Randomized Trial Comparing Resection of Primary Tumor with No Surgery in Stage IV Breast Cancer at Presentation: Protocol MF07-01.

BACKGROUND: The MF07-01 trial is a multicenter, phase III, randomized, controlled study comparing locoregional treatment (LRT) followed by systemic therapy (ST) with ST alone for treatment-naïve stage IV breast cancer (BC) patients. METHODS: At initial diagnosis, patients were randomized 1:1 to either the LRT or ST group. All the patients were given ST either immediately after randomization or after surgical resection of the intact primary tumor. RESULTS: The trial enrolled 274 patients: 138 in the LRT group and 136 in the ST group. Hazard of death was 34% lower in the LRT group than in the ST group (hazard ratio [HR], 0.66; 95% confidence interval [CI], 0.49-0.88; p = 0.005). Unplanned subgroup analyses showed that the risk of death was statistically lower in the LRT group than in the ST group with respect to estrogen receptor (ER)/progesterone receptor (PR)(+) (HR 0.64; 95% CI 0.46-0.91; p = 0.01), human epidermal growth factor 2 (HER2)/neu(-) (HR 0.64; 95% CI 0.45-0.91; p = 0.01), patients younger than 55 years (HR 0.57; 95% CI 0.38-0.86; p = 0.007), and patients with solitary bone-only metastases (HR 0.47; 95% CI 0.23-0.98; p = 0.04). CONCLUSION: In the current trial, improvement in 36-month survival was not observed with upfront surgery for stage IV breast cancer patients. However, a longer follow-up study (median, 40 months) showed statistically significant improvement in median survival. When locoregional treatment in de novo stage IV BC is discussed with the patient as an option, practitioners must consider age, performance status, comorbidities, tumor type, and metastatic disease burden.

Effects of Beta-d-glucan on diabetic colon anastomosis.

OBJECTIVE: The purpose of this study was to evaluate the effects of beta-D-glucan on the experimental diabetic rat colon anastomosis model. BACKGROUND: Beta-D-glucan is a commonly used macrophage activator and promotes wound healing by increasing macrophage infiltration into the wound. The decrease in the function of macrophages and impaired wound healing can be observed in diabetes mellitus (DM). METHODS: Eighty Spraque-Dawley rats were divided into 4 groups: colon anastomosis (group 1); colon anastomosis + DM (group 2); colon anastomosis + beta-D-glucan (group 3); and colon anastomosis + beta-D-glucan + DM (group 4). Diabetes was induced with streptozotocin (85 mg/kg), and glycemia was assessed before induction at days 14 and 17. Colon anastomosis was performed at day 14. Beta-D-glucan (100 mg/kg/day) was administered 2 days before colon anastomosis and given orally for 5 days. Relaparotomies were done 3 days after colon anastomosis, and anastomotic bursting pressures, anastomotic hydroxyproline levels, malondialdehyde (MDA) levels, and histopathology examinations were studied. RESULTS: There were no differences among groups for hydroxyproline levels. The mean values of anastomotic bursting pressures in group 4 were significantly higher than those of group 2. The mean values of MDA levels in group 2 were significantly lower than those of group 4. Group 2 showed a significant difference in the amount of necrosis, accumulation of polmorphonuclear cells, and edema when compared with groups 1, 3, and 4 (P < 0.001, P < 0.002, and P < 0.001, respectively). CONCLUSION: This study indicates that oral administration of beta-D-glucan significantly improves the impaired anastomotic healing in rats with diabetes mellitus.

[Not Available].

