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[Influence of histologic type on prognosis of patients undergoing curative intervention for gastric adenocarcinoma. Italian multicenter study].

BACKGROUND: The prognostic significance of the histological type in gastric cancer is still debated. The correlation between intestinal-diffuse type and tumor recurrence was investigated in a prospective multicentric study which collects the cases from three surgical Departments of Italy. PATIENTS AND METHODS: Four-hundred and twelve patients who underwent a potentially curative resection between 1988 and 1995 were considered; 273 cases were classified as intestinal type (group A), and 139 cases as diffuse type (group B). Mixed cases were excluded from the study. All patients were included in a complete follow-up program for the early diagnosis of recurrence. Clinical, histopathological and surgical factors were examined for their influence on tumor recurrence by univariate and multivariate analysis. RESULTS: Recurrence rate was 41.4% in intestinal type, and 65.5% in diffuse type cases (p < 0.0001). In group A, multivariate analysis identified nodal status (p < 0.0001), depth of invasion (p < 0.005), lymph node dissection (D1 vs. D2-D4, p < 0.01), advanced age (p < 0.01) and male sex (p < 0.05) as significant prognostic factors. In group B, depth of invasion (p < 0.0005), lymph node dissection (p < 0.005), tumor size (p < 0.01) and nodal status (p < 0.05) resulted as significant variables; no preventive effect on tumor recurrence was found for D2 vs. D1 lymphadenectomy. Multivariate analysis performed on the totality of the cases demonstrated diffuse type as an independent predictor of poor prognosis (relative risk: 1.67, p < 0.001). CONCLUSIONS: Diffuse type of gastric cancer is an independent risk factor for tumor recurrence as compared with intestinal type; clinical and pathological variables play a different role as prognostic factors in the two histotypes.

Adenocarcinoma↗

A novel rescue drug, 15-deoxyspergualin. First clinical trials for recurrent graft rejection in renal recipients.

The present multicentral clinical study performed in 6 institutes demonstrated that the novel immunosuppressive agent, 15-deoxyspergualin (DSG), is very effective on rejection. In 34 cases of rejection, 30 were treated with DSG at 40 mg/m2 (1 case), 80 mg/m2 (7 cases), 120 mg/m2 (9 cases), 180 mg/m2 (9 cases), and 220 mg/m2 (8 cases). The overall remission rate was 79% in 34 cases of rejection including accelerated, acute, and chronic rejection in different periods after transplantation. Analyzing the remission rates of early phase acute rejection occurring within 3 months after transplantation according to treatment pattern, the remission rate was 100% in 3 cases treated with DSG alone (using DSG 1 week or longer after other agents), 88% in 8 cases treated by rescue use of DSG (using DSG within 1 week after other agents), and 86% in 7 cases treated by combined use of DSG with other agents. Adverse reactions included reductions in WBC and platelets, anemia, perioral numbness, gastrointestinal troubles, and others. However all these symptoms were so mild that DSG treatment was not discontinued. Further studies are necessary on the effect of DSG, especially in acute rejection under conditions that reduce the many influences of other agents as much as possible.

Adult↗

Recurrent melanotic neuroectodermal tumour of infancy. Case report and survey of 16 cases.

A case of melanotic neuroectodermal tumour of infancy (MNTI) with rapid recurrence is described, together with a survey of 16 reported recurrent cases. The recurrent lesion was successfully treated by wide excision of the maxilla. The recurrent tumour had two lesions of different natures, one consisting of a lobular mass indistinguishable from the primary tumour but located remote from the original site and the other showing diffuse infiltration of tumour cells deep in the medulla of the maxilla. A survey of the recurrent cases indicated that, although incomplete removal of the primary tumour, dissemination of tumour cells during surgery and a multicentric origin could be the causes of a recurrence, the presence of a silent lesion which may express an aggressive growth on stimulation may also explain the complex behaviour of the tumour.

Humans↗

Nipple-sparing mastectomy in association with intra operative radiotherapy (ELIOT): A new type of mastectomy for breast cancer treatment.

