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Impact of multicentricity on clinical outcome in patients with T1-2, N0-1, M0 breast cancer.

BACKGROUND: The objective was to determine the impact of multicentric breast cancer on recurrence and survival and to evaluate the current tumor, node, metastasis staging system recommendations for multicentricity in the breast. METHODS: This study included 284 nonpregnant patients with T1-2, N0-1, M0 breast cancer, without previous cancer, who were treated by modified radical mastectomy followed by doxorubicin-based adjuvant chemotherapy. Clinical and pathological data were collected retrospectively and survival was calculated from the date of initial diagnosis using the Kaplan-Meier method. RESULTS: The median follow-up time was 8 years (range, 0.3-24.0), and the median age was 47 years (range, 23-76). The median clinical size of the index tumor was 2.5 cm. In 17% of patients, the clinical nodal status was N1. In 84% of patients, pathology of the index lesion was invasive ductal +/- in situ. Multicentric breast cancer was detected in 60 patients (21%): 30 patients with two lesions, 13 patients with three lesions, and 17 patients with four or more lesions. Locoregional recurrence, contralateral breast cancer, distant metastasis, and survival (disease-specific and disease-free) were similar in both groups of multicentric versus unicentric breast tumors. There was a significant difference between groups in estrogen receptor and axillary lymph node positivity, but these did not contribute significantly to outcome on multivariate analysis. CONCLUSIONS: Multicentricity does not increase the risk of poor outcomes in patients with early-stage breast cancer. This supports the current recommendations of the tumor, node, metastasis staging system that tumor size should be based on the diameter of the largest lesion in patients with multicentric breast cancer.

Adult↗

Prospective multicentre study of risk factors associated with delayed healing of recurrent duodenal ulcers (RUDER). RUDER Study Group.

Risk factors for delayed duodenal ulcer healing during treatment with ranitidine (300 mg daily) were examined in a multicentre German study of 1923 patients with endoscopically proved, recurrent duodenal ulceration. Healing rates, per protocol, were 39.5% at two weeks, 70.9% at four weeks, and 93.2% at eight weeks. Prospective testing of five, predefined risk factors indicated that smoking (p = 0.0039) was associated with a decreased healing rate at two weeks. Frequent prior recurrence (p = 0.464), a heavy physical workload (p = 0.145), and psychological stress (p = 0.062) were not associated with a decreased healing rate and there were too few patients at risk to allow assessment of the effect of regular NSAID intake. Exploratory analysis identified prior slow healing, a large ulcer, multiple ulcers, and prior ulcer complications, in addition to smoking, as markers of slow healing. In the absence of these risk factors, the mean healing time was 3.3 weeks (95% confidence interval 3.0, 3.5), rising to 3.7 weeks (3.5, 3.9) for one, 4.4 weeks (4.1, 4.7) for two, and 5.1 weeks (4.5, 5.6) for three to five risk factors. Delayed duodenal ulcer healing is associated with multiple factors whose effect is cumulative; for patients with two or more of five easily identified risk factors, more than four weeks' treatment with a histamine H2 receptor antagonist is required to achieve ulcer healing.

Adult↗

Familial endocrine myxolentiginosis.

We present an unusual case of a left atrial myxoma as a feature of a familial mesoectodermal disorder and review the literature. The new term "familial endocrine myxolentiginosis" is proposed, which is descriptive of the major clinical components of the syndrome. Myriad features of this disorder include (1) cardiac myxomas; (2) cutaneous myxomas; (3) multiple lentigines or blue nevi, particularly of the head and neck; (4) bilateral primary pigmented nodular adrenocortical hyperplasia; (5) unusual testicular tumors; (6) pituitary tumors; (7) myxoid fibroadenomas of the breast; (8) myxomatous disorder of the stroma of the breast; (9) ductal adenoma of the breast; and (10) psammomatous melanotic schwannoma. A tentative diagnosis is suggested by identifying two features and a definitive diagnosis is made by three or more features. The clinical and pathologic features of cardiac myxoma in familial endocrine myxolentiginosis are identical to those of familial cardiac myxoma: age < 40 years, atypical locations, multicentric origins, and recurrent presentations. A Venn diagram classification for cardiac myxomas is proposed. We include photographic, echocardiographic, biopsy, and adrenal computerized tomography documentation in our patient. Recognition of this disorder is important because of its clinical, surgical, and genetic implications. The availability of transesophageal echocardiographic technology should allow early diagnosis of this underdiagnosed entity. Clinicians should consider this entity in the differential diagnosis of their patients with any one of these manifestations.

