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Biomedical subjects

N Colombo

Publications and source records attributed to N Colombo.

At least 109 records · Page 6Linked to original sources

Spontaneous CSF rhinorrhea through the lamina cribrosa associated with primary empty sella.

Spontaneous CSF rhinorrhea associated with primary empty sella is a recently recognized condition. Because of its surgical indication, the preoperative evaluation of the possible site of the fistulous tract could be of fundamental importance. Most cases of primary empty sella reported in the literature have shown evidence of leakage through the sellar floor into the sphenoid sinus, thus requiring a transphenoidal approach. Non-traumatic defects in the anterior fossa are rarely reported in the literature. We have collected three new cases in which CT cisternography with non-ionic water-soluble contrast medium ruled out the possibility of a transellar fistula, thus suggesting a possible leak in the area of the lamina cribrosa. This was confirmed by the surgical outcome and by the follow-up of each patient.

Adult↗

Rapid size reduction of giant prolactinoma following medical treatment.

A giant macroprolactinoma causing hydrocephalus was demonstrated by computed tomography in a 13-year-old boy complaining of headache and visual disturbances. Three weeks after beginning of medical treatment with dopaminergic drugs, an impressive reduction of tumor size and disappearance of hydrocephalus was noted. The patient is doing well at 5 months follow-up.

Adolescent↗

The role of surgery in gestational trophoblastic disease.

Fifty-eight consecutive patients with malignant trophoblastic tumors of gestational origin were treated at the 1st Department of Obstetrics and Gynecology of the University of Milan between 1975 and 1981. Thirty-five (60.3%) of the patients were treated with combined surgery and chemotherapy. Of these, 44.8% had genital surgery, 12% extragenital surgery, and 5.1% had emergency laparotomies. Minor surgery was done to 17.1% of the patients. Five patients (20.8%) with tumors limited to the uterus and treated with chemotherapy only became drug-resistant, whereas 3 patients (9%) later developed lung metastases. All the patients are alive without any clinical signs of the disease. When there were metastatic tumors, the survival of the group first submitted to a "debulking" operation of the primary focus was 80%, and the survival of the group treated only with chemotherapy was 78.5%. Seven cases required extragenital surgery for the indications discussed in detail and because they had measurable HCG. Six of these had thoracotomies and one had a craniotomy. Five of the 6 patients who underwent thoracotomy (83.4%) had a complete remission. Chemotherapy remains the treatment of choice for trophoblastic tumors. Nevertheless, our data confirm that for some cases, mostly in the high risk group, complete eradication cannot be obtained with antitumor agents. Adjuvant surgery of carefully selected patients helps to save some of those who no longer respond to chemotherapy.

Adult↗

Lack of activity of cyclophosphamide in ovarian cancer patients refractory to cis-dichlorodiammine platinum.

Twenty-three ovarian cancer patients refractory to first-line chemotherapy consisting of cis-dichlorodiamminoplatinum used as a single agent (50 mg/m2 IV every 4 weeks) were admitted to this study. They received cyclophosphamide as an IV push at a dose of 1 g/m2 every 3 weeks. They were evaluable for response after at least two cycles. None of the 18 evaluable patients responded: 15 (83%) showed rapid progression and three (17%) no change. Except in one case of severe leukopenia hematological toxicity was acceptable. Some (30%) of the patients experienced intractable vomiting on the day of cyclophosphamide administration.

Adult↗

Effect of a streptococcal preparation (OK432) on natural killer activity of tumour-associated lymphoid cells in human ovarian carcinoma and on lysis of fresh ovarian tumour cells.