BACKGROUND: Breast-conserving surgery has become the standard approach for about 80% of patients treated for primary breast cancer in most centres. However, mastectomy is still required in case of multicentric and/or large tumours or where recurrences occur after conservative treatment. When a total mastectomy is performed, the removal of the nipple areola complex (NAC) is a strongly debated issue. In fact, although removal of the NAC greatly increases the patient's sensation of mutilation, and the risk of tumor involvement of the areola is reported as a very variable percentage, NAC excision still remains the standard treatment. PATIENTS AND METHODS: From March 2002 to September 2003, 106 nipple sparing mastectomies (NSM) were peformed in 102 patients, 63% of whom had invasive carcinoma and 37% of whom had in situ carcinoma. Four patients underwent bilateral surgery. In all cases, a large or multicentric tumour and/or diffuse microcalcifications, clinically distant from the NAC, were present. During surgery, the tissue under the areola was routinely sampled to exclude the presence of tumor. If disease-free at the frozen sections, the NAC was spared and a NSM was performed. Additionally, a total dose of 16 Gy of radiotherapy (ELIOT) was delivered intraoperatively in the region of the NAC. All the patients underwent an immediate plastic breast reconstruction. RESULTS: In eleven patients (10.4%), the breast tissue under the areola resulted infiltrated at the definitive histological examination: in 10 cases a single or multiple foci of in situ carcinoma and in one case an invasive component were present. Eleven patients (10.4%) developed a superficial skin areolar slough followed by spontaneous healing, and 5 patients (4.7%) lost their NAC due to total necrosis. Among these, one patient had a poor cosmetic result on the NAC with asymmetrical location and required further surgical removal and reconstruction with tattoo and local flap in a better position. When rating the results from 0 (bad) to 10 (excellent), on average, the colour of the areola was rated 9/10, the sensitivity of nipple 3/10, the overall aesthetic result was rated 8/10 by both the surgeon and the patients. Early radiodystrophy (pigmentation) was observed in eight cases (7.5%). After an average follow up of 13 months, one local recurrence, located under the clavicula, far from the NAC, was observed. The preliminary results of the psychological study show a very high satisfaction with the preservation of the nipple (97.6 %), with younger women expressing a higher satisfaction than older counterparts. CONCLUSIONS: In selected cases, NSM with ELIOT of NAC has so far permitted good local control of the disease and satisfactory cosmetic results. Wider surgical experience is required to minimise the risk of leaving tumor cells in the region of the spared NAC and a longer follow up is necessary to evaluate the long term tumor recurrence rate at the NAC.

Breast Neoplasms↗

Comparative efficacy of lithium and amitriptyline in the maintenance treatment of recurrent unipolar depression: a randomised study.

The present study, including 81 depressive patients, compares the prophylactic efficacy of lithium and amitriptyline in recurrent unipolar depression over a treatment period of 2.5 years in a randomised multicentre design. Hospitalisation, re-emergence of depressive or subdepressive recurrences, unwanted side-effects and need of concomitant psychotropic medication were considered to indicate treatment failures. Average dosage for amitriptyline was 98 +/- 37 mg/day, average lithium blood level was 0.59 +/- 0.12 mmol/l. Survival analyses demonstrated a significant superiority of lithium (P = 0.015) regarding the outcome criteria 'recurrences and/or subclinical recurrences' and non-significantly better results of lithium compared to amitriptyline concerning 'recurrence' (P = 0.059) or 'recurrence and/or concomitant medication' (P = 0.066).

Adolescent↗

Intraepithelial neoplasia in the vulvar region.

From 1978 to 1982, 49 patients with intraepithelial neoplasia in the vulvar region were included in a prospective investigation. The main purpose was to evaluate the effect of treatment by local excision with a free margin of 2 mm and to estimate the importance of colposcopy. In 28% of the patients, the disease recurred after primary treatment, and in one patient microinvasion was shown. No patients died of cancer. A risk factor of recurrence was involvement of resection margins. Multicentric localization of the vulvar disease was found more frequently among patients treated for intraepithelial neoplasia of the cervix. In 66% of the patients the colposcopic findings were consistent with intraepithelial neoplasia. Local excision represents an improvement in the treatment of intraepithelial neoplasia of the vulva, but frequent follow-up is necessary.