Adult↗

Angiosarcoma with sacral origin metastasizing to the lung.

A 73-year-old man with fever, lumbago and hemosputum showed ground-glass opacity around multiple lung nodules on chest computed tomography. Examination of the man revealed anemia. Specimens obtained by video-assisted thoracic surgery revealed angiosarcoma, but the primary site of angiosarcoma could not be detected before autopsy. Angiosarcoma is a rare malignant neoplasm with rapid proliferation and they can arise at any region of the body. It can originate in the skin, soft tissue, liver or heart. Their multicentric and local recurrence easily leads us to misdiagnosis, and we have struggled to reach diagnosis and its origin. Angiosarcoma should be included in the different diagnosis of diffuse pulmonary hemorrhage with multiple lung nodules.

Aged↗

Evaluation of curability and prediction of prognosis after surgical treatment for hepatocellular carcinoma by lens culinaris agglutinin-reactive alpha-fetoprotein.

The clinical significance of serum lens culinaris agglutinin-reactive alpha-fetoprotein (AFP-L3), which can distinguish between hepatocellular carcinoma and hepatitis by detecting a sugar chain micro heterogeneity, was evaluated for its possible ability to recognize previously undetectable residual tumors, and for increasing the accuracy of prognosis after surgical treatment for hepatocellular carcinoma. Serum lens culinaris agglutinin-reactive alpha-fetoprotein was measured pre- and post-operatively in 130 patients who underwent curative surgical treatment for hepatocellular carcinoma. The preoperative AFP-L3 positive rate was 35.4%. AFP-L3 remained positive postoperatively in 28 of the 46 preoperative AFP-L3 positive patients, and converted to positive in 4 of the 84 preoperative AFP-L3 negative patients. Regardless to preoperative AFP-L3, the postoperative AFP-L3 positive patients had a poorer recurrence-free rate (p<0.0001). The postoperative L3 positive patients had a high incidence of recurrence due to metastasis, but did not have recurrence due to multicentric origin. Multivariate analysis revealed that AFP-L3 (p<0.0001) was the most independently significant factor for predicting survival after surgery among several conventional prognostic factors. Thus, AFP-L3 is a valuable marker for evaluation of curability of surgical treatment and for improving the accuracy of prognosis.

Aged↗

[Synchronous bilateral renal adenocarcinoma. Our experience with conservative kidney surgery].

OBJECTIVE: To present our experience with synchronous bilateral renal adenocarcinoma. The indications for conservative surgery, the different types and the controversies are discussed. METHODS: 5 patients with bilateral renal adenocarcinoma from our series of 320 renal adenocarcinomas were analyzed for gender, age at presentation, tumor location, size, presenting features and type of surgery performed. RESULTS: Bilateral renal adenocarcinoma accounted for 1.56% in our series. Mean age at presentation was 57.8 years (range 43-69 years). All 5 patients were male. All patients underwent conservative surgery by tumor excision or partial nephrectomy of the side with less involvement followed by delayed radical surgery of the contralateral side. Follow-up ranged from 19 months to 14 years. To date all patients are disease-free and only one is on dialysis 14 years postoperatively. CONCLUSIONS: Bilateral renal adenocarcinoma has been reported to account for 1.4%-5% of all renal masses. The incidence in our series was 1.56%. Conservative renal surgery is indicated in patients like those described herein to prevent the need for dialysis. In our view, conservative renal surgery is a good therapeutic option that carries a small risk of tumor multicentricity and future recurrence.

