Evaluation of changes in biologic markers ER, PR, HER 2 and Ki-67 index in breast cancer with administration of neoadjuvant dose dense doxorubicin, cyclophosphamide followed by paclitaxel chemotherapy.

PURPOSE: The aim of this study was to assess the changes in biologic markers of breast cancer ER, PR, HER 2 and Ki-67 in locally advanced breast cancer patients after neoadjuvant chemotherapy. METHODS: Data from 63 locally advanced breast cancer patients (stage II or III), whose histological diagnosis was made by core biopsies were retrospectively evaluated. The patients were given 4 cyles of 600 mg/m(2) cyclophosphamide, 60 mg/m(2) doxorubicin every 15 days followed by 4 cycles of paclitaxel 175 mg/m(2) every 15 days, and they underwent surgery within two weeks after the last chemotherapy cycle. Expressions in the preoperative and postoperative status of ER, PR, HER 2 and Ki-67 were compared. RESULTS: The patient mean age was 49.2 ±10.7 years and most (57.1%) were premenopausal. Clinical stages of patients ranged between T2N1 and T3N2. The pathological complete response (pCR) rate was 14.9 % (N=9). Two (5.7%) patients who were ER positive prior to treatment showed ER negativity after treatment. In 7 (21.17percnt;) patients PR became negative after neoadjuvant chemotherapy and in 3 (9.0%) patients PR became positive. Changes in ER and PR receptors were not statistically significant (ER p=0.500 and PR p=0.549, respectively), whereas in 2 (5. 8%) patients hormonal status changed significantly when compared to initial biopsies (p=0.003). In addition, median value for PR intensity decreased from 20 to 10% (p=0.003) and Ki-67 values decreased from 10 to 1% (p<0.001) following neoadjuvant therapy. Six (17%) patients exhibited some changes in HER 2 staining. HER 2 expression became 2+ in 3 patients who were HER 2 negative prior to treatment, and HER 2 expression became negative in two patients with HER 2 1+ and 2+ prior to treatment following neoadjuvant chemotherapy. CONCLUSION: The biological markers ER, PR, HER 2 and Ki- 67 index demonstrated differences after neoadjuvant treatment in breast cancer patients. These changes may affect the treatment decision.

Evaluation of changes of biologic markers ER, PR, HER 2 and Ki-67 in breast cancer with administration of neoadjuvant dose-dense doxorubicin, cyclophosphamide followed by paclitaxel.

PURPOSE: To assess the changes of biologic markers estrogen receptors (ER), progesterone receptors (PR), HER 2 and Ki-67 in locally advanced breast cancer patients after neoadjuvant chemotherapy. METHODS: Data from 63 locally advanced breast cancer patients (stage II or III), whose histological diagnosis was made by core biopsies were retrospectively evaluated. The patients were given 4 cycles of 600 mg/m(2) cyclophosphamide, 60 mg/m(2) doxorubicin every 15 days, followed by 4 cycles of paclitaxel 175 mg/m(2), followed by mastectomy within 2 weeks after the last chemotherapy cycle. The changes in ER, PR, HER 2 and Ki-67 status of the operated tumor tissue were compared with the material obtained by initial core biopsies. RESULTS: The patient mean age was 49.2±10.7 years. Most (57.1%) were premenopausal. Clinical disease stages ranged between T2N1 and T3N2. Pathological complete response (pCR) rate was 14.9 7 percent; (n=9). Two (5.7%) patients who were ER positive prior to treatment showed ER negativity after treatment. In 7 (21.1%) patients PR became negative and in 3 (9.0%) became positive after neoadjuvant chemotherapy. Changes in ER and PR receptors were not statistically significant (p=0.500 and PR p=0.549, respectively), whereas in 2 (5.8%) patients hormonal status changed significantly when compared to initial biopsies (p=0.003). In addition, the median value of PR intensity decreased from 20 to 10% (p=0.003) and Ki-67 decreased from 10 to 1% (p<0.001) following neoadjuvant therapy. Five (14.1%) patients exhibited some changes in HER 2 expression: HER 2 expression became 2+ in 3 patients previously being HER 2 negative, and in 2 patients HER 2 became negative whilst it was 1+ and 2+ prior to neoadjuvant chemotherapy. CONCLUSION: It was observed that the biologic markers ER, PR, HER 2 and Ki-67, from the same tumor material demonstrated differences after neoadjuvant treatment in breast cancer patients. These changes may affect the treatment decision.