Adult↗

Dynamic contrast enhanced magnetic resonance imaging of the breast is superior to triple assessment for the pre-operative detection of multifocal breast cancer.

BACKGROUND: Inadequately treated multifocal and multicentric disease results in increased local recurrence following breast-conserving surgery. The accurate preoperative diagnosis of multifocal/ centric breast cancer would facilitate the planning of appropriate surgery and prevent reoperation for residual disease. While triple assessment remains the established diagnostic technique, its sensitivity for the diagnosis of multifocal disease remains poor. Dynamic contrast enhanced Magnetic Resonance Imaging (DCE-MRI) of the breast represents an alternative emerging diagnostic modality that has been shown to be highly sensitive for the delineation of primary breast cancer. The aim of this study was to prospectively compare the diagnostic accuracy of DCE-MRI of the breast with conventional triple assessment for the preoperative diagnosis of multifocal/centric breast cancer. METHODS: Patients were recruited from the symptomatic breast clinics. All patients underwent standard triple assessment and DCE-MRI. The MRI scans were reported by a single radiologist blinded to the results of the triple assessment. Surgery was then planned accordingly to all available scan results and the specimens examined by a single pathologist. All patients who did not undergo surgery have been followed up for a minimum of 18 months. RESULTS: A total of 334 women were recruited. There were 178 (52%) cancers that were histologically confirmed and multifocal/centric breast cancer was diagnosed provisionally by the preoperative investigations in 68 (38%); multifocal n = 33, multicentric n = 35, of these patients. In this group, subsequent histology confirmed multifocal/centric disease in 50 (73.5%): multifocal n = 15, multicentric n = 35. Unifocal cancer was found in 15 (22%) and benign disease in 3 (4.4%). The resultant sensitivity, specificity, positive, and negative predictive values were 18%, 100%, 100%, and 76% for triple assessment and 100%, 86%, 73%, and 100% for DCE-MRI. CONCLUSION: DCE-MRI identified a subgroup of breast cancer patients with multifocal/centric disease not evident on standard triple assessment. MRI of the breast should be considered for the preoperative planning of surgery for primary breast cancer.

Aged↗

Histology of familial thyroid tumours linked to a gene mapping to chromosome 19p13.2.

This paper describes the pathology of thyroid tumours showing an autosomal mode of inheritance linked to a gene that maps to chromosome 19p13.2. All the affected members from the family (seven males and two females; mean age 23 years) were clinically euthyroid and presented with nodular goitre; tumour recurrence after thyroidectomy was observed in four. In four of the five patients studied, the tumours were multifocal, bilateral well demarcated or encapsulated and composed of follicles, papillae, trabeculae/solid areas (often resembling hyalinizing trabecular adenoma of the thyroid) or an admixture, formed by cells with pale to intense cytoplasmic eosinophilia. A diagnosis of multiple adenomatous goitre was made in the thyroidectomy specimen from two patients, while the other two patients showed, in addition to multiple adenomas, a co-existent oxyphil papillary carcinoma. The fifth patient had an oxyphil cell carcinoma. All tumours were of follicular cell origin as shown by immunocytochemistry. Less than a third of the benign tumours and all three carcinomas showed a variable number of neoplastic cells diffusely immunostained for mitochondria. Histological findings of a 'multiple adenomatous goitre', non-endemic 'multinodular goitre' or multiple neoplasms of follicular cell origin with the morphology of those described here, particularly in young patients, should alert the pathologist and physician to the possibility of an inherited trait, with its implications for family screening. The tumours are usually benign and well demarcated but because of multicentricity and consequently increased risk of recurrence and/or progression to carcinoma, total thyroidectomy should be advocated.

Adenoma↗

Famciclovir vs. aciclovir in immunocompetent patients with recurrent genital herpes infections: a parallel-groups, randomized, double-blind clinical trial.

