Correction to: The mTOR inhibitor rapamycin down-regulates the expression of the ubiquitin ligase subunit Skp2 in breast cancer cells.

After the publication of this work [1], an error was noticed in Fig. 2b, Fig. 3a and Fig. 5b. The Skp1 loading control was accidentally duplicated. We apologize for this error, which did not affect any of the interpretations or conclusions of the article.

Outcome of Delayed Cholecystectomy after Percutaneous Cholecystostomy for Acute Cholecystitis.

BACKGROUND: Recent studies have suggested that urgent cholecystectomy is the preferred treatment for acute cholecystitis. However, initial conservative treatment followed by delayed elective surgery is still common practice in many medical centers. OBJECTIVES: To determine the effect of percutaneous cholecystostomy on surgical outcome in patients undergoing delayed elective cholecystectomy. METHODS: We conducted a retrospective analysis of all patients admitted to our medical center with acute cholecystitis who were treated by conservative treatment followed by delayed cholecystectomy between 2004 and 2013. Logistic regression was calculated to assess the association of percutaneous cholecystostomy with patient characteristics, planned surgical procedure, and the clinical and surgical outcomes. RESULTS: We identified 370 patients. Of these, 134 patients (36%) underwent cholecystostomy during the conservative treatment period. Patients who underwent cholecystostomy were older and at higher risk for surgery. Laparoscopic cholecystectomy was offered to 92% of all patients, yet assignment to the open surgical approach was more common in the cholecystostomy group (16% vs. 3%). Cholecystostomy was associated with significantly higher conversion rates to open approach (26% vs. 13%) but was not associated with longer operative time, hemorrhage, surgical infections, or bile duct or organ injuries. CONCLUSIONS: Treatment with cholecystostomy is associated with higher conversion rates but does not include other major operative-related complications or poorer clinical outcome.

Cyclin-dependent kinase inhibitor p27 as a prognostic biomarker and potential cancer therapeutic target.

The prognosis and clinical management of patients with cancer is commonly determined by traditional clinical and pathological factors. Nevertheless, patients may present with significantly different clinical outcomes despite similar clinicopathological features. This has prompted intense research to find biological markers that may closely reflect tumor biology and thereby clinical outcome. This article presents the current knowledge on the prognostic significance of p27 expression in cancer and its potential role as a target for future therapy.

The expression and prognostic significance of Cks1 in salivary cancer.

Cks1 is an essential factor in facilitating Skp2-dependent degradation of p27, but its role in salivary malignancies is unknown. Expression of cyclin-dependent kinase subunit 1 (Cks1) was examined in 64 salivary malignancies, compared with p27, S-phase kinase protein 2 (Skp2), Ki-67, p53, and TDT-mediated dutp-biotin nick end labeling (TUNEL) expression, and with THE patient's clinical and pathological parameters. Cks1 expression was markedly increased in 30 patients (47%) and strongly correlated with increased expression of Skp2, Ki-67, p53, and TUNEL, but inversely with p27 levels. High expression of Cks1 WAS strongly associated with lymph node metastases and poor prognosis and survival. Cks1 alterations may have a significant biological role in the pathogenesis of salivary cancer.

Over-expression of Skp2 is associated with resistance to preoperative doxorubicin-based chemotherapy in primary breast cancer.

INTRODUCTION: Preoperative chemotherapy is often used in patients with locally advanced breast cancer. However, commonly used clinical and pathological parameters are poor predictors of response to this type of therapy. Recent studies have suggested that altered regulation of the cell cycle in cancer may be involved in resistance to chemotherapy. Over-expression of the ubiquitin ligase Skp2 results in loss of the cell cycle inhibitor p27Kip1 and is associated with poor prognosis in early breast cancer. The purpose of the present study was to examine the role of these proteins as predictors of clinical outcome and response to chemotherapy in locally advanced breast cancer. METHODS: The expression levels of Skp2 and p27Kip1 were determined by immunohistochemistry both before and after preoperative chemotherapy in 40 patients with locally advanced breast cancer. All patients were treated with cyclophosphamide/doxorubicin (adriamycin)/5-fluorouracil (CAF) and some patients received additional treatment with docetaxel. Expression data were compared with patients' clinical and pathological features, clinical outcome, and response to chemotherapy. RESULTS: Skp2 expression before preoperative chemotherapy was inversely related to p27Kip1 levels, tumor grade, and expression of estrogen and progesterone receptors. Both Skp2 and p27Kip1 were found to be accurate prognostic markers for disease-free and overall survival. High preoperative expression of Skp2 was associated with resistance to CAF therapy in 94% of patients (P < 0.0001) but not with resistance to docetaxel. CONCLUSION: Skp2 expression may be a useful marker for predicting response to doxorubicin-based preoperative chemotherapy and clinical outcome in patients with locally advanced breast cancer.