Stimulation of gap junctional intercellular communication by thalidomide and thalidomide analogs in human fetal skin fibroblasts (HFFF2) and in rat liver epithelial cells (WB-F344).

Gap junction channels maintain cell-cell communication and are essential for the coordination of tissues, playing a pivotal role in embryonal development. Gap junctional intercellular communication (GJIC), studied here in human fetal skin fibroblasts (HFFF2) and in rat liver epithelial cells (WB-F344), was almost doubled upon exposure to thalidomide (10 microM) in the presence of NADH or NADPH (20 microM). Neither in HFFF2 nor in WB-F344 cells did any detectable alteration in GJIC occur with the thalidomide analog EM 16 (10 microM), known as a non-teratogenic compound. The thalidomide analog EM 364 (10 microM) increased GJIC without prior metabolic activation. It is suggested that GJIC modification may be related to the pharmacological and toxicological properties of thalidomide.

An experimental study of the effect of aprotinin on intestinal adhesion formation.

BACKGROUND: Depression of fibrinolysis is known to be a major mechanism for postoperative adhesion formation. Because aprotinin inhibits fibrinolysis it may lead to an increase in adhesion formation whereas its anti-inflammatory effects may lead to a decrease in adhesion formation. Our aim is to clarify conflicting results in previous literature. METHODS: Basal levels of intestinal hydroxyproline (OHP) content and local fibrinolytic activity (LFA) were determined using naive groups. In the experiment groups, adhesions were created by scraping and creating a transient ischemia of a segment of terminal ileum. Group I and II rats were injected subcutaneous (s.c.) normal saline (NS) for 3 days and single dose intraperitoneal (i.p.) NS, respectively. Group III and IV rats were injected s.c. aprotinin for 3 days and single dose i.p. aprotinin, respectively. Group V rats were injected intramuscular methylprednisolone (MP) for 3 days. LFA and OHP levels were determined on the second and fifth postoperative days. The severity of adhesion formation was graded on the fifth day. RESULTS: Aprotinin decreased both the severity of adhesions and OHP levels whereas MP decreased only the severity of adhesions. There was an early depression of LFA at the second day in both NS and MP groups increasing to basal levels at the fifth day. OHP levels showed significant correlation with adhesion severity. CONCLUSION: Results showed that aprotinin decreased intra-abdominal adhesion formation probably by preventing early depression of LFA.

Effect of persistently elevated intraabdominal pressure on healing of colonic anastomoses.

BACKGROUND: The adverse effects of elevated intraabdominal pressure (IAP) on abdominal organs are realized, but its influence on anastomotic healing has not been studied. The aim of this study was to evaluate the effect of elevated IAP on healing of colonic anastomoses. METHODS: Thirty rats, which all had right colonic anastomoses, were divided into five groups. Group 1 was the control group, and group 2 had fecal peritonitis. IAP was maintained between 4 to 6 mm Hg in group 3, 8 to 12 mm Hg in group 4, and 14 to 18 mm Hg in group 5 until all rats were sacrificed on day 4. Bursting pressures and tissue hydroxyproline concentrations of anastomoses were then analyzed and compared. RESULTS: Mean +/- SEM of bursting pressures were 143+/-2.9 mm Hg in group 1, 72+/-14.4 mm Hg in group 2, 77.3+/-7.9 mm Hg in group 3, 57.5+/-11.2 mm Hg in group 4, and 40.1+/-9.6 mm Hg in group 5 (P<0.0001, one-way analysis of variance [ANOVA]). Mean +/- SEM of tissue hydroxyproline concentrations were 5.3+/-0.3 microg/mg in group 1, 4.7+/-0.5 microg/mg in group 2, 4.6+/-0.6 microg/mg in group 3, 3.6+/-0.5 microg/mg in group 4, and 2.4+/-0.2 microg/mg in group 5 (P = 0.0026, one-way ANOVA). The bursting pressure and hydroxyproline concentrations had good correlation (P<0.001, r = 0.76). CONCLUSIONS: Elevated IAP delays healing of colonic anastomoses and 4 to 6 mm Hg IAP delays healing as much as fecal peritonitis. More elevated IAP delays healing more than fecal peritonitis. These events may be clinically important and may result from local-systemic effects of IAP.

