The secretory route of the leaderless protein interleukin 1beta involves exocytosis of endolysosome-related vesicles.

Interleukin 1beta (IL-1beta), a secretory protein lacking a signal peptide, does not follow the classical endoplasmic reticulum-to-Golgi pathway of secretion. Here we provide the evidence for a "leaderless" secretory route that uses regulated exocytosis of preterminal endocytic vesicles to transport cytosolic IL-1beta out of the cell. Indeed, although most of the IL-1beta precursor (proIL-1beta) localizes in the cytosol of activated human monocytes, a fraction is contained within vesicles that cofractionate with late endosomes and early lysosomes on Percoll density gradients and display ultrastructural features and markers typical of these organelles. The observation of organelles positive for both IL-1beta and the endolysosomal hydrolase cathepsin D or for both IL-1beta and the lysosomal marker Lamp-1 further suggests that they belong to the preterminal endocytic compartment. In addition, similarly to lysosomal hydrolases, secretion of IL-1beta is induced by acidotropic drugs. Treatment of monocytes with the sulfonylurea glibenclamide inhibits both IL-1beta secretion and vesicular accumulation, suggesting that this drug prevents the translocation of proIL-1beta from the cytosol into the vesicles. A high concentration of extracellular ATP and hypotonic medium increase secretion of IL-1beta but deplete the vesicular proIL-1beta content, indicating that exocytosis of proIL-1beta-containing vesicles is regulated by ATP and osmotic conditions.

A randomized study comparing filgrastim versus lenograstim versus molgramostim plus chemotherapy for peripheral blood progenitor cell mobilization.

We conducted a prospective randomized clinical trial to assess the mobilizing efficacy of filgrastim, lenograstim and molgramostim following a disease-specific chemotherapy regimen. Mobilization consisted of high-dose cyclophosphamide in 45 cases (44%), and cisplatin/ifosfamide/etoposide or vinblastine in 22 (21%), followed by randomization to either filgrastim or lenograstim or molgramostim at 5 microg/kg/day. One hundred and three patients were randomized, and 82 (79%) performed apheresis. Forty-four (43%) patients were chemonaive, whereas 59 (57%) were pretreated. A median number of one apheresis per patient (range, 1-3) was performed. The median number of CD34+ cells obtained after mobilization was 8.4 x 10(6)/kg in the filgrastim arm versus 5.8 x 10(6)/kg in the lenograstim arm versus 4.0 x 10(6)/kg in the molgramostim arm (P=0.1). A statistically significant difference was observed for the median number of days of growth factor administration in favor of lenograstim (12 days) versus filgrastim (13 days) and molgramostim (14 days) (P<0.0001) and for the subgroup of chemonaive patients (12 days) versus pretreated patients (14 days) (P<0.001). In conclusion, all three growth factors were efficacious in mobilizing peripheral blood progenitor cells with no statistically significant difference between CD34+ cell yield and the different regimens, and the time to apheresis is likely confounded by the different mobilization regimens.

Operative cholangiography during laparoscopic cholecystectomy: considerations about routine or selective policy.

Operative cholangiography (OC) during laparoscopic cholecystectomy (LC) is still a matter of debate regarding its routine or selective use. The present report is based upon a series of 30 selective cholangiographies performed in 290 LC during the years 1999-2004. Indications to OC were decided according to clinical data, liver chemistries, ultrasonographic (US) and intraoperative findings. In cases of unequivocal common bile duct (CBD) stones, a preoperative ERCP was performed and OC was not applied to confirm clearing of the biliary tract. OC was successful in 26 cases (86.6%): in 18 cases a normal cholangiogram was obtained and in 3 cases stones were detected into CBD. These patients underwent a postoperative successful ERCP at a variable interval of time. In 4 cases cholangiograms showed a delayed transit and in a single case a lack of contrast into the duodenum. Such occurrence was due to morphine derivatives employed during anesthesia. The Authors evaluate advantages and drawbacks of routine and selective OC according to personal and other Authors experience. Decision on selective or routine policy should be taken according to each surgeon experience and local facilities. Each laparoscopic surgeon must be able to perform and interpret an OC, specially if he has in mind to develop competence in laparoscopic CBD exploration.

