The incidence of aberrant breast tissue remains unknown. The development of malignancy within these anomalies is rare. In the following paper, the case report of a patient with an ectopic breast cancer and a second primary cancer of the left anatomic breast is described. A review of the world literature on ectopic breast cancer follows. Specific characteristics of ectopic breast cancer are defined and recommendations for management are made.

Disruption of transforming growth factor-β signaling through β-spectrin ELF leads to hepatocellular cancer through cyclin D1 activation

Transforming growth factor-β (TGF-β) signaling members, TGF-β receptor type II (TBRII), Smad2, Smad4 and Smad adaptor, embryonic liver fodrin (ELF), are prominent tumor suppressors in gastrointestinal cancers. Here, we show that 40% of elf+/− mice spontaneously develop hepatocellular cancer (HCC) with markedly increased cyclin D1, cyclin-dependent kinase 4 (Cdk4), c-Myc and MDM2 expression. Reduced ELF but not TBRII, or Smad4 was observed in 8 of 9 human HCCs (P<0.017). ELF and TBRII are also markedly decreased in human HCC cell lines SNU-398 and SNU-475. Restoration of ELF and TBRII in SNU-398 cells markedly decreases cyclin D1 as well as hyperphosphorylated-retinoblastoma (hyperphosphorylated-pRb). Thus, we show that TGF-β signaling and Smad adaptor ELF suppress human hepatocarcinogenesis, potentially through cyclin D1 deregulation. Loss of ELF could serve as a primary event in progression toward a fully transformed phenotype and could hold promise for new therapeutic approaches in human HCCs.

Laparoscopic cholecystectomy in pediatric patients

Laparoscopic cholecystectomy has gained increasing application as an operative approach for adults with gallbladder disease. We assessed the safety and feasibility of this technique in five pediatric patients with symptomatic cholelithiasis, two of whom had sickle cell disease. With several technical modifications, we found that laparoscopic cholecystectomy was safe and effective in children. This technique permitted early discharge with expedient return to full activity.

Extended surgical resection in T4 gastric cancer.

BACKGROUND Some physicians still consider invasion of adjacent organs by the carcinoma of stomach as a sign of incurable disease. METHODS This retrospective study has been done with particular reference to 353 T4 gastric cancer patients who underwent combined gastrectomies with adjacent organs. RESULTS Subtotal gastrectomy was performed in 237 (67.1%) patients and total gastrectomy was performed in 116 (32.9%) patients. Organs most commonly resected with the stomach were the transverse colon in 159 (45%) cases, the tail of pancreas and spleen in 150 (42.5%), the left lobe of liver in 101 (28.5%), and the head of pancreas in 37 (10.5%) patients. A total of 110 postoperative complications occurred in this subset of patients corresponding to a complication rate of 31.2%. A total of 48 postoperative deaths occurred in this subset of patients corresponding to a mortality rate of 13.6%. The 5-year survival rate for all patients who underwent combined gastrectomy with adjacent organs was 25%. Of the node-negative T4 gastric cancer resections, 37% survived 5 years whereas the T4 node-positive resections have only a 15% 5-year survival. CONCLUSIONS Patients who present with T4 gastric cancer (about 20% of the patient population) will benefit from aggressive en bloc surgical resection and should not be considered unresectable.

Intensive preoperative radiotherapy with local hyperthermia for the treatment of gastric carcinoma

In order to devitalize maximally tumour tissue and improve the prognosis of gastric cancer patients, a method employing preoperative intensive radiotherapy with local hyperthermia as adjuvant treatment was evaluated. In order to estimate the effectiveness of preoperative intensive radiation and radiation with local microwave hyperthermia in radical gastric cancer treatment, 293 patients were randomized into three respective treatment groups: surgery alone, surgery preceded by preoperative radiation; and surgery followed by preoperative radiation and hyperthermia. Preoperative radiation therapy to a total dose of 20 Gy in four 5 Gy fractions did not improve 3- or 5-year survival in gastric cancer patients in comparison with surgery alone. Local hyperthermia in combination with radiation therapy followed by surgery produced a significant improvement in 3-year survival of 22.1% (from 35.5 +/- 4.9% to 57.6 +/- 6.3%, P < 0.05) and 5-year survival of 21.3% (from 30.1 +/- 4.7 to 51.4 +/- 6.6%, P < 0.05). In unresectable gastric cancer patients, radiation therapy and radiation therapy with hyperthermia both increase mean survival. In conclusion; intensive preoperative radiation therapy in total dose 20 Gy plus local microwave hyperthermia significantly improved 3- and 5-year survival in comparison with surgery alone. Further development and evaluation of equipment to produce reliable and safe delivery systems for hyperthermia is needed.

