Effet de la chimiothérapie sur la fonction testiculaire et ovarienne

Recent advances in the treatment of cancer now permits long-term remissions and can cure a large amount of young. It is now well established that infertility and premature menopause are common consequences of successeful treatment. Much is known about the fertility and sexual effects of chemotherapy and allow development of new strategies to reduce infertilty. Alkylating agents are among the most commonly used chemotherapy agents and are for the most part highly gonadotoxic. Other drugs like cisplatin, vinca alkaloids, epipodophyllotoxins and antibiotics have moderate intrinsic toxicity whereas antimetabolites exert little if any toxic effect. Nevertheless, drugs are often used in combinations which are more toxic than single agents. Gonadal toxicity is usually dose dependant. Infertility is more frequent in males than in females and prepubertal girls have better prognosis though prepubertal ovaries are profoundly affected by chemotherapy. The onset of chemotherapy-related ovarian failure is age related but the risk of premature menopause still exists in women who recover menstrual cycles after amenorrhea. Fertility is usually worse after Hodgkin’s disease and testes cancer than after other cancers. No teratognesis in the offspring was published so far after chemotherapy. Nevertheless, men and women should be expressly discouraged from being party to a conception while they are receiving cancer therapy. Adults surviving to cancer should wait at least two years after completion of therapy before attempting parenthood.     

Postoperative adjuvant irradiation: effects on tranverse rectus abdominis muscle flap breast reconstruction

The use of postoperative irradiation following oncologic breast surgery is dictated by tumor pathology, margins, and lymph node involvement. Although irradiation negatively influences implant reconstruction, it is less clear what effect it has on autogenous tissue. This study evaluated the effect of postoperative irradiation on transverse rectus abdominis muscle (TRAM) flap breast reconstruction. A retrospective review was performed on all patients undergoing immediate TRAM flap breast reconstruction followed by postoperative irradiation between 1988 and 1998. Forty-one patients with a median age of 48 years received an average of 50.99 Gy of fractionated irradiation within 6 months after breast reconstruction. All except two received adjuvant chemotherapy. Data were obtained from personal communication, physical examination, chart, and photographic review. The minimum follow-up time was 1 year, with an average of 3 years, after completion of radiation therapy. Nine patients received pedicled TRAM flaps and 32 received reconstruction with microvascular transfer. Fourteen patients had bilateral reconstruction, but irradiation was administered unilaterally to the breast with the higher risk of local recurrence. The remaining 27 patients had unilateral reconstruction. All patients were examined at least 1 year after radiotherapy. No flap loss occurred, but 10 patients (24 percent) required an additional flap to correct flap contracture. Nine patients (22 percent) maintained a normal breast volume. Hyperpigmentation occurred in 37 percent of the patients, and 56 percent were noted to have a firm reconstruction. Palpable fat necrosis was noted in 34 percent of the flaps and loss of symmetry in 78 percent. Because the numbers were small, there was no statistical difference between the pedicled and free TRAM group. However, as a group, the findings were statistically significant when compared with 1,443 nonirradiated TRAM patients. Despite the success of flap transfer, unpredictable volume, contour, and symmetry loss make it difficult to achieve consistent results using immediate TRAM breast reconstruction with postoperative irradiation. TRAM flap reconstruction in this setting should be approached cautiously, and delayed reconstruction in selected patients should be considered. Patients should be aware that multiple revisions and, possibly, additional flaps are necessary to correct the progressive deformity from radiation therapy.     

The outcome of long-term follow-up after palatoplasty

The speech outcome was studied retrospectively in 140 cleft-palate patients who underwent push-back palatoplasty. Velopharyngeal function and articulation disorders were evaluated serially at 4, 7, 10, and more than 10 years of age. On comparison of velopharyngeal function between 4 years of age and the most recent review (>10 years), it was unchanged in 90 patients (64.3 percent), whereas it showed deterioration in 14 patients and showed improvement in 8 patients. The other 28 patients underwent pharyngeal flap surgery; this group also included patients with functional deterioration. Changes of velopharyngeal function often occurred between 4 and 7 years of age but sometimes occurred after 10 years of age. Articulation disorders were observed in 49 subjects (35.0 percent) at 4 years of age. Many of the patients with glottal stop showed improvement from 4 to 7 years of age. Palatalized articulation showed less improvement than glottal stop (p < 0.01). The number of patients with articulation disorders decreased significantly between 4 years of age and the most recent review (p < 0.001). These findings suggest that speech does not become stable before 10 years of age and that patients with cleft palate should be carefully followed until they are beyond this age.     

