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[Diffuse bile duct papillomatosis: high rate of recurrence and risk of malignant transformation].

Bile duct papillomatosis is a rare disease. It is characterised by multicentric papillary lesions of the intra- and/or extrahepatic biliary epithelium. Because of its slow progression, its high rate of recurrence and significant risk of malignant transformation, it is an important cause of obstructive neoplastic bile duct diseases. We report one of these rare cases with the typical clinical signs and exceptional long survival time of eight years: After a history of fifteen years of recurrent epigastric pains the diagnosis of a diffuse biliary papillomatosis was made after surgery. Five years postoperatively a bile duct carcinoma has developed. After a R1-resection of the tumor, the patient was again free of complaints up to the appearances of multiple metastases two years later. He died a year later of metastasizing disease. We discuss the pathological and clinical aspects of this disease and review the literature.

Aged↗

[Diagnostic and therapeutic concepts of HPV infection in HIV-positive women].

Among HIV-seropositive women there is a high prevalence of anogenital human papillomavirus (HPV) infection. HPV-DNA is more frequent detected in cervicovaginal-lavage specimens from HIV-seropositive women as in those from HIV-seronegative women. We and others suggest that HIV-infection increases the risk to have HPV-associated lesions of the lower female genital tract, especially the risk for developing a squamous intraepithelial lesion of the cervix. In this report we describe the current diagnostic and therapeutic strategies in HIV-seropositive women with HPV-infection. The gynecological examination should be performed at six to twelve month intervals, including the colposcopy and the Pap smear test. We hope to improve the quality of our screening program by doing an additional HPV-test. At last we investigate the CD4+ T-lymphocyte counts because it is observed that women with low CD4+ cell counts (< 200/microliter) were more likely to have persistent HPV-infection as those with higher counts (> 500/microliter). The treatment method is dependent on the development of the HPV-associated lesion and the clinical status of the HIV infected women. In cases with external warts local application of Condylox should be the first line treatment. Probably in about few months we could use other drugs like Wartec or Aldara in Germany. But the effectiveness of these drugs in HIV-positive women has to be proven yet. In the cause of persistence of external warts or recurrence of the disease the systemical application of Intron A or Roferon A is possible. The CO2-lasertreatment is performed under colposcopic guidance, especially in cases with multicentric condylomatous lesions. The treatment of cervical intraepithelial neoplasia (CIN) by CO2-laservaporisation or Loop Electrosurgical Excision Procedure (LEEP) is based on the clear colposcopic visualisation of the upper limit of the lesion. If CIN reaches the endocervix, being out of colposcopic view, and the squamocolumnar junction is localised in the endocervical canal conisation by laser or cold knife has to be performed. Before performing the treatment of CIN one should exclude multicentric cervical, vaginal and vulval intraepithelial neoplasia by colposcopy, because multicentric intraepithelial neoplasia of the lower female genital tract is more frequently than in HIV-seronegative women. Multicentric disease seems to be one cause of the high recurrence of HIV-seropositive women. However, higher levels of immunosuppression (CD4+ T-lymphocyte counts < 200/microliter) are also important determinants of recurrence of the disease. Therefore, an accurate short-term follow-up with colposcopy, Pap test and HPV test should be carried out after the treatment of HIV-seropositive women with low CD4+ counts.

Comorbidity↗

Clinical analysis of the risk factors for recurrence of HCC and its relationship with HBV.

AIM: To comprehend the risk factors of recurrence of hepatocellular carcinoma (HCC) and its relationship with the infection patterns of hepatitis B virus (HBV). METHODS: All materials of 270 cases of postoperative HCC were statistically analyzed by SPSS software. Recurrence and metastasis were classified into early (< or =2 years) and late phase (>2 years). Risk factors for recurrence and metastasis after surgery in each group were analyzed. RESULTS: Out of 270 cases of HCC, 162 cases were followed up in which recurrence and metastasis occurred in 136 cases. There were a lot of risk factors related to recurrence and metastasis of HCC; risk factors contributing to early phase recurrence were serum AFP level, vascular invasion, incisal margin and operative transfusion, gross tumor classification and number of intrahepatic node to late phase recurrence. The HBV infective rate of recurrent HCC was 94.1%, in which "HBsAg, HBeAb, HbcAb" positive pattern reached 45.6%. The proportion of HBV infection in solitary large hepatocellular carcinoma (SLHCC) evidently decreased compared to nodular hepatocellular carcinoma (NHCC) (P<0.05). CONCLUSION: The early and late recurrence and metastasis after hepatectomy of HCC were associated with different risk factors. The early recurrence may be mediated by vascular invasion and remnant lesion, the late recurrence by tumor's clinical pathology propert, as multicentric carcinogenesis or intrahepatic carcinoma de novo. HBV replication takes a great role in this process. From this study, we found that SLHCC has more satisfactory neoplasm biological behavior than NHCC.