The effect of extracellular calcium on colonocytes: evidence for differential responsiveness based upon degree of cell differentiation

Calcium supplementation decreases the incidence of colon cancer in animal models and may prevent colon cancer in man. Potential mechanisms include binding of mitogens and direct effects of calcium on colonic epithelial cells. In this study, the effects of extracellular calcium on epithelial cell growth and differentiation were studied in three colon carcinoma and two colonic adenoma cell lines. The characteristics studied included morphology, cell cycle kinetics, [Ca2+]IC (intracellular calcium concentration), proliferation, and expression of differentiation markers such as carcinoembryonic antigen (CEA) and alkaline phosphatase (AP). Sodium butyrate (NaB) and 1,25‐dihydroxyvitamin D3 were used as controls in the latter three assays as these two agents are known differentiating agents. Alteration of [Ca+2]EC (extracellular calcium concentration) did not affect carcinoembryonic antigen (CEA) or alkaline phosphatase (AP) expression. NaB enhanced the expression of AP three‐fold and CEA five‐fold. This effect was augmented by increasing [Ca2+]EC. The exposure of cells to 1,25‐(OH)2‐Vitamin D3 increased CEA but not AP. [Ca2+]IC increased in response to 1,25‐(OH)2‐vitamin D3 and NaB but not with variation in [Ca2+]EC. Increased [Ca2+]EC inhibited proliferation of well‐differentiated cells, but had no effect on poorly‐differentiated cells. Morphological studies showed that extracellular calcium was necessary for normal cell—cell interactions.

Chest wall fibromatosis associated with silicone breast implants

Aggressive fibromatosis is a well described locally destructive benign lesion, comprising 0.3% of all solid tumors. Although the chest wall is a common location, this tumour has rarely been associated with breast tissue or breast implants. Herein is only the fourth case described in conjunction with a breast implant and the only case linked to a ruptured silicone implant. This tumour was locally aggressive and required wide surgical resection, including removal of the chest wall, to gain control. Wide surgical resection is recommended with the application of adjuvant radiation therapy being more controversial.

Modulation of vitamin D receptor and estrogen receptor by 1,25(OH)2-vitamin D3 in T-47D human breast cancer cells

1,25(OH)2-Vitamin D3 inhibits breast cancer cell proliferation through interaction with the vitamin D receptor (VDR). Regulation of VDR is under the influence of several factors which include the functional ligand for this receptor (1,25(OH)2-vitamin D3) as well as heterologous steroid hormones. We evaluated the nature of homologous regulation in T-47D human breast cancer cells with a radiolabelled ligand binding assay and a ribonuclease protection assay for VDR. Significant VDR up-regulation, as measured by hormone binding assays, occurred with pre-incubations with 10(-9)M through 10(-6)M 1,25(OH)2-vitamin D3 (P < 0.05). A 7-fold VDR up-regulation with 10(-8)M 1,25(OH)2-vitamin D3 occurred at 4 h treatment and was not associated with an increase in VDR mRNA expression on ribonuclease protection assay. This supports the hypothesis that up-regulation of VDR is probably the result of ligand-induced stabilization of pre-existing receptor. All-trans-retinoic acid, the progesterone analog R-5020, and prednisone were found to induce heterologous up-regulation of the VDR. We then determined with ligand binding assays whether 1,25(OH)2-vitamin D3 could influence receptor levels for another hormone in a manner analogous to the heterologous regulation of VDR. Regulation of estrogen receptor (ER) by 1,25(OH)2-vitamin D3 was studied in T-47D and MDA-MB-231 breast cancer cells. Incubation of T-47D cells, which are ER (+), with 10(-8)M 1,25(OH)2-vitamin D3 did not result in up-regulation of ER. Yet estrogen binding was significantly up-regulated in a cell line that is ER(-), MDA-MB-231. The increased estrogen binding was associated with a shift in binding affinity and ribonuclease protection assay showed absence of ER mRNA in these cells, suggesting an up-regulation of estrogen binding proteins and not of the ER itself.