Prophylactic laparoscopic-assisted total gastrectomy for hereditary diffuse gastric cancer.

BACKGROUND: Ten percent of gastric cancer (GC) cases are familial, with one third resulting from a mutation in the tumor suppressor gene CDH1. Loss of this important structure can result in hereditary diffuse gastric cancer (HDGC), which carries a high mortality if early diagnosis is not made. Despite its clear genetic origin, optimal management of HDGC family members is controversial, as the utility and efficacy of current cancer screening programs for mutation carriers are unproven. METHODS: A 53-year-old Caucasian woman was initially seen for genetic screening because multiple family members had mutations of the CDH1 gene. Her pedigree analysis demonstrated 4 generations of gastric cancer, and 2 of the generations carried the CDH1 germline mutation, consistent with HDGC. At endoscopy, the patient's gastric mucosa was normal and random biopsies were also normal. The patient underwent a laparoscopic total gastrectomy. RESULTS: The gross examination of her stomach appeared normal. On histologic examination, however, the stomach was found to have diffuse (signet ring cell) adenocarcinoma in-situ with 11 microscopic foci of invasive adenocarcinoma limited to the lamina propria. CONCLUSION: Our case is the first reported prophylactic total gastrectomy utilizing a laparoscopic approach, and it highlights the importance of taking a thorough family history and obtaining a pedigree analysis. Endoscopic screening in HDGC cannot rule out diffuse GC, because the stomach and biopsies can be normal despite the presence of adenocarcinoma. Therefore, our case supports the recommendation for prophylactic gastrectomy in HDGC.     

Correlation of paramesangial deposits and glomerular sclerosis and/or hyalinosis in patients with IgA nephropathy

Correlation of paramesangial deposits ("hemispherical body") and glomerular sclerosis and/or hyalinosis was examined by light microscopical analysis in 40 patients of IgA nephropathy. Correlation of paramesangial deposits and intensity of IgA or C3 deposition in glomeruli was also evaluated in these patients. The number of paramesangial deposits was markedly increased in patients with moderate and advanced stages of IgA nephropathy who showed marked glomerular sclerosis and/or hyalinosis. There was a significant correlation between the number of paramesangial deposits and the intensity of IgA deposits in glomeruli. It is suggested that the accumulation of paramesangial deposits might induce severe glomerular injuries such as glomerular sclerosis and/or hyalinosis.     

Markers of cell-proliferation as prognostic factors in differentiated thyroid-cancer

Age is the most accepted prognostic factor in differentiated thyroid cancer. Other parameters, such as tumor size, grading, extrathyroidal extension, have also been associated with the prognosis of these tumors. Since the identification of reliable prognostic factors is essential to avoid unnecessary aggressive treatment for a disease, such as thyroid carcinoma, which only rarely is fatal, we studied two indices of cell proliferation in patients with differentiated thyroid cancer, in relation to their outcome. We studied two groups of patients with differentiated thyroid cancer, selected in a way to have one group (33 patients) with a good outcome and one (16 patients) with a fatal outcome, after a follow-up of at least 5 years. By immunohistochemistry the primary tumors of all patients were analyzed for the expression of the proliferating cell nuclear antigen (PCNA)/cyclin. In 38 (77.5%) of them also the nuclear DNA content and the percentages of S-phases were analyzed by flow cytometric analysis. At diagnosis the two groups of patients differed significantly with regard to age and extrathyroidal extension, but not for tumor size and grading. A significant difference (p=0.02) was found in the positivity of PCNA/cyclin expression between the fatal outcome group (66.6%) and the surviving patients (27%), and in the percentage of cells in the S-phase, 16.4+/-7.7% in the fatal outcome group patients and 6.0+/-2.6% in the surviving patients (p=0.0001). No difference was found in the nuclear DNA content of the two groups. A positive correlation was found between PCNA expression and S-phase (r(s)=0.55; p<0.001). A positive correlation was found between age and both the percentage of S-phase cells (r(s)=0.48; p<0.002) and PCNA expression (r(s)=0.36; p<0.009). In a multivariate analysis (Cox model) age and S-phase had independent prognostic significance (regression coefficient: 3.85 and 1.70, respectively), while PCNA was not an independent variable (0.98). Our results indicate that differentiated thyroid tumors with fatal outcome are characterized by two parameters of active cell proliferation (S-phase cell fraction and PCNA expression), which can be used as useful prognostic factors.     