Adult↗

Approaches to discontinuing efalizumab: an open-label study of therapies for managing inflammatory recurrence.

BACKGROUND: Efalizumab is a humanized recombinant monoclonal IgG1 antibody for the treatment of moderate-to-severe plaque psoriasis. When treatment discontinuation is necessary, however, some patients may experience inflammatory recurrence of the disease, which can progress to rebound if untreated. This analysis evaluated approaches for managing inflammatory recurrence after discontinuation of efalizumab. METHODS: An open-label, multicentre, investigational study was performed in 41 patients with moderate-to-severe plaque psoriasis who had recently completed clinical studies with efalizumab and had developed signs of inflammatory recurrence following abrupt cessation of treatment. Patients were assigned by the attending physicians to receive one of five standardised alternative systemic psoriasis treatment regimens for 12 weeks. Efficacy of the different therapy options was assessed using the physician's global assessment (PGA) of change over time. RESULTS: More favourable PGA responses were observed in patients changing to cyclosporin (PGA of 'good', 'excellent' or 'cleared': 7/10 patients, 70.0%) or methotrexate (9/20, 45.0%), compared with those receiving systemic corticosteroids (2/8, 25.0%), retinoids (0/1, 0.0%) or combined corticosteroids plus methotrexate (0/2, 0.0%). While the majority (77.8%) of patients showed inflammatory morphology at baseline, following 12 weeks of the alternative therapies the overall prevalence of inflammatory disease was decreased to 19.2%. CONCLUSION: Inflammatory recurrence after discontinuation of efalizumab therapy is a manageable event, with a number of therapies and approaches available to physicians, including short courses of cyclosporin or methotrexate.

Adrenal Cortex Hormones↗

[Diagnosis and treatment for recurrent hepatocellular carcinoma].

In order to investigate the mechanism of recurrence of hepatocellular carcinoma (HCC), 322 patients with HCCs (size: < or = 3 cm) treated by percutaneous ethanol injection (PEI), transcatheter arterial embolization (TAE) or radiation therapy were evaluated. Cumulative recurrent rates of new lesions after the initial therapy were 25% (1-year), 57% (2-year) and 71% (3-year). In 116 patients whose tumors were multiple at the time of initial therapy, the recurrent rates were higher compared with 206 patients with a single tumor. In 228 of all patients, new lesions were observed in the noncancerous liver after initial therapy. We observed a single new lesion in 67% of the 134 patients, whose HCC was single at the time of initial therapy. In the remaining 33% of these patients, multiple new lesions were observed. As for the recurrence site, we found new lesions at a different segment of the liver from the initial HCC in 52% of these 134 patients. In the patients with multiple recurrent HCCs, the survival rates were lower in comparison with the patients whose recurrent HCC was single. In the patients whose new lesions were found within 1 year after the initial therapy, the survival rates were also lower compared with the patients whose new lesions were not detected during 1 year. In conclusion, the mechanism of multicentric occurrence may be closely correlated with the intrahepatic recurrence of HCC in consideration of the high incidence of recurrent rates of HCCs and their recurrent pattern.

Antineoplastic Agents↗

Definition of local recurrence after surgery for rectal carcinoma.

Local recurrence rates of rectal carcinoma have been analysed among 284 patients in a prospective randomized multicentre trial of adjuvant preoperative radiotherapy for locally advanced rectal carcinoma. Wide variations in local recurrence rates are demonstrated depending on the definition of local recurrence employed and the subgroup studied. Thus after surgical operation alone, rates as high as 43.3 per cent or as low as 12.7 per cent can be calculated. After both adjuvant preoperative radiotherapy and operation the overall local recurrence rate is 12.8 per cent, although the local recurrence rate inside the radiotherapy field (true recurrence) may be as low as 2.3 per cent. It is recommended that local recurrence after operation for rectal carcinoma be defined as any detectable local disease at follow-up, occurring either alone or in conjunction with generalized recurrence, in patients who have undergone resection. A rate should be given both for all patients and for those operated on for cure, but not for the latter group alone as this could introduce bias.