Regulation of the cell cycle inhibitor p27 and its ubiquitin ligase Skp2 in differentiation of human embryonic stem cells.

Embryonic stem cells combine the features of robust proliferation with precise differentiation capacity. p27 is a cell cycle inhibitor that is involved in the regulation of proliferation and differentiation in many developing tissues. Recent studies in murine embryonic stem cells have suggested that p27 is involved in the progression of normal differentiation programs in these cells. However, the expression and regulation of p27 and its role in the differentiation of human embryonic stem cells (hESc) has not been previously explored. Herein we show that p27 expression was low in undifferentiated hESc, but increased markedly in differentiated cells. The expression of Skp2, the ubiquitin ligase that targets p27 for degradation, was inversely related to p27 expression. Moreover, embryoid bodies (EBs) with low p27 expression and high Skp2/p27 ratio showed poorer differentiation than those with high p27 expression. Modulation of Skp2 expression is mainly regulated by its rate of degradation. In contrast to somatic cells, which have high levels of Skp2 mainly in S and G2/M, in undifferentiated hESc Skp2 levels were also high in G1. These results point to a potentially important role for p27 regulation in hESc.

The mTOR inhibitor rapamycin down-regulates the expression of the ubiquitin ligase subunit Skp2 in breast cancer cells.

INTRODUCTION: Loss of the cyclin-dependent kinase inhibitor p27 is associated with poor prognosis in breast cancer. The decrease in p27 levels is mainly the result of enhanced proteasome-dependent degradation mediated by its specific ubiquitin ligase subunit S phase kinase protein 2 (Skp2). The mammalian target of rapamycin (mTOR) is a downstream mediator in the phosphoinositol 3' kinase (PI3K)/Akt pathway that down-regulates p27 levels in breast cancer. Rapamycin was found to stabilize p27 levels in breast cancer, but whether this effect is mediated through changes in Skp2 expression is unknown. METHODS: The expression of Skp2 mRNA and protein levels were examined in rapamycin-treated breast cancer cell lines. The effect of rapamycin on the degradation rate of Skp2 expression was examined in cycloheximide-treated cells and in relationship to the anaphase promoting complex/Cdh1 (APC\C) inhibitor Emi1. RESULTS: Rapamycin significantly decreased Skp2 mRNA and protein levels in a dose and time-dependent fashion, depending on the sensitivity of the cell line to rapamycin. The decrease in Skp2 levels in the different cell lines was followed by cell growth arrest at G1. In addition, rapamycin enhanced the degradation rate of Skp2 and down-regulated the expression of the APC\C inhibitor Emi1. CONCLUSION: These results suggest that Skp2, an important oncogene in the development and progression of breast cancer, may be a novel target for rapamycin treatment.

The expression of the ubiquitin ligase subunit Cks1 in human breast cancer.

INTRODUCTION: Loss of the cell-cycle inhibitory protein p27Kip1 is associated with a poor prognosis in breast cancer. The decrease in the levels of this protein is the result of increased proteasome-dependent degradation, mediated and rate-limited by its specific ubiquitin ligase subunits S-phase kinase protein 2 (Skp2) and cyclin-dependent kinase subunit 1 (Cks1). Skp2 was recently found to be overexpressed in breast cancers, but the role of Cks1 in these cancers is unknown. The present study was undertaken to examine the role of Cks1 expression in breast cancer and its relation to p27Kip1 and Skp2 expression and to tumor aggressiveness. METHODS: The expressions of Cks1, Skp2, and p27Kip1 were examined immunohistochemically on formalin-fixed, paraffin-wax-embedded tissue sections from 50 patients with breast cancer and by immunoblot analysis on breast cancer cell lines. The relation between Cks1 levels and patients' clinical and histological parameters were examined by Cox regression and the Kaplan-Meier method. RESULTS: The expression of Cks1 was strongly associated with Skp2 expression (r = 0.477; P = 0.001) and inversely with p27Kip1 (r = -0.726; P < 0.0001). Overexpression of Cks1 was associated with loss of tumor differentiation, young age, lack of expression of estrogen receptors and of progesterone receptors, and decreased disease-free (P = 0.0007) and overall (P = 0.041) survival. In addition, Cks1 and Skp2 expression were increased by estradiol in estrogen-dependent cell lines but were down-regulated by tamoxifen. CONCLUSION: These results suggest that Cks1 is involved in p27Kip1 down-regulation and may have an important role in the development of aggressive tumor behavior in breast cancer.