OBJECTIVE: The purpose of this study was to reveal the effect of N-acetylcysteine (NAC) on random-skin flaps in rats. INTRODUCTION: N-acetylcysteine is an agent among free radical scavengers which is used primarily as a mucolitic agent. Experimental studies have demonstrated protective effects of NAC on hepatic, renal, lung, and intestinal injuries. METHODS: Wistar female rats were divided into 2 groups (control and NAC group), and the NAC group received intramuscular injections for 7 days. Flaps were raised on day 2 and rats were sacrified on day 7. Skin samples from the second cm and fifth cm of the skin flap were collected for biochemical and histopathological examinations. RESULTS: The mean necrotic area ratios in the control and NAC group were 38% and 12%, respectively (P <0.001). Malondialdehyde (MDA) levels were significantly lower in skin samples collected from the control group as compared to samples obtained from the NAC group (P = 0.002). Superoxide dismustase (SOD) activity was significantly higher in the NAC group (P < 0.0001). Histopathologically, a significant increase in macrophage and fibroblast activity was observed in the NAC group. Mononuclear cell infiltration and fibroblast activity had increased, especially in samples from the fifth cm of the skin flap in the NAC group. The histopathological evaluation in the NAC group revealed protective effects of NAC. CONCLUSIONS: Treatment of rats with NAC significantly reduced flap necrosis and MDA levels while increasing SOD levels. These data suggest that NAC has a protective role in flap survival and demonstrates preventive effects against flap necrosis. .

Early complications of a reduction mammoplasty technique in the treatment of macromastia with or without breast cancer.

UNLABELLED: This study was planned to investigate the early postoperative complications of reduction mammoplasty done for benign or malignant reasons on 286 patients. Minor and major complication rates were 16.3% and 1.9%, respectively.There was no significant difference in terms of complications between the patients with and those without breast cancer. Body mass index was found to be the only factor associated with the complication rates. BACKGROUND: This study was planned to investigate the early postoperative complications after reduction mammoplasty applied either for benign or malignant reasons and reliability of the technique with respect to wound healing. PATIENTS AND METHODS: Two hundred and eighty-six reduction procedures were evaluated prospectively. Fifty-two patients underwent reduction mammoplasty for macromastia and 101 for macromastia with breast cancer. The wound complications were evaluated in 2 groups, as minor and major complications. Seroma, hematoma, surgical site infection, delayed wound healing, and minor wound dehiscence were included in the minor complication group. Severe complications, such as necrosis of nipple-areola complex and major incisional wound dehiscence, were included in the major complications group. RESULTS: Mean (SD) age of the patients was 48.8 ± 10.3 years, mean (SD) body mass index was 29 ± 3.3 kg/m(2), and mean (SD) weight of resected specimen was 958 ± 72 g. Mean (SD) preoperative and postoperative volumes for each breast were 1245 ± 75 cm(3) and 436 ± 27 cm(3), respectively. Minor and major complication rates were 25/153 (16.3%) and 3/153 (1.9%), respectively. There was no significant difference in terms of complications between the patients with and without breast cancer. Body mass index was found to be the only factor associated with the complication rates. DISCUSSION: Reduction mammoplasty is a surgical technique that has satisfactory cosmetic results in the treatment of macromastia. This technique also is safe in the treatment of breast cancer patients with macromastia and does not increase complication rates.

Glucan improves impaired wound healing in diabetic rats .

UNLABELLED:  Purpose. Diabetes mellitus (DM) is a contributing factor to impaired wound healing in humans. A large body of evidence indicates that the diabetic state is associated with delayed or reduced wound repair capacity. The present study was designed to evaluate the efficacy of glucan on improving abdominal wall wound healing in rats with DM. METHODS: Ninety-six female, Sprague-Dawley rats that weighed between 250 g and 300 g were used. A laparotomy was performed on all of the rats on the 14th day. Twenty-four healthy rats (group 1) served as the control. Streptozotocin was used to induce DM in groups 2 and 3 (n = 48). Rats in group 3 received glucan (n = 24). Rats in group 4 were not rendered with DM but received glucan (n = 24). The sutures were removed and abdominal bursting pressure was measured and recorded on the seventh postoperative day for all of the groups. Tissue samples were taken from the incision line for histopathological evaluation and hydroxyproline measurement. RESULTS: In group 2, the bursting pressure was significantly lower than in groups 1, 3, and 4; the hydroxyproline content and histopathological evaluations also supported these findings. CONCLUSION: These results demonstrate that glucan improves impaired wound healing in rats with DM. .

Results of breast conserving surgery in clinical stage I-II breast carcinoma.

