Multiple primary tumors: 17 cases of renal-cell carcinoma associated with primary tumors involving different steroid-hormone target tissues

The aim of this study was to analyze the characteristics of 17 women with renal-cell carcinoma (RCC) associated with other primary neoplasms occurring in steroid-hormone target tissues. The reproductive history of these patients and the use of exogenous hormones were taken into consideration. In all, 10 RCCs were associated with breast carcinoma; 4, with endometrial carcinoma; and 3, with ovarian carcinoma. The presentation of a second primary tumor was described as synchronous or metachronous by evaluation of the interval between the discovery of the two neoplasms. Hormone and surgical treatment as well as pathologic findings for each primary tumor were also reported. In these 17 RCCs the overall rate of disease-specific survival recorded after a mean follow-up period of 32.7 months (range 9–66 months) was 58.8%; 7 patients died of metastatic disease after surviving for a mean of 14.7 months. In terms of the pathologic stage of RCC, a significant difference in mean survival was found between pN0 (mean survival 22.1 ± 3.4 months) and pN 1 RCCs (mean survival 13.7 ± 3.5 months). A total of 13 (76.4%) women were postmenopausal at the time of diagnosis of the first primary tumor; the mean age of these women at menopause was 51.7 ± 1.2 years. No prior use of oral contraceptives was reported by 12 (70.5%) of the 17 patients. Plasma 17-beta-estradiol and estrone levels were determined in only 7 patients at the diagnosis of each of the primary tumors. High plasma estrogen levels were found in 4 women with RCC and breast carcinoma and in 1 patient with RCC and endometrial carcinoma; in the remaining 2 patients low-normal values were found. A relationship appears to exist between certain reproductive and hormone-related factors and the risk of developing these tumor associations. Data emerging from the present study do not provide strong support for the hypothesis of hormone dependency of RCC; however, a role for estrogens in cases in which RCC is associated with other primary tumors involving steroid-hormone target tissues can be hypothesized.     

Persistence of Mammary Artery Branches and Blood Supply to the Left Anterior Descending Artery

Background. Partial harvesting of the left internal mammary artery (LIMA) is a widespread technique used during minimally invasive coronary operations performed through a left anterior small thoracotomy. The influence of persisting LIMA branches was investigated to evaluate their effect on the blood flow of the left anterior descending artery.

Methods. Thirty patients, 15 with totally (group A) and 15 with partially (group B) harvested LIMAs, were evaluated. All the patients underwent postoperative angiography, during which a flow map of the LIMA was performed. The average peak velocity and the diastolic-to-systolic peak velocity ratio were recorded. The LIMA graft flow pattern was recorded in the proximal and distal thirds of the artery. Intramammary adenosine (12 to 14 μg) was injected and the average peak velocities before and after injection were calculated.

Results. The average peak velocity was similar in both groups in the proximal and distal thirds of the LIMA (25 ± 7 and 26 ± 5 cm/sec, respectively, in group A versus 27 ± 5 and 25 ± 5 cm/sec, respectively in group B; p = NS). The diastolic-to-systolic peak velocity ratio was similar proximally (0.78 ± 0.3 in group A versus 0.69 ± 0.3 cm/s in group B; p = NS), but not distally (1.72 ± 0.1 in group A versus 0.97 ± 0.3 in group B; p < 0.0005). The LIMA graft flow reserve was similar both proximally and distally (2.6 ± 0.6 and 2.5 ± 0.3 cm/s, respectively, in group A versus 2.6 ± 0.5 and 2.6 ± 0.3 cm/s, respectively, in group B; p = NS).

Conclusions. The persistence of LIMA branches does not influence the blood flow of the left anterior descending artery after acute adenosine-induced myocardial hyperemia. If a left anterior small thoracotomy is used in left anterior descending artery direct revascularization, complete LIMA harvesting is not mandatory and depends on the personal preference of the surgeon.     