Transanal endoscopic microsurgery for rectal cancer.

BACKGROUND: Transanal endoscopic microsurgery has recently gained acceptance as an alternative minimally invasive surgical technique for the curative management of large rectal adenomas and selected early rectal carcinomas. OBJECTIVES: To analyze our 8 year experience using TEM for the management of rectal cancer. METHODS: Local resection by TEM was performed in patients with benign tumors and early rectal cancer. In addition, selected patients with T2 and T3 rectal cancers who were either medically unfit or unwilling to undergo radical surgery were also treated with this modality. Radical surgery was offered to all patients with incomplete tumor excision by TEM. RESULTS: Overall, 116 TEM operations for rectal tumors were carried out between 1995 and 2003, including 74 patients with rectal adenomas and 42 patients with rectal carcinomas. In 25 patients, TEM successfully removed all T1 tumors with clear tumor margins. Fourteen patients had T2 cancer and 3 of them (21%) required additional radical surgery due to incomplete excision. Local recurrence was observed in one patient with T2 cancer. There was no mortality. Major surgery or radiotherapy-related complications requiring additional surgical intervention was needed in five patients with T2 cancer. CONCLUSIONS: Local excision by TEM is a safe surgical procedure and should be offered to highly selected patients with early rectal cancer.

Sepsis upregulates the gene expression of multiple ubiquitin ligases in skeletal muscle.

Muscle wasting during sepsis reflects increased expression and activity of the ubiquitin-proteasome proteolytic pathway and is at least in part mediated by glucocorticoids. The ubiquitination of proteins destined to be degraded by the proteasome is regulated by multiple enzymes, including ubiquitin ligases. We tested the hypothesis that sepsis upregulates the gene expression of the newly described ubiquitin ligases, MuRF1 and atrogin-1/MAFbx. Sepsis was induced in rats by cecal ligation and puncture. Control rats were sham-operated. In some experiments, rats were treated with the glucocorticoid receptor antagonist RU 38486 before induction of sepsis. At various time points after induction of sepsis, mRNA levels for MuRF1 and atrogin-1/MAFbx were determined in extensor digitorum longus muscles by real-time PCR. Sepsis resulted in a 10-16-fold increase in gene expression of the ubiquitin ligases studied here. These changes were much greater than those observed previously for another ubiquitin ligase, E3alpha, in muscle during sepsis. Treatment of rats with RU 38486 prevented the sepsis-induced increase in mRNA levels for MuRF1 and atrogin-1/MAFbx, suggesting that glucocorticoids participate in the upregulation of these genes in muscle during sepsis. The present results lend further support to the concept that the ubiquitin-proteasome pathway plays an important role in sepsis-induced muscle proteolysis and suggest that multiple ubiquitin ligases may participate in the development of muscle wasting during sepsis.

IL-1beta activates C/EBP-beta and delta in human enterocytes through a mitogen-activated protein kinase signaling pathway.

The enterocyte is an active participant in the inflammatory and metabolic response to sepsis, endotoxemia and other critical illnesses and is the site for cytokine and acute phase protein production in these conditions. The role of the CCAAT/enhancer binding protein (C/EBP) family of transcription factors in the response to inflammatory stimuli in the enterocyte is not well understood. In the present study, we treated Caco-2 cells with IL-1beta and determined C/EBP DNA binding activity by electrophoretic mobility shift assay. The involvement of the alpha, beta, and delta isoforms was determined by supershift analysis and Western blot analysis of proteins from the nuclear fraction. The role of the mitogen-activated protein kinase (MAPK) signaling pathway was assessed by treating cells with the MAPK inhibitor PD-98059. Treatment of the Caco-2 cells with IL-1beta resulted in increased CCAAT/enhancer binding protein DNA binding activity. Supershift analysis and Western blotting indicated that this response to IL-1beta mainly reflected the delta isoform, and to a lesser degree the beta isoform. Treatment of the cells with PD-98059 inhibited the IL-1beta-induced increase in beta and delta activity. The results suggest that members of the CCAAT/enhancer binding protein family of transcription factors are activated in enterocytes during inflammatory conditions characterized by high levels of IL-1beta.