Carcinoma In Situ of the Uterine Cervix—A Review of Some Present Clinical Problems

The vaginal smear reveals a spectrum of borderline lesions of the uterine cervix. This spectrum is the source of new clinical problems involving both the recognition and treatment of these various entities. A review of the literature of the past decade indicates that vaginal smears should be obtained regularly every year or two in all women beginning at the onset of sexual activity, but the initial smear may be falsely negative in 10 to 30 percent of cases. When patients have abnormal smears, the precise diagnosis can be established more accurately by cold-knife conization than by multiple punch biopsy.While hysterectomy has been considered “definitive treatment,” late recurrence in the vagina occurs in 1.24 percent of patients so treated. A compilation of 1,100 patients with carcinoma in situ of the cervix treated by conization and follow-up smear reveals that in over 90 percent the disease was controlled by the cone alone, and the remainder by repeat cone or hysterectomy.Precise definition is required in treatment decisions concerning micro-invasive lesions, but these may be well treated by non-radical measures. In almost 500 patients so treated, no death occurred from therapy or tumor metastasis.When carcinoma in situ is found during pregnancy, a coexisting invasive carcinoma must be excluded by appropriate conization or punch biopsy and definitive therapy completed after vaginal delivery.     

Prognosis of children with malignant pheochromocytoma. Report of 2 cases and review of the literature

Malignant pheochromocytomas are rare in childhood and the prognosis of children with this tumor is not well known. We present 2 pediatric observations of malignant pelvic pheochromocytoma. Symptoms in both cases were headache and hypertension. The tumor invaded the sacral bone. Angiogram helped to localize the tumor and metastases, and allowed preoperative embolization of the tumor in 1 case. The first child underwent incomplete surgical resection, (131)I-MIBG therapy and radiotherapy, and is still alive 2 years after diagnosis. The second child died from metastatic invasion a few weeks after discovery of the tumor. We reviewed previous reports of children with malignant pheochromocytomas (30 cases). Primary tumor was extraadrenal in 50% of cases. The 3-year survival rate was 73 +/- 9% (mean +/- SD). Apart from surgical resection, no particular treatment appeared to be more effective than others in reducing mortality.     

Surgical Treatment of Pulmonary Metastases from Testicular Tumours

Isolated pulmonary metastases from testicular tumours were treated by surgery in nine patients. Six are alive and well with no clinical evidence of recurrence. Three of the survivors were operated on more than 10 years ago. Surgical treatment should be considered in such patients, particularly as the metastases are often solitary and may be better differentiated histologically than the primary tumour. Mortality and morbidity rates after thoracotomy are minimal.     

Treatment of Malignant Pheochromocytoma

Pheochromocytoma is a tumor derived from chromaffin tissue, which secretes catecholamines. Today, about 90 percent of patients with this tumor are cured by surgical procedures. In 8 to 15 percent of patients with this tumor there is unresectable, recurrent or metastatic disease, which causes significant morbidity and mortality. The natural history of metastatic disease includes long-term survivors; many, however, die early of disseminated disease. The most common site of metastatic lesions is the skeleton. Palliation for these lesions can often be achieved with the use of radiation therapy. Other sites are, in general, less responsive to radiation therapy. Chemotherapy has been used in combination with radiation therapy, but the results generally have been disappointing. Chemotherapy with doxorubicin hydrochloride and cyclophosphamide in combination with radiation therapy has provided good palliation for skeletal disease for about five months, when disease progression was again noted. Further information is needed concerning the optimal chemotherapeutic treatment of this unusual tumor.     