Adenocarcinoma, Clear Cell↗

[Helicobacter pylori and gastric cancer. The incidence of infection in personal experience].

BACKGROUND: Helicobacter pylori is an identified carcinogen for gastric cancer, but the underlying mechanisms remain to be defined. The aim of this study is to analyze the incidence of Hp infection in our series of patients with gastric carcinoma. METHODS: Between 1988 and 1998, 60 patients with diagnosis of gastric adenocarcinoma underwent partial or total gastrectomy. Forty-one were males and 19 females with an average age of 62 years (range 36-79). Twenty-seven cancers (45%) were localized in the lower third of the stomach, 17 (28%) in the middle third and eight (13%) in the upper third or cardias. In six patients (10%) the tumor was multicentric, while a recurrence on gastric stump after subtotal gastrectomy was present in two cases (3%). According to Lauren's criteria 39 cancers (65%) were of intestinal type, 16 (27%) of diffuse type and five (8%) of mixed type. The histologic preparations have been re-examined in order to verify the presence or not of Hp on gastric mucosa around neoplasm. RESULTS: Hp was found in 35 (58%) of the analyzed specimens and therefore a significant percentage of patients was Hp-positive at the time of diagnosis and surgery. Between 35 Hp-positive samples, 24 were adenocarcinomas of intestinal type, nine of diffuse type and two of mixed type, with a prevalence of Hp in intestinal type cancer. CONCLUSIONS: This study confirmed the high incidence of Hp infection in patients with gastric carcinoma, particularly in those with intestinal type cancer.

Adenocarcinoma↗

[Orthotopic ileal neobladders in men and women: techniques and comparison].

PURPOSE: evaluation of results and complications of ileal orthotopic neobladders in men and women with transitional cell carcinoma. MATERIALS AND METHODS: between 12-89 and 12-95 we performed 146 radical cystectomy for bladder neoplasm, in 32 patients we can perform ileal orthotopic neobladder, 29 were male and 3 were female. Oncologic indications to this kind of operation were: clinical stage T2, T3a, T3b, T1G3 multicentric and or recurrence, absence of metastasis absence of nodal metastasis, negativity of urethral biopsy. General contraindications were urethral stenosis and incontinence. Oncological contraindications, in woman, were bladder neck neoplasm or urethral neoplasm. In 4 patients we use Camey II technique, in 19 pts we performed the paduan ileal neobladder, in 9 pts we use Hautmann technique. 7 patients performed neoadjuvant chemotherapy with 4 circles of MVAC, 4 pts underwent adjuvant chemotherapy, and 2 pts salvage chemotherapy. In woman we take care during cystectomy to dissect cardinal ligament very close to cervix uteri, to resect the uterosacral ligament far to the sacrum. We did not dissect under the ureter and we cut the urethra 0.5-1 cm far from the bladder neck. RESULTS: follow up was between 6 and 66 months. 24 patients are now alive and disease free, 2 patients are alive with disease progression, 1 have a pelvic recurrence and 1 have pulmonary recurrence. 4 pts died for disease progression and 2 for non oncological cause, quality of life was considered as regard to continence and sexual activity. 1 pts was completely incontinent and 1 pts has nocturnal incontinence with a daily micturation every 1 hour. We can evaluate only 18 patients for sexual activity and 4 reported normal erection. COMPLICATIONS: in three cases we had to reoperate for early complications due to mechanical bowel obstruction, ileocutaneous fistula and wound dehiscence. In three cases we had the formation of stones, in two patients ureteroileal stenosis, in two cases urethro-ileal stenosis and 1 reflux from the neobladder. Orthotopic ileal neobladder allows a very good quality of life and is the first choice derivation after radical cystectomy.