Interleukin-10 activates the transcription factor C/EBP and the interleukin-6 gene promoter in human intestinal epithelial cells.

BACKGROUND: Interleukin (IL)-6 is produced by enterocytes in response to sepsis and after treatment with IL-1beta. The IL-6 promoter contains binding sites for multiple transcription factors, including nuclear factor-kappaB and C/EBP. The anti-inflammatory cytokine IL-10 downregulates nuclear factor-kappaB activity, but its effects on C/EBP activation and IL-6 production in the enterocyte are not known. METHODS: Caco-2 cells were treated with IL-1beta, IL-10, or a combination of the cytokines. C/EBP DNA binding activity was determined by electrophoretic mobility shift assay and IL-6 levels by enzyme-linked immunosorbent assay. IL-6 promoter activation was assessed by luciferase assay. RESULTS: IL-10 treatment of cultured Caco-2 cells resulted in increased C/EBP DNA binding activity. Supershift analysis revealed upregulated DNA binding activity of C/EBP-beta but not C/EBP-delta. To examine if the increased DNA binding reflected gene activation, cells were transfected with a wild-type IL-6 promoter luciferase construct or with a mutated C/EBP binding site. IL-10 potentiated IL-1 beta-induced IL-6 promoter activity. Replacing the wild-type promoter with the promoter containing a mutated C/EBP DNA binding sequence blocked the effect of IL-10. When cells were treated with 0.5 ng/mL of IL-1 beta for 24 hours, IL-6 production increased, and this response to IL-1 beta was potentiated several-fold by IL-10. CONCLUSIONS: IL-10 may activate the IL-6 gene in stimulated enterocytes by upregulating the expression and activity of C/EBP.

Hyperthermia-induced heat shock activates the transcription factor c/EBP-beta and augments IL-6 production in human intestinal epithelial cells.

BACKGROUND: Interleukin (IL)-6 production is increased in gut mucosa during sepsis and endotoxemia. The heat shock response augments IL-6 production under these conditions, but the mechanism is not known. We hypothesized that heat shock stimulates IL-6 production in enterocytes by increasing expression and activity of the transcription factor C/EBB. STUDY DESIGN: Cultured Caco-2 cells, a human intestinal epithelial cell line, underwent induction of the heat shock response by hyperthermia (43 degrees C for 1 hour). Other cells were kept at 37 degrees C. Cells were then treated with 0.5 ng/mL human recombinant IL-1beta for 4 hours. C/EBP-beta and delta DNA binding activity was determined by electrophoretic mobility shift assay and supershift analysis. In additional experiments, Caco-2 cells were transfected with expression plasmids for C/EBP-beta and delta, after which cells were subjected to hyperthermia and treatment with IL-1beta. RESULTS: C/EBP-beta, but not delta, protein levels and DNA binding activity were increased in Caco-2 cells expressing the heat shock response. Induction of the heat shock response augmented IL-6 production in IL-1beta-treated cells overexpressing C/EBP-beta, but not delta. CONCLUSIONS: Increased IL-6 production in IL-1beta-treated enterocytes expressing the heat shock response might be caused by upregulated expression and activity of CIEBP-beta. Because recent studies suggest that IL-6 might be an antiinflammatory cytokine and might exert protective effects in gut mucosa and enterocytes, understanding mechanisms by which the heat shock response augments IL-6 production might have important clinical implications.

The role of selective computed tomography in the diagnosis and management of suspected acute appendicitis.

The negative appendectomy rate in patients with clinically diagnosed acute appendicitis is 20 to 40 per cent. Recently CT has emerged as a powerful diagnostic tool in the evaluation of suspected appendicitis and its routine use has been advocated. The objective of this study was to evaluate the impact of selective use of abdominal CT on the negative appendectomy rate. Three hundred eight patients were enrolled in this prospective study. Abdominal CT was performed in patients with uncertain clinical signs of appendicitis. CT was not performed in patients with either a very high or a very low index of suspicion. The results were compared with a retrospective analysis of 85 consecutive patients operated by clinical diagnosis alone. One hundred twenty-seven patients had a final diagnosis of acute appendicitis. CT was performed in 198 patients (64%). The sensitivity, specificity, and accuracy of CT scans were 91, 92, and 91 per cent, respectively. Surgical management plans were altered in 54 patients after obtaining the CT results; unnecessary delay in surgical treatment or unnecessary operations were prevented in 28 and 26 patients, respectively. In addition CT detected unrelated pathologies in 23 patients. CT was not performed in patients with low index of suspicion and none were found to suffer from acute appendicitis. The negative appendectomy rate was 17 per cent (7% men and 24% women) in patients selected for surgery on the basis of very high clinical suspicion alone. Overall the negative appendectomy rate with the selective use of CT was 16 per cent, which is significantly lower than the rate achieved by diagnosing patients on clinical grounds alone (24%). CT is highly accurate in diagnosing or ruling out acute appendicitis and may substantially decrease the negative appendectomy rate as well as unnecessary delayed observation. We believe that CT should be performed routinely in women with suspected appendicitis and selectively in men.