Prognostic and predictive value of intratumoral microvessels density in operable non-small-cell lung cancer.

Experimental evidence suggests that tumor growth and progression depend on angiogenesis. In a retrospective study we evaluated the relationship between tumor angiogenesis and survival in patients with NSCLC treated with potentially curative surgery between 1992 and 1997. The study population consisted of 76 patients. An anti-CD34 monoclonal antibody was used to measure angiogenesis in tumor samples. Angiogenesis was quantified in terms of microvessel count (MVC): in each sample the three most intense regions of neovascularization were identified under low microscopic power. A x250 field in each of the three areas was then counted and the highest count of the three fields was recorded. Disease free (DFS) and overall survival (OS) during follow up were evaluated. Gender, age, stage, histologic type and KI-67 were the other factors considered for analysis. The median MVC in our series was 41.5. Among the clinicopathologic parameters examined the microvessel count was the only one to show a significant association with disease free survival in univariate analysis (P = 0.04). MVC value is a new indicator of tumor aggressiveness in patients with NSCLC who underwent potentially curative surgery and should be taken into consideration in selecting patients for adjuvant treatment.

Peripheral blood progenitor cell (PBPC) mobilization in heavily pretreated patients with germ cell tumors: a report of 34 cases.

The aim of the study was to evaluate peripheral blood progenitor cell mobilization by disease-specific chemotherapy in heavily pretreated patients with germ cell tumor (GCT), scheduled for high-dose chemotherapy. Thirty-four consecutive patients, 29 males and five females, with advanced GCT referred to our department for high-dose chemotherapy were evaluated retrospectively. Sixteen patients were mobilized by vinblastine 0.11 mg/kg on days 1 and 2, ifosfamide 1200 mg/m2 days 1-5 and cisplatin 20 mg/m2 days 1-5 (VeIP). In 10 patients, etoposide 75 mg/m2 days 1-5 was used instead of vinblastine (VIP), while in eight patients the mobilization was attempted by administering 7 g/m2 of cyclophosphamide. The choice of either etoposide or vinblastine was predicated upon which of these two drugs was associated with best results during premobilization chemotherapy. Cyclophosphamide was selected in patients refractory to previous cisplatin-based salvage chemotherapy. Twenty-five out of 34 patients underwent a successful PBPC collection. In 17 of them one leukapheresis procedure was sufficient to collect the target number of CD34+ cells, while in eight patients a double procedure was necessary. Altogether 33 aphereses were performed in 25 patients. In nine patients leukapheresis was not attempted. This was due to the fact that the chemotherapy failed to mobilize the target number of CD34+ cells in eight of them, treated with the VeIP mobilizing regimen, while one patient treated with high-dose cyclophosphamide rapidly progressed during therapy and for this reason leukapheresis was not undertaken. In conclusion, in heavily pretreated patients with GCT, PBPC mobilization is feasible by a further course of salvage chemotherapy. The choice of either etoposide (VIP) or vinblastine (VeIP) can be predicated upon which of these two drugs was associated with best results during premobilization chemotherapy. In our hands, VeIP seems to be less satisfactory as mobilizing treatment than VIP, possibly due to a superior number of premobilization courses of chemo therapy in some patients. Moreover, high-dose cyclophosphamide remains a good alternative for mobilizing patients refractory to salvage chemotherapy.

Is there any difference in PBPC mobilization between cyclophosphamide plus G-CSF and G-CSF alone in patients with non-Hodgkin's Lymphoma?