The biological relevance of gastric neuroendocrine tumors.

Gastric neuroendocrine tumors were originally thought to have a low incidence (three percent). Since endoscopic diagnostic procedures have become clinical routine, they are now found more frequently (relative incidence up to 41 percent). In recent years, classifications have been developed that attempt to consider the biological relevance of these tumors. Four types of gastric neuroendocrine tumor may be distinguished: Type 1 gastric neuroendocrine tumor is most common. It is associated with chronic atrophic fundus gastritis, hypergastrinemia and often with pernicious anemia. Usually it is multicentric and smaller than one cm, does not produce any symptoms and has an excellent prognosis. Type 2 gastric neuroendocrine tumor is second in frequency. It has no association with other diseases, is solitary and has no predilection for a particular localization. It may be larger than 1 cm, produce a carcinoid syndrome or Zollinger-Ellison syndrome and have a metastasis rate of up to 30 percent. Type 3 gastric neuroendocrine tumor is rare and always associated with Zollinger-Ellison syndrome and multiple endocrine neoplasia type I. It occurs as multiple lesions in the gastric body fundus and has a lower metastatic rate than type 2 gastric neuroendocrine tumor. Type 4 gastric neuroendocrine tumor corresponds to a small-cell carcinoma.     

Deaths From Bites and Stings of Venomous Animals

Data abstracted from 34 death certificates indicate that the three venomous animal groups most often responsible for human deaths in California from 1960 through 1976 were Hymenoptera (bees, wasps, ants and the like) (56 percent), snakes (35 percent) and spiders (6 percent). An average incidence of 2.0 deaths per year occurred during these 17 years, or an average death rate of 0.01 per 100,000 population per year. Nearly three times more males than females died of venomous animal bites and stings. Half of the deaths from venomous snake bites occurred in children younger than 5 years of age. Susceptible persons 40 years or older appeared to be particularly vulnerable to hymenopterous insect stings and often quickly died of anaphylaxis. Fatal encounters with venomous animals occurred more often around the home than at places of employment or during recreational activities. Deaths resulting from spider bites are rare in California but many bites are reported. Medical practitioners are urged to seek professional assistance in identifying offending animals causing human discomfort and to use these animals'' scientific names on death certificates and in journal articles.     

Chemotherapy of lung cancer

The potential for substantial improvement in the outcome of patients with carcinoma of the lung seem most likely to develop in the field of chemotherapy. In the past decade, striking advances in the management of small cell carcinoma have yielded response rates and longer survival. While the greatest improvement can be predicted for patients whose disease is limited in extent, combination chemotherapy and combined modality therapy generally are effective in causing tumor regression for the majority of patients. About 20 percent of patients with disease limited to the thorax and lymph nodes will survive two years. In non-small cell tumors, response rates are improved with intensive drug combinations, although the majority of cases are unresponsive to present regimens. Careful staging and evaluation of patients indicates that patients with good performance status and limited extent of disease appear to obtain the most benefit from intensive treatment. The considerable morbidity of some treatments often influences the choice for or against chemotherapy in patients with non-small cell carcinomas. For the future, problems of particular interest will be in investigation of factors-biologic, pharmacokinetic, immunologic-that are related to the failure to cure small cell carcinoma, the most therapeutically responsive pulmonary tumor. Additionally, in the non-small cell tumors, more effective therapies as well as clarification of the basis for relative resistance to cytotoxic agents are areas for intensive investigation.     