BACKGROUND: Twice-daily therapy with famciclovir (FCV) was shown to be effective for episodic therapy for recurrent genital herpes in a large placebo-controlled trial. However, no study has been published to date comparing FCV and aciclovir (ACV). OBJECTIVES: We have evaluated the effectiveness of FCV vs. ACV in the treatment of recurrent genital herpes infection. METHODS: A multicentre, double-blind, double-placebo, randomized, parallel-design study, assessed for equivalence, was conducted. As the analysis was based on confidence intervals, a difference of lesion healing time between ACV and FCV (Delta) of 1.05 days with a standard deviation of 2.30 days was chosen. Two hundred and four outpatients were included. Patients self-initiated oral therapy with 125 mg of FCV twice daily or ACV 200 mg five times daily for 5 days. The principal end-point of the study was the complete healing of lesions. Duration of the complete resolution of all symptoms, and safety were also considered. RESULTS: The mean healing time was 5.1 days and 5.4 days for FCV and ACV, respectively, with a crude value of Delta = 0.25 days (CI 95%: -0.32; 0.82) in the intent-to-treat population. Therefore, the confidence interval for the difference between the two treatments lies entirely within the equivalence range (-1.05-1.05). The value of Delta in the per-protocol population [0.35 day (CI 95%: -0.24; 0.93)] was comparable between the two groups. No differences were detected in the proportion of patients having complete healing at the different days of evaluation as well as in the duration until the complete resolution of all the symptoms. The frequency, nature and severity of adverse events did not differ among the two treatment groups. CONCLUSIONS: Twice-daily FCV was as effective and safe in the treatment of recurrent genital herpes simplex virus infection as five times daily ACV.

2-Aminopurine↗

The prognosis of patients with hepatocellular carcinoma of multicentric origin.

BACKGROUND/AIMS: The characteristics of patients with multicentric hepatocellular carcinoma (HCC) differ from those of patients with intrahepatic metastatic HCC. However, there are few reports regarding the long-term results in patients with HCC of multicentric occurrence. The purpose of this study was to clarify the prognosis of a group of patients with multicentric HCCs. MATERIALS AND METHODS: We evaluated the outcome in 28 patients with multiple hepatocellular carcinoma (HCC) suggestive of multicentric occurrence, all of whom underwent hepatic resection. The disease-free survival, recurrence pattern and survival were analyzed in the two subgroups of 12 patients with single advanced HCC (AdHCC) nodule and an early HCC (eHCC) or early advanced HCC (eAdHCC) nodule [Group A] and 16 patients with two AdHCC lesions [Group B]. These data were also compared with those of 58 patients with solitary AdHCC [Group C]. RESULTS: Both the disease-free survival and survival periods for Groups A and C were significantly longer than those for Group B, while no significant difference was seen between Group A and C. No significant differences among the three groups were recognized in the incidence of various types of recurrence pattern. CONCLUSIONS: The long-term results in patients with multicentric HCC apparently vary depending on the pathological condition at the time of operation. Among patients with multicentric HCC, those with AdHCC combined with an eHCC or eAdHCC are likely to show improved prognosis as a result of hepatic resection.

Carcinoma, Hepatocellular↗

Reviparin: a review of its efficacy in the prevention and treatment of venous thromboembolism.