We attempted to analyze whether the use of high-dose cyclophosphamide (CTX 7g/m2, group A) plus hematopoietic growth factor (G-CSF) or G-CSF alone (10 microg/Kg, group B) as a mobilizing regimen, could result in harvesting different numbers of CD34+ cells, committed progenitors and CD34+ cells subsets. The number of CD34+ cells considered as the target for each high-dose chemotherapy was > or = 2 x 10(6) /Kg/bw. Fifteen leukaphereses procedures were necessary in group A, while 16 procedures were performed in group B. We did not observe any difference between the two groups in terms of CD34+ cells/microl in the peripheral blood (117 vs 78; p = NS), whereas in the aphereses product we found a significant difference between the two groups of patients in terms of CD34+ cells (6.41 vs 2.89 x 10(6) /Kg/bw; p = .009), CFU-GM (82.5 vs 52.3 x 10(4) /Kg/bw; p = .04). Interestingly, we noted a different distribution of CD34+/33- cells between the 2 groups (mean value 39% vs 65%; p < .05), whereas we did not find any differences regarding CD34+/38-, CD34+/Thy1+, CD34+/HLADR-. The higher number of CFU-GM/Kg/bw collected in the former group did not translate into a superior plating efficiency (27.75 vs 30.29). Furthermore, we observed a strong correlation between CD34+ cells/microl in the peripheral blood and the total number of CD34+ cells in the leukaphereses product (r = 0.97), whereas this correlation was not found in group B (r = 0.15). In both groups of patients the number of CD34+ cells collected correlated well with CFU-GM (r = 0.93; r = 0.94), but definitely we did not observe any correlation between CD34+ cells/microl and CFU-GM in patients mobilized with G-CSF alone and this did not allow us to predict the harvest accurately. Finally, we evaluated the engraftment kinetics and we did not observe any statistically significant difference between the two groups of patients.

Teniposide (VM26) as second-line treatment for small cell lung cancer.

Twenty-six out of 53 patients with small cell lung cancer (SCLC) who relapsed or progressed following a first treatment (induction plus maintenance), were treated by a second-line chemotherapy consisting of: Teniposide (VM26), 60 mg/m2 i.v., days 1-5, every 3 weeks until further progression. The response rate obtained in 24 evaluable patients was: 7 (29%) partial response, 4 (17%) minor response, 8 stable disease, 5 progressive disease and 2 patients with early death. In the whole group, median survival time from the start of VM26 treatment, was 4 months (range 1-11). These data were compared to the median survival (1.5 months, range 1-7) of the remaining 27 patients, the control group, who at the time of progression did not receive further treatment. The difference between survivals was statistically significant (Log-rank test: p less than 0.05). According to these data VM26 seemed to be active, but larger studies better focused on all clinical variables are needed before firm conclusions can be drawn.

A sequential chemo-radiotherapeutic treatment for patients with malignant gliomas: a phase II pilot study.

BACKGROUND: The purpose of our study was to evaluate the activity and toxicity of a sequential chemo-radiotherapeutic treatment on the basis of an earlier report by The Johns Hopkins Oncology Center. MATERIALS AND METHODS: Eighteen patients with histologically diagnosed malignant gliomas entered the study. Fifteen patients had glioblastoma multiforme (83%). BCNU (40 mg/sqm/die) and Cisplatin (40 mg/sqm/die) were administered concurrently for 3 days every 3-4 weeks. Radiotherapy consisted of 45 Gy whole cranial irradiation plus a 15 Gy boost on the preoperative volume. RESULTS: Thirteen patients had measurable disease and were evaluable for response. After chemotherapy we obtained 3 CRs (complete remission) and 4 PRs (partial remission) (RR (response rate 54%). Three PRs were converted to CRs after radiotherapy, for a complete remission rate of 46% (6/13). The median duration of response was 10 months. The median survival of the entire patients population was 9 months with 33% survival rates at 1 year. Hematological toxicity grade 4 in one patient and grade 3 in two patients were the major complications due to chemotherapy. CONCLUSIONS: Our sequential chemo-radiotherapeutic regimen appears to have significant activity in adults with newly diagnosed high-grade gliomas.