BACKGROUND: The role of breast conserving surgery with radiotherapy is well established and has become a widely used procedure in breast cancer. Patient selection, a multidisciplinary approach, and expert surgical technique are important factors to avoid locoregional recurrence. The aim of this study was to analyse the outcomes of patients treated with breast conserving surgery in stage I-II breast cancer. METHODS: In this study, the results of 135 breast conserving surgery cases are reported. The majority of patients received radiotherapy and adjuvant systemic treatment. RESULTS: At a median follow-up period of 54 months, 5 patients (3.7%) developed locoregional recurrence. The 5 years overall and disease-free survival rates were 90% and 84%, respectively. Young age, lymph node involvement, and oestrogen receptor negativity were independent predictors for overall survival. CONCLUSION: In selected patients, breast conserving surgery using good surgical technique in conjunction with radiotherapy can achieve a high survival rate with a low locoregional recurrence rate.

Temporal variation in the recovery from impairment in adriamycin-induced wound healing in rats.

BACKGROUND: An adriamycin-induced impairment of wound healing has been demonstrated experimentally in rats. The purpose of this study is to investigate a possible temporal variation in recovery from the impairment of wound healing caused by adriamycin administration. METHODS: The subjects were 120 female Spraque-Dawley rats. They were divided into eight groups, undergoing adriamycin administration (8 mg/kg, i.v.) at 9 a.m. or 9 p.m. on day 0 and laparotomy on day 0, 7, 14 or 21. Blast pressures were recorded after the incision line had been opened, and tissue samples were kept at -30 degrees C for later measurement of hydroxyproline levels. RESULTS: Adriamycin treatment in rats at 9 p.m. resulted in significantly lower blast pressure levels than treatment at 9 a.m. between days 7 and 21, indicating a lag effect of healing time in wounded tissues. However the decreased hydroxyproline levels were not changed at these days and sessions. CONCLUSION: It is concluded that adriamycin-induced impairment of wound healing in adult female rats exhibits nycthemeral variation.

Prognostic factors determining survival in differentiated thyroid cancer.

BACKGROUND: Differentiated thyroid cancer (DTC) is among the most curable cancers. We evaluated the prognoses of patients with DTC from an iodine-deficient area. MATERIALS AND METHODS: Four hundred twenty-two patients with thyroid cancer who underwent surgery between 1992 and 2000 at the Ankara Oncology Hospital were evaluated. Three hundred eighty-two patients with DTC were included. Gender, age, histopathological type, tumor size, capsular invasion and vascular invasion, distant metastasis, TNM, and AMES-MACIS scoring were analyzed. RESULTS: The 10-year disease-free survival rate was 72% and the overall survival rate was 88%. Age >/=45 years at presentation, follicular thyroid cancer, tumor extension beyond the thyroid capsule, vascular invasion, distant metastasis, increasing tumor size, stage, and high MACIS-AMES scores were found to be statistically significant adverse prognostic factors in univariate analysis for DFS and OAS. Multivariate analysis for DFS and OAS confirmed that distant metastasis, follicular thyroid cancer, tumor extension beyond the thyroid capsule, vascular invasion, primary tumor size, TNM stage, and high MACIS score were independent prognostic factors. CONCLUSION: In DTC patients, in addition to traditional risk factors, prognostic factors, such as vascular invasion and capsular invasion, need to be evaluated; not only for achieving an adequate therapeutic approach, but also for avoiding overtreatment of low-risk patients.

Long term administration of granulocyte-macrophage colony stimulating factor decreases development of 1-2 dimethylhydrazine-induced colon cancer in rats.