The streptococcal preparation OK432 was studied for its effects on natural killer (NK) activity of peripheral blood lymphocytes (PBL) from normal donors and from ovarian cancer patients, and of tumour-associated lymphocytes (TAL) from peritoneal effusions. OK432 augmented NK activity against the susceptible K562 line and induced killing of the relatively resistant Raji line. Freshly isolated ovarian carcinoma cells were relatively resistant to killing by unstimulated PBL and TAL. OK432 induced significant, though low, levels of cytotoxicity against 51Cr-labelled ovarian carcinoma cells. Augmentation of killing of fresh tumour cells by OK432 was best observed in a 20 h assay and both autologous and allogeneic targets were lysed. PBL were separated on discontinuous Percoll gradients. Unstimulated and OK432-boosted activity were enriched in the lower density fractions where large granular lymphocytes (LGL) and activity against K562 were found. Thus, OK432 augments NK activity of PBL and TAL in human ovarian carcinomas and induces low, but significant, levels of killing of fresh tumour cells. Effector cells involved in killing of fresh ovarian tumours copurify with LGL on discontinuous gradients of Percoll.

Adult↗

Defective natural killer activity within human ovarian tumors: low numbers of morphologically defined effectors present in situ.

Tumor-associated lymphocytes (TAL) were isolated from 17 ascites and 7 solid ovarian carcinomas. TAL had defective natural killer (NK) activity against K562. Large granular lymphocytes, the morphologically identified effectors of NK activity, were poorly represented in TAL from ovarian carcinomas as compared to peripheral blood lymphocytes from the same patients or from normal donors. Similar results were obtained when effectors of NK activity were identified with an anti-NK (HNK-1) monoclonal antibody. When four TAL preparations were separated on discontinuous Percoll gradients, they were able to be enriched for NK activity and large granular lymphocyte morphology in the lower density fractions as observed with blood. These observations suggested that a low concentration of the relevant effector cells was the major factor determining the defective NK cytotoxicity of lymphoid cells associated with these human neoplasms.

Antibodies, Monoclonal↗

Antibody-dependent and -independent cytotoxicity of human mononuclear phagocytes: defective stimulation of tumoricidal activity in milk macrophages.

Human peripheral blood monocytes, milk macrophages and peritoneal exudate macrophages were purified by adherence. antibody-dependent cellular cytotoxicity (ADCC) was measured using the murine TLX9 lymphoma pre-labelled with 3H-thymidine. Direct, antibody-independent tumoricidal activity was measured against the murine TU5 line pre-labelled with 3H-thymidine. All mononuclear phagocyte populations tested were similarly effective in mediating ADCC against TLX9 cells. In the absence of deliberate stimulation blood monocytes and peritoneal macrophages had appreciable spontaneous cytotoxicity against the susceptible TU5 line. In contrast, four out of 10 milk macrophage preparations lacked detectable spontaneous killing activity on this target. In vitro exposure to partially purified fibroblast interferon (IFN) or to lymphokine supernatants from PHA stimulated lymphocytes augmented the direct tumoricidal activity of blood monocytes and peritoneal exudate macrophages. Milk macrophages were completely unresponsive to IFN and lymphokines. therefore the capacity to mediate antibody-dependent and -independent cytotoxicity against tumour cells can be dissociated to some extent in human mononuclear phagocyte populations from diverse anatomical sites.

Animals↗

Characterization of small combinatorial chemistry libraries by (1)H NMR. Quantitation with a convenient and novel internal standard.

A novel silane standard, 1,4-bis(trimethylsilyl)benzene (BTMSB), is introduced for the generic quantitation of small organic molecules in DMSO-d(6) solution by (1)H NMR. This standard is an easily weighable solid and is stable for at least 1 month in DMSO solution, and its (1)H NMR spectrum contains a strong singlet in a region usually free of signals. With a set of certified standards, concentration determination with about 2% precision and accuracy is verified after solution preparation with fully automated procedures, thus making very effective the characterization of small combinatorial chemistry libraries for identity and purity when combined with other physicochemical or biochemical tests. As an example, for a set of about 400 compounds, results of (1)H NMR characterization are compared to the more customary LC-UV-MS method. NMR and MS data agree for identity on the vast majority of cases (84% positive and 5% negative), whereas the remaining cases (11%) are marked as highly impure only after NMR spectra analysis. Most importantly, determination of concentration rather than that of relative purity appears the right choice for a correct evaluation of biochemical potency.

Chromatography, High Pressure Liquid↗

MR imaging of intradural extramedullary tumors of the cervical spine.