Global approach to hepatic metastases from colorectal cancer: indication and outcome of intra-arterial chemotherapy and other hepatic-directed treatments.

Liver metastases of colorectal cancer is present in more than 20% of new diagnosed patients and in 40-60% of relapsed patients. It is a life-threatening prognostic aspect. Hepatic resection, when possible, is the best therapeutic modality, although the overall survival rate is still low (30%). Angiography and intraoperative ultrasonography are useful for resection. The number of hepatic metastases and the surgical margin are probably the most significant prognostic factors. Colorectal cancer may spread predominantly to the liver making regional treatment strategies viable options. Subtotal hepatic resections and segmentectomies are potentially curable procedures for single or small numbers of hepatic metastases without other sites of disease. However, there have been no prospective randomized trials comparing patients with unresected liver metastases and resected metastases. Regional chemotherapy with floxuridine seems usefull combined with hepatic resection or as palliative therapy. Gastric ulcer and biliary sclerosis are the main related toxicities. Patients with localized, unresectable hepatic metastases or concomitant bad medical condition may be candidates for radiation, percutaneous ethanol injection, cryosurgery, percutaneous radiofrequency, hypoxic flow-stop perfusions with bioreductive alkylating agents, hepatic arterial ligation, embolization and chemoembolization. These new hepatic-directed modalities of treatment are being investigated and may offer new approaches to providing palliation and prolonging survival. This review will report the possibilities of intra-arterial chemotherapy and other novel hepatic-directed approaches to the treatment of liver metastases from colorectal cancer.

Amifostine (Ethyol) as modulator of hepatic and biliary toxicity from intraarterial hepatic chemoembolization: results of a phase I study.

BACKGROUND/AIMS: Hepatic and biliary toxicity are still significant problems after intraarterial hepatic chemoembolization for liver metastases from large bowel cancers. In about 30-60% of the patients hepatic and biliary toxicity are the limiting aspects of intraarterial hepatic chemoembolization and exclude a lot of patients from a repeated beneficial treatment. Amifostine (Ethyol) is a prodrug that must be dephosphorylated to the free thiol in which form it can detoxify free oxygen radicals generated by radiation, hypoxia and by drugs such anthracyclines, platinum analogues and alkylating agents. Amifostine as inactive prodrug is primarily metabolized at the tissue site by membrane alkaline phosphatase, which is highly active in the cell membranes of normal endothelial cells and biliary tree cells but not in the cell membranes and neovascular capillaries of tumor. When dephosphorylated to WR-1065, amifostine is rapidly taken up into normal liver cells by a carrier-mediated facilitated diffusion transport process. The resulting high thiol content in normal liver tissue (biliary cells and hepatocytes) compared with the negligible concentration in liver metastases from large bowel cancers probably provides for selective drug resistance to intraarterial hepatic chemoembolization protecting normal tissue and allowing full therapeutic effect on tumor. METHODOLOGY: From May 1997 we planned a phase I study in patients receiving intraarterial hepatic chemoembolization for liver metastases from large bowel cancers. We started at 200 mg/m2 dissolved in 250 cc of normal saline given in 15 min in the intrahepatic artery 20 min before an intraarterial hepatic chemoembolization consisting of mitomycin 10 mg/m2, epirubicin-50, cisplatin-60 diluted in 10 mL of contrast media, mixed in 15 mL of lipiodol UF followed by a gelfoam powder solution until stagnation of the flow. The escalating dose, every 3 patients, was: 200 mg/m2, 250 mg/m2, 300 mg/m2, 350 mg/m2. RESULTS: Toxicity has been observed at 350 mg/m2: 1 patient reported transient hypotension (Blood pressure 70/50 mm Hg), 1 patient had skin flushing and dyspnoea. 300 mg/m2 are well tolerated and seem to reduce the level of transaminases, lactic acid dehydrogenase, and gamma-glutamyl transferase. Also the duration of necrotic damage, always observed after intraarterial hepatic chemoembolization, seems shorter compared with historical controls. CONCLUSIONS: Amifostine can be certainly administered at 300 mg/m2 as intraarterial infusion and could be a significant step to ameliorate the therapeutic ratio of intraarterial hepatic chemoembolization.