BACKGROUND AND OBJECTIVES: The antitumoral activities of granulocyte-macrophage colony stimulating factor (GM-CSF) were shown earlier. In this study, the effects of GM-CSF were investigated on colon cancer induced by 18 weeks of 1-2 dimethylhydrazine (DMH) administration in rats. METHODS: Four groups received subcutaneous saline (n = 20), 15 mg/kg DMH (n = 30), DMH +6 microg/kg GM-CSF (n = 30), and DMH +12 microg/kg (n = 30) GM-CSF. RESULTS: The average number of tumors (2.8 vs. 1.5) and mean tumor volume (179 +/- 36 vs. 27 +/- 9 mm(3); means +/- SEM) were reduced in DMH + GM-CSF groups as compared to the DMH group (n = 30, P < 0.01). DMH-induced enhancement of free radicals and lipid peroxidation were decreased in DMH + GM-CSF group (n = 8-12, P < 0.05). The magnitude of DMH-induced alterations in superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities was lowered in the DMH + GM-CSF group (n = 12-16, P < 0.05). DMH-induced increases in the total nitrite/nitrate levels and the nitric oxide synthase (NOS) activity (n = 10-12, P < 0.05) were also reduced in the DMH + GM-CSF group (n = 8-9, P < 0.05). CONCLUSIONS: The results indicate that GM-CSF inhibits the development of DMH-induced colon cancer in rats and suggest that inhibition of oxidative stress and NO pathway are involved in the observed antitumoral effects.

Methylene blue prevents surgery-induced peritoneal adhesions but impairs the early phase of anastomotic wound healing.

OBJECTIVES: Adhesion formation continues to be an important problem in gastrointestinal surgery. In recent years, methylene blue (MB) has been reported to be an effective agent for preventing peritoneal adhesions. However, its effects on the wound healing process are unknown. In the present study, we investigated the effects of MB on the early and late phases of anastomotic wound healing and on adhesion formation. METHODS: We randomly categorized 92 rats into 2 groups in bursting pressure measurements and 50 rats into 3 groups in the adhesion model. We divided the animals into saline-treated (n = 46) or MB-treated (n = 46) groups. Bursting pressures of the anastomoses were measured on postoperative days 3 and 7. In biochemical studies, tissue hydroxyproline levels, total nitrite/nitrate levels and nitric oxide synthase activity were measured on postoperative days 3 and 7. In the adhesion model, we randomly categorized rats into sham (n = 10), saline-treated (n = 20) and MB-treated (n = 20) groups, and the formation of intraperitoneal adhesions was scored on postoperative day 14. We compared the measurement of bursting pressure and biochemical measurements of tissue hydroxyproline levels, total nitrite/nitrate levels and nitric oxide synthase activity. Histopathological findings of specimens were presented. RESULTS: During the early phase of wound healing (postoperative day 3), bursting pressures, tissue hydroxyproline, total nitrite/nitrate levels and nitric oxide synthase activity in the MB-treated group were significantly lower than those of the saline-treated group. On postoperative day 7, there was no significant difference in these parameters between MB and saline-treated groups. In the adhesion model, MB caused a significant reduction in the formation of peritoneal adhesions. CONCLUSION: MB prevents peritoneal adhesions but causes a significant impairment of anastomotic bursting pressure during the early phase of the wound healing process by its transient inhibitory effect on the nitric oxide pathway.

The incidence of hyperthyroidism in patients with thyroid cancer in an area of iodine deficiency.

BACKGROUND: The incidence of hyperthyroidism among thyroid malignancy varies greatly depending on the geographical area and iodine intake. The aim of the study was to evaluate the association of hyperthyroidism and thyroid cancer (TC) in an iodine deficient area. PATIENTS AND METHODS: Medical records of 422 patients who underwent operation for TC between 1992 and 2000 in Ankara Oncology Hospital were reviewed. The characteristics of TC patients with hyperthyroidism were analyzed in respect to gender, age, histopathological type, thyroid function status, tumor size, extrathyroidal invasion, local recurrences, distant metastasis, AMES and MACIS scoring. RESULTS: In the present patient series, among 422 patients with TC, hyperthyroidism was found in 12 patients (2.8%). None of the patients had Graves' disease. Of 12 patients with hyperthyroidism, 9 patients had papillary carcinoma, 1 patient had follicular carcinoma and 2 patients had follicular variant of papillary carcinoma. The tumor was in the active nodule in 5 patients. CONCLUSION: The existence of hyperthyroidism among patients with differentiated TC is a clinical entity. Patients with hyperthyroidism and nodules require a careful approach in order to establish or exclude the possibility of TC especially in formerly iodine deficient areas.

Local granulocyte-macrophage colony-stimulating factor improves incisional wound healing in adriamycin-treated rats.