Magnetic resonance imaging was performed in eight patients with extramedullary cervical tumors; two were studied with a 0.15 T resistive system and six with a 0.5 superconductive unit. All tumors were verified surgically: Five meningiomas and three schwannomas were found. Magnetic resonance demonstrated the location and size of the tumors as well as their relationship with and mass effect on the adjacent spinal cord. Meningiomas showed a tendency to have relaxation times close to those of the normal parenchyma; in multiple echo sequences their signal tends to decay in a way similar to that of the spinal cord. The different signal from the surrounding cerebrospinal fluid sometimes provides a visual cleavage to define the extramedullary location of the neoplasm. Schwannomas and neurofibromas have a less constant behavior; their T2 relaxation time may be slightly longer than that of the spinal cord and the tumor may display a more intense signal in the T2 weighted images. Usually, however, the signal intensity of the extramedullary tumors is lower than that of the intramedullary.

Adolescent↗

What have we learned from ICON1 and ACTION?

Still, 20-30% of women with early-stage ovarian cancer eventually die from their disease. Adequate treatment for this subset of patients has not yet been identified, the greatest dispute being about the role of adjuvant therapy after surgical staging. No randomized trial has reliably demonstrated a survival advantage for one of the many approaches over another or over careful observation without immediate further adjuvant therapy. A combined analysis of two parallel randomized clinical trials in early ovarian cancer, ICON 1 and ACTION, comparing platinum-containing adjuvant chemotherapy to observation following surgery was performed, with survival as primary end point and time to recurrence as a secondary one. A total of 924 patients were randomized. With over 4 years median follow up for survivors, the hazard ratio for recurrence-free survival is 0.64 (95% CI, 0.50-0.82; P = 0.001) in favor of adjuvant chemotherapy, with an absolute difference of 11%. For overall survival, the hazard ratio is 0.67 (95% CI, 0.50-0.90; P = 0.008) in favor of adjuvant chemotherapy. These results translate into an absolute difference of 8% in the adjuvant chemotherapy group and indicate that adjuvant platinum-containing chemotherapy improves the survival and disease-free survival. Sub-group analysis demonstrated in the ACTION trial that completeness of surgical staging was an independent factor for prognosis, both for progression-free and for overall survival (along with histological type and tumor grade), while in suboptimally staged patients, adjuvant chemotherapy did improve the outcome.

Chemotherapy, Adjuvant↗

Role of conservative surgery in ovarian cancer: the European experience.

Although less frequently than in older women, about 15% of invasive epithelial ovarian cancer may occur in young women, for whom preservation of fertility potential is an important clinical goal. We reviewed the published evidences from the European literature on the role of conservative surgery in women with invasive epithelial ovarian cancer. Three reports were identified from the Italian and French literature; the data were analyzed together with our own experience in terms of relapse rate, relapse in the preserved ovary, survival, and fertility outcome. A total of 152 conservative surgeries were reported: 88 patients with stage IA, 2 with stage IB, 51 with stage IC, 2 with stage II, 3 with stage IIIA, and 6 with stage IIIC. Relapses occurred in 18/152 patients (11.8%) and involved the preserved ovary in 11 cases (7%). Fifty-three pregnancies were recorded with 38 uneventful term deliveries, 2 ectopic pregnancies, 6 spontaneous abortions, 4 terminations, and 2 with unknown outcome. Nine patients (5.9%) have died of disease. These findings confirm that young women with stage I invasive epithelial ovarian cancer may receive a successful treatment of their disease without sacrificing fertility.

Adolescent↗

Detection of sentinel nodes by lymphoscintigraphy and gamma probe guided surgery in vulvar neoplasia.