Antineoplastic Combined Chemotherapy Protocols↗

Primary ureteral carcinoma. Report of 15 cases and comparison of the effectiveness of diagnostic methods.

Fifteen cases of primary urothelial carcinomas of the ureter are reported (14 transitional cell carcinoma and 1 mixed transitional cell carcinoma and squamous cell carcinoma). There was a clear male predominance (11/4); the peak incidence was in the sixth decade. Most tumors originated from the distal third of the ureter. Multicentricity and high recurrence rate after partial ureterectomy were noted. The clinical signs were hematuria and flank pain. Urine cytology and IVU were diagnostic in a limited number of cases. Retrograde pyelography was very helpful. CT showed to be the image modality of choice for diagnosis and preoperative staging.

Aged↗

Recurrent genital herpes suppressed by oral acyclovir: a multicentre double blind trial.

Eighty-eight of 111 patients with frequently recurring genital herpes attending five centres completed a randomized, double-blind, cross over trial with 200 mg oral acyclovir four times daily for 84 days before or after a similar course of placebo tablets. During the course of placebo 77 (88%) patients reported the development of lesions, four (5%) the development of symptoms and/or erythema but no further signs of a recurrence and seven (8%) remained entirely free of symptoms and signs. In contrast during acyclovir therapy only 11 (13%) patients reported lesions, a further 37 (42%) the development of symptoms and/or erythema only, while 40 (45%) patients remained entirely free of symptoms and signs. For each parameter the difference between active and placebo treatments was highly significant (P less than 0.001). Median times to recurrence after the end of both courses were similar. The drug was well tolerated and the findings indicate that continuous oral acyclovir therapy has a place in the management of frequent recurrences of genital herpes though the indications are not entirely clear. One possibility is the suppression of recurrence at times when it would be especially unwelcome such as during examinations or holidays.

Acyclovir↗

A controlled study of intravesical epirubicin with or without alpha 2b-interferon as prophylaxis for recurrent superficial transitional cell carcinoma of the bladder. Finnish Multicentre Study Group.

OBJECTIVES: To evaluate the efficacy of intravesical epirubicin with or without alpha 2b-interferon (alpha 2b-IFN) as a prophylactic treatment for recurrent superficial transitional cell carcinoma (TCC) of the urinary bladder. PATIENTS AND METHODS: A total of 81 patients with superficial (stage Ta and T1), well or moderately differentiated (grades 1 and 2) TCC were treated between June 1988 and December 1993. The patients were randomized into three groups: Group 1 was treated by transurethral resection (TUR) alone; Group 2 received 50 mg epirubicin and Group 3 received 50 mg epirubicin combined with 10 MU alpha 2b-IFN, intravesically in 50 mL sterile buffer solution. The instillations were started 1 week after TUR and were performed weekly during the first month and then once a month for one year. The patients were followed for a total of 2 years. Recurrence rate and tumour rate were calculated to assess the behaviour of the disease. RESULTS: The patients were followed for a mean of 20 months. Patients receiving intravesical chemoimmunotherapy (Group 3) had the most favourable outcome; they had comparatively lower recurrence and tumour rates, fewer patients with recurrences and, most importantly, the longest disease-free interval. Side-effects were mostly mild and transient, and no differences were found among the groups. CONCLUSIONS: In reducing the number of patients having recurrences and extending the recurrence-free interval, intravesical chemoimmunotherapy with epirubicin and alpha 2b-IFN had a promising effect on the natural course of superficial bladder cancer, particularly in patients with a history of prior recurrences.

Administration, Intravesical↗

Recurrence patterns of hepatocellular and fibrolamellar carcinoma after liver transplantation.