PURPOSE: Neoadjuvant treatment is often given for locally advanced malignancies; however, clinical and experimental studies have shown that some chemotherapeutic agents impair wound healing. It has been reported that granulocyte-macrophage colony-stimulating factor (GM-CSF) applied locally improves dermal wound healing. Thus, we investigated the effects of locally injected GM-CSF on abdominal wounds impaired by adriamycin, a widely used chemotherapeutic agent. METHODS: We divided 120 female Sprague-Dawley rats into five treatment groups of 24 rats. Group 1 received saline 8 mg/kg intravenously (i.v.) + laparotomy 14 days later (control); group 2 received 8 mg/kg i.v. adriamycin + laparotomy 14 days later; group 3 received adriamycin 8 mg/kg i.v. + laparotomy + local GM-CSF 50 microg 14 days later; group 4 received saline 8 mg/kg i.v. + laparotomy + local GM-CSF 50 microg 14 days later; and group 5 received adriamycin 8 mg/kg i.v. + laparotomy + systemic GM-CSF 50 microg 14 days later. Sutures were removed on postoperative day (POD) 7 in all five groups, and the abdominal bursting pressures were measured and recorded. Tissue samples were taken from the incision line for histopathological evaluation and hydroxyproline content measurement. RESULTS: The bursting pressure was significantly lower in groups 2 and 5 than in groups 1, 3, and 4. The hydroxyproline content and histopathological findings supported this result. CONCLUSION: The local injection of GM-CSF improved impaired wound healing in adriamycin-treated rats.

Efficacy of granulocyte-macrophage colony-stimulating factor on the survival of ischaemic skin flaps in rats.

Our objective was to find out whether granulocyte-macrophage colony-stimulating factor (GM-CSF) improves the survival of skin flaps in rats. Random skin flaps were raised in 30 male Sprague-Dawley rats, and recombinant GM-CSF 50 microg in 0.5 ml saline solution (n=15) or 0.5 ml saline solution alone (n=15) was injected intradermally into the area of the flap after it had been raised. Surviving areas were measured after seven days, and the median area surviving in the group treated with GM-CSF was greater than that in the control group (728 mm2 (range 565-1120) compared with 985 mm2 (range 636-1368), p=0.005). These results suggest that in this model, GM-CSF given postoperatively improves the viability of ischaemic skin flaps.

Locally applied molgramostim improves wound healing at colonic anastomoses in rats after ligation of the common bile duct.

BACKGROUND: Several systemic factors, including jaundice, long-term corticosteroid therapy, diabetes and malnutrition, increase the risk of anastomotic dehiscence. The local application of molgramostim (recombinant human granulocyte-macrophage colony stimulating factor) has been reported to improve impaired dermal wound healing. Since jaundice, one of the systemic risk factors for anastomotic dehiscence, causes significant impairment of anastomotic healing, we hypothesized that locally injected molgramostim could improve the healing of bowel anastomoses in bile-duct-ligated rats used as an experimental model for jaundice. METHODS: Eighty-six Sprague-Dawley rats were randomized into 4 groups of 20-22 animals each as follows: group 1--colonic anastomosis only; group 2--laparotomy followed 7 days later by colonic anastomosis; group 3--common-bile-duct ligation (CBDL) followed 7 days later by colonic anastomosis (control group); group 4--CBDL followed by colonic anastomosis with locally applied molgramostim. Laparotomy was performed under anesthesia in group 2 rats. In groups 3 and 4, laparotomy was followed by ligation and dissection of the common bile duct. After 7 days, colonic anastomosis was performed; in group 4 rats, molgramostim (50 microg) was injected into the perianastomotic area. On postoperative day 3, rats were killed, and the bursting pressures and hydroxyproline levels measured. Two rats from each group were selected for histopathological examination. RESULTS: The mean bursting pressure in group 4 was significantly higher than that in group 3 (37.8 v. 30.5 mm Hg [p < 0.01]). The mean hydroxyproline level in group 3 was significantly lower than that of the other groups (2.7 v. 3.1-3.5 mg/g tissue [p < 0.01]). On histopathological examination, specimens from group 4 rats showed an increased mononuclear cell population and a smaller gap on the anastomotic line than those from group 3. CONCLUSION: The local injection of molgramostim improves healing of the impaired wound in rats subjected to CBDL.

