Innovative therapeutic approach: sequential treatment with plasma exchange and eculizumab in a pregnant woman affected by atypical hemolytic-uremic syndrome.

The atypical HUS (aHUS) is a rare genetic disease, with poor prognosis, characterized by microangiopathic hemolytic anemia, thrombocytopenia and acute renal failure. This syndrome is often related to mutations in the genes encoding complement regulatory proteins. A 26-year-old woman with homozygous mutation in complement factor H (CFH) developed a relapse of aHUS at 17th week of pregnancy. Despite treatment with plasma exchange (PEX), at the 26th week of gestation eculizumab was started. The sequential treatment with eculizumab after PEX was well tolerated and it has led to clinical remission.

[Prognostic value of psychotropic drugs for the risk of accidental falls]. / Valore prognostico dei farmaci psicotropi nel rischio caduta.

Falls in the elderly are common and often serious. Older adults often take numerous medications for multiple chronic conditions, so they have an increased risk for drugs that potentially cause falls. We studied the association between psychotropic drugs and falls in residential care people in order to identify medications that may increase the falls risk. A prospective case control study was performed in the nursing home of Local Health Care. We assessed the incidence of patient falls during admission in nursing home in 2007 and 2008. We compared psychotropic medications (antipsychotic drugs N05B, anxiolytics N05B, antidepressants NO6A, anticholinesterases NO6D) taken by all patients who fell (140 cases) with those taken by patients who did not fall (140 controls), paired with an allocation ratio of 1:1 for the same age (quinquennial classes), sex, time of admission to nursing home. The probability of falls increased when the patients used antipsychotic drugs (OR 1.91; 95% CI 0.47, 0.19; p = 0.0114) and when the number of psychotropic drugs is equal to or greater than 2 the risk of falling increases more. (OR 2.3; 95% CI 0.56, 0.18;p = 0.0036). This work reinforces the importance of routine medication reviews, especially in elderly exposed to psychotropic polypharmacy regimens that include antipsychotic drugs.

Liver transplantation for hepatocellular carcinoma: results of down-staging in patients initially outside the Milan selection criteria.

Conventional criteria for liver transplantation for patients with hepatocellular carcinoma are single HCC

p27 and Skp2 immunoreactivity and its clinical significance with endocrine and chemo-endocrine treatments in node-negative early breast cancer.

BACKGROUND: Low p27 and high Skp2 immunoreactivity are associated with a poor prognosis and other poor prognostic features including resistant phenotypes and antiestrogen drug resistance. We investigated these proteins in two International Breast Cancer Study Group trials studying node-negative early breast cancer. PATIENTS AND METHODS: Trial VIII compared chemotherapy followed by goserelin with either modality alone in premenopausal patients. Trial IX compared chemotherapy followed by tamoxifen with tamoxifen alone in postmenopausal patients. Central Pathology Office assessed p27 and Skp2 expression in the primary tumor by immunohistochemistry among 1631 (60%) trial patients. RESULTS: p27 and Skp2 were inversely related; 13% of tumors expressed low p27 and high Skp2. Low p27 and high Skp2 were associated with unfavorable prognostic factors including larger size and higher grade tumors, absence of estrogen receptor and progesterone receptor, human epidermal growth factor receptor 2 overexpression and high Ki-67 (each P < 0.05). Low p27 and high Skp2 were not associated with disease-free survival (P = 0.42 and P = 0.48, respectively). The relative effects of chemo-endocrine versus endocrine therapy were similar regardless of p27 or Skp2. CONCLUSIONS: We confirm the association of low p27 and high Skp2 with other poor prognostic features, but found no predictive or prognostic value, and therefore do not recommend routine determination of p27 and Skp2 for node-negative breast cancer.

Pelvic factor infertility: diagnosis and prognosis of various procedures.

Infertile women are examined to exclude tubal occlusion or a pelvic factor through indirect tests, such as hysterosalpingography (HSG), sonohysterosalpingography/hysterosalpingosonography (SH), and/or laparoscopy (Lps). Assisted reproductive technologies (ART) are proposed to resolve infertility according to the results of the above-mentioned diagnostic procedures. Today, Lps still represents the second option after several failures of in vivo attempts and before moving to conceive in vitro. The aim of this study was to establish the diagnostic power of HSG and SH compared with that of Lps and the efficacy of ART when each single test is used as an inclusion criterion. We recruited 2560 infertile women (aged 20 to 35) to undergo diagnostic and therapeutic procedures to address their infertility in our clinical theatre. Of these, 1080 women underwent Lps and hysteroscopy (Group 1), 525 underwent HSG (Group 2), and 955 underwent SH (Group 3). The positive and negative predictive values of sonosalpingosonography were 75.8% and 91.2% and those of hysterosalpingography were 71.8% and 88.2%, respectively. Endometriosis (stage II-IV of the revised American Society for Reproductive Medicine [ASRM] classification) was diagnosed laparoscopically in 344 out of 1080 women (32%). Only 44 women (13%) with endometriosis showed bilateral tubal occlusion. Pelvic factors other than tubal occlusions are neither diagnosed nor treated in a timely manner by indirect tubal patency tests. The conventional use of HSG and/or SH may increase the time required to find an adequate treatment by which to achieve a successful pregnancy.