Genetic analysis of the interleukin‐1 receptor antagonist and its homologue IL‐1L1 in alopecia areata: strong severity association and possible gene interaction‡

Alopecia areata is an inflammatory hair loss disease with a major genetic component. The presence of focal inflammatory lesions with perifollicular T‐cell infiltrates reflects the importance of local cytokine production in the pathogenesis. In addition to its fundamental pro‐inflammatory role, the interleukin‐1 (IL‐1) system has major effects on hair growth regulation in vitro, with the inhibitory actions of IL‐1α and IL‐1β being opposed by the receptor antagonist IL‐1ra. The novel interleukin‐1 like molecule 1 (IL‐1L1) which has greatest gene sequence homology with IL1RN, the gene encoding IL‐1ra, is another potential IL‐1 antagonist. In view of previous studies suggesting a significant role for IL1RN polymorphisms in the pathogenesis of autoimmune/inflammatory disease, we have analysed polymorphisms of IL‐1ra (IL1RN+2018) and its homologue IL‐1L1 (IL1L1+4734) in a case–control association study on 165 patients and a large number of matched controls. Homozygosity for the rare allele of IL1RN (IL1RN*2) was significantly associated with alopecia areata [odds ratio (OR) = 1.89, 95% CI (1.09, 3.28); P = 0.02], confirming our previous findings of significant association with the IL1RN variable number tandem repeat (VNTR). The results also revealed a novel association involving a polymorphism of the interleukin‐1 receptor antagonist homologue IL1L1 at position + 4734, IL1RN+2018, and alopecia areata. The effect of a genotype combining three copies of the rare alleles at the IL1RN and IL1L1 loci conferred a more than additive increase in the risk of disease compared to IL1RN+2018 or IL1L1+4734 alone [OR 3.37 (1.60, 7.06); P = 0.002], suggesting possible synergy between the IL1RN and IL1L1 genes. This effect was stronger in patients with severe disease (alopecia totalis/universalis) [OR 4.62 (1.87, 11.40), P = 0.0022], and in those with early age at onset (< 20 years) [OR = 6.38 (2.64, 15.42), P = 0.0002]. Our results suggest that these polymorphisms within IL1RN and IL1L1 themselves or a gene in linkage disequilibrium with IL1RN and IL1L1 predispose to the more severe forms of alopecia areata.     

Interleukin-3 dependent c-myc protein expression during the cell cycle of murine mast cells.

Aim of the study was to evaluate the relationship between the mitogenic stimulus interleukin-3 to normal murine mast cells and the cell cycle dependent expression of the nuclear c-myc protein. In order to do that on a cell by cell basis, we measured the nuclear c-myc protein simultaneously by flow cytometry, via specific monoclonal antibodies, and the DNA content via the intercalating dye propidium iodide. When cells were deprived from interleukin-3 (IL-3), proliferation was inhibited and the majority of cells arrested in early G1 (G1A, characterized by low c-myc content). Readdition of IL-3 resulted in a slow transition of cells from G1A to late G1 (G1B, at higher c-myc content) before DNA synthesis started. G1A cells with low c-myc content do not undertake DNA synthesis. Using a stathmokinetic methodology we confirmed that the G1A cells are early postmitotic G1 phase cells. The low content of c-myc within these cells appears a direct consequence of reduced c-myc levels during mitosis. Cumulatively, the data suggest that c-myc protein levels of murine mast cells fall at mitosis and that these levels must rise before cells can traverse the G1 phase. Our data are compatible with a model in which c-myc protein content of G1 phase cells has to reach a critical threshold before the cells can move further into the cell cycle.     

Ovarian and uterine findings in pelvic sonography: comparison between prepubertal girls, girls with isolated thelarche, and girls with central precocious puberty.

