Role of surgery in patients with synchronous metastatic breast cancer: Is there a need for axillary lymph node removal?

INTRODUCTION: About 6% of women with breast cancer present with synchronous metastases. Treatment remains palliative in international recommendations but the impact of loco-regional surgery remains controversial. OBJECTIVE: We conducted a multicentre, cohort study to evaluate the impact of axillary lymph node (ALN) surgery on overall survival in stage IV breast cancer at diagnosis. METHODS: Patients presenting with breast cancer and synchronous metastases between 2005 and 2014 were included. Follow up was conducted up to 1st June 2018. The only exclusion criterion was a history of previous malignancies. Breast surgery was defined as lumpectomy or mastectomy. Axillary surgery included full ALN dissection, and sentinel lymph node biopsy (SLNB). If the SLN was invaded on the frozen section, full axillary dissection was performed. RESULTS: 152 patients were included. 71 women had no surgery, 81 had primary site surgery of which 64 (79%) had breast and axillary surgery and 17 (21%) breast surgery only. 5-year overall survival was 59.8% (95% CI=[49.5; 69.5]) for women with breast and axillary surgery, 23.5% (95% CI=[15.6; 33]) for women with breast surgery only and 9.8% (95% CI=[4.7; 17.5]) for women without any surgery, p < 0.001. Combined with breast surgery, axillary surgery significantly added a mean of 33 months to patient overall survival. CONCLUSION: ALN surgery combined with breast surgery in metastatic breast cancer significantly increased overall survival. Thus surgical indications should not differ from those in women with breast cancer without metastases.

Survival impact of primary site surgery on metastatic breast cancer patients at diagnosis.

BACKGROUND: Stage IV breast cancer was considered to be an incurable disease. Primary site surgery used to be reserved to control local complications. In the present study, we compared the survival of women who received therapeutic breast surgery for stage IV breast cancer at initial diagnosis to the survival of those who did not. METHODS: Two French hospitals databases were retrospectively screened from 2005 to 2012. We identified all women with metastatic breast cancer at diagnosis. Patients' data were obtained by a review of their medical history. Data were analyzed according the four breast cancer subtypes (luminal A, luminal B, her 2 and triple negative). RESULTS: One hundred thirty nine women were included, of whom 69 had primary site surgery. TNM stage and phenotypes of breast cancer were comparable in the two groups but operated women were younger than women who did not (p<0.0001). Average follow-up was 31±23.3 months [1-97]. Through logistic regression, we observed that tumor resection decreased death hazard ratio vs no surgery: HR 0.33, 95% CI [0.16-0.66] p=0.001. In the surgery group, there was no survival difference if women received chemotherapy (p=0.23). There were more patients with only one metastatic site in the surgery group (p=0.002) and they had been more treated with systemic therapy. When we compared tumor phenotypes individually, surgery increased survival on luminal A breast cancer patients (p<.0001). CONCLUSION: Women with luminal A breast cancer and synchronous metastasis seemed to benefit from surgery. The development of a national reporting system or registers for outcomes would facilitate the investigation of the disease across a multitude of aspects of stage IV breast cancer.

[Benign pulmonary metastases from a leiomyoma]. / Métastases pulmonaires bénignes d'un léiomyome.

INTRODUCTION: Benign metastasizing leiomyoma (BML) is a rare cause of pulmonary nodules. They can occur in women of reproductive age who have undergone hysterectomy for uterine leiomyoma. OBSERVATION: We report the case of a 46-year-old women, who was incidentally found to have bilateral pulmonary cavitating nodules. Pathology exam was consistent with BML. CONCLUSION: Although BML is a rare cause of pulmonary nodules, it should be considered as one of the possibilities especially in young women with a history of hysterectomy for leiomyoma.

Pathological prognostic factors of invasive breast carcinoma in ultrasound-guided large core biopsies-correlation with subsequent surgical excisions.