Randomized trial of omeprazole or ranitidine versus placebo in the prevention of chemotherapy-induced gastroduodenal injury.

PURPOSE: Anticancer drugs may induce acute mucosal injury to stomach and duodenum. This study was planned to evaluate the efficacy of omeprazole or ranitidine in preventing such an injury. PATIENTS AND METHODS: Two hundred twenty-eight cancer patients with normal stomach and duodenum or with less than three erosions, who were selected to be treated with cyclophosphamide, methotrexate, and fluorouracil (90 breast carcinoma patients) or fluorouracil alone (138 colon carcinoma patients), were randomly assigned to treatment with omeprazole 20 mg, ranitidine 300 mg, or one placebo tablet a day. Seven days after the second course of chemotherapy (CT), the patients underwent a further esophagogastroduodenoscopy to evaluate the mucosal injury. Endoscopic findings were quantified on the basis of an arbitrary score, and the occurrence of epigastric pain or heartburn was assessed weekly. RESULTS: A significant difference was found among the three groups (P =.0032), as well as between pre- and postCT endoscopic findings (P =.00001). Endoscopic scores after CT were significantly higher than pretreatment scores in the placebo (P =.003) and ranitidine (P =.003) groups but not in the omeprazole group (P =.354). Acute ulcers were significantly less frequent in patients receiving omeprazole or ranitidine than in those receiving placebo (P =.0001 and P =.0315, respectively). Epigastric pain and/or heartburn were significantly less frequent in patients receiving omeprazole (P =.00124) or ranitidine (P =.038) than in those receiving placebo. CONCLUSION: Omeprazole is effective in preventing chemotherapy-induced gastroduodenal injury. Ranitidine is effective in reducing the frequency of ulcers and upper gastrointestinal symptoms but is not effective in preventing the global endoscopic worsening caused by chemotherapy. The different efficacy of omeprazole and ranitidine can be explained by their different pharmacodynamics.

The use of indocyanine green to detect sentinel nodes in breast cancer: a prospective study.

BACKGROUND: Although Indocyanine green (ICG) is used to find sentinel nodes (SN) in patients with breast cancer (BC), its role in clinical practice is still debated, and needs a definitive validation to be included in the standard approach to finding sentinel nodes in breast cancer. MATERIALS AND METHODS: To validate the ICG methods of detecting the SN in BC we have recently concluded a prospective validation trial. Patients with clinically node-negative, invasive early BC scheduled for breast surgery and SN biopsy were included in the trial. All the patients underwent SN detection using both the standard-of-care procedure using radioisotope technetium (99mTc) and the ICG, using the Photodynamic Eye camera. A comparison of the detection rate and the diagnostic accuracy of the two methods was performed to detect the equivalency of the two approaches. RESULTS: At the end of the enrollment, 301 patients were considered eligible and included in the trial, and 589 nodes were removed. Five hundred and eighty-three nodes (99%) were identified with ICG (median 2 nodes per patient) and 452 (76.7%) were identified with 99mTc (median 2 nodes per patient). A concordance index of 98.75% (CI, 95% = 97.1%-99.5%) was detected. The dosage given ranged from 0.3 to 1.4 ml. ICG was used in all patients eligible for SN biopsy without any significant acute side effects. CONCLUSIONS: The index of concordance between 99mTc and ICG seems to be extremely high, suggesting that ICG could be validated as an alternative method to 99mTc in the detection of SN in BC.

Vinorelbine chemotherapy in non small cell lung cancer: experience in elderly patients.