Anaplastic thyroid-carcinoma - a retrospective clinical and immunohistochemical study

We reviewed 34 patients with histologically proven anaplastic thyroid carcinoma, representing 3.1% of all thyroid carcinomas treated from 1970 to 1992 in our Institution. Mean age at diagnosis was 63.1+/-10.3 years. Initial treatment consisted of near total thyroidectomy in 14 patients, partial thyroidectomy in 6 and no more than a biopsy in 14. After surgery 11 patients received external radiotherapy associated with chemotherapy (R+C), 8 patients had only chemotherapy (C), and 11 patients had only radiotherapy (R). Two patients, both in the group treated with R+C, are still alive, with a survival from the diagnosis of 23 and 26 months, respectively. Mean survival of the group treated with R+C (16.1+/-8.2 months) was significantly higher than that of patients treated only with C (6.2+/-4.4 months; p<0.01) or only with R (5.1+/-2.6 months; p<0.0004). In the group treated with R+C, patients submitted to near total or partial thyroidectomy had a mean survival of 15.0+/-8.8 months, similar to that of patients who had only a biopsy (17.2+/-7.9 months), suggesting that the outcome was affected by post-surgical therapy rather than by surgery per se. Twenty-two tumors were also assayed by immunohistochemistry for p53 and PCNA expression. p53 was expressed in 16/22 (72.2%) cases, with no correlation with sex, age, presence of differentiated component or survival. Comparing tumors with <30% or >30% p53 positive cells a tendency to longer (but not significant) survival was found in tumors with lower p53 expression. PCNA was expressed in all cases, with a percentage of positive cells ranging from 15% to 90%, and was not correlated with sex, age, differentiation, or survival. A positive correlation was found between PCNA and p53 expression (r=0.58; p=0.0039). In conclusion, our data indicate that in anaplastic thyroid carcinoma the use of combined R+C has some advantages with respect to single therapy. As in other aggressive malignancies; p53 and PCNA expression is increased irrespective of the response to therapy or the outcome.     

Bronchial carcinoid tumors: clinical and radiological correlation

PURPOSE: To evaluate the incidence of bronchial carcinoid tumor (BCT) in population affected by various lung tumors, retrospectively reviewed between 1986-2001, and to emphasize the radiographic patterns if they are characteristic. MATERIALS AND METHODS: In the above mentioned period, chest x-ray and CT were performed in 1110 patients, both male and female, affected by lung neoplasms. RESULTS: 20 patients were affected by BCT (16 males, and 13 females), aged between 26 and 75 years (mean age 57.5), with histopathologic diagnosis of typical (9 cases, 31%) and atypical (20 cases, 69%) bronchial carcinoid tumors. Localized right lung lesion were as follows: 7 cases in superior, 9 in middle and 4 in inferior lobes; in the left lung, 5 cases in superior, and 4 in inferior lobes. Size of the lesions was as average 2.4 cm in diameter (with a range of 0.5-12 cm). On x-ray and CT images, BCT appeared as a well marginated nodule, of which 9 were peripheral and 20 central. DISCUSSION AND CONCLUSION: BCT are classified as neuroendocrine carcinomas,and are divided in typical and atypical forms, with variable grade of malignancy. Central neoplasms are symptomatic due to bronchial obstruction (i.e., pneumonia, atelectasis, bronchiectasis, emphysema and/or lung abscess); if airway obstruction is partial, then cough, wheezing and recurrent pulmonary infections occur. Peripheral tumors are generally asymptomatic and they are discovered occasionally, when chest x-ray is made for other reasons. Radiographic features are similar in typical and atypical BCT. In central tumors a rounded well circumscribed hilar mass is noted, with lobulated or bumpy margins. Central cavitation is not referred to. Peripheral BCT appear as a solitary nodule, inferioer then 3 cm in size, marginated, surrounded by normal pulmonary tissue. Signs and symptoms of BCT are evasive and vague. No current clinical or laboratory procedures are useful in confirming the diagnosis; particularly, no imaging modalities are able to differentiate between BCT and other pulmonary tumors. For this reason, a clinical radiologic endoscopic and histopathologic approach is necessary. CT is more sensiticve then conventional radiography, especially in detecting small lesions, calcification and enlarged lymph nodes. MRI may be useful in those patients, who cannot tolerate IV contrast media. Scintigraphy may be employed in discovering relapses and long standing metastases.     