Intraocular tumours

Intraocular tumours may be benign or malignant. The latter are more numerous, and endanger not only vision but life as well. Two of them deserve special attention: melanoma malignum oculi in adults and retinoblastoma in children. Melanoma malignum may arise from all three areas of the uvea: the iris, the ciliary body and the choroid. The more malignant growths are those which are situated closer to the posterior pole. Histologically the epitheloid cell-type of melanoma is more malignant than those containing only spindle cells. Their treatment depends on the size: in the case of large tumours enucleation is required, while for the smaller ones, radiation therapy can be applied. Retinoblastoma is most common in children of 1-2 years of age. It has familial and sporadic forms. Sixty-seven percent of the inherited-type cases are bilateral. An early symptom in small children is strabismus. A white tissue mass growing into the vitreous is seen on the fundus. A diagnostic feature that can be detected by ultrasound examination is calcification. The tumour may also present intracranially, therefore CT of the skull should be performed in each case. Histologically the tumour contains malignant neuroepithelial cells, which may form a rosette. In the case of large tumours the treatment is enucleation; in bilateral processes the bulbus with the larger mass is removed and the other eye is treated with radiation therapy. In both cases chemotherapy is used according to a prescribed schedule. Metastases to the eye occur most frequently from carcinomas of the breast, lungs or gastrointestinal tract. These are treated with radiotherapy, chemotherapy and hormone therapy. Primary intraocular lymphoma often occurs bilaterally, and may be accompanied by primary lymphoma of the central nervous system (CNS). Some benign tumours are found by chance on routine eye examinations, others due to subjective and objective symptoms.     

Psychiatric patients' experiences in complementary and alternative medicine (CAM), and in religious support--a pilot study

In the Psychiatric Hospital "Vrapce" an investigation on a 200 patient sample was carried out in the year 2000. The purpose of the investigation was to analyze the examinees' experiences of complementary and alternative medicine (CAM) and religious support. 35.5% of the examinees had had previous experiences of CAM and religious support. The examinees born in towns used CAM methods and religious support significantly more often. The schizophrenic patients used CAM methods and religious support significantly more frequently than the patients with affective and anxiety disorders. Non-significantly more often CAM methods and religious support were utilized by women, examinees between 21 and 30 years of age, persons who graduated from junior college, those who live in cohabitation and patients of Islamic religion. Patients consulted priests most often. Significantly more often patients did not pay for the CAM treatments and religious support and non-significantly more often patients considered CAM therapy and religious support to be successful. Non-significantly more often patients consulted CAM practitioners and religious practitioners without being previously advised by their relatives or friends. Relatives ofthe patients advised them to consult CAM practitioners and religious practitioners significantly more often than the friends of the patients did. Considering the possible missed benefits and harm effects of CAM treatment as well as of the interaction between utilization of CAM methods/religious support and conventional treatment, this problem should be given full attention. Further investigations are required.     

Is the umbilicus truly midline? Clinical and medicolegal implications

A common misconception is that the umbilicus is a midline structure. To date, an anatomical survey examining whether the umbilicus is located at the midline has not been reported. This study measured the position of the umbilicus among 136 subjects, in two separate experiments. The results demonstrated that the umbilicus was not at the midline for nearly 100 percent of subjects and was more than 2 percent from the midline for more than 50 percent of subjects. This finding is of great importance for patient counseling in preoperative and postoperative settings. Because the discerning eye has repeatedly been demonstrated to be able to detect smaller asymmetries, these findings are significant and should be discussed with patients undergoing cosmetic abdominoplasty or reconstructive procedures, for preoperative informed consent. Education and preoperative demonstration can help prevent medicolegal ramifications. The umbilicus is rarely midline and, when critically analyzed, is located lateral to the midline axis more often than not.     

Complications of systemic corticosteroid therapy for problematic hemangioma.