This study involved 25 elderly (> 65 years old) patients (pts) with unresectable non small cell lung cancer (NSCLC) who were not eligible for polychemotherapy. The diagnosis of NSCLC was histologically or cytologically documented, and all of them had measurable or evaluable disease. The median age of the patients was 71 (range 65-77); 9 had been pretreated. The pts received 25 mg/m2 of vinorelbine weekly or bi-weekly depending on the results of blood tests. The treatment continued until disease progression or tolerance. No complete response was achieved: 3 pts (12%) had a partial response (RP) (8-12-14 months), 13 (52%) stable disease (SD) with an improvement in symptoms, such as cough and/or pain, and 9 pts (36%) progressed. Compliance with the therapy was acceptable. The main toxicity was hematological: neutropenia was observed in 16 pts, with only 1 case of grade 4 neutropenia without sepsis; grade 1-2 anemia occurred in 8 patients. The other toxicities included grade 1-2 neurotoxicity in 8 pts, chemical phlebitis in 2 pts and grade 3 cardiotoxicity reversible with medical treatment in 1 patient. The median survival time was 10 months (lower quartile 5 months, upper quartile 23 months) (Kaplan and Meyer method). Vinorelbine can be considered a rational choice in elderly pts with advanced NSCLC who are not suitable for aggressive polychemotherapy, with the aim of improving their quality of life in terms of symptoms and outpatient treatment.

Paclitaxel efficacy and tolerability in second-line treatment of refractory and relapsed ovarian cancer patients.

Nineteen patients with recurrent or refractory ovarian carcinoma after a first-line platinum-based chemotherapy were treated with a 3-hour i.v. infusion of paclitaxel 175 mg/m2 every 3 weeks from November 1992 to October 1996. The major hematologic toxicity was neutropenia (63.2%). No febrile neutropenia was observed. Other hematologic effects were leukopenia (47.4%) and anemia (47.4%). The main non-hematologic toxicities were as follows: neuropathy (52.6%), nausea and vomiting (36.8%), myalgia (36.8%), cardiac toxicity (15.8%) and mucositis (10.5%). Alopecia was observed in the majority of cases. The overall response rate was 47.4%, with 5 (26.3%) complete responses (CRs) and 4 (21.1%) partial responses (PRs). The median duration of response was 7 months (range: 3-19), with a median follow-up of 17 months (range: 3-61). Quality of life of responding patients was good. Our results confirm that paclitaxel as second-line therapy in relapsed and refractory ovarian cancer patients is an acceptable treatment with a good safety profile, and can be safely administered at the dose of 175 mg/m2. In our study paclitaxel was more active in relapsed than in refractory patients. Consequently, further studies are needed to identify more effective drugs for the refractory subset.

[Subacute cerebellar degeneration and pleural mesothelioma. Report of a case]. / Degenerazione cerebellare subacuta e mesotelioma pleurico. Descrizione di un caso.

Subacute cerebellar degeneration is an autoimmune disorder and represents the paraneoplastic neurologic syndrome most frequently occurring in the central nervous system. To our knowledge, until now, no case of such a paraneoplastic syndrome as been described in patients with mesothelioma; on the contrary, some non-neurologic paraneoplastic syndromes have been described in patients with mesothelioma, and an aberrant production of cytokines has been suggested as the main pathogenetic event. In our report it can be supposed that an aberrant production of cytokines might have triggered an autoimmune reaction, causing anti Purkinje cells antibodies production, neurological damage and clinical outcome.

Lipoplatin monotherapy: A phase II trial of second-line treatment of metastatic non-small-cell lung cancer.

Lipoplatin is a liposome encapsulated form of cisplatin. phase i studies on lipoplatin have demonstrated that the compound has an excellent toxicity profile. therefore we performed a phase ii trial in heavily pre-treated patients with advanced non-small-cell lung cancer (NSClC), performance status 0-2 in which the primary endpoint was response rate and secondary endpoints were safety and overall survival.Nineteen patients, average age 64 years old, with stage iV NSClC, were treated with lipoplatin 100 mg/m(2) every two weeks, as second line chemotherapy.We observed 1 partial remission (5.2%) and 3 stable diseases (15.9%). Time to progression (ttp) was 16 weeks and median overall survival (OS) was 31 weeks (7.2 months). We observed G1-G2 toxicity during chemotherapy, mainly gastrointestinal with nausea and vomiting (4 patients), asthenia (3 patients), mucositis (2 patients) and anemia (4 patients).Our phase ii study does not support a more extensive use of lipoplatin in phase III studies. An increase of dosage and a better selection of patients are mandatory to understand the real therapeutic activity of lipoplatin.

Hemolytic-uremic syndrome during therapy with estramustine phosphate for advanced prostatic cancer.

3 weeks after commencing treatment with estramustine phosphate, typical manifestations of hemolytic-uremic syndrome occurred in a 66-year-old patient with prostate cancer. Urinary tract obstructions were excluded and no renal damage could be identified. An improvement in renal function was achieved by stopping estramustine phosphate and infusing adequate amounts of fluids and electrolytes. Anemia and thrombocytopenia also progressively improved after the discontinuation of chemotherapy. Nausea and vomiting, hepatotoxicity, impotence, reduced libido and hypercalcemia are major side effects of estramustine phosphate, and would be difficult to explain our observations without considering the role played by estramustine phosphate. Our observations suggest that estramustine phosphate might play either a direct role or produce a side effect within the context of latent paraneoplastic syndrome. The improvement in renal function which occurred when treatment stopped might confirm our hypothesis.

