Effectiveness of bevacizumab added to standard chemotherapy in metastatic colorectal cancer: final results for first-line treatment from the ITACa randomized clinical trial.

BACKGROUND: We report the results from a first-line phase III randomized clinical trial on metastatic colorectal cancer (mCRC) aimed at evaluating the effectiveness of adding bevacizumab (B) to standard first-line chemotherapy (CT). PATIENTS AND METHODS: mCRC patients were randomized to receive first-line CT (FOLFIRI or FOLFOX4) plus B (arm A) or CT only (arm B). The primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS), response rate (ORR) and safety. Three hundred and fifty patients and 310 events were required to have an 80% statistical power to detect a difference in PFS between the groups. RESULTS: Between November 2007 and March 2012, 376 patients were randomized. About 60% of patients received FOLFOX4 and 40% FOLFIRI. After a median follow-up of 36 months, 343 progressions and 275 deaths had been observed in the overall population. The median PFS was 9.6 [95% confidence interval (CI) 8.2-10.3] and 8.4 (95% CI 7.2-9.0) months for arms A and B, respectively, with a hazard ratio of 0.86 (95% CI 0.70-1.07; P = 0.182). No statistically significant differences in OS or ORR were observed. B-containing regimens were associated with more frequent hypertension, bleeding, proteinuria and asthenia. CONCLUSIONS: The addition of B to standard first-line CT for mCRC did not provide a benefit in terms of PFS, OS or ORR. Further research is warranted to better identify the target population. CLINICAL TRIAL NUMBER: NCT01878422.

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.

Percutaneous ultrasonography-guided core needle biopsy of gastrointestinal lesions: what's its actual role in clinical practice? A retrospective study for safety and effectiveness.

PURPOSE: Endoscopic biopsy is commonly performed to obtain a pathological diagnosis of gastrointestinal (GI) lesions. When the lesions are submucosal, subserosal, or exophytic, endoscopic biopsy is often unsuccessful, and endoscopic ultrasound (EUS)-guided biopsy is considered the procedure of choice in these cases. Nevertheless, in some patients both endoscopic and EUS-guided biopsy are not indicated, or yield inconclusive cyto-histological results. The aim of this study was to assess the efficacy and safety of percutaneous ultrasonography (US)-guided biopsy of GI wall lesions, and to define its actual role in clinical practice. MATERIALS AND METHODS: A retrospective study was conducted on 45 consecutive US-guided biopsies of GI lesions. All biopsies were performed in patients unsuitable for endoscopic or EUS-guided biopsy, or with lesions inaccessible to endoscopic techniques, or with inconclusive results from endoscopic or EUS-guided biopsy. Biopsies were performed with an 18 or 20-gauge Tru-cut needle under US guidance. Biopsy results were compared with the final diagnosis that was based on surgical pathological findings or clinical instrumental follow-up of at least 20 months. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), overall accuracy, and complication rate of the procedure were calculated. RESULTS: One biopsy specimen (2.2 %) was inadequate for cyto-histologic examination. In the remaining 44 cases, US-guided biopsy correctly identified 39 / 40 (97.5 %) malignant lesions, and 4 / 4 (100 %) benign lesions. One case resulted in a false negative (2.2 %). The sensitivity, specificity, PPV, NPV, and overall diagnostic accuracy were 97.5 %, 100 %, 100 %, 80 % and 97.7 %, respectively. Including also the inadequate specimen into the analysis, they were 95.1 %, 100 %, 100 %, 66.7 % and 95.6 %, respectively. No procedure-related complications were observed. In ten cases (22.2 %), US-guided biopsy results made it possible to avoid unnecessary surgical exploration. CONCLUSION: Percutaneous US-guided core biopsy of GI wall lesions is an accurate and safe technique that makes it possible in select cases to obtain a correct pathological diagnosis and prevent unnecessary surgical exploration. Although it has been replaced by EUS-guided biopsy as the procedure of choice to sample submucosal or subserosal GI lesions, US-guided biopsy can still play a useful role in the diagnostic workup of GI lesions when endoscopy or EUS is unsuccessful for various reasons or yields inconclusive cyto-histological results.

[Acute respiratory stridor in infancy]. / Stridore respiratorio ingravescente nella prima infanzia.

Infantile subglottic hemangioma is a pediatric tumor of endothelial cells characterized by an initial phase of rapid proliferation (around 6 months), followed by slow involution, often leading to complete regression following the first year of life. It is most frequently found in females and it usually it occurs also in the skin. From its position it can cause a progressive airway obstruction, so early diagnosis and treatment are very important. Many treatments have been described in the literature, including systemic steroids, intralesional steroid injection, carbon dioxide laser therapy, submucous resection, interferon alfa-2 and also tracheostomy as last approach. This case report discusses a 6-month old infant, that arrived to our attention for an acute two-way stridor. Laringoscopy under general anesthesia showed a subocclusive subglottic haemangioma that closed 70% of the laryngeal airway. In agreement with our ENT specialist it was decided to begin systemic steroid therapy, first by i.v. ingection during intensive therapy with rinotracheal intubation and mechanic ventilation; after the canula removal and the hemangioma reduction, the patient took oral steroids with a gradual reduction of the dose. This case evidences the importance of laryngoscopy in the diagnosis of subglottic haemangioma; it also proves the importance of multi-disciplinary collaboration with ENT specialist and dermatologist for the diagnosis and treatment of this kind of patient. It also shows that systemic steroids are an effective alternative in the management of obstructive pediatric subglottic hemangiomas.