OBJECTIVE: To describe pelvic sonographic findings in girls as old as 7 years, to compare prepubertal girls with girls who had isolated thelarche or central precocious puberty, and to verify the accuracy of sonographic variables for distinguishing prepubertal girls from girls with central precocious puberty. METHODS: Ninety-six prepubertal girls and 2 reference groups (8 girls with isolated thelarche and 8 with idiopathic central precocious puberty) were included. Ovaries were classified morphologically as homogeneous, paucicystic, macrocystic, multicystic, and having isolated cysts. Receiver operating characteristic curves were used to choose the best cutoff points. RESULTS: Chronologic and bone age were correlated with uterine length, area, and volume and ovarian volume in prepubertal girls (P < .0001). Ovarian morphologic characteristics in prepubertal girls differed significantly from those of the reference groups (P < .0001). The best cutoff points were uterine length of 4.0 cm, uterine area of 4.5 cm2, uterine volume of 3.0 cm3, and ovarian volume of 1.0 cm3. CONCLUSIONS: Uterine and ovarian growth are proportional to age in prepubertal girls. Mean ovarian volume greater than 1 cm3 showed 100% sensitivity and specificity for discriminating between prepubertal girls and girls with central precocious puberty. Microcysts are common in prepubertal girls, but the presence of 6 or more follicles up to 10 mm in diameter may suggest central precocious puberty in girls younger than 8 years.     

Complications of lymphangiomas in children.

One hundred ninety-three cases of lymphangioma presenting in children were reviewed over a 10-year period. The diagnosis was established before 5 years of age in 87.0%. The distribution of lymphangiomas was: cervical (31.4%), craniofacial (18.9%), extremity (18.9%), trunk (9.2%), intraabdominal (9.2%), cervicoaxillothoracic (4.9%), multiple (3.8%), cervicomediastinal (2.2%), and intrathoracic (1.6%). Of 164 patients undergoing primary therapy, total excision was performed in 77.4% and partial excision in 20.7% with recurrence rates of 11.8% and 52.9%, respectively. Thirty-eight percent of all operations for lymphangiomas were performed for resection of recurrent or residual disease. The incidence of postoperative complications was 31.3%. Forty-four additional procedures were required to manage these complications. Sclerotherapy with 50% dextrose was used as an adjunct in 9.5%. Recurrences were seen after total resection in 17.6% of operations in which 50% dextrose was used and 11.8% in which it was not used. Seroma formation was noted in 3.5% of total resections and 40.0% of resections for recurrent disease in which adjunctive sclerotherapy with 50% dextrose was used. Seromas occurred in 9.8% of wounds in which local drains were used and 3.6% of wounds in which drains were not used. Infectious complications occurred after 6.6% of operations using perioperative antibiotics and 3.5% not using antibiotics. The management of lymphangiomas in children remains a difficult problem. Despite being benign lesions, lymphangiomas are attended by a high rate of morbidity from complications of the disease and its management. Complete excision still offers the best chance for complete cure. Sclerotherapy with 50% dextrose is not beneficial in the management of recurrent disease or postoperative seromas. Local drains and perioperative antibiotics do not appear to diminish the incidence of seromas and infectious complications, respectively.     

Magnetic resonance in the staging of multiple myeloma]

The authors retrospectively reviewed the MR examinations of 46 patients with clinical and laboratory findings of monoclonal gammopathies (MG). All cases had been submitted to radiographic examination which had shown skeletal involvement in 22 cases and osteoporosis in 11, with rupture of the vertebral body in 3 patients. Scintigraphy had been performed on all patients and CT on 12; 36 patients were subsequently submitted to follow-up (at 6, 12 and 24 months). MR examinations were performed with dedicated coils and standard sequences for the subjects with skeletal localizations on X-ray images. The extant cases, with no radiographic evidence of skeletal involvement, were submitted to MRI of the spine, skull and pelvis. In agreement with clinical and laboratory findings and with follow-up results (in 36 patients), MRI diagnosed MG with no skeletal involvement in 13 cases, osteoporosis in 8 (with rupture of the vertebral body in 2), asymptomatic non-progressive myeloma in 4, solitary myeloma in 3, and multiple myeloma in 18 cases. The good identification of bone marrow and its multiplanarity make MRI the method of choice in the study of patients with suspected or known gammopathies. If compared with other modalities, MRI is more sensitive and accurate in depicting the tumor, its size and relationship to periskeletal tissues, and its possible multifocality. Moreover, the technique has proven to be a valid tool during the follow-up, showing tumor response to therapy.