Neoadjuvant chemotherapy in locally advanced breast cancer: a preliminary report. Turkish Oncology Study Group.

AIMS AND BACKGROUND: A pilot study of neoadjuvant chemotherapy with cyclophosphamide-epirubicin-5-fluorouracil (FEC) was performed on 85 patients with locally advanced breast cancer. METHODS AND STUDY DESIGN: Patients received four cycles of neoadjuvant chemotherapy followed by surgery, radiotherapy and a treatment with cyclophosphamide-methotrexate-5-fluorouracil for three cycles. RESULTS: Major clinical response was obtained in 76 (89%) patients. Complete response was documented in 14 (17%) patients at pathologic examination of surgical specimen. Grade 1-2 nausea and vomiting was the most common (77%) side effect. Grade 2-3 alopecia was 66%. Grade 2-3 neutropenia occurred in 16% of patients. None of the patients developed febrile neutropenia. Sinus tachycardia was observed only in one patient. Three patients had a more than 10% decrease in the left ventricular ejection fraction without any clinical signs. Nine patients had progressive or stable disease and 4 did not undergo surgery or receive radiation therapy; thus 13 were excluded from survival analysis. After a median followup of 31 months (range, 15-41), disease-free survival and overall survival were 20 (range, 13-32) and 23 months (range, 17-32). CONCLUSIONS: The FEC combination is safe and effective for a neoadjuvant setting in locally advanced breast cancer. A longer follow-up is necessary for the end point results.

Factors affecting postoperative mortality in abdominal trauma.

Records of 345 patients in whom laparatomies were performed because of blunt and penetrating abdominal trauma were reviewed retrospectively with respect to factors affecting mortality. One hundred and twenty-eight patients had blunt abdominal trauma (Group I), 114 patients had gunshot wounds of the abdomen (Group II), and 103 patients had stab wounds of the abdomen (Group III). Mortality rates were 14.8%, 12.3% and 1.9% in groups I, II and III respectively. The presence of head trauma especially if accompanied by hypotension in group I, and the presence of chest trauma (hemothorax and/or pneumothorax) and hypotension (less than 90 mmHg) in group II were associated with a high mortality rate (p less than 0.05). Of the two patients who died in group III, one had septic shock due to massive intestinal necrosis and the other had hemorrhagic shock due to multiple organ injury and bleeding from an injured internal thoracic artery as the cause of death.

A case of renal artery stenosis secondary to chronic pancreatitis.

We report a case of renal artery stenosis most probably secondary to chronic pancreatitis. The patient had a traumatic pancreatic fistula. This was followed by numerous attacks of pancreatitis in the following years. At a relatively young age, he developed hypertension. Examinations revealed a right renal artery stenosis which was successfully treated by a percutaneous angioplasty. This rare complication should be kept in mind as a possible complication of pancreatitis.

Diagnosis and treatment of uncomplicated hydatid cyst of the liver.