Humans↗

Vascular tumors of bone: A study of 17 cases other than ordinary hemangioma, with an evaluation of the relationship of hemangioendothelioma of bone to epithelioid hemangioma, epithelioid hemangioendothelioma, and high-grade angiosarcoma.

Cases filed as vascular tumor of bone other than ordinary hemangioma were reviewed. They were included in the study if there was adequate histologic material and clinical information, clear evidence of bone origin, and at least 5 years follow-up. The study group comprised 17 cases, of which 13 were categorized as hemangioendothelioma of bone, 1 as epithelioid hemangioendothelioma, and 3 as high-grade angiosarcoma. Hemangioendothelioma of bone had growth patterns varying from vasoformative to solid, but well-formed vessels were present in at least some area in all cases. The cells generally had a rounded, epithelioid character, regular nuclei, and relatively few mitotic figures; occasional features included spindle cells and scattered enlarged, hyperchromatic or pleomorphic nuclei. Lymphoplasmacytic and eosinophilic inflammatory infiltrate ranged from prominent to slight or absent, and myxoid or hyaline stroma was never more than focal. Epithelioid hemangioma could not be separated from hemangioendothelioma of bone. The single epithelioid hemangioendothelioma for the most part had cords of relatively uniform epithelioid cells in a prominent myxoid stroma but focally demonstrated an angiosarcoma-like appearance, with irregular vascular spaces and marked nuclear pleomorphism. The high-grade angiosarcomas exhibited predominantly irregular vasoformation combined with solid areas, diffuse nuclear hyperchromatism and pleomorphism, and, in 2 cases, numerous mitotic figures (the third case had only a small biopsy and a postradiation amputation specimen). Of the hemangioendotheliomas of bone, 7 were unicentric and 6 were regionally multicentric either concurrently or sequentially. Three patients had intraosseous local recurrence, 2 had discontinuous regional skin or soft tissue involvement (including the popliteal artery in 1), and 1 had a solitary lung metastasis, but none died of tumor. The patient with epithelioid hemangioendothelioma had multicentric tumors in widely separated bones and died with liver and lung metastases. Two of the high-grade angiosarcomas were unicentric, and the third was regionally multicentric, with a popliteal artery-soft tissue component as well. All 3 of these patients died with metastases in various sites.

Adolescent↗

[Recurrence of intracardiac myxoma. A propos of 6 patients among 85 surgically treated].

It was sought to determine whether recurrent cardiac myxomas had special etiological, surgical and/or pathological features differentiating them from usual forms. This involved study of 6 recurrences occurring in 85 patients treated surgically between 1959 and 1989, as well as 33 well documented recurrences in the literature. True recurrent myxomas in young adults have a definite familial nature, frequently occurring within the context of Craney's complex and are due to a multicentre onset. Closer postoperative monitoring is therefore required in such cases. Recurrence of sporadic myxomas is generally due to incomplete excision and can be avoided by precautions regarding operative technique.

Adolescent↗

Accuracy of radiology in detection of hepatocellular carcinoma before liver transplantation.

BACKGROUND/AIMS: Recurrence of hepatocellular carcinoma (HCC) after orthotopic liver transplantation (OLT) depends on tumor size and number; the accuracy of radiology in detecting HCC is uncertain. This study compared tumor size at radiological and pathological examination in 30 patients with HCC who underwent OLT. METHODS: Pre-OLT radiology included ultrasonography (US), computerized tomography (CT), and hepatic angiography (HA). Sensitivity of radiology was calculated by comparison with pathology. RESULTS: Radiology missed HCC in two patients but showed five with small (< 4 cm) and eight with large (> 4 cm) lesions. Multicentricity was shown in 15 cases at radiological examination and 24 at pathological examination, including one incidental and 4 of 5 radiologically small HCC. Mean tumor bulk was 3.4, 74, 338, and 1375 cm3, respectively, in patients with incidental, small, large, and multicentric HCC at radiology. Sensitivities of US, CT, and HA in detection of HCC (and multicentricity) were 80% (16.6%), 86.6% (58.3%), and 90% (58.3%). No recurrence was found in patients with incidental or small HCC; even when multicentric. CONCLUSIONS: US, CT, and HA identified patients with small or large tumor bulk, but sensitivity in detecting satellites was poor; their finding in patients with radiologically small or incidental tumors does not affect outcome. The failure of US, CT, and HA to detect satellites must be considered in patients undergoing partial hepatectomy for HCC.

Carcinoma, Hepatocellular↗

Intrahepatic distant metastasis and metachronous multicentric occurrence in solitary hepatocellular carcinoma of less than five centimeters in diameter.