Locoregional therapy for liver metastases from colorectal cancer: the possibilities of intraarterial chemotherapy, and new hepatic-directed modalities.

Liver metastasis of colorectal cancer is a life-threatening prognostic factor. Hepatic resection, when possible, is the best therapeutic modality, although the overall survival rate is still low (30%). The diagnosis has been carried out by clinical examination, abnormal alkaline phosphatase, lactic acid dehydrogenase and tumor markers, abdominal liver echography and computed tomography scan. Angiography and intraoperative echography are useful for resection. The number of hepatic metastases and the surgical margin are probably the most significant prognostic factors. Colorectal cancer may spread predominantly to the liver making regional treatment strategies viable options. Subtotal hepatic resections and segmentectomies are potentially curable procedures for single or small numbers of hepatic metastases without other sites of disease. However, there have been no prospective randomized trials comparing patients with unresected liver metastases and resected metastases. Regional chemotherapy with floxuridine seems useful combined with hepatic resection or as palliative therapy. Gastric ulcer and biliary sclerosis are the main related toxicities. Patients with localized, unresectable hepatic metastases or concomitant bad medical condition may be candidates for radiation, percutaneous ethanol injection, cryosurgery, radiofrequency, hypoxic flow-stop perfusions with bioreductive alkylating agents, hepatic arterial ligation, embolization and chemoembolization. These new hepatic-directed modalities of treatment are being investigated and may offer new approaches to providing palliation and prolonging survival. This review reports the possibilities of intraarterial chemotherapy and other novel hepatic directed approaches to the treatment of liver metastases from this common disease.

Conservative treatment for T2-T4 bladder cancer with primary chemotherapy and radiotherapy: a pilot study.

AIMS AND BACKGROUND: After radical cystectomy, with or without pelvic radiotherapy, more than 50% of patients affected by infiltrating bladder cancer died of distant metastases. Polychemotherapy yields 25% complete remissions (CR) in patients with invasive transitional cell bladder carcinoma; although many concerns exist about the duration of such CR. This study was undertaken with the aim of evaluating the efficacy and safety of an integrated chemo-radiotherapeutic treatment, in order to broaden indications to a conservative surgical therapy. METHODS: Thirty-three consecutive patients with bladder urothelial cancer T2-T4, N0, M0, have been treated. Patients received neoadjuvant chemotherapy (rescue-M-VEC) consisted of methotrexate 30 mg/sqm plus folinic acid 15 mg after 24 h on days 1, 15, 22; vinblastine 3 mg/sqm on days 1, 15 and 22; epidoxorubicin 30 mg/sqm on day 1; cisplatin 70 mg/sqm on day 1. This cycle was repeated on day 29. After 2 cycles of rescue-M-VEC, patients underwent pelvic cobalt teletherapy 40 Gy combined with low dose cisplatin 25 mg/sqm/week. After restaging, responding patients underwent further radiation therapy (24 Gy) as booster consolidation. RESULTS: After 2 cycles of chemotherapy and pelvic radiotherapy 14/31 evaluable patients (45.2%) achieved CR and 11/31 (35.4%) partial remission, with an overall response rate of 80.6% (25/31). With a median follow up of 21 months the actuarial survival rate at 24 months was equal to 79.8%. Eleven radical cystectomies were performed, 6 of which at restaging in non responding patients and 5 during the follow up due to relapse. Of the 25 patients selected for bladder conservation, 12 (48%) have not yet shown relapses. Three out of 31 (9.7%) patients died of distant metastases. No severe toxicity has been observed: moreover no patient developed stomatitis after chemotherapy. CONCLUSIONS: Our results seem encouraging but longer follow-up and further phase III studies need to be carried out to demonstrate the feasibility of conservative treatment in muscle infiltrating bladder cancer.

