Paget’s disease of the breast: the experience of the European institute of oncology and review of the literature

Background Paget’s disease of the breast is an uncommon presentation of breast malignancy, accounting for 1–3% of all the breast tumors and presents in different histopathologic patterns: in association with an underlying invasive or non invasive carcinoma, or without any underlying neoplasia. In the literature, different methods are used for the treatment. Mastectomy with or without axillary dissection has been considered as the standard treatment procedure for many years. Several studies have already shown that breast conservation with radiation therapy is an oncologically safe option. Regarding the axillary approach, several studies have documented the presence of positive sentinel lymph node even in Paget’s disease alone. The objective of this study was to retrospectively analyze outcome of patients affected by Paget’s breast disease and to define our institutional experience. Patients and methods Between May 1996 and February 2003, 114 patients with confirmed Paget’s disease of the breast were retrieved and underwent surgery at the European Institute of Oncology of Milan, Italy. The median age of the patients was 54 years at the time of the diagnosis. In our study, the histopathological examination of the operated specimen revealed one hundred seven patients with Paget’s disease associated with an underlying invasive or non invasive carcinoma, and seven patients without underlying carcinoma. Patients underwent either conservative breast surgery or mastectomy, with or without sentinel lymph node biopsy and/or axillary surgery. Each patient was evaluated after surgery at a multidisciplinary meeting to selecting systemic therapy. Results Seven patients had “pure” Paget’s disease of the breast and one hundred seven had the disease associated with an underlying carcinoma. As surgical techniques 71 mastectomies and 43 breast conserving surgeries have been performed. Complete axillary dissection was done in patients with clinically positive lymph node and/or sentinel lymph node biopsy positive. Sentinel lymph node biopsy was performed in nineteen patients with invasive component and five were positive and underwent axillary dissection. Eleven sentinel lymph node biopsies were done in patients with non invasive component and none of them was positive. Adjuvant systemic therapies were based on the final tumor, node and metastasis stage: thirty patients received adjuvant chemotherapy alone, fourteen received endocrine treatment alone, twenty-six patients were evaluated to receive both chemo and endocrine therapy. The median duration of follow up was 73 months and was updated in the last 6 months. Five patients developed local recurrence, one had regional recurrence, another two had loco-regional recurrences and fourteen had distant metastasis as a first event. Malignancy-related deaths were censored in the statistical analyses cancer for and due to another tumor in eleven patients. Additionally, deaths were not related to malignancy totally in thirteen patients. Conclusions Screening examination and imaging techniques are fundamental. Breast conserving surgery combined with breast irradiation for patients with invasive and non invasive breast carcinoma has become the treatment of first choice. All surgical conservative approaches should include the complete nipple–areolar complex and margins of resected specimen free of tumor. Thanks to the evolution of the conservative approach, good cosmetic result can be obtained. To be informed about the axillary lymph node status and to avoid the patient to have a second surgical approach, sentinel lymph node biopsy should be performed.     

Potentiation of the antitumor activity of 5-trifluoromethyl-2′-deoxyuridine by the use of depot forms of the parent compound