Granulocyte macrophage-colony stimulating factor improves impaired anastomotic wound healing in rats treated with intraperitoneal mitomycin-C.

PURPOSE: Intraperitoneal chemotherapy (IPCT) delivers higher local concentrations of cytotoxic drugs than intravenous (i.v.) chemotherapy, but it can adversely affect the healing of intestinal anastomoses if given in the early postoperative period. Intestinal anastomotic leakage is a serious surgical complication. Experimental and clinical studies have shown that the local administration of granulocyte macrophage-colony stimulating factor (GM-CSF) improves would healing. Therefore, we evaluated the effects of locally applied GM-CSF on anastomotic wound healing in rats treated with intraperitoneal mitomycin-C immediately after surgery. METHODS: We performed colon anastomoses in albino rats, which were then divided into three treatment groups. Group A was a control group that received no treatment, Group B was given intraperitoneal mitomycin-C postoperatively, and Group C was given intraperitoneal mitomycin-C with a local injection of GM-CSF postoperatively. We measured bursting pressures and hydroxyproline content, and histologically examined the resected anastomoses on postoperative day (POD) 3. RESULTS: Anastomotic healing was impaired after intraperitoneal mitomycin-C, but this was overcome by the injection of GM-CSF into the perianastomotic area. CONCLUSION: Local GM-CSF administration counteracts the detrimental effects of intraperitoneal mitomycin-C treatment on intestinal anastomoses in rats.

Optimal timing for surgery after adriamycin treatment in rats.

PURPOSE: To determine the optimal timing of surgery after adriamycin treatment, we investigated the time-related effect of adriamycin on wound healing over a long period. METHODS: We divided 119 female Sprague-Dawley rats into seven treatment groups. Group 1 was subjected to laparatomy only. All the other groups were given 8 mg/kg adriamycin intravenously followed by laparotomy on the same day (group 2), 7 days later (group 3), 14 days later (group 4), 21 days later (group 5), 28 days later (group 6), or 35 days later (group 7). On postoperative day 7, the sutures were removed, abdominal bursting pressure was measured, and tissue samples were taken for histopathological evaluation and analysis of hydroxyproline content. RESULTS: Bursting pressures were significantly lower in groups 3, 4, 5, and 6 than in group 1. The hydroxyproline content and histopathological evaluation supported these findings. CONCLUSIONS: Our results showed that the optimal timing for surgery after adriamycin treatment is before the 7th day or after the 35th day. If surgery is performed between these days, there is a high risk of impaired wound healing.

Prognostic significance of apex axillary invasion for locoregional recurrence and effect of postmastectomy radiotherapy on overall survival in node-positive breast cancer patients.

Postmastectomy irradiation substantially reduces the risk of locoregional recurrences (LRR) of breast carcinoma. However, debates continue on the prognostic factors for radiotherapy and the effect of radiotherapy on overall survival. The present study was undertaken to investigate the prognostic significance of level III positive nodes, along with the other factors for LRR, and to evaluate the effect of postmastectomy radiotherapy on overall survival among node-positive breast carcinoma treated systemically. Data from 549 consecutive node-positive breast cancer patients who underwent modified radical mastectomy and received adjuvant systemic therapy were studied retrospectively. Prognostic factors for LRR and the effect of postmastectomy radiotherapy on overall survival were analyzed. Survival curves were generated by the Kaplan-Meier method, and multivariate analysis was performed by the Cox proportional hazard model. The 5-year locoregional recurrence rate is 7%. Apical invasion was found to be an independent prognostic factor for LRR (HR 2.6, CI 1.29-5.35) along with a finding of 4 or more positive nodes and T3 tumor. Adjuvant radiotherapy decreased LRR and improved survival significantly. Apical invasion, 4 or more positive axillary lymph nodes, and T3 tumor are the predictors of LRR, and patients with these adverse factors are candidates for adjuvant radiotherapy. Postmastectomy radiotherapy improves overall survival.