Hydatid disease of the liver is still endemic in certain parts of the world. The diagnosis of noncomplicated hydatid cyst of the liver depends on clinical suspicion. Ultrasonography and computed tomography, the most important diagnostic tools, are helpful for determining the complications and planning treatment. The modern treatment of hydatid cyst of the liver varies from surgical intervention to percutaneous drainage or medical therapy. Surgery is still the treatment of choice and can be performed by the conventional or laparoscopic approach. Percutaneous drainage and treatment of the cyst with hypertonic saline or alcohol seems to be a good alternative to surgery in selected cases. Currently, we treat types I and II by ultrasound-guided percutaneous drainage and types IV and V (excluding totally calcified cysts) surgically. Type III cysts can be managed either way depending on the presence of drainable content. We believe that the laparoscopic approach should be limited to noncomplicated cysts.

Effect of alpha-tocopherol and silibin dihemisuccinate on the proliferation of human skin fibroblasts.

Cell proliferation is a complex and important event in atherosclerosis, aging and cancer, and is under the control of signalling pathways. These signalling pathways in turn are effected by the presence of a number of chemicals. For this purpose, we have checked the effect of two chemicals on the proliferation of skin fibroblasts. alpha-Tocopherol and silibin dihemisuccinate (SDH) negatively regulate proliferation of human skin fibroblasts. To check the cell-cycle time intervals, a [3H]thymidine incorporation assay was performed, showing DNA replication at around 24 h; this indicated the time required for the incubation with the chemicals. When alpha-tocopherol was added to the growth medium at a physiological concentration of 50 microM, cell proliferation was inhibited by 40% in 72 h. A similar inhibitory effect of cell proliferation was achieved when 500 microM SDH was used (39% inhibition in 72 h). From the dose-response curves obtained it was concluded that both duration of treatment and the concentration of the chemicals are important parameters. The actual mechanism of the inhibition of cell proliferation may be due to the anti-oxidative potential of these chemicals as well as another mechanism effecting signal transduction pathways.

Restoration of bactericidal activity of peritoneal fluid by cimetidine but not ranitidine or famotidine in burned mice.

OBJECTIVE: To find out the effect of 20%, third degree burns and H2 receptor antagonists on peritoneal bactericidal activity. DESIGN: Animal experiment. SETTING: Research laboratory of university school of medicine. SUBJECTS: 52 mice in five groups. INTERVENTIONS: Sham burn (n = 5, group I), burned, and received subcutaneous injections of saline (0.3 ml/kg day, n = 14, group II); ranitidine (10 ml/kg/day, n = 15, group III); cimetidine (10 mg/kg/day, n = 8, group IV); or famotidine (0.7 mg/kg/day, n = 10, group V); for 14 days. MAIN OUTCOME MEASURE: Peritoneal bactericidal activity in all groups measured 15 days after the burn. RESULTS: There was a significant difference in peritoneal bactericidal activity between the control and burned mice, but no significant difference between the control group and the burned mice that were given cimetidine and famotidine. CONCLUSION: Peritoneal bactericidal activity is suppressed in mice after 20% third degree burns and this effect may be partly reversed by cimetidine and famotidine.

Effects of laparotomy, and carbon dioxide and air pneumoperitoneum, on cellular immunity and peritoneal host defences in rats.

OBJECTIVE: To assess the effects of laparotomy, and insufflation of carbon dioxide and air, on the immune system in rats. DESIGN: Randomised laboratory study. SETTING: Teaching hospital, Turkey. ANIMALS: 77 Wistar rats randomly allocated to 2 groups one of which was sensitised with dinitrofluorobenzene (DNFB, n = 43) and one of which was not (n = 34). INTERVENTIONS: The DNFB group was sensitised and subdivided into control (n = 8), laparotomy alone (n = 7), and insufflation with carbon dioxide (CO2) for 30 and 60 mins (n = 7 in each) or room air for 30 and 60 mins (n = 7 in each). A week later DNFB was reapplied to the ears. In the group not sensitised with DNFB the animals were subdivided similarly, the corresponding numbers in each group being, 6, 6, 6, 6, 5, and 5. MAIN OUTCOME MEASURES: Delayed type hypersensitivity (DTH) measured by ear swelling in the DNFB group, and peritoneal bactericidal activity, total free peritoneal cell counts (TPC), and cell types in the non-sensitised group. RESULTS: There were significant differences in the degree of ear swelling in the DNFB group between control and laparotomy groups (p = 0.0001) and between control and both insufflations of air (p = 0.002 and p = 0.0003, respectively). In the non-sensitised group peritoneal bactericidal activity was significantly increased after 7 hours in the 60 mins air insufflation group (p = 0.04). At 24 hours there were no differences among the groups. TPC were not affected. The number of peritoneal polymorphonuclear leucocytes (PMN) was significantly higher in the laparotomy alone group than in the control or any of the insufflation groups (p < 0.05). CONCLUSIONS: Laparotomy and air insufflation depressed cell-mediated immunity. Peritoneal bactericidal activity was affected only after 60 minutes of air insufflation.