Summary 5-Trifluoromethyl-2-deoxyuridine (CF₃dUrd), an antitumor agent, is known to be short-lived in human plasma. Since its rapid elimination from the blood-stream seems to have descouraged the clinical evaluation of this drug, we explored the potential use of masked derivatives of CF₃dUrd as depot forms of the parent compound. First, we observed that the toxicity of CF₃dUrd against HeLA cells in culture was 10⁴ times greater for a 24-h treatment as compared with a 1-h treatment at identical concentrations of the drug, which suggests the importance of using a prolonged treatment period. In fact, the divided dosing of CF₃dUrd to L1210-bearing mice was markedly more effective than its single administration. 5-O-Hexanoyl-,N ³-p-butylbenzoyl-, 5-O-benzyloxymethyl-, and 3-O-benzyl-CF₃dUrd were found to be effective in maitaining the CF₃dUrd concentration in plasma. The oral doses of these agents required to achieve 50% growth inhibition (ED₅₀) in mice bearing sarcoma 180 tumors were 19, 34, 10, and 13 mg kg^–1 day^–1, respectively, whereas that of CF₃dUrd was 63 mg kg^–1 day^–1. The ED₅₀ values for these compounds were inversely correlated with the residence time of CF₃dUrd in plasma. The therapeutic indices of these compounds, calculated as the dose producing a 50% inhibition of body-weight gain (IB₅₀) divided by the ED₅₀ value (1.89, 1,21, 1.40, and 2.15, respectively), were significantly higher than that of CF₃dUrd (0.78). Consequently, these depot forms of CF₃dUrd, particularly 3-O-benzyl-CF₃dUrd, are expected to be more useful than the parent compound as antitumor agents.Abbreviations CF₃dUrd 5-trifluoromethyl-2-deoxyuridine - CF₃dUMP 5-trifluoromethyl-2-deoxyuridine-5-monophospate - S180 sarcoma 180 - L1210 L1210 leukemia - k_el elimination rate constant - T1/2 half-life time - AUC area under the curve - ILS increase in life span - TS thymidylade synthase - FdUMP 5-fluoro-2-deoxyuridine-5 monophosphate - FUra 5-fluorouracil     

Study of the Value of Combined Multiorgan Resection in Surgical Treatment of Carcinoma of the Gastric Cardia

OBJECTIVE:To determine the value of resection of combined visceral organs in surgical treatment of gastric cardiac carcinoma. METHODS:We retrospectively analyzed 217 random patients with car- cinoma of the gastric cardia who underwent a gastric cardiac resection.The patients had been treated as fol ows:186 with partial gastrectomy,31 with total gastrectomy,97 with a combined-visceral resection,of which 82 under- went a splenectomy plus partial pancreatectomy,10 with splenectomy alone and 5 with partial hepatectomy and diaphragmatectomy. RESULTS:The total patients were divided into 3 groups:128 with a gas- trectomy alone,10 with gastrectomy and splenectomy,and 82 with gastrec- tomy and splenectomy plus pancreatectomy.The operating times for these 3 groups were respectively 3.0 h,3.1 h and 3.8 h.The hospitalization times were respectively 23.8 d,31.2 d and 25.9 d.No differences in post-operative complications were found between these 3 groups.There were 92 patients who underwent a gastrectomy combined with a splenectomy and(or)the pancreatectomy,in which 92 No.10 lymph nodes were eliminated,with an average of one in each patient.Among the 125 patients not receiving a sple- nectomy but with elimination of lymph nodes,82 underwent a gastrectomy combined with partial pancreatectomy,of which 107 lymph nodes were elimi- nated for the No.11 group,with an average of 1.3 in each patient.There was a statisticaly significant difference between the 2 groups.The overal survival rates were similar in the 3 groups showing no statistical differences, but was higher in the Stage III patients with a combined resection of multi- organs.For patients in the Stage IV without resection of multi-organs,the survival rate was higher,but there was no significant difference between the 2 groups. CONCLUSION:It is difficult to determine precisely the involvement of para-tumorous organs with the eye during an operation.Combining a sple- nectomy with a pancreatectomy does not increase the post-operative compli- cations following surgical treatment for carcinoma of the gastric cardia.The combination of a splenectomy and partial pancreatectomy results in a higher survival rate and has an important significance for eliminating the lymph nodes of group 10 and 11,especially for patients in Stage III.In the applica- tion of a resection combining multi-organs,the doctor should make every effort to decrease the trauma and the complications based on the condition that the cancerous tissue is totally resected.     