Prognostic factors affecting survival and disease-free survival in lymph node-negative breast carcinomas.

BACKGROUND AND OBJECTIVES: The objective of this study was to identify the patients who are at low or high-risk by defining the prognostic factors in node-negative breast carcinomas. METHODS: Medical records of 384 consecutive breast cancer patients with negative axillary lymph nodes who had been operated on between January 1994 and January 1997 at our hospital were retrospectively reviewed. Several clinical and pathological characteristics of patients were categorized. Univariate analyses of survival and disease-free survival (DFS) were performed by the Kaplan-Meier method and the log-rank test. Independent prognostic and predictive factors affecting survival and DFS were assessed by Cox proportional hazard method. RESULTS: 5-year survival and DFS were 91.4 and 85.7%, respectively. Size, grade, age, and lymphovascular invasion (LVI) were the prognostic factors that independently affected survival and DFS. Tamoxifen improved survival and DFS. While age younger than 35 was an adverse factor for both survival and DFS, age older than 49 was a detrimental factor for DFS. CONCLUSIONS: Patients who have a tumor with size greater than 2 cm, with histologic grade 3, with LVI, and patients with age under 35 or older than 49 have poorer prognosis among node-negative breast carcinomas, and are candidates for adjuvant therapy.

Effects of intraperitoneal chemotherapy and GM-CSF on anastomotic healing: an experimental study in rats.

BACKGROUND: Intraperitoneal chemotherapy (IPCT) is an alternative local adjuvant treatment for patients with resectable colonic and gastric cancers. This is the simplest and safest method for systemic toxicity, but it can affect the healing of colonic anastomoses. Granulocyte macrophage-colony stimulating factor (GM-CSF) may be used to prevent this side effect by means of macrophage activity stimulation. METHODS: In this experimental study the effects of early postoperative intraperitoneal 5-fluorouracil (5-FU) and local administration of recombinant human GM-CSF (rGM-CSF) were studied on rats. The anastomotic bursting pressures, hydroxyproline contents of tissues, and histological appearance were assessed. RESULTS: It was found that anastomotic healing of colon was impaired after intraperitoneal 5-FU administration, but when rGM-CSF was injected to the both sides of the anastomoses locally, this side effect could be prevented. CONCLUSIONS: IPCT may diminish the activity of macrophages and impair the wound healing; locally applied rGM-CSF enhanced wound healing on colonic anastomoses.

Locally applied granulocyte-macrophage colony-stimulating factor improves the impaired bowel anastomoses in rats with long-term corticosteroid treatment.

Inflammation is an essential component of the first phase of anastomotic wound healing, and it is suppressed by corticosteroids. The anti-inflammatory effect of corticosteroids is largely responsible for the impairment of wound healing in bowel anastomosis. It has been reported that local application of granulocyte-macrophage colony-stimulating factor (GM-CSF) improves the healing process in dermal wounds. In the present study, we investigated the effects of locally injected GM-CSF on anastomotic wound healing in long-term corticosteroid treated rats. Eighty male Sprague-Dawley rats were randomized into four groups. (1) control, (2) steroid, (3) steroid + local GM-CSF, (4) steroid + systemic GM-CSF. In groups 2, 3, and 4, methylprednisolone (5 mg/kg) was injected IM daily for 14 days. After 14 days, following anesthesia and laparotomy, colonic anastomosis was performed 3 cm away from the peritoneal reflection. In group 3, 50 mg GM-CSF was injected into the perianastomotic area. In group 4, 50 mg GM-CSF was applied subcutaneously. On postoperative day 3, repeat laparotomies were performed and bursting pressures, hydroxyproline levels, and histopathology examinations were studied. The mean values of bursting pressures and hydroxyproline levels in group 3, treated with steroid + local GM-CSF, were significantly higher than that of the group 2 and group 4 values. In the histopathology examination, the mean score of group 3 was significantly higher than that of groups 2 and 4. Our study indicates that local application of GM-CSF significantly improves the impaired anastomotic wound healing in rats treated with long-term corticosteroid.