UNLABELLED: Reviparin (reviparin sodium) is a low molecular weight heparin (LMWH) that catalyses the inactivation of factors Xa and IIa by binding to antithrombin, which ultimately leads to the inhibition of the clotting cascade. It is administered subcutaneously. Reviparin 7,000 to 12,600 anti-XaIU/day was found to be as effective as intravenous unfractionated heparin in preventing the clinical recurrence of acute deep vein thrombosis (DVT) and/or pulmonary embolism in 1 large randomised, multicentre trial (COLUMBUS) and was significantly more effective than intravenous unfractionated heparin in the prevention of recurrent venous thromboembolism in another large randomised, multicentre trial (CORTES). Reviparin has also been compared with unfractionated heparin in children with established DVT. However, the trial was under-powered and no conclusion could be made regarding comparative efficacy. As prophylaxis, reviparin 1,750 anti-XaIU once daily was as effective as unfractionated heparin 5,000IU twice daily in 1,311 patients undergoing abdominal surgery and, in a once daily dosage of 4,200 anti-XaIU, was as effective as subcutaneous enoxaparin sodium 40 mg/day or acenocoumarol in patients undergoing hip replacement surgery. Reviparin 1,750 anti-XaIU also effectively prevented DVT. compared with no treatment, in patients undergoing knee arthroscopy. It was also more effective than placebo in patients with brace immobilisation of the lower extremity. Reviparin was compared with 'standard care' in children with central venous lines. However, the trial was too small to make conclusions regarding its efficacy. Comparative data indicate that reviparin is at least as well tolerated as heparin and enoxaparin sodium. However, in a large (n = 1,279) trial there were significantly fewer major bleeding episodes in patients receiving reviparin than in patients given the oral anticoagulant acenocoumarol. The most commonly reported adverse events in therapeutic trials have been intraoperative blood loss and postoperative bleeding complications such as wound haematoma, bruising and injection site haemorrhage. Reviparin was also well tolerated in 2 studies in children aged < or = 16 years. CONCLUSION: Reviparin has shown efficacy in the treatment of established DVT and in the prevention of postoperative DVT after moderate and high risk surgery and was as effective as enoxaparin sodium or acenocoumarol in patients undergoing hip replacement surgery. As an effective and well tolerated antithrombotic agent, reviparin is likely to assume a significant role in the treatment and prevention of DVT, as it appears to have a preferable tolerability profile to subcutaneous heparin after moderate risk surgery and is at least as effective as intravenous heparin in the treatment of established DVT.

Adult↗

Pheochromocytoma surgery: epidemiologic peculiarities in children.

Manifestations of pheochromocytoma have some specific features in children. The aim of this study was to explore epidemiologic differences of the disease course in children and adults, the principal causes of pheochromocytoma recurrence, and the optimal extent of an operative intervention in a group of patients with initial manifestation of their tumor during childhood. A total of 520 patients with pheochromocytoma underwent surgery from 1957 to 2001. The mean age of the patients was 39.3 +/- 9.2 years; 50 patients (9.6%) were 16 years or under (children's group). There were 213 males (41%) in the general group and 32 males (62%) in the children's group. Bilateral adrenal lesions were present in 68 patients (13.1%), including 16 of the 50 children (32%). The tumors were extraadrenal in 36 patients (6.9%), including 9 of the 50 children (18%). The combination of pheochromocytoma and a hereditary syndrome was present in 36 cases (6.9%). Follow-up was obtained in 260 patients, including 46 children. Length of follow-up varied from 4 to 25 years (average 8.4 +/- 1.9 years). The pheochromocytoma recurred in 49 patients (18.8% of surveyed patients), with a true recurrence (a tumor in the region of the primary operation or metastases) in 16 patients (6.15%). A true pheochromocytoma recurrence was noted in 6 of the 50 children (12.0%). Organ-sparing tactics for multicentric adrenal lesions was a principal cause of the true recurrence. Therefore we believe it is necessary to perform a radical operation, which includes adrenalectomy and removal of the tumor, in patients with a high risk of recurrence.

Adolescent↗

The cause of Kaposi's sarcoma: an avian retroviral analog.

Changes in the epidemiologic patterns of Kaposi's sarcoma prior to and during the epidemic of acquired immunodeficiency suggest that a virus transmitted similarly to the human immunodeficiency virus (HIV) may be responsible. We propose a natural avian model for Kaposi's sarcoma. Hemangiomatosis of fowls corresponds clinically and pathologically to the human disease, with characteristics including predilection for distal skin, multicentricity with organ involvement, bleeding and recurrence after excision. Pathologic stages are also similar and include initial dissection of collagen by benign endothelial cells, the formation of large blood-filled spaces, spindle cell growth, and progression to fibrosarcomalike tumors. Avian hemangiomatosis is induced by a retrovirus of the lymphoid leukosis group and has been associated with laboratory transmission of lymphomatosis. An etiopathologic parallel should be sought in man.