A novel frame-shift deletion causing analbuminaemia in an Italian paediatric patient.

BACKGROUND: Analbuminaemia (OMIM #103600) is a rare autosomal recessive disorder manifested by the absence or severe reduction of circulating serum albumin in homozygous or compound heterozygous subjects. The trait is caused by a variety of mutations within the albumin gene. DESIGN: We report here the clinical and molecular characterization of a new case of congenital analbuminaemia in a 4-year-old Italian girl diagnosed on the basis of the low level of circulating albumin (= 10.0 g L(-1)). The albumin gene was screened by single-strand conformation polymorphism and heteroduplex analysis and the mutated region submitted to DNA sequencing. RESULTS: The proband was found to be homozygous, and both parents heterozygous, for a novel deletion in exon 8 (c.920delT). The subsequent frame-shift should have given rise to a putative polypeptide chain of 304 amino acid residues, which we could not identify in the proband's serum. CONCLUSIONS: A novel analbuminaemia causing mutation was identified and characterized at the clinical level in a child. The molecular diagnosis of the trait is based on the rapid localization of the mutation within the albumin gene by single-strand conformation polymorphism and heteroduplex analysis, followed by DNA sequencing of the mutated region.

Transthoracic ultrasonography-guided core needle biopsy of pleural-based lung lesions: prospective randomized comparison between a Tru-cut-type needle and a modified Menghini-type needle.

PURPOSE: The diagnostic yield of the different types of cutting needles used to perform transthoracic biopsy is scarcely investigated. Aim of the study was to compare a Tru-cut-type (TCT) needle and a modified Menghini-type needle (MMT) in ultrasonography (US)-guided biopsy of pulmonary lesions. MATERIALS AND METHODS: 307 subjects (191 males and 116 females, mean age 58 years) with peripheral lung lesions selected to undergo US-guided biopsy were randomized to undergo biopsy by using an 18-gauge TCT or MMT needle. The specimens were imprinted on two to three slides for cytology and then put into a formalin solution for histology. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and overall accuracy were calculated. Fisher's exact test was used to compare histology recovery rate (HRR), diagnostic accuracy, and diagnostic yield of the combination of cytology and histology in comparison with cytology alone and histology alone. RESULTS: 155 biopsies were performed using the MMT needle, 152 using the TCT needle. HRR was 112 / 155 (72.3 %) and 144 / 152 (94.7 %), respectively (p < 0.0001). Sensitivity, specificity, PPV, and NPV were 81.6 %, 100 %, 100 %, and 62 % for the former, respectively, and 93.6 %, 100 %, 100 %, and 86 % for the latter. A correct diagnosis was achieved in 133 / 155 biopsies (85.8 %) performed with the MMT needle, and in 145 / 152 biopsies (95.4 %) performed with the TCT needle (p = 0.0041). The combination of cytology and histology had a higher diagnostic yield than cytology alone (p < 0.001) and histology alone (p < 0.001). CONCLUSION: The TCT needle performs better than the MMT needle, and improves the diagnostic accuracy of US-guided transthoracic biopsy of superficial lung lesions.

Palliative care in advanced cancer.

Palliative care represents a new field among clinical approaches to patients with advanced or terminal cancer. The modern concept of palliative care can be considered in several ways: 1) the relationship between palliative care and primary treatments of cancer (surgery, radiotherapy or chemotherapy); 2) the treatment of symptoms and the relationship between symptom control and quality of life; 3) end-of-life care. With regard to the relationship between palliative care and primary cancer treatments, it is common opinion that a continuity of care is needed from diagnosis to the terminal phase of the disease, and oncology departments could represent the ideal dimension in which to fulfil this requirement. In a continuity-of-care setting, symptom control becomes vitally important to improve quality of life of the patient throughout all the stages of the disease. Moreover, support for the patient and his/her family during the terminal phase of the disease is one of the most important dimensions of palliative care. In addition, assistance provided during the last hours of life and support for the family after the patient's death represent the so-called global assistance, which is distinctive of palliative care.

Efficacy of two different platinum- or anthracycline-containing chemotherapy regimens for the treatment of small cell lung cancer.

The records of 190 consecutive patients referred to our department to be treated for small cell lung cancer were retrospectively evaluated, and the outcomes were compared on the basis of their first-line treatment. 113 patients were treated with 4-6 courses of cyclophosphamide, epidoxorubicin and etoposide (CEVP16), 77 with 4-6 courses of carboplatin and etoposide (CBE). 72 patients had limited disease and 118 extensive disease. Response rates were 58.4% for CEVP16 and 28.6% for CBE (p=0.0001), with no significant difference in the time to progression (255 vs 246 days, p=0.21). Overall survival was 334 days and 212 days, and the 1-year survival rate was 46% and 22.1%, respectively (p=0.0018). In patients with limited disease, overall survival was 434 days and 249 days (p=0.08) in both treatment group respectively and 281 and 208 days in those with extensive disease, respectively (p=0.02). No difference in side effects was observed between the two groups of patients. Our data suggest a role for anthracycline-containing regimens as first-line treatment of small cell lung cancer.