Systemic corticosteroid therapy has been used to treat hemangiomas for 30 years; yet, there are no studies of possible complications. We reviewed the database of the Vascular Anomalies Center at the Boston Children's Hospital and gathered information on short- and long-term side effects in children who were given systemic corticosteroids for problematic hemangiomas. In addition, a questionnaire regarding early and late consequences was sent to the families of children who were treated with corticosteroids from 1983 to 1997. Of 300 patients with hemangiomas, 80 children were identified as having received a full course of systemic corticosteroids for problematic tumors. Complete data were collected on 62 of these children. The response rate to the questionnaire was 78 percent (n = 62 of 80). The initial dose of corticosteroid varied from 2 to 3 mg/kg/ day. Duration of therapy ranged from 2 to 21 months (mean, 7.9 months; median, 6.5 months). The follow-up interval from the cessation of therapy ranged from 6 months to 15 years (mean, 4 years; median, 3 years). Short-term complications included cushingoid facies (n = 44; 71 percent), personality changes (n = 18; 29 percent), gastric irritation (n = 13; 21 percent), fungal (oral or perineal) infection (n = 4; 6 percent), and diminished gain of height (n = 22; 35 percent) and weight (n = 26; 42 percent). A total of 91 percent of children who had diminished gain of height (n = 20) returned to their pretreatment growth curve for height by 24 months of age. One child, who was treated at another institution with a dose of 20 mg/kg/day for 6.5 months that was slowly tapered over 18 months, was petite 6 years after ending therapy. Another child treated with an initial dose of 2 mg/kg/day for 5 months was smaller than predicted at the age of 6 years, but she was born prematurely and was on ventilatory support for respiratory distress. Three children treated with the standard dose and duration were at a low percentile for weight 4, 5, and 10 years after the cessation of therapy. Statistical analysis showed a correlation between diminished gain of height with duration of therapy and age at initiation of treatment. One child had corticosteroid myopathy that resolved with cessation of therapy. We found no evidence for immunologic suppression, i.e., there was no increase in the number of bacterial infections during corticosteroid administration. In conclusion, systemic corticosteroids can be safely given to treat endangering hemangiomas in infants at doses of 2 to 3 mg/kg/day, which are slowly tapered and stopped before the age of 1 year. Short-term side effects were minor and transient, and no serious long-term complications occurred.     

Immunosuppressive Therapy in Patients with Aplastic Anemia: A Single-Center Retrospective Study

BackgroundAplastic anemia (AA) is a rare disease in which hematopoietic stem cells are severely diminished resulting in hypocellular bone marrow and pancytopenia. Etiology of AA includes auto immunity, toxins, infection, ionizing radiation, drugs and rare genetic disorders, but in the majority of cases no cause can be identified. In the present study we assessed response rate, survival, relapse and clonal evolution in patients with AA treated with immunosuppressive therapy.MethodsPatients with AA who received immunosuppressive therapy between May 1998 and September 2013 were included in this study. Patients with non-severe AA (NSAA) were treated with cyclosporine (CsA) and danazol while patients with severe AA (SAA) as well as patients with NSAA who progressed to SAA after beginning of the treatment, were candidates for receiving antithymocyte globulin in addition to CsA and danazol.ResultsAmong the 63 studied patients, 29 (46%) had NSAA and 34 (54%) had SAA. Three months after treatment, overall response was 58.6% in NSAA and 12.9% in patients with SAA. Survival of all patients at 5, 10 and 15 years were 73%, 55% and 49%, respectively. Survival rates were significantly higher in patients with NSAA compared to patients with SAA as well as in patients who responded at 6 months compared to non-responders. The relapse risk was 39.7% at 10 years. Relapse occurred in patients who discontinued the therapy more than those who continued taking CsA (p value<0.01). The risk of clonal evolution was 9.9% at 10 years and 22.8% at 15 years after treatment.ConclusionThis long-term retrospective study indicated that immunosuppressive therapy should be recommended to patients with AA. Also, our experience indicated that immunosuppressive therapy should not be discontinued after response to therapy in patients with both NSAA and SAA due to high risk of relapse. Low dose of CsA should be continued indefinitely.     