During the 7 years from 1984 to 1990, 36 patients underwent liver resection for solitary hepatocellular carcinoma (HCC) measuring less than 5 cm in diameter, with no intrahepatic vascular invasion on imaging diagnoses and no macroscopic infiltration into the tumor capsule or surrounding tissues. Although HCC is less likely to cause intrahepatic adjacent metastasis to the cut liver surface, an analysis revealed the possibility of intrahepatic distant metastasis and metachronous multicentric occurrences, even after complete removal of the primary tumor. The 5-year cumulative survival rate was 53%, while the 5-year cumulative recurrence-free survival rate was 19%. Of the 36 patients, 18 (50%) had suffered a recurrence by April, 1992, one with extrahepatic metastasis. Recurrence of intrahepatic metastasis was multifocal in 5 patients, single and adjacent in 1, and single (or a few) and distant in 11. Multifocal recurrence was observed within 1 year after liver resection. The sole single and adjacent metastatic case occurred in one of eight patients in the recurrent group in whom distance of the surgical margin was less than 1 cm [TW(+)]. Multicentric occurrence was found in 6 of 13 patients (46%) whose recurrent tumors were examined histologically, and all belonged to the "single (or a few) and distant" type of recurrence. In this report, we also present two typical cases of metastasis, one being multifocal metastasis occurring within 3 months after liver resection and the other being intrahepatic metastasis occurring after a 4-year-dormant state, to demonstrate the complicated nature of the intrahepatic metastatic pattern.

Adult↗

Prevention of early recurrence of high risk malignant melanoma by coumarin. Irish Melanoma Group.

Coumarin (1,2-benzopyrone) as a daily oral dose of 50 mg was evaluated in a multicentre prospectively randomized, double-blind, placebo-controlled trial to prevent early recurrence of malignant melanoma TNM Stage IB (Breslow thickness greater than 1.70 mm) and Stage II. Intake for the trial started in 1984 and was stopped prematurely, after review, in 1987. There were two recurrences in 13 treated patients and 10 in 14 controls which was significant (P 0.01). The sites of the metastases differed in each group, being local and in bone in the treated group, and in lymph nodes, skin and lung in the control group. There were no toxic effects associated with coumarin treatment and all patients without recurrence are now receiving coumarin.

Adult↗

Chemotherapy with cisplatin and paclitaxel in patients with locally advanced, recurrent or metastatic oesophageal cancer.

Single-agent therapy with paclitaxel is effective against both squamous cell carcinoma and adenocarcinoma of the oesophagus. However, only limited data are available on the combination of paclitaxel with other cytotoxic drugs in this entity. Patients with unresectable stage III, recurrent or metastatic tumours were treated in a multicentre setting with paclitaxel 90 mg m(-2) given over 3 h intravenously, followed by cisplatin 50 mg m(-2). The courses were repeated every 14 days. Twenty patients with squamous cell carcinoma or adenocarcinoma of the oesophagus were evaluable for response. The overall remission rate was 40% (8/20), including 15% (3/20) clinically complete responses. Clinical benefit response, defined as relief of dysphagia and/or significant gain in weight, was achieved in 70% of the patients. Neutropenia of CTC grade 3 occurred only in 10% of the patients; no grade 4 neutropenia and no severe thrombocytopenia was encountered. CTC grade 4 neurotoxicity was seen in 5% of patients. Cisplatin/paclitaxel administered every 14 days, was effective in patients with poor prognosis oesophageal cancer and toxicity was acceptable.

Adenocarcinoma↗

Laparoscopic cure of small ventral hernias with composite mesh.

BACKGROUND: The use of mesh is recommended to reduce the rate of recurrence after the curing of ventral hernias. METHODS: A multicentre prospective trial was conducted to assess the laparoscopic cure of small ventral hernias with a composite mesh. RESULTS: Around 222 patients entered the trial and received laparoscopic repair for ventral hernias of less than 5 cm. There was one conversion. The mean length of post-operative hospitalisation was 2.5 days. At 1 year, the recurrence rate was 2%. Two meshes were removed due to infection, 3% of the patients were using analgesics and 86.1% of the patients described no pain on EVA scoring. CONCLUSION: The laparoscopic cure of small ventral hernias with composite mesh is efficient. Further technical progress is warranted to reduce the rate of seroma formation.

Adult↗

[Conservative treatment of sub-clinical noninfiltrating cancers of the breast (102 EOA in situ, TONO)].