Multi-Analysis of Non-Thyrogenous Masses of the Neck

OBJECTIVE To systematically analyze and summarize non-thyroge-nous masses of the neck(NTMN)by consideration of new areas,a large sample size and multiple-aspect analysis.METHODS Our research involved 3,125 NTMN cases.We summarized the proportion of various NTMN and the distribution of the neck diseases based on the new international classification.The clinical traits such as sexual proportion and age,etc,were analyzed along with the unknown pri-mary cervical metastatic carcinomas(UPCMC),multiple nodular NTMN and tubercular lymphadenitis.RESULTS There were 68 different diseases identified.Among all the NTMN,the percentage of metastatic carcinomas was 63.3%.The neck masses with a focus above the clavicle comprised 62.3% of the metastatic carcinomas whose focuses were clear.Moreover,other results almost sup-ported the “rule of 80%”.There was an obvious distribution of traits at every sub level.For example,there were 23 different diseases in level III,of which the most common was lymphoma.UPCMC made up 12.3% of all metastatic carcinomas.Multiple NTMN were composed of lymphoma,metastatic car-cinoma and tubercular lymphadenitis,etc.For tubercular lymphadenitis pa-tients,the patients without tubercular toxic symptoms comprised 77.1% of all tubercular lymphadenitis patients.CONCLUSION NTMN are complex and various,with a definite distribu-tion in each neck level.Data relating the sex ratio,UPCMC,multiple nodular NTMN and tubercular lymphadenitis to the clinical traits of NTMN will provide support for clinical applications.     

Measurement of Microcirculation of the Gastric Conduit

The standard reconstruction after esophagectomy is the formation of a gastric tube with cervical or intrathoracic esophagogastrostomy. This type of reconstruction is associated with a considerable morbidity and mortality due to anastomotic leakage of the esophagogastrostomy,. Although several etiological factors have been discussed to contribute to this clinically relevant complication ischemia is considered to be the most important one. It is evident that the formation of a gastric tube with mobilization of the stomach, ligation of the left gastric artery and short gastric arteries,     

Measurement of Microcirculation of the Gastric Conduit

IntroductionThe standard reconstruction after esophagectomy isthe formation of a gastric tube with cervical or intratho-racic esophagogastrostomy.This type of reconstructionis associated with a considerable morbidity and mortal-ity due to anastomotic leakage of the esophagogastrosto-my.Although several etiological factors have beendiscussed to contribute to this clinically relevant com-     

Does the professional image of the social worker in oncology correspond to the current challenges of the job? Apropos of a survey of patients and care professionals

Care professionals (physicians and nurses), administrative staff and hospitalised patients were interviewed to find out the necessary qualities for social workers in oncology, as well as the roles and tasks that they must fulfil. On the one hand, the results of this study show that the needs of the interested parties are indeed met by social service from an empirical perspective of psychosocial support and expert advice. On the other hand, they bring to light the fact that the current status of the social worker is hardly recognized. Confronted with new occupational challenges, the social worker should rethink his/her profession and reevaluate his/her practice. Furthermore, he/she should develop professional links intra- and extramural and participate in social research programs whose aim is to improve the rehabilitation of patients and their families.     

Do the results of the new trials change the standard treatment of metastatic renal cell cancer?

With the emergence of novel angiogenesis inhibitors, we are moving to a new era for patients with metastasized renal cell carcinoma. Since the results achieved reflect more a modification of the natural course of the disease than a cure, past achievements should not be neglected. Low-risk patients with clear cell histology, especially those with pulmonary metastasis only, should still be offered cytokine therapy. For intermediate-risk patients sunitinib is the treatment of choice. For high-risk patients, temsirolimus has to date provided the most convincing data, its availability is however limited. Data with sorafenib and sunitinib in the high-risk group are still anecdotal. The toxicity profiles of these 2 drugs are different and might particularly relate to patients with known cardiovascular co-morbidity. No sufficient data are available regarding sequential use. After cytokine failure, sorafinib is the treatment of choice. Patients should preferably be treated within clinical trials to answer unaddressed questions. It is well known that the strict entry criteria used within the clinical studies were applied very flexibly when drugs have been approved. These aspects require a careful follow-up to ascertain optimal use and to prevent misuse. Finally, the costs of prolonged treatment will be enormous, and only meaningful survival advantages will convince the health authorities to make these new treatments available for all patients.     