Longevity of silicone and polyurethane catheters in long-term enteral feeding via percutaneous endoscopic gastrostomy.

BACKGROUND: As percutaneous endoscopic gastrostomy (PEG) is often used for many months or years, the longevity of the feeding tubes plays an important role in the global outcome and costs of PEG. AIM: A retrospective study to evaluate the longevity of silicone and polyurethane PEG catheters. METHODS: The records of 297 patients who were fed via PEG for over 90 days were evaluated. The material of the PEG catheter, duration of follow-up, local complications, need to remove PEG because of tube deterioration or local complications and time from PEG placement to PEG removal were recorded and compared. RESULTS: Two hundred and twenty-eight patients had polyurethane and 69 had silicone PEG catheters. The follow-up ranged from 116 to 3207 days for the polyurethane group and from 98 to 1861 days for the silicone group. No differences were observed in either local complications or PEG removal because of local complications. Tube deterioration causing PEG removal occurred in 36 of the 228 polyurethane PEG catheters and in 25 of the 69 silicone PEG catheters (P = 0.0005). Tube deterioration occurred significantly earlier in the 25 silicone catheters than in the 36 polyurethane catheters. The mean time from PEG placement to PEG removal was 287 days (95% confidence interval, 239-335) for silicone tubes and 573.9 days (95% confidence interval, 425-723) for polyurethane tubes (P = 0.0024). CONCLUSION: Polyurethane PEG catheters seem to be more resistant to deterioration than silicone PEG catheters, and at present they should be preferred for long-term enteral feeding via PEG.

Evaluation of a standardized protocol of intracavitary recombinant interferon alpha-2b in the palliative treatment of malignant peritoneal effusions. A prospective pilot study.

OBJECTIVE: Several schedules with variable doses of intracavitary interferon have been proposed for the management of metastatic peritoneal effusions. This prospective pilot study evaluated the efficacy of a standardized schedule of intraperitoneal interferon alpha(2b). METHODS: In 41 cancer patients with malignant ascites a 9-french intraperitoneal catheter was placed under sonographic guidance, and ascites was drained until abdominal ultrasound showed complete absence of effusion. Interferon alpha(2b), 6 or 9 million units (body weight 50 kg, respectively), was then administered via the tube, which was clamped for 6 h. 6 courses were given at 4-day intervals. In comparison with pretreatment levels, the 30-day response was classified as complete (CR) = no fluid recurrence, partial (PR) = fluid recurrence <50% and no response (NR) = >50%. Responders were monitored until fluid recurrence requiring paracentesis. RESULTS: 12 patients had CR, 15 PR, 14 NR. Global response (GR) was 65.9%. In ovarian cancer, GR was 75% and was not influenced by the quantity of the pretreatment daily fluid production. In the other cancers, a pretreatment fluid production

Acute lung injury associated with 5-fluorouracil and oxaliplatinum combined chemotherapy.

Diarrhoea, T-CD4+ lymphopenia and bilateral patchy pulmonary infiltrates developed in a male 60 yrs of age, who was treated with oxaliplatinum and 5-fluorouracil for unresectable rectum carcinoma. The findings from transbronchial lung biopsy and bronchoalveolar lavage (BAL) were consistent with an organizing diffuse alveolar damage pattern. Once extensive microbiological studies proved negative, corticosteroids were given and a complete remission of clinical and radiological abnormalities was achieved. It is concluded that the aforementioned pathological manifestations were due to chemotherapy and included a pulmonary adverse reaction, a feature never previously associated with oxaliplatinum and 5-fluorouracil regimens.

Final height of short subjects of low birth weight with and without growth hormone treatment.

AIM: To compare final height in two groups of low birth weight children examined for short stature: the first group untreated because of normal growth hormone (GH) secretion, the second treated with human growth hormone (hGH) because of abnormal secretion. METHODS: A total of 49 subjects born at term of birth weight below the 10th centile were consecutively examined for idiopathic short stature. The first group of subjects (n = 20) with normal GH peaks after pharmacological tests (>8 microg/l) spontaneously reached final height. The second group (n = 29) with abnormal secretion were treated with hGH (20 U/m(2)/week) for 36-84 months. At diagnosis the two groups were of similar height for chronological age and bone age, and had similar target height. RESULTS: In both groups final height was significantly lower than target height (-0.65 (SEM 0.20) in untreated cases, -0.61 (0.18) in treated cases). Fewer than one third of subjects had a final height above target height. Final height data of untreated and treated cases were not different. In the treated group the best results were obtained by those subjects who improved their height for bone age after three years of therapy. CONCLUSIONS: Our subjects with birth weight below the 10th centile remained as short adults with final height below target height. Treatment with hGH 20 U/m(2)/week in those diagnosed as deficient was not effective, with final results overlapping those of untreated subjects.

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.