Core biopsy is currently used as the initial diagnostic procedure in breast cancer. Prognostic information is required before decisions on subsequent therapy are possible. The aim of this study was to compare prognostic data observed in ultrasound-guided core biopsies and in surgical specimens. We conducted a retrospective study of a mean of 1.2 biopsies from a total of 110 consecutive malignant breast masses. Histological tumour type and grade, presence of a ductal carcinoma in situ (DCIS) component and hormonal status were evaluated. Our results showed excellent sensitivity (100%) of core biopsy for the diagnosis of breast cancer and for the assessment of tumour type (concordance of 73.6%). We also reached a reasonable level of agreement between core biopsy and surgical excision specimens for histological grading (73.1%). Underestimation of grading on core biopsy was due predominantly to underscoring of mitotic counts (32.3%). The presence of DCIS associated with infiltrative carcinomas was widely underestimated in biopsy specimens. There were good levels of agreement for oestrogen receptors and for progesterone receptors: 90.3% and 89.3%, respectively. Diagnoses were made on the basis of a small number of ultrasound-guided core biopsy specimens taken from breast masses. Grade and hormonal status were reliably evaluated.

Quinone reductase activity in the first trimester placenta: effect of cigarette smoking and polycyclic aromatic hydrocarbons.

Quinone reductase (QR) is considered a major protective enzyme against cancer in the organism. In this study, the activity of QR was measured in first trimester placental tissue using colorimetric techniques. There were no significant differences between the mean enzyme activity of women who smoked more than 20 cigarettes per day during pregnancy and of nonsmokers (0.50 +/- 0.09 compared with 0.51 +/- 0.15 mumol/mg protein/10 min, respectively). Among the polycyclic aromatic hydrocarbons (PAH) studied, dimethyl benzanthracene (DMBA) increased QR activity in a dose-dependent manner in the first trimester placental explants at the 10- to 100-microM range after 6 h of incubation (440% increase) with the highest concentration. The effect of other PAH of different potency added at 50-microM concentrations showed that benz(a)anthracene (BA), dibenzo(a,h)anthracene (DBHA), dibenzo(a,c)anthracene (DBCA), or chrysene (CH) caused a significant 2- to 3-fold increase in the enzymatic activity after 6 h of incubation. At 24 h 50-microM DBCA effect was also stimulatory, while the 10-microM DMBA effect almost reached statistical significance. However, no differences were encountered in the response of placental tissues to PAH between cigarette smokers and nonsmokers at 6 and 24 h. The present data indicate that placental QR activity is increased by exposure to PAH in vitro, but it does not appear to be affected by in vivo exposure to cigarette smoking. Thus, the early placenta appears to have a significant potential to inactivate carcinogens/mutagens locally, thereby limiting their transfer to the embryo.

[Essential thrombocythemia and pregnancy. A review of the literature]. / Thrombocytémie essentielle et grossesse. Etude de la littérature.

Essential thrombocythemia is a myeloproliferative syndrome confined to platelet production. Once the character of a megakaryocyte abnormality has been confirmed, the prognosis is good depending on thrombotic and haemorrhagic complications. The authors report the outcome of a pregnancy in a patient who had essential thrombocythemia treated by anti-aggregating drugs from the 10th week of amenorrhoea. In the previous history there were two obstetrical complications of the illness (one spontaneous abortion and one intrauterine fetal death). A caesarean section carried out after 32 weeks of amenorrhoea led to the birth of a baby weighing 1890 gm. Only a few cases have been reported in the literature. There is always a drop in the number of platelets in pregnancy. After delivery the number of platelets becomes pathological within a few weeks. The prognosis for the fetus is linked to the risk of placental thrombosis, not to the numbers of platelets. The problem lies in the choice of indications for the use of acetylsalicylic acid in low dosage, particularly since cases of pregnancy taken to term without any specific type of treatment have been reported.

[Subclinical breast lesions manifested by microcalcifications. Historadiologic correlations. Apropos of a retrospective series of 127 cases]. / Lésions mammaires infracliniques révélées par des microcalcifications. Corrélations historadiologiques. A propos d'une série rétrospective de 127 cas.