Influence of the Application of MRI on the T, N Staging System of Nasopharyngeal Carcinoma

OBJECTIVE To investigate the influence of utilizing MRI on the T, N staging system (the 5th edition, UICC) and on the 1992 China staging systems (Fuzhou-Guangzhou,China) by comparing the results of CT and MRI examinations of nasopharyngeal carcinoma (NPC).METHODS All 56 NPC patients, which were confirmed by histology,accepted both CT and MRI examinations. CT system scans were obtained by using an Elscient CT Twin Flash with the conventional axial scan. Three cases were examined by an additional coronary scan and 16 patients received an enhanced CT. The MR imaging was performed with a 0.5T MR system (Philips T5- II Ultra-Magnetic). The conventional axial, sagittal and coronary sections with SE sequences were obtained. The scan field was from the supra sellar cistern to the inferior border of C2. Most patients (50/56) accepted contrast enhanced MRI.RESULTS The pharyngobasilar fascia can clearly be seen on MRI but not on CT, so MRI can accurately determine the lesion in the nasopharyngeal cavity. MRI is more sensitive for evaluation of tumor involvement of soft tissue such as the Iongus colli muscle (14 cases by CT and 26 by MRI), tensor veli patalini muscle and levator veli palatini muscle (17 cases by CT and 23 by MRI), and skull-base bone marrow invasion (15 cases by CT and 42 by MRI). MRI can also demonstrate the invasion of the carotid sheath area and the enlargement of retropharyngeal lymph nodes more definitely than CT.The involvement of the trigeminal nerve can be detected on MRI, which may influence the clinical staging directly.CONCLUSION Of the 56 cases examined, 16 (28.6%) changed the staging based on UICC staging; while 33.9% (19/56) cases changed based on the 1992 China-stagin9 system. The major influence of MRI examinations on the 1992 staging was to differentiate the involvement of the carotid sheath area from metastasis of the retropharyngeal lymph nodes. There also was a significant difference in finding early invasion of the skull base.     

The Use of Chronobiotics in the Resynchronization of the Sleep–wake Cycle

Treatment of circadian rhythm disorders, whether precipitated by intrinsic factors (e.g., sleep disorders, blindness, mental disorders, aging) or by extrinsic factors (e.g., shift work, jet-lag) has led to the development of a new type of agents called ‘chronobiotics’, among which melatonin is the prototype. The term ‘chronobiotic’ defines as a substance capable of shifting the phase of the circadian time system thus re-entraining circadian rhythms. Melatonin administration synchronizes the sleep–wake cycle in blind people and in individuals suffering from delayed sleep phase syndrome or jet lag, as well in shift-workers. The effect of melatonin on sleep is probably the consequence of increasing sleep propensity (by inducing a fall in body temperature) and of a synchronizing effect on the circadian clock (chronobiotic effect). We successfully employed the timely use of three factors (melatonin treatment, exposure to light, physical exercise) to hasten the resynchronization after transmeridian flights comprising 12–13 time zones, from an average of 8–10 days to about 2 days. Daily melatonin production decreases with age, and in several pathologies, attaining its lowest values in Alzheimer’s dementia patients. About 45% of dementia patients have severe disruptions in their sleep–wakefulness cycle. Both in aged subjects having very minimal sleep disorders as well as in demented patients with a very severe disorganization of the sleep–wake cycle, melatonin treatment reduced the variability of sleep onset and restored sleep.     

Incidence of endomycoses in the autopsy material of the Berlin Charité Hospital

From 1970 to 1993, a total of 93 endomf1p4es confirmed by post-mortem examination was diagnosed in the autopsy material of the Berlin Charité, a large hospital with an average of 1,500 hospital beds and maximum medical care. These comprised 51 candidoses (54.8%), 24 aspergilloses (36.6%), five cryptococcoses (5.4%), one zygomycosis, 1 trichosporosis and one coccidioidomycoses. This corresponded to 0.7% of the 13,375 decreased persons autopsied during this period. The frequency of autopsy was 85.3%. In 3,770 cases (2,418 adults and 1,352 children), brain dissection was performed. An adequate clinical putative diagnosis was made in only six out of 28 patients (18 adults, 10 children) with histologically confirmed cerebral mycosis [11 candidoses (39.3%), 10 aspergilloses (35.7%), five cryptococcoses (17.9%), one trichosporosis and one coccidioidomycosis]. About 80% of the mycoses of the CNS thus remained undetected while the patients were alive. Against the background of the continuing reduction in the frequency of autopsy in the Federal Republic of Germany, the observations made in the present paper underscore the demand for improved efficiency of mycological in-vivo diagnoses in the hospital and laboratory.