[Lymph node biopsy in the study of lymphomas: from the incisional biopsy to videolaparoscopic lymphadenectomy]. / La biopsia linfonodale nello studio dei linfomi: dalla biopsia incisionale alla linfoadenectomia videolaparoscopica.

The role of the surgeon in the treatment of lymphoproliferative diseases is mainly addressed to histological diagnosis and staging. The aim of this study was to analyze the results of lymph node biopsies in patients with Hodgkin's disease (HD) and non-Hodgkin's lymphoma NHL). Between January 1992 and March 2003, 37 patients (17 males and 20 females, mean age 57 years, range 17-90) were submitted to a node biopsy to determine type of lymphoma and clinical staging: there were 8 HD and 29 NHL. In a single case laparoscopy was adopted to remove abdominal nodes; the procedure was uneventful and the patients discharged in the third postoperative day. The Authors stress the importance of the minimally invasive approach in the management of lymphoproliferative diseases.

High-dose intra-arterial plus intraperitoneal chemotherapy combined with hemofiltration in liver metastases from colorectal cancer.

AIMS: Twenty-three patients with liver metastases from colorectal cancer were entered into a prospective, phase II pilot study to evaluate the efficacy and feasibility of intra-arterial high-dose chemotherapy (IAHC) + intraperitoneal chemotherapy (IPC) combined with hemofiltration. METHODS: All patients had abdominal laparotomy to position a hepatic artery infusion port and in 15 cases an implantable system for IPC. A double-lumen filtration catheter was placed in the vena cava via the saphenous or femoral vein and connected to a modified hemofiltration unit. The treatment schedule consisted of mitomycin (30-50 mg/m2) and epirubicin (60-90) mg/m2) as IAHC combined with cisplatin (60 mg/m2) given in a 2000 ml saline solution by IPC. The high-dose IAHC-IPC was followed by 4 cycles of intra-arterial standard dose chemotherapy through the arterial port-a-cath (6 mg/m2 mitomycin and 20 mg/m2 epirubicin) and if possible by another cycle of high dose IAHC-IPC. RESULTS: We delivered a total of 31 cycles of IAHC, 21 of which were combined with IPC. Ten cycles of IAHC were administered without concurrent IPC because of painful adhesions, clinical contraindications or patient refusal. Seven of 23 patients (30%) were pretreated and with progressive disease after systemic chemotherapy. Among 22 evaluable patients, we obtained 2 complete remissions (9%) and 11 partial remissions (50%); moreover, 4 of 7 pretreated patients obtained a response to treatment. As a result, an objective tumor response was observed in 59% of patients (13/22). Therefore, a dose-response behavior was demonstrated also in tumors with a low chemosensitivity. The median duration of response and survival was 10 and 14 months, respectively. Toxicity was usually mild, but we reported one toxic death due to treatment complications. CONCLUSIONS: Further prospective randomized studies are needed to confirm the results of our study.

[High-dose chemotherapy and peripheral hemtopoietic cells (PBPC) in solid tumors]. / Chemioterapia ad alte dosi e cellule progenitrici periferiche (PBPC) nei tumori solidi.

