Efficacy and safety of factor VIII/von Willebrand's factor concentrate (Haemate-P) in preventing bleeding during surgery or invasive procedures in patients with von Willebrand disease.

BACKGROUND AND OBJECTIVES: To evaluate the efficacy and safety of the factor VIII/von Willebrand factor concentrate Haemate-P as replacement therapy in patients with von Willebrand's disease (VWD) undergoing surgical or invasive procedures. DESIGN AND METHODS: Between January 1996 and October 2002, 26 patients (12 males and 14 females, median age 41.5 years, range 9-80 years), followed at three Italian Hemophilia Centers (Trento, Verona and Parma), with VWD type 1 (19 cases) and VWD type 2B (7 cases), underwent 43 surgical or invasive procedures: major surgery (14 cases), minor surgery (11 cases), dental extractions (11 cases), invasive diagnostic procedures (7 cases). Replacement therapy with factor VIII/von Willebrand factor concentrate (Haemate-P) was administered in the surgical setting as perioperative prophylaxis against excessive bleeding. RESULTS: The mean total dose (range) of Haemate-P used for major surgery was 284.1 IU VWF:RCo/kg (range 125.0-976.4), for minor surgery it was 120.8 IU VWF:RCo/kg (range 42.9-173.3), for dental extractions it was 38.4 IU VWF:RCo/kg (range 23.5-100.0) and for invasive procedures it was 87.3 VWF:RCo/kg (range 27.3-160.0). We recorded one bleeding episode 3 days after multiple dental extractions in a patient with severe periodontal disease; this bleeding was controlled with 2 further administrations of concentrate. We did not observe thrombotic episodes or other side effects following infusion of the concentrate. INTERPRETATION AND CONCLUSIONS: In conclusion, Haemate-P was effective and safe in preventing excessive bleeding after major and minor surgery or invasive procedures in VWD patients.

The prognostic role of time to diagnosis and presenting symptoms in patients with pancreatic cancer.

BACKGROUND: The aim of this study was to investigate the prognostic role of diagnostic delay and clinical presentation (regarding pain, jaundice, and weight loss) in pancreatic carcinoma. METHODS: One hundred and seventy patients with pancreatic cancer were diagnosed and treated in the decade 2001-2010 (100 males and 70 females, with a mean age of 65.8 years [range, 36-91]). Patients were staged with spiral computed tomography and 75% were found to have advanced disease (28 stage III, 99 stage IV disease). Ductal adenocarcinoma was diagnosed in 147 cases, other subtypes of carcinoma in the remaining 23. Fifty patients were operated with radical intent, 19 had palliative surgery, 101 were considered inoperable because of advanced disease or heavy anesthesiologic risk; 31 of these inoperable patients underwent biliary decompression by insertion of an endoluminal or percutaneous stent. Gemcitabine-containing regimens were administered to 143 patients and radiotherapy was combined in 19. Overall and relative survival were the parameters studied. Multivariate analysis was performed by multiple regressions applied to proportional-hazards model. RESULTS: From all the clinical, pathological and therapeutical factors evaluated the statistically significant ones were time to diagnosis and surgery. Among symptoms pain was related to the shortest mean time to diagnosis, weight loss to the longest, with corresponding differences in survival. These differences of observed survival were substantially confirmed in terms of relative survival. CONCLUSIONS: The poor prognosis of pancreatic carcinoma seems to depend, in part, on diagnostic delay and this, in turn, is influenced by the type of presenting symptoms.

Tumors of the gastroesophageal junction have intermediate prognosis compared to tumors of the esophagus and stomach, but share the same clinical determinants.

The issue of whether carcinoma of the gastroesophageal junction (GEJ) should be considered a distal esophageal, a proximal gastric or an independent tumor, at least with regards to clinical evaluation and management remains controversial. This study included 613 retrospective consecutive patients with carcinoma of the upper digestive tract, 64 of the esophagus, 58 of the GEJ and 491 of the stomach. The prognostic impact of the main clinical and histological parameters was analyzed in relation to relative survival as an estimate of the excess mortality. Relative survival and standardized mortality ratio (SMR) were calculated from the observed survival and the expected survival of the general population with identical age, gender and calendar years of observation. Multivariate analyses were applied to the proportional hazards model of the relative survival. The excess mortality, expressed by the relative survival and SMR of the patients with GEJ carcinoma are intermediate compared to those of patients with esophageal and gastric tumors. However, prognosis is not determined by tumor location, histology or administration of adjuvant chemotherapy, but mainly by stage and radical surgical resection. Gender has a minor but significant prognostic effect and age showed a slight inverse correlation with excess mortality. In conclusion, the excess mortality related to the tumors of the upper digestive tract is determined by stage, radical resection, gender and age. The intermediate prognosis of GEJ tumors mainly depends on a particular combination of such elementary determinants.

Improving the AJCC/TNM classification for use in early gastric cancer.

PURPOSE: The current TNM classification is still unsatisfactory for collecting all the prognostic information from the clinical presentation of early gastric cancer: "T" is limited to two levels, the classes of "N" are still wide and "M" is generally absent. PATIENTS AND METHODS: This study involved 99 patients who underwent radical gastric resection for early gastric cancer. Clinical and histological parameters were prognostically analyzed for both observed and relative survival. Univariate and multivariate analyses were applied to the proportional hazards model. RESULTS: Number of metastatic lymph nodes and measure of the largest diameter of the tumor were the only independent prognosticators of observed and relative survival. Their similar relative hazards allowed an additive use of them in the N class. Two cut-off values of this composite clinical parameter are proposed for a good discrimination of the relative survival. DISCUSSION: The number of metastatic lymph nodes is the cornerstone of the current TNM system and was confirmed as adequate. The possibility of adding tumor size to the number of the involved lymph nodes improves and amplifies the prognostic ability, which is presently limited by the rarity of lymph node involvement and the small number of the lymph nodes usually involved.

Role of conventional salvage multiple-drug chemotherapy in relapsed and refractory aggressive non-Hodgkin lymphomas.

Autologous stem cell transplantation is the standard care for patients with relapsed or refractory aggressive non-Hodgkin lymphomas. Of the patients who are sensitive to second-line chemotherapy, approximately 40-50% are likely to be cured using this approach. The optimal salvage regimen for pre-transplant debulking is controversial and these second-line chemotherapies are particularly important for patients who cannot undergo transplantation for various reasons including age, comorbidity and insufficient stem cell collection. Numerous reports regarding this topic are available. This study evaluated reports published in the last 5 years, focusing on conventional multiple-drug second-line chemotherapies (with or without rituximab), and disregarding single-agent investigational phase-II trials. Results are encouraging, particularly when considering that the more recent and less toxic combinations appear to be equivalent to or even more favourable than previous, more aggressive approaches. Previous results obtained using a combination of mitoxantrone, carboplatin, cytarabine and methylprednisolone, are further updated and included in this study. In conclusion, the most effective conventional chemotherapy currently available for patients with relapsed or refractory non-Hodgkin lymphomas obtains complete remission rates of up to 50-70%; the achievement of a complete remission is the most important factor associated with a better outcome. Although the addition of rituximab is beneficial and safe, it is more effective in patients who have previously not been exposed to this monoclonal antibody. The addition of cycles of salvage chemotherapy to those strictly required for mobilization of peripheral blood stem cells ultimately improves the response rate.