Home oxygen therapy: adjunct or risk factor?

The use of home oxygen therapy has become increasingly commonplace and is frequently prescribed by medical specialists. In this study, we have identified a generally unexpected risk of home oxygen therapy. We performed a retrospective review of 3673 consecutive patients treated at our adult burn center over a 10-year period from 1992 to 2001. We identified 27 patients with burns directly attributable to oxygen therapy and also noted an increased incidence of these injuries over the study period. The average age of the patients was 68.1 +/- 9.2 years (range, 40-82 years). Twenty-three were using oxygen at home, three in nursing homes, and one was an inpatient in an acute care facility. Twenty-five patients (93%) were receiving oxygen therapy for the diagnosis of chronic obstructive pulmonary disease. Twenty-four patients (89%) were smoking while using oxygen, two were lighting pilot lights, and one was lighting his wife's cigarette. Four patients (15%) sustained burns greater than 10% TBSA. Seventeen patients (63%) had only partial thickness burns. Thirteen patients (48%) required admission for treatment of their burn injuries. The average length of stay for those admitted was 4.4 days. The average hospital charge for admitted patients was US dollars 8055. There were four deaths (15%), all of which were correlated only with the extent of injury. Although intuitively obvious to most health care professionals, not all patients understand that oxygen therapy and cigarettes or open flame can result in a significant injury. Although some practitioners have advocated not prescribing home oxygen for those who continue to smoke, an alternative means of reducing the incidence of this preventable complication appears warranted. Prevention efforts should focus on the counseling of patients and their caregivers as well as educating primary care physicians, nurses, and home health providers as to the dangers of oxygen use.

Sentinel lymph node biopsy in early breast cancer: the first 100 cases performed in a teaching institute.

BACKGROUND: The histologic status of axillary lymph nodes is one of the most important prognostic factors in breast cancer and influences the management of these patients. Axillary lymph node dissection was traditionally performed in all patients to obtain this information but this procedure carries a considerable rate of complications. Recently, sentinel lymph node biopsy has emerged as an accurate and minimally invasive tool for predicting the axillary nodal status and has become the standard of care in selected patients with breast cancer. OBJECTIVE: To examine the accuracy of SLN biopsies performed by surgical residents during surgical resident training. METHODS: This prospective, randomized controlled study included 100 consecutive patients with clinically early breast cancer (T1-T2, N0, M0). Lymphatic mapping was performed using radiotracers, blue dye, or both. Formal axillary lymph node dissection completed the operations in all patients. All operations were performed by surgical residents under the supervision of senior surgeons. RESULTS: The overall rate of identification of sentinel lymph nodes was 92%. The accuracy of SLN biopsy in reflecting the axillary nodal status was 96% with a false negative rate of 5.7%. CONCLUSIONS: Sentinel lymph node biopsy is an accurate method for the evaluation and staging of regional lymph nodes in breast cancer patients. A dedicated instruction program for surgical residents may increase the standard of care and lead to highly trained surgeons in the management of early breast cancer.

Regulation of APC/C (Cdh1) ubiquitin ligase in differentiation of human embryonic stem cells.

We have recently shown that Skp2 levels are high in undifferentiated human embryonic stem cells, but decline rapidly following induction of differentiation, thereby leading to accumulation of p27. Changes in Skp2 levels were found to be caused mainly by its rate of degradation. Here we show that the activity of APC/C (Cdh1), the ubiquitin ligase that targets Skp2 for degradation, increases markedly during the differentiation process of human embryonic stem cells. APC/C (Cdh1) is present but inactive in undifferentiated embryonic stem cells and becomes active in the differentiated state. The rise in APC/C (Cdh1) activity with differentiation appears to be due, at least in part, to a dramatic decline in the levels of its inhibitor Emi1. In addition, protein kinase activity also appears to contribute to the suppression of APC/C (Cdh1) activity in undifferentiated stem cells, possibly by inhibitory phosphorylation of Cdh1.