PURPOSE: Tumor recurrence is the major limitation of long-term survival after liver transplantation for hepatocellular carcinoma (HCC) or fibrolamellar carcinoma (FLC). Understanding tumor-biologic characteristics is important for selection of patients and for development of adjuvant therapeutic strategies. PATIENTS AND METHODS: The study included 69 patients who underwent potentially curative liver transplantation for HCC/FLC and survived for more than 150 days; minimum follow-up was 33 months. Frequency, localization, and timing of recurrence were analyzed and compared with primary tumor and patient characteristics. RESULTS: Tumor recurrence was observed in 39 patients at 67 locations. Hematogenous spread was the major route of tumor recurrence (87%), and the most frequent sites were the liver (62%), lung (56%), and bone (18%). Parameters associated with recurrence were absence of cirrhosis, tumor size greater than 5 cm, more than five nodules, vascular infiltration, and International Union Against Cancer (UICC) stage IVA. Selective intrahepatic recurrence was found in nine patients (23%); it was associated with highly differentiated tumors, lack of vascular infiltration, and male sex. Recurrence at multiple sites was found predominantly in young patients (< or = 40 years) and for multicentric (> 5) primary tumors. Recurrences were observed within a wide time range after transplantation (43 to 3,204 days; median, 441 days); late recurrences (> 1,000 days, n = 8) were associated with highly differentiated or fibrolamellar tumors and low UICC stages. Surgical treatment was the only therapeutic option associated with prolonged survival after recurrence. CONCLUSION: In transplant recipients, hepatocellular carcinomas vary considerably in their pattern and kinetics of metastases. Tumor cells may persist in a dormant state for long time periods before giving rise to clinical metastases. Surgical treatment of recurrence should be considered whenever possible.

Adult↗

[Local recurrence after conservative therapy of breast cancer: risk factors, site of recurrence, evolution].

The identification of factors associated with breast recurrence as first event (62 cases, 10%) following conservative surgery and radiation therapy are drawn out from a series++ of 618 mammary carcinomas of clinical size less than 40 mm, stage I and II (UICC), with a median follow up of 8 years. The most powerful predictive characteristic associated with the likelihood of breast recurrence is multiple foci of invasion (42.9% vs 8.9, P = 0.0001, relative risk [RR]: 6). After this rarely cited feature, young age, less than 40 years (20% vs 7.3%, P = 0.0001, RR: 2.8), extensive in situ carcinoma more than 25% (19.2% vs 8.7%, P = 0.003, RR: 2.5) were found also persistent in the Cox model, but not histologic size more than 25 mm (18.9% vs 9.1%, P = 0.01, RR: 2.3). The site of recurrence was studied on the 54 salvage mastectomy done. A high rate of recurrence at distance of the initial site was found: 37% whose more than half, 22%, were multicentric. No significant difference in the mean delay of appearance was noted between recurrence near or at distance of the initial cancer (mean delay 52 months vs 64 months). From the recurrence the evolution is not very favourable: excluding simultaneous metastases found at the preoperative investigation, ten cases, mammary recurrence is followed by a metastatic syndrome in 36% of cases against 17% without it (P = 0.01, RR: 1.9). Metastatic evolution is not significantly linked with the time, early or late, of the mammary recurrence (54.5% before 5 years vs 39% after) but with the association of a controlateral cancer (P = 0.03). Locally ten of the 54 mastectomy presented a thoracic recurrence, often in case of multicentric breast recurrence (P = 0.05) and not significantly when skin or areola were invaded by carcinoma.

Adenocarcinoma↗

Significant influence of accompanying chronic hepatitis status on recurrence of hepatocellular carcinoma after hepatectomy. Result of multivariate analysis.