Combination chemotherapy of carboplatin and gemcitabine against solid tumors: a phase I trial.

BACKGROUND: Some trials have suggested that the combination of gemcitabine and platinum compounds can have a synergistic effect on several solid tumors, but, at present, the data concerning carboplatin-gemcitabine combinations are not sufficient to allow the planning of phase II trials. The present phase I trial was planned to define the maximum tolerated dose and the dose-limiting toxicity of a carboplatin-gemcitabine combination. METHODS: Thirty-two patients with advanced, pretreated solid tumors were treated with carboplatin on day 1 and gemcitabine on days 1, 8, and 15 every 28 days. The starting doses of carboplatin and gemcitabine were 3.5 mg/ml per min (area under the curve; AUC), and 600 mg/m2, respectively. The doses of the two agents were alternately increased to 4, 4.5, and 5 mg/ml per min and to 800 and 960 mg/m2, respectively. At each dose level, three patients were initially enrolled. If one of them experienced grade IV hematological toxicity or grade III-IV nonhematological toxicity (with the exception of alopecia), an additional three patients were enrolled at the same dose level. If two or more patients experienced grade IV hematological toxicity or grade III-IV non-hematological toxicity (with the exception of alopecia), the maximum tolerated dose was considered to have been reached, and the dose below this was recommended for further studies. All patients were evaluated weekly for toxicity and after every two courses of chemotherapy for response. RESULTS: Dose-limiting toxicity was hematological, and the maximum tolerated doses were 4.5 mg/ml per min for carboplatin and 800 mg/m2 for gemcitabine. The activity of the carboplatin/gemcitabine combination was encouraging, with a 21.9% response rate (7/32), three complete disease regressions, and a median time to progression of 30 weeks. The gemcitabine doses of day 15 or days 8 and 15 were omitted for hematological toxicity in 57 (50%) and 17 (14.9%) courses of chemotherapy, while no courses of chemotherapy were delayed for grade III-IV hematological or nonhematological toxicity. CONCLUSION: The maximum tolerated doses suggested by this trial are lower than those in other similar phase I trials, but they are consistent with those reported by most of the trials investigating gemcitabine either in combination with cisplatin or in heavily pretreated patients. Carboplatin 4.5 mg/ml per min on day 1 plus gemcitabine 800 mg/m2 on days 1, 8, and 15 every 28 days may represent a promising schedule for further phase II trials.

Staging of breast cancer: what standards should be used in research and clinical practice?

BACKGROUND: Bone scan (BS), chest X-rays (CXR), liver ultrasonography (LUS) and laboratory parameters (LP) are frequently used as routine staging procedures for breast cancer patients. These procedures are not always appropriate in either clinical or research settings, regardless of the stage. The aim of this study was to identify groups of patients with differing risks for metastases in order to select more precise standard staging procedures. PATIENTS AND METHODS: The staging data relating to 406 breast cancer patients consecutively referred to our institution between November 1989 and October 1996 were analysed including pathological TNN grading and biological parameters. All of the cases with a positive or suspicious pre-operatory staging and who proved to have metastatic disease before surgery or during the first six months of follow-up were considered true-positive; all of the other cases with a positive or suspicious initial staging but with no evidence of distant metastasis before surgery and with a disease-free survival longer then six months were considered false-positive. In the same way all cases with negative initial staging who relapsed during the first six months of follow-up were considered false-negative and those with negative initial staging and with a disease-free survival longer then six months were considered true-negative. Statistical analysis was performed using Fisher's exact test. RESULTS: BS, CXR and LUS, 388, 399 and 398 examinations respectively, were considered available, and 17 (4.38%), six (1.5%) and four (1%), respectively, proved to be true-positive. A statistically significant difference was observed when our cases were grouped according to T status (T4 vs. T1-T2-T3, P < 0.01) and nodal status (N0-N1 cases with less than three involved nodes and N1 with more than three positive lymph nodes N2 patients, P < 0.01). CONCLUSIONS: The present study suggests that breast cancer patients can be divided into three subgroups with different detection rates for distant metastases at staging (0.59%, 2.94% and 15.53%), and that the standard practice should be changed. In the first (T1N0 and T1N1 patients with < or = 3 positive lymph nodes--41.13% of the patients) and the second group (T2N0, T2N1 with < or = 3 positive lymph nodes, T3N0 and T3N1 patients with < or = 3 positive lymph nodes--33.49% of the patients) there is no need for a complete set of staging procedures, whereas full procedural staging is needed in the third group of patients (T4, N1 with > 3 lymph nodes and N2, 25.37% of the patients).