Oncogenic properties and prognostic implications of the ubiquitin ligase Skp2 in cancer.

The expression of Skp2, the ubiquitin ligase subunit that targets p27(Kip1) for degradation, is commonly overexpressed in human cancers. p27(Kip1) is a negative regulator of the cell cycle that plays an important role in tumor suppression. Loss of p27(Kip1) secondary to enhanced ubiquitin-mediated degradation results in uncontrolled proliferation and promotes tumor progression. In the present study the prognostic implications of Skp2 are reviewed and the mechanisms that regulate its expression in different human cancers. A review and analysis of the English literature was undertaken. Overexpression of Skp2 mRNA and protein levels was observed in many aggressive cancers and was commonly associated with down-regulation of p27(Kip1) levels and loss of tumor differentiation. Skp2 is an independent prognostic marker for disease-free and overall survival and may provide additional predictive information to that provided by p27(Kip1) alone. Targeting Skp2 in experimental models resulted in up-regulation of p27(Kip1) and arrested cellular proliferation. Alterations in Skp2 expression have profound effects on cancer progression and may serve as an accurate and independent prognostic marker. Thus, determination of levels of Skp2 and p27(Kip1) by readily available immunohistochemical studies may be a useful tool in the assessment of prognosis, especially in patients with intermediate disease, and may potentially assist in the planning of adjuvant therapy. Skp2 may be an attractive target for the development of novel interventional therapy.

Outcome of transanal endoscopic microsurgery and adjuvant radiotherapy in patients with T2 rectal cancer.

PURPOSE: The use of transanal endoscopic microsurgery for local excision of rectal cancer has recently gained wide acceptance as a valid and safe alternative for the surgical treatment of T1 tumors. The adequacy of such treatment for T2 tumors, however, is still controversial. This study was designed to evaluate our results with local excision of T2 cancers. METHODS: Patients with T2 cancer admitted to our hospital between 1995 and 2005 were offered surgery by transanal endoscopic microsurgery if found medically unfit or were unwilling to undergo radical surgery. Patients who were preoperatively staged as T1 tumor but were found to be pathologically T2 also were included. RESULTS: Overall, we performed 59 transanal endoscopic microsurgery operations for rectal cancers, of which 21 were for T2 cancers. In 16 (76 percent) of the T2 patients, the tumors were completely removed with clear margins by transanal endoscopic microsurgery and no additional surgery was performed, except for 2 patients who developed radiation-induced complications. Radical surgery was performed in a second operation in five patients because of involved margins and residual disease was found in two. At a median follow-up of three years, all 12 patients who received local excision and radiotherapy remained disease free, whereas a 50 percent recurrence rate was observed in patients who refused adjuvant radiotherapy. CONCLUSIONS: The results of this study support the feasibility of transanal endoscopic microsurgery for the treatment of selected patients with T2 rectal cancer. The addition of radiotherapy may decrease the rates of early local recurrence. However, at present, this treatment strategy should not be routinely considered for patients who may undergo radical procedures.

Safety of elective hand surgery following axillary lymph node dissection for breast cancer.

The development of lymphedema is the most feared complication shared by breast cancer survivors undergoing hand surgery after prior axillary lymph node dissection (ALND). Traditionally, these patients are advised to avoid any interventional procedures in the ipsilateral upper extremity. However, the appropriateness of some of these precautions was recently challenged by some surgeons claiming that elective hand operations can be safely performed in these patients. The purpose of this study was to evaluate our experience and determine the safety of elective hand operations in breast cancer survivors. The medical records of patients operated for different hand conditions after prior breast surgery and ALND at our institution between 1983 and 2002 were reviewed. The techniques and preventive measures performed, use of antibiotics, and upper extremity complications associated with the operations were analyzed. Overall, we operated on 27 patients after prior ALND performed for breast cancer. Follow-up was available for 25 patients. Four patients had pre-existing lymphedema. The surgical technique used was similar to that performed in patients without prior ALND and antibiotic prophylaxis was not given. Delayed wound healing was observed in one patient and finger joint stiffness in another. Two patients with pre-existing lymphedema developed temporary worsening of their condition. None of the patients developed new lymphedema. The results of the present study support the few previous studies, suggesting that hand surgery can be safely performed in patients with prior ALND. Based on these findings, the appropriateness of the rigorous precautions and prohibitions regarding the care and use of the ipsilateral upper extremity may need to be reconsidered.