OBJECTIVE: To ascertain the correlations between the histology and radiology of microcalcifications revealing subclinical carcinoma. TYPE OF STUDY: A retrospective series of 127 exereses of microcalcifications of the breast identified on preoperative radiographs. RESULTS: Histology revealed 43 (33.9%) carcinomas including 72% in situ cancers and 17 borderline lesions (13.3%) for a total of 47.2% cancerous or high risk lesions. 56% of the malignant lesions were diagnosed by mammography during screening. In most cases, conservative treatment was carried out. Axillary node invasion was not found in any of the cases of in situ carcinoma. 16% of the invasive carcinomas were pN+. Re-examination of the radiographs revealed that there was a correlation between the histology and the radiographic findings. 68% (n = 59) of the localizations with less than 30 microcalcifications were benign and 73% (n = 30) were malignant. The triangular appearance of the microcalcification localizations rwas in favour of a carcinoma in 88% (n = 22) cases. The polymorphism microcalcifications within a given localization was suggestive of malignancy in 69% (n = 25%). On the basis of data in the literature, different criteria can be used to provide precise information preoperatively.

[The presence of an ovarian granulocytic sarcoma concurrent with a type M2 acute myeloblastic leukemia: a case]. / Localisation ovarienne d'un sarcome granulocytaire contemporain d'une leucémie aiguë myéloblastique type M2: un cas.

The authors report a case of granulosa cell tumor principally located in the ovary associated with M2 type acute myeloblastic leukemia (AML) in a trisomy 22 patients. Surgery and chemotherapy were combined with a bone marrow allograft. Frequency of granulosa cell tumor is 8 percent or less of AML cases. Diagnosis is particularly difficult when haematologic expression occurs late in the disease course. An immunohistochemical work-up is required in these cases. Aetiopathogenesis is discussed. Treatment relies essentially on chemotherapy. The prognostic is variable according to different case reports in the literature.

[Association of Takayasu's arteritis, pregnancy and Still's disease]. / A propos de l'association artérite de Takayasu, grossesse et maladie de Still.

Two pregnant patients presented with Takayasu's disease predominating in the major branches of the aorta. There was no extention below the diaphragm and no complications. One of the patients had Still's disease which is a predominantly cutaneous form without chronic arthritis. Both pregnancies were uneventful excepting dysgravidia in one case. Two eutrophic infants were born at term. The risk of Takayasu's arteritis associated with pregnancy, as reported in the literature, is mainly due to the consequences of arterial hypertension with pre-eclampsia (60%), heart failure and cerebral vascular events (5%). The major fetal risk is in utero death (2 to 5%), but intra-uterine growth retardation is more frequent (18%). The risk is greatest during the third trimester and during the perinatal period. Fetal involvement is greatest in sever cases and in those treated late. Prevention is based on the initial work-up to identify the disease and possible complications, programming pregnancies and increasing surveillance during periods of risk, defining the delivery route with cesarean section reserved for complications of arteritis (30%), and planned labour with instrumental extraction and epidural anaesthesia with control of the blood pressure. Still's disease has no particular consequence on pregnancy, although sequellae of chronic arthritis of the pelvis may have an impact on obstetrical technique. An association with Takayasu's disease is rare with only one case being reported in the literature; aetiopathology remains unknown.

[Catamenial sciatic pain due to endometriosis of the sciatic nerve. Review of the literature, apropos of a case]. / Sciatalgie cataméniale par endométriose du nerf sciatique. Revue de la littérature, à propos d'un cas.

Sciatic nerve endometriosis is rare but must be included in the sciatic pain aetiology diagnosis. Typically the patient's sciatic pain is cyclic. Electromyography and computed tomographic scanning or nuclear resonance imagery contribute to the diagnosis. Different mechanisms of this localization have been proposed. The patient often requires conservative surgery with excision of endometriosis from the nerve. Medical treatment (LH-RH analogues) may be associated in young patients who need to preserve reproductive function. Total hysterectomy with bilateral salpingo-oophorectomy may be mandatory in stage III or IV endometriosis and older patients.

[Pseudo-unicornuate uterus. Diagnostic difficulties and obstetrical complications. Nine cases]. / Utérus pseudo-unicorne. Difficultés diagnostiques et complications obstétricales. A propos de 9 cas.

Diagnostic procedures used in 9 cases of pseudo-uterus unicornis were presented. There are no manifestations of this malformation excepting during pregnancy and rare episodes of uncontrollable dysmenorrhoea. If pregnancy develops in the rudimentary cornis, major complications require hemihysterectomy.