Modeling evolutionary dynamics of epigenetic mutations in hierarchically organized tumors

The cancer stem cell (CSC) concept is a highly debated topic in cancer research. While experimental evidence in favor of the cancer stem cell theory is apparently abundant, the results are often criticized as being difficult to interpret. An important reason for this is that most experimental data that support this model rely on transplantation studies. In this study we use a novel cellular Potts model to elucidate the dynamics of established malignancies that are driven by a small subset of CSCs. Our results demonstrate that epigenetic mutations that occur during mitosis display highly altered dynamics in CSC-driven malignancies compared to a classical, non-hierarchical model of growth. In particular, the heterogeneity observed in CSC-driven tumors is considerably higher. We speculate that this feature could be used in combination with epigenetic (methylation) sequencing studies of human malignancies to prove or refute the CSC hypothesis in established tumors without the need for transplantation. Moreover our tumor growth simulations indicate that CSC-driven tumors display evolutionary features that can be considered beneficial during tumor progression. Besides an increased heterogeneity they also exhibit properties that allow the escape of clones from local fitness peaks. This leads to more aggressive phenotypes in the long run and makes the neoplasm more adaptable to stringent selective forces such as cancer treatment. Indeed when therapy is applied the clone landscape of the regrown tumor is more aggressive with respect to the primary tumor, whereas the classical model demonstrated similar patterns before and after therapy. Understanding these often counter-intuitive fundamental properties of (non-)hierarchically organized malignancies is a crucial step in validating the CSC concept as well as providing insight into the therapeutical consequences of this model.     

Women who wish breast reconstruction: characteristics,fears, and hopes

The aims of the present study were to identify the characteristics of a consecutive series of women with newly diagnosed breast cancer and to evaluate the perceived benefits and disadvantages of breast reconstruction. A consecutive series of 125 women completed the Breast Reconstruction Questionnaire, the Hospital Anxiety and Depression Scale, and the Eysenck Personality Questionnaire. The median age was 48 years (range, 28 to 75 years). A total of 49.6 percent (n = 62) indicated that, if it were possible, they would like breast reconstruction. Logistic regression (simultaneous entry) revealed that younger women (p = 0.0001) and more depressed women (p = 0.026) were more likely to wish reconstruction. Marital status, tumor size, extroversion, neuroticism, and tough-mindedness did not independently predict the desire for reconstruction. If given a choice of reconstruction at 3 months or 6 months after mastectomy, of the women who wished reconstruction, 74 percent would prefer it at 3 months. Of the women who wished reconstruction and expressed a preference, 63 percent were afraid reconstruction might mask recurrence, 39 percent were afraid that reconstruction might cause the cancer to return, and 89 percent thought they would be concerned with their appearance after the operation. Positively, 94 percent considered that reconstruction would be beneficial in terms of their self-esteem, 86 percent indicated that reconstruction would give greater freedom to wear any clothing, and 86 percent thought that the cosmetic appearance of breast reconstruction was better than that of a prosthesis. Concerns about recurrence were common. A better understanding of the concerns of women with regard to reconstruction would allow more informed preoperative discussion.     