Surgical treatment of splanchnic artery aneurysms secondary to medial degeneration: report of two cases.

Although splanchnic artery aneurysms are an uncommon form of vascular disease, splenic artery aneurysms are the third most common intraabdominal aneurysms, followed by aneurysms of the infrarenal aorta and iliac arteries. In this report, we present two splanchnic artery aneurysms, one symptomatic located in the superior mesenteric artery and one found incidentally in the splenic artery. In the first case reconstructive surgery was carried out. In the second patient the splenic artery aneurysm was excised and splenectomy was performed. The incidence, clinical presentation, pathophysiology, evaluation, and treatment modalities are discussed.

Risk factors in perforated peptic ulcer disease: comparison of a new score system with the Mannheim Peritonitis Index.

OBJECTIVE: To construct a score that would accurately predict outcome for patients with perforated peptic ulcers. DESIGN: Retrospective study. SETTING: University Hospital. SUBJECTS: 173 patients who were operated on for perforated peptic duodenal ulcers over a 14 year period. MAIN OUTCOME MEASURES: Results of multivariate discriminant function analysis of derived set of clinical variables known to be associated with high mortality, and comparison with the Mannheim Peritonitis Index. RESULTS: Serious coexisting medical illness, acute renal failure, white cell count of more than 20 x 10(9)/l, and male sex were the most significant factors influencing mortality. The Hacettepe score for perforated peptic ulcer was established using these four variables. The sensitivity was 83%, the specificity 94%, and the overall predictive accuracy 93%. The corresponding figures for the Mannheim Peritonitis Index were 75%, 96%, and 94% respectively. CONCLUSION: The Hacettepe score is useful in predicting whether a patient will survive after perforation of a peptic duodenal ulcer.

Effects of polyglycolic acid and polypropylene meshes on postoperative adhesion formation in mice.

The purpose of this study was to investigate the effects of polyglycolic acid (PGA), an absorbable (ABS) mesh, and polypropylene (PP), a nonabsorbable (NA) mesh, on intestinal adhesion formation. Altogether 72 mice were divided into a control group of 24, an ABS mesh group of 23, and an NA mesh group of 25. All three groups were divided into two subgroups for evaluation of adhesion severity at postoperative (po) days 5 and 90. Adhesion severity was measured with adhesion grading and tissue hydroxyproline (OHP) levels. Adhesion degree was minimal (1) in all subjects on day 5. Also there was no difference in tissue OHP levels between three groups on day 5 (p > 0.05). Adhesion degree and tissue OHP levels as determinants of adhesion severity were higher in the PGA mesh group than the control group and the PP mesh group on day 90 (p < 0.001). There was no difference between the control group and the PP mesh groups (p > 0.05). Adhesion degree was higher on day 90 than on day 5 in the control group and the PGA mesh group (p < 0.05), whereas tissue OHP level was higher on day 90 than on day 5 in all three groups (p < 0.001). Also there was linear correlation between adhesion degree and tissue OHP levels (r = 0.86, p < 0.001). The study demonstrates that ABS PGA mesh has higher potential for adhesion formation than the NA PP mesh, probably related to the increased foreign body and inflammatory reactions during the absorption process of the mesh.