Acquired Immunodeficiency Syndrome↗

Multiple schwannomas of the ulnar nerve: a case report.

Multiple schwannomas may occur as visible tumors or may occur as tumors in situ. The tumors in situ may be missed when the visible tumors are excised. In time, the schwannomas in situ grow and appear to be recurrent, while in fact, they are multicentric. The prognosis on multicentric schwannomas thus remains guarded.

Adult↗

Frequency and types of chest wall recurrences among node negative breast cancer patients.

From 1979 to 1982 a total of 2,467 patients with invasive breast carcinoma were included in the DBCG low-risk group (protocol 77a) and treated with mastectomy only. During a follow-up period from 4 to 7 years, 246 cases (10%) were reported with chest wall recurrence as first site of failure. For several reasons 58 cases were omitted. The material therefore comprises 188 cases. By a histo-pathologic re-evaluation the material was classified in three groups, i.e. 1) 31 cases with an evident new primary cancer, 2) 9 cases with a questionable new primary cancer, and 3) 148 cases with a true recurrence. Demonstration of residual breast tissue, multicentricity, and high differentiation of the original cancer, were features significantly related to the group of evident and questionable new primary cancers. Within the follow-up period no difference in mortality between the three groups were found.

Adult↗

[The Pap test in women after hysterectomy].

Neoplasm of the vaginal vault may occur up to years after a hysterectomy for CIN in 0.9-6.8% It is less commonly observed following hysterectomy for benign disease. The explanations for the pathogenesis of dysplastic abnormalities in the vaginal epithelium after hysterectomy are: residual disease indicating inadequate excision of the original lesion; multicentre focus of origin; new or recurrent lesion due to persistent carcinogenic stimulus. The subsequent development of VAIN justified the intensive cytology follow-up after hysterectomy? The general population are not screened for vaginal carcinoma, but they are screened for cervical carcinoma. The risk of vaginal carcinoma after hysterectomy for pre-invasive carcinoma of the cervix is similar to the incidence of pre-invasive carcinoma of the cervix in the general population. In the absence of any definite evidence that the natural history of the two diseases is different, most authorities recommend that vault cytology must be continued for life, although some people think that screening for vaginal carcinoma in women who have had CIN completely excised at hysterectomy is not an efficient use of resources. There is a need for continuing cytological follow-up, even after hysterectomy for benign conditions.

Adult↗

Stone recurrence after lithotripsy in patients with recurrent idiopathic calcium urolithiasis: efficacy of treatment with fiuggi water.

A multicentric study was carried out on 384 patients (231 males, mean age 28.3 years; 153 females, mean age 40.8 years) previously treated with extracorporeal shock wave lithotripsy for recurrent idiopathic calcium urolithiasis. Patients were selected and submitted to different types of high fluid intake treatment (oligomineral water with a calcium content of 15 mg/l vs. tap water with a calcium content ranging between 55 and 130 mg/l) to evaluate stone recurrence and to identify any potential risk factors. During follow-up (range 14-34 months, mean 19 months) 44 (23%) of the 192 patients treated with tap water presented recurrence versus 32 (17%) of the 192 patients treated with Fiuggi mineral water, the difference in incidence between the two groups being 6%. Of the possible predictors of recurrence, evaluated at the beginning of follow-up and analyzed in a multivariate statistical study, the 24-hour diuresis and calciuria were seen to be directly related to the recurrence.

Adult↗

[Second primary cancers of the bronchi treated surgically (recurrence excluded). Results of a national survey (1987)].

A multicentre study conducted by a number of French Thoracic Surgery centres has collected a total of 88 cases of operated metachronous cancers. After defining the concept of metachronous cancer, the reporters of this survey successively analyse the frequency, histological type and clinical course of such lesions. The various types of resection and the results (postoperative course and long-term acturial survival) are also examined in detail. The good long-term survival of such metachronous cancers justifies a deliberately "aggressive" surgical approach.

Actuarial Analysis↗