[Mucocele-like lesions of the breast: management after diagnosis on ultrasound guided core biopsy or stereotactic vacuum-assisted biopsy]. / Mucocèles du sein: conduite à tenir après diagnostic sur micro- ou macrobiopsie.

OBJECTIVES: Clinical and pathological features of mucocele-like lesions in the breast are well-known though rare. The aim of this study is to evaluate the frequency of other breast proliferations association, the underestimation with ultrasound guided core biopsy or stereotactic vacuum-assisted biopsy and its implication on patient's management. PATIENTS AND METHODS: Retrospective study conducted in the gynecology departments of Tours and Orleans between January 1997 and December 2007, reviewing the records of all patients with diagnosis of mammary mucocele-like lesion on core or stereotactic biopsy. RESULTS: Eight cases were identified, all screen-detected (mammographic abnormalities) on asymptomatic women. For the five cases diagnosed by core biopsy, initial histological examination found isolated mucocele-like lesions in four cases, and association with atypical ductal hyperplasia in the other case. Vacuum-assisted biopsy and/or surgical excision were always done finding an association with mucinous carcinoma and another case of association with atypical ductal hyperplasia. For cases diagnosed by vacuum-assisted biopsy, histological examination was almost similar to the surgical one. DISCUSSION AND CONCLUSION: High rate of associated lesions (especially atypical ductal hyperplasia) makes necessary the advice of complementary surgical excision after a diagnosis of a mucocele-like lesion on a biopsy specimen. Vacuum-assisted biopsies could have their place as a curative method in certain conditions.

Aryl hydrocarbon hydroxylase activity in the first-trimester human placenta: induction by carcinogens and chemoprotectors.

The activity of aryl hydrocarbon hydroxylase (AHH) was measured in the placenta using radioenzymatic techniques and benzo(a)pyrene (BP) as substrate. The optimal assay conditions were defined, including cofactor dependence. The Km of BP to the enzyme was 2 microM and Vmax 0.02 nmol/min. When compared to the AHH activity at term (0.35 +/- 0.03; mean +/- SEM), 1st-trimester activity was significantly lower (0.18 +/- 0.05; p less than 0.05). However, in the rat liver the enzyme activity was even higher than that found at term. In order to determine whether the 1st-trimester placental AHH activity is sensitive to environmental exposures, explants were incubated with two classes of xenobiotics: carcinogens and chemoprotectors. The carcinogen BP at 50 microM caused a significant (2.7-fold; p less than 0.05) increase in the enzyme activity after an incubation period of 6 h. After an incubation period of 24 h, however, no effect was noted. In contrast, 50 microM 20-methylcholanthrene had no effect. The effect of chemoprotectors was also examined: at 25 microM, coumarin, 2-(3)-tert-butyl-4-hydroxy-anisole, and 1-phenylazo-2-naphthol significantly increased 1.7, 1.7-, and 1.8-fold, respectively, the enzyme activity after an incubation period of 24 h (p less than 0.05). In conclusion, AHH in the 1st-trimester placenta is sensitive to environmental exposures and is induced in vitro by both carcinogen and chemoprotectors.

Coordinated induction of estrogen hydroxylase and catechol-O-methyl transferase by xenobiotics in first trimester human placental explants.

The estrogen phenol A-ring metabolism was investigated in the first trimester placenta using radioenzymatic techniques. In untested explants cultured for 16 h, estrogen hydroxylase (EH) but not catechol-O-methyl transferase (COMT) activity was increased significantly 1.8-fold (P less than 0.05). Cultures made in the presence of chemoprotectors, 25 microM of 1-phenylazo-2-naphthol (Sudan I) and coumarin but not 2(3)-tert-butyl-4-hydroxyanisole (BHA) caused a significant increase in EH activity, 1.8- and 2.2-fold, respectively (P less than 0.05). This was coupled with a significant, P less than 0.05, increase in the COMT activity by 25 microM of all three chemoprotectors, BHA, Sudan I, and coumarin, 2.7-, 2.3-, and 2-fold respectively. The carcinogens benzo(a)pyrene and 20-methylcholanthrene at 50 microM concentration, however, had no effect upon both enzymes' activity. Finally, the two enzymes's activities were correlated under the experimental conditions tested. Except for zero time where no correlation was found (r2 = 0.3), in all other experimental conditions, a significant (r2 = 0.75) correlation was observed. In conclusion, EH and COMT enzyme activities appear to undergo a coordinated induction in cultured placental explants in the first trimester. The implications of catechol metabolism for embryonal development are discussed.