OBJECTIVE: The aim of this study was to evaluate the correlation between the histologic status of accompanying chronic hepatitis and the recurrence rate of hepatocellular carcinoma (HCC) after hepatectomy by multivariate analysis. SUMMARY BACKGROUND DATA: Recent studies have suggested that a considerable number of intrahepatic recurrence of HCC after hepatectomy might be the results of metachronous multicentric hepatocarcinogenesis. The authors hypothesized that the incidence of recurrence due to metachronous multicentric hepatocarcinogenesis would depend on the histologic status of accompanying chronic viral liver disease, which is a main promoter of HCC. METHODS: One hundred ten patients with HCC who underwent curative resection were studied. Histologic status of accompanying chronic hepatitis was classified into the three categories: 1) normal liver or chronic persistent hepatitis (CPH, n = 13), 2) chronic aggressive hepatitis (CAH, n = 50), and 3) liver cirrhosis (LC, n = 47). RESULTS: The Cox multivariate proportional hazard model showed that the accompanying chronic viral hepatitis status (p = 0.0133), extent of hepatectomy (p = 0.0078), and number of tumors (p = 0.0475) were significantly predictive variables for recurrence-free survival. By the log-rank test, recurrence-free survival rate in patients with CPH was significantly higher than those in patients with CAH (p = 0.0005) and LC (p = 0.0075). Patients with CAH had the lowest recurrence-free survival rate (vs. LC, p = 0.028). CONCLUSIONS: The results of this study indicated the significant influence of histologic activity of hepatitis on recurrence of HCC. This might support the concept of significant contribution of multicentric hepatocarcinogenesis to recurrence of HCC after hepatectomy.

Adult↗

[Recurrence of varicose veins after treatment. Multicenter study by the Italian Doppler Club, Clinical and Technological Society].

BACKGROUND: The first results of a multicentric study dealing with recurrent varicose veins after surgery are presented. The aims of the study are: identifying the type of varicose vein, specifying the most frequent complaints (esthetical or functional), locating the causes of recurrence, establishing the causes and the most frequent seat of recurrence, clarifying whether it is enough to call recurrent all the varicose veins which appear after surgery or whether it is necessary to distinguish various typologies. METHODS: 194 patients (139 women and 55 men) aged 51.6 average (range 28-87), have been studied up to now with duplex and color scanner following a precise protocol which consisted of three stages: before treatment, within 2 months from treatment and after recurrence of varicose veins or venous insufficiency symptoms. RESULTS: Recurrent varicose veins represented 65.7%, residual ones 14.3%, new ones 2.5%. It has not been possible to identify the type of varicose vein in 8.3% of cases. Stripping of the great saphenous veins was carried out in 88% of cases, short stripping in 4.1%, stripping of the short saphenous veins in 6.9%. Recurrent varicose veins were due to technical error in 78.7% of cases, to diagnostic error in 9.2%, to unidentifiable causes in 12% of cases. CONCLUSIONS: Data relating to the prospective study of the research will be published in subsequent papers.

Adult↗

Recurrence of intracranial meningiomas: the role played by regional multicentricity. Part 2: Clinical and radiological aspects.

Globular single meningiomas are generally regarded as benign tumors that can be completely removed. Nevertheless, after a total macroscopic resection including the insertion zone (Grade 1 operation according to Simpson's classification), the incidence of recurrence ranged from 9% to 14% at the 5-year follow-up review. The authors have shown that single meningiomas represent only the visible predominant growth in the midst of a wide neoplastic field in the dura mater. Regional multiplicity in meningiomas would thus seem to be the rule. With this in mind, the authors propose to divide recurrences after Grade 1 operations into true local and false regional. A local recurrence is defined as a regrowth within the limits of the previous dural flap. Regional recurrence is when new growth develops outside the previous craniotomy site; this should not be considered as a recurrence but as a new primary site. These regional recurrences might explain some unexpected late tumor growth occurring after a Grade 1 operation. Five illustrative cases in which regional recurrence was detected by computerized tomography are presented. The authors also propose to add a supplementary grade to Simpson's surgical grading: Grade 0. This operation would entail a wide resection of the dura around the attachment zone of the meningioma. The authors hope that with a Grade 0 operation the incidence of recurrence might be reduced.

Adult↗