BACKGROUND: Pathologic lymph node status is the most important prognostic factor in vulvar cancer; however, complete inguinofemoral node dissection is associated with significant morbidity. Intraoperative lymphoscintigraphy associated with gamma detecting probe-guided surgery has proved to be reliable in the detection of sentinel node (SN) involvement in melanoma and breast cancer patients. The present study evaluates the feasibility of the surgical identification of inguinal sentinel nodes using lymphoscintigraphy and a gamma detecting probe in patients with early vulvar cancer. METHODS: Technetium-99-labeled colloid human albumin was administered perilesionally in 44 patients. Twenty patients had T1 and 23 had T2 invasive epidermoid vulvar cancer; one patient had a lower-third vaginal cancer. An intraoperative gamma detecting probe was used to identify SNs during surgery. Complete inguinofemoral node dissection was subsequently performed. SNs underwent separate pathologic evaluation. RESULTS: A total of 77 groins were dissected in 44 patients. SNs were identified in all the studied groins. Thirteen cases had positive nodes: the SN was positive in all of them; in 10 cases the SN was the only positive node. Thirty-one patients showed negative SNs: all of them were negative for lymph node metastasis. CONCLUSIONS: Lymphoscintigraphy and SN biopsy under gamma detecting probe guidance proved to be an easy and reliable method for detection of SNs in early vulvar cancer. If these preliminary data will be confirmed, the technique would represent a real progress towards less aggressive treatment in patients with vulvar cancer.

Adult↗

Medical therapy of advanced malignant epithelial tumours of the ovary.

Despite improvements seen in median and overall survival using a combination of platinum-compounds and paclitaxel (PTX), long-term survival rates for patients with advanced epithelial ovarian carcinoma remain disappointing and ongoing efforts have aimed to develop more effective primary therapy. In the early 1990Os the drug PTX was first tested in ovarian cancer. In the Gynaecological Oncology Group (GOG) trial 111 the cisplatin (CP)+PTX regimen was judged to be superior compared to the platinum-based control arm with an improvement of overall response rate, median progression-free interval and overall median survival. These favourable data were confirmed by a European-Canadian Intergroup trial (OV10). In contrast, in a further GOG trial (GOG132) there was no difference in survival between CP alone and the combination of PTX and CP. The International Collaborative Ovarian Neoplasm Study (ICON)3 is the first and only trial comparing PTX plus carboplatin against carboplatin alone or a (non-taxane) CP-based control arm. The last analysis performed with a total of 1,293 events showed an estimated absolute difference in one-year progression-free survival of 1% and in two-year overall survival of 2% both in favour of PTX plus carboplatin. The results of ICON3, in accordance with GOG132 study, appear to contradict the earlier positive results seen for PTX and CP in the GOG-111 and OV10 trials and suggested that single agent carboplatin, CY-adriamycin-CP are safe and effective first-line treatments for women requiring chemotherapy for ovarian cancer. A meta-analysis with individual patient data is warranted to better clarify the issue of PTX in the front line therapy of advanced ovarian cancer. Salvage chemotherapy is often utilised in patients with advanced ovarian cancer, due to the high frequency of recurrent disease even after a clinical or pathological complete response after primary chemotherapy. Main objectives of salvage chemotherapy include: i. improvement in quality of life and symptoms; ii. tumour load reduction and survival advantage; iii. evaluation of potentially active new drugs to be included in first-line. Since the goal is palliation in most cases, monotherapy is generally indicated. However, the chances of response are directly related to the treatment-free interval, with a response rate nearly equivalent to that of primary chemotherapy when the treatment-free interval exceeds 24 months. Extension of the platinum-free interval before re-treatment with platinum or taxanes may allow partial reversal of resistance to these agents which can therefore still show significant activity in relapsing patients. Unfortunately, durable response to salvage chemotherapy is rare and cure is almost impossible. The sequential use of the agents currently available for salvage treatment in monotherapy may transform ovarian cancer into a chronic disease and confers long survival to the patients. Perhaps, the most interesting role of second-line chemotherapy is to identify new potentially active drugs, which can be moved up-front. Most of the compounds used in second line (gemcitabine, topotecan, liposomal doxorubicin) are in fact under investigation to develop alternative schedules and sequences of drug administration. A new phase III multi-national randomised study for patients with advanced stage epithelial ovarian or primary periperitoneal carcinoma will evaluate the impact of incorporating a new drug within either a platinum-based triplet (new drug + platinum + PTX) or a sequential-doublet (new drug + platinum followed by platinum + PTX) in order to identify one or more experimental regimens able to improve long-term survival with acceptable toxicity.

Antineoplastic Agents, Phytogenic↗