Effects of thyroid hormones on urinary and renal kallikreins.

The effects of thyroid hormones on the urinary excretion of kallikrein and on renal kallikrein were studied in rats. Total and active urinary kallikrein was decreased after thyroidectomy, but renal kallikrein content remained unchanged. Diuresis increased, and kidney weight and plasma aldosterone concentration decreased. Treatment with 3,5,3'-triiodo-L-thyronine restored the urinary kallikrein in thyroidectomized rats to normal and increased it in intact rats. It also produced increases in kidney weight and plasma aldosterone and a decrease in diuresis. The effect of thyroid hormones on the urinary kallikrein response to mineralocorticoids was also tested. Deoxycorticosterone acetate increased urinary kallikrein more in normal than in thyroidectomized rats. These results suggest that thyroidectomy decreases renal kallikrein synthesis and lowers the turnover rate of the enzyme, changes not detectable by a single measurement of the renal kallikrein content but reflected by an alteration in the urinary excretion of the enzyme. Thyroid hormones participate in the control of urinary kallikrein. This effect, however, is probably indirect and may be mediated by mineralocorticoids since thyroid function affects both the plasma level of aldosterone, which is known to influence renal kallikrein, and the kallikrein response to exogenous mineralocorticoids.

Effect of xenobiotics on quinone reductase activity in first trimester explants.

The placental protective enzyme quinone reductase (QR) has recently been reported to be induced by exposure to mercury, which is a toxic metal in vitro at term. In the present study we have examined the effect of three groups of xenobiotics-carcinogens, chemoprotectors and a natural antioxidant, ascorbic acid (vitamin C) on this enzyme activity in the first trimester placenta in vitro. Incubations with the carcinogen benzo[a]pyrene (BP) at 10-50 microM doses increased the enzyme activity at 6 h. At 24 h the effect of 10 microM BP was significant while that of 50 microM BP was not consistent. On the other hand the effect of 50 microM 3-methylcholanthrene at both time points was not significant. Ascorbic acid (5-25 microM) added for 24 h caused a 2- and 4-fold increase in the enzyme activity, respectively (P < 0.005). Exposure to a 25 microM concentration of different classes of chemoprotectors 2(3)-tert-butyl-4-hydroxyl-anisole (BHA), dicoumarol and Sudan I caused a 2.5- to 3.6-fold significant increase in the enzyme activity after 24 h (P < 0.01). Present data suggest that QR activity in the early placenta is responsive to a wide variety of xenobiotics in vitro. Vitamin C in concentrations usually consumed, exerted a potent effect on local QR activity in vitro which may protect pregnant women and their conceptus in an adverse environment.

Large-bowel mucosal biotransformation activity in persons at high risk for colorectal cancer. A preliminary report.

The transformation of xenobiotics and endogenous compounds to active carcinogens and their subsequent deactivation as an aid to eradication may be important in the etiology of some gastrointestinal cancers. In mammals the gastrointestinal tract has been shown to be an important site of inducible enzyme systems active in mucosal biotransformation, but few data are available in man. The mucosal activity of CYPIA1 (formerly aryl hydrocarbon hydroxylase), a potential carcinogen-activating enzyme, and catechol-O-methyl transferase, a potential carcinogen-inactivating enzyme were determined in colonic tissue obtained by biopsy. There were no significant differences in activity rates in normal mucosa between colorectal cancer and healthy persons, but significant differences are seen in patients with a history of neoplasia with no evidence of recurrence. The levels of activity of these carcinogen-inductive and -protective enzymes may be prognostic markers, in that the balance or imbalance could play a role in the recurrence of neoplasia. This will require confirmation and prospective studies.