Local therapy of cancer with free IL-2

This is a position paper about the therapeutic effects of locally applied free IL-2 in the treatment of cancer. Local therapy: IL-2 therapy of cancer was originally introduced as a systemic therapy. This therapy led to about 20% objective responses. Systemic therapy however was very toxic due to the vascular leakage syndrome. Nevertheless, this treatment was a break-through in cancer immunotherapy and stimulated some interesting questions: Supposing that the mechanism of IL-2 treatment is both proliferation and tumoricidal activity of the tumor infiltrating cells, then locally applied IL-2 should result in a much higher local IL-2 concentration than systemic IL-2 application. Consequently a greater beneficial effect could be expected after local IL-2 application (peritumoral = juxtatumoral, intratumoral, intra-arterial, intracavitary, or intratracheal = inhalation). Free IL-2: Many groups have tried to prepare a more effective IL-2 formulation than free IL-2. Examples are slow release systems, insertion of the IL-2 gene into a tumor cell causing prolonged IL-2 release. However, logistically free IL-2 is much easier to apply; hence we concentrated in this review and in most of our experiments on the use of free IL-2. Local therapy with free IL-2 may be effective against transplanted tumors in experimental animals, and against various spontaneous carcinomas, sarcomas, and melanoma in veterinary and human cancer patients. It may induce rejection of very large, metastasized tumor loads, for instance advanced clinical tumors. The effects of even a single IL-2 application may be impressive. Not each tumor or tumor type is sensitive to local IL-2 application. For instance transplanted EL4 lymphoma or TLX9 lymphoma were not sensitive in our hands. Also the extent of sensitivity differs: In Bovine Ocular Squamous Cell Carcinoma (BOSCC) often a complete regression is obtained, whereas with the Bovine Vulval Papilloma and Carcinoma Complex (BVPCC) mainly stable disease is attained. Analysis of the results of local IL-2 therapy in 288 cases of cancer in human patients shows that there were 27% Complete Regressions (CR), 23% Partial Regressions (PR), 18% Stable Disease (SD), and 32% Progressive Disease (PD). In all tumors analyzed, local IL-2 therapy was more effective than systemic IL-2 treatment. Intratumoral IL-2 applications are more effective than peritumoral application or application at a distant site. Tumor regression induced by intratumoral IL-2 application may be a fast process (requiring about a week) in the case of a highly vascular tumor since IL-2 induces vascular leakage/edema and consequently massive tumor necrosis. The latter then stimulates an immune response. In less vascular tumors or less vascular tumor sites, regression may require 9–20 months; this regression is mainly caused by a cytotoxic leukocyte reaction. Hence the disadvantageous vascular leakage syndrome complicating systemic treatment is however advantageous in local treatment, since local edema may initiate tumor necrosis. Thus the therapeutic effect of local IL-2 treatment is not primarily based on tumor immunity, but tumor immunity seems to be useful as a secondary component of the IL-2 induced local processes. If local IL-2 is combined with surgery, radiotherapy or local chemotherapy the therapeutic effect is usually greater than with either therapy alone. Hence local free IL-2 application can be recommended as an addition to standard treatment protocols. Local treatment with free IL-2 is straightforward and can readily be applied even during surgical interventions. Local IL-2 treatment is usually without serious side effects and besides minor complaints it is generally well supported. Only small quantities of IL-2 are required. Hence the therapy is relatively cheap. A single IL-2 application of 4.5 million U IL-2 costs about 70 Euros. Thus combined local treatment may offer an alternative in those circumstances when more expensive forms of treatment are not available, for instance in resource poor countries.     

Complications of postmastectomy breast reconstructions in smokers, ex-smokers, and nonsmokers

Smoking results in impaired wound healing and poor surgical results. In this retrospective study, we compared outcomes in 155 smokers, 76 ex-smokers, and 517 nonsmokers who received postmastectomy breast reconstructions during a 10-year period. Ex-smokers were defined as those who had quit smoking at least 3 weeks before surgery. Transverse rectus abdominis musculocutaneous (TRAM) flap surgery was performed significantly less often in smokers (24.5 percent) than in ex-smokers (30.3 percent) or nonsmokers (39.1 percent) (p < 0.001). Tissue expansion followed by implant was performed in 112 smokers (72.3 percent), 50 (65.8 percent) ex-smokers, and 304 nonsmokers (58.8 percent) (p = 0.002). The overall complication rate in smokers was 39.4 percent, compared with 25 percent in ex-smokers and 25.9 percent in nonsmokers, which is statistically significant (p = 0.002). Mastectomy flap necrosis developed in 12 smokers (7.7 percent), 2 ex-smokers (2.6 percent), and 8 nonsmokers (1.5 percent) (p < 0.001). Among patients receiving TR4AM flaps, fat necrosis developed in 10 smokers (26.3 percent), 2 ex-smokers (8.7 percent), and 17 nonsmokers (8.4 percent). Abdominal wall necrosis was more common in smokers (7.9 percent) than in ex-smokers (4.3 percent) or nonsmokers (1.0 percent). In this large series, tissue expansion was performed more often in smokers than was autogenous reconstruction. Complications were significantly more frequent in smokers. Mastectomy flap necrosis was significantly more frequent in smokers, regardless of the type of reconstruction. Breast reconstruction should be done with caution in smokers. Ex-smokers had complication rates similar to those of nonsmokers. Smokers undergoing reconstruction should be strongly urged to stop smoking at least 3 weeks before their surgery.