102 patients with sub-clinical intra ductal non invasive breast cancer (T0N0) treated by limited surgery and curative radiation therapy. Follow-up ranged from 2 to 10 years with a median follow-up of 59 months. The long term survival rate of this therapeutic approach, consisting of simple excision without any adjuvant treatment and radical mastectomy was close to 100%. The actuarial local recurrence rate was only 8.6% at 10 years (confidence interval: 4.6 to 12.6%), which strongly suggests that radiation therapy is active on multicentric foci. Salvage surgery could be performed in every case of local recurrence. The survival rate of in situ breast cancer (T0N0) treated by conservative radio-surgery is comparable to that of radical mastectomy, while cosmetic results and psychological impact appear to be better for the conservative technique (breast preservation rate = 91 to 96%).

Breast Neoplasms↗

Pancreatic carcinoma recurrence in the remnant pancreas after a pancreaticoduodenectomy.

CONTEXT: We report a rare case of a repeated pancreatic resection in the remnant distal pancreas 18 months after a Whipple R0 procedure. CASE REPORT: In September 2003, a 63-year-old man underwent a Whipple procedure with an extended lymphadenectomy, portal vein resection and direct reconstruction for pancreatic cancer. In September 2004, the tumor marker level increased and MR revealed a tumor in the remnant pancreas. There were no findings of invasion into the surrounding tissue or distant metastasis. After three months of systemic chemotherapy and a radiological reevaluation (PET and CT) in March 2005, we removed the remnant pancreas. Histopathologically, the tumor was classified as a ductal adenocarcinoma like the tumor which had been removed during the first operation, with infiltration of peripancreatic adipose tissue and a segmentary tract of the transverse mesocolon, without lymph node metastasis. CONCLUSIONS: There are very few reports of pancreatic carcinoma recurrence in the remnant pancreas after a pancreaticoduodenectomy in the literature. In most of these cases, it is difficult to assess whether the remnant pancreatic cancer is a recurrence or a second primary cancer. In our patient, the first hypothesis seems to be more realistic due to the brief recurrence-free survival period. Otherwise the high rate of multicentricity in pancreatic cancer may also explain the development of a secondary cancer in the remnant pancreas, even though the interval was relatively brief.

Adenocarcinoma↗

Analysis of treatment failures in patients with early-stage uterine leiomyosarcoma.

This retrospective study aimed to investigate the treatment failures in 26 patients with stages I-II uterine leiomyosarcoma (> or = 10 mitoses per 10 high-power field (HPF) who underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy +/- adjuvant external pelvic irradiation. Thirteen (50%) patients developed recurrent disease, after a median time of 10 months from surgery (range = 4-72 months). Recurrence was pelvic in 3 (23%) patients, extrapelvic in 9 (69%) patients, and both pelvic and extrapelvic in 1 (8%) patient. Disease-free survival was better for premenopausal than for postmenopausal patients (p = 0.002) and for patients with < 20 mitoses per 10 HPF than for those with > or = 20 mitoses per 10 HPF (p = 0.006). In conclusion, patients with early-stage disease who had undergone locoregional treatment experienced a high recurrence rate. Most of the treatment failures were extrapelvic. Multicentric randomized trials on the role of adjuvant chemotherapy are advocated.

Combined Modality Therapy↗

Assumptions in the radiotherapy of glioblastoma.

In the light of advances in computerized tomography (CT), we have retrospectively evaluated the assumptions that underlie the radiation therapy of glioblastoma: (1) No neuroradiologic technique provides an accurate delineation of tumor bulk and location, (2) glioblastoma is commonly multicentric, and (3) a major source of therapeutic failure is recurrence beyond radiotherapy fields. 1. CT scans, performed on glioblastoma patients within 2 months of postmortem examination, defined both gross and microscopic tumor extent (within a 2-cm margin) in all but 6 of 35 patients evaluated. The major source of error was subependymal spread (four patients). 2. Multicentricity occurred in only 4% of untreated and 6% of treated (radiotherapy with or without chemotherapy) patients. All multicentric lesions were identified on CT scans. 3. Serial CT scans on 42 patients revealed that glioblastoma recurred within a 2-cm margin of the primary site in 90%. Occurrences outside this margin were accurately delineated by CT in all instances. Because most patients show recurrence within or in close proximity to the original site, current radiation doses would appear to be inadequate for therapy of the primary tumor. CT scan accuracy may permit smaller-field and higher-dose irradiation therapy for glioblastoma.

Brain Neoplasms↗