Radiological contrast media in the breastfeeding woman: a position paper of the Italian Society of Radiology (SIRM), the Italian Society of Paediatrics (SIP), the Italian Society of Neonatology (SIN) and the Task Force on Breastfeeding,Ministry of Health,Italy

Objectives

Breastfeeding is a well-recognised investment in the health of the mother-infant dyad. Nevertheless, many professionals still advise breastfeeding mothers to temporarily discontinue breastfeeding after contrast media imaging. Therefore, we performed this review to provide health professionals with basic knowledge and skills for appropriate use of contrast media.

Methods

A joint working group of the Italian Society of Radiology (SIRM), Italian Society of Paediatrics (SIP), Italian Society of Neonatology (SIN) and Task Force on Breastfeeding, Ministry of Health, Italy prepared a review of the relevant medical literature on the safety profile of contrast media for the nursing infant/child.

Results

Breastfeeding is safe for the nursing infant of any post-conceptional age after administration of the majority of radiological contrast media to the mother; only gadolinium-based agents considered at high risk of nephrogenic systemic fibrosis (gadopentetate dimeglumine, gadodiamide, gadoversetamide) should be avoided in the breastfeeding woman as a precaution; there is no need to temporarily discontinue breastfeeding or to express and discard breast milk following the administration of contrast media assessed as compatible with breastfeeding.

Conclusions

Breastfeeding women should receive unambiguous professional advice and clear encouragement to continue breastfeeding after imaging with the compatible contrast media.

Key Points:

? Breastfeeding is a well-known investment in the health of the mother-infant dyad. ? Breastfeeding is safe after administration of contrast media to the mother. ? There is no need to temporarily discontinue breastfeeding following administration of contrast media.     

BsmI vitamin D receptor genotypes influence the efficacy of antiresorptive treatments in postmenopausal osteoporotic women. A 1-year multicenter, randomized and controlled trial

Vitamin D receptor (VDR) gene polymorphisms could be considered one of the factors influencing the efficacy of the anti-osteoporotic treatments. In this multicenter, prospective, randomized and controlled trial we evaluated whether BsmI vitamin D receptor (VDR) genotypes influence the efficacy of antiresorptive treatment regimes (administered alone or in combination) in postmenopausal osteoporotic women. Using restriction endonuclease, we identified the BsmI VDR polymorphism in 1,100 postmenopausal women with osteoporosis. The women were randomized, taking account of genotype, into five treatment groups: (1) alendronate (Aln, 10 mg/day) plus raloxifene (Rlx, 60 mg/day); (2) Aln plus hormone replacement therapy (HRT, 0.625 mg/day conjugated equine estrogens plus 2.5 mg/day medroxyprogesterone acetate); (3) Aln alone; (4) HRT alone; and (5) Rlx alone. Lumbar-spine bone mineral density (BMD) and bone turnover markers were measured at study entry and after 1 year of treatment. Using the general linear model (GLM) repeated-measures procedure, the means of BMD and bone turnover markers significantly differed from baseline after a period of treatment. In particular, the mean change from baseline for BMD was –0.034 (95% confidence interval [CI]: –0.037 to –0.031, P <0.001); for serum osteocalcin (OC) it was 1.369 (95% CI: 1.289 to 1.448, P <0.001); and for urinary deoxypyridinoline (DPD) it was 1.322 (95% CI: 1.242 to 1.401, P <0.001), indicating a considerable variation before and after treatment of these indicators. In all three cases these effects appeared significantly influenced by treatments, genotypes, and the treatments*genotypes interaction term (P <0.001 each, except for the BMD and genotype effect with P =0.02), and not by the investigational centers involved in the study. In conclusion, in postmenopausal osteoporotic women, BsmI VDR genotypes influence the efficacy of antiresorptive drugs particularly when used in combination.