High-dose chemotherapy is a policy which is increasing in the field of solid tumors both in Europe and in North America. Hundreds of patients undergo ABMT or PBPCT in Europe every year especially for breast carcinoma. Waiting for the results of several ongoing trials, high-dose chemotherapy has shown to be of extreme interest in the adjuvant setting of patients with high risk breast cancer in phase II trials. The best results had been reported by Peters and Gianni; with a minimum follow-up of 5 years 65 and 56% of their patients with ten or more axillary lymph nodes are alive disease free. These results are better than any others with standard doses. The only one published trial (from South Africa) on advanced disease clearly favours high-doses of cyclophosphamide, mitoxantrone and etoposide versus standard doses of cyclophosphamide, mitoxantrone and vincristine in terms of overall survival and time to relapse. The use of PBPC replacing ABMT has allowed an easier tolerability of the procedure and a reduction of the costs. There is a clear reduction of the toxic death rate to 1% in 1995 for breast cancer patients compared with 20% of fifteen years ago. Germ cell tumors in responding relapse after salvage chemotherapy seem to be ideal candidates for ABMT/PBPC programs with an expected 40% disease free survival. The clinical impact of the PBPC contamination by tumor cells is still nowadays a matter of debate at least for breast carcinoma and neuroblastoma. This review will focus on the present situation of high-dose chemotherapy for solid tumors with some insights to new technologies and their applications.

The use of granulocyte colony-stimulating factors following peripheral blood progenitor cell rescue after high-dose chemotherapy for advanced breast cancer: a prospective study.

The use of high-dose chemotherapy followed by hematopoietic rescue is increasing worldwide for solid tumors. Several studies have suggested that the period of absolute neutrophil count (ANC, < 500/ml) may be shortened in patients who receive peripheral blood progenitor cells (PBPC). To estimate the clinical value of granulocyte-colony-stimulating factor, we examined a cohort of 26 consecutive patients with advanced breast cancer who received one or two cycles of high-dose chemotherapy with PBPC rescue with or without filgrastim. Thirty-five courses of high-dose ICE (ifosfamide, carboplatin, etoposide) chemotherapy were administered and evaluated. All patients received PBPC rescue. Sixteen patients (21 courses) received subcutaneous filgrastim (5 mg/kg) following PBPC infusion. Recovery to > or = 500 ANC occurred at a median time of 7 days post PBPC infusion among patients who received filgrastim versus 10 days among patients who received standard support care only (P < 0.01). The administration of filgrastim was not associated with a reduction in the duration of hospitalization, in the total number of days on nonprophylactic antibiotics, number of red blood cell transfusions, time to platelet engraftment, or number of febrile days. This could be the consequence of the high hematopoietic cell dose administered in the study. Therefore, any effect of filgrastim was probably masked by the use of a large number of PBPC. Larger prospective randomized studies, specifically focused on the utility of the administration of growth factors following high-dose chemotherapy and PBPC rescue, may be warranted to know whether the administration of filgrastim after PBPC transplantation is really necessary.

Treatment of small cell lung cancer.

Small cell lung cancer represents approximately 25% of all lung cancers. During the 1980s enormous efforts have been made to try to create a breakthrough in this peculiar disease but, despite the excellent results obtained in the early 1980s with multidrug chemotherapy, no significant improvements have been achieved in the 1990s. Overall response rates are in the range of 60-90% for patients with limited disease and 40-70% for those with extended disease, with pathological remissions in the range of 20-50%. Nevertheless, the majority of patients with small cell lung cancer continues to relapse and ultimately dies of the disease. New strategies under clinical evaluation are the multimodality approach, such as concurrent chemoradiation, and the use of dose-intensive regimes or even high-dose chemotherapy supported by autologous haemopoietic rescue. In the near future other strategies will be possible, owing to the tremendous increase in the knowledge of biological properties of this disease. This article aims to summarize the research so far, the current strategies and the probable future of the treatment of small cell lung cancer.

[Long-term evaluation of the treatment of perforated gastroduodenal ulcer using a median suture]. / Valutazione a distanza del trattamento dell'ulcera gastro-duodenale perforata mediante rafia.

Simple suture associated with treatment using H2-antagonists has replaced gastroduodenal resection in the treatment of peptic ulcer. Forty-four patients were submitted to rafia suture for perforated gastric or duodenal ulcer (1972-1986). Fourteen were treated in the pre-H2-antagonist period and 30 in the post-H2 antagonist period. Patients were followed up: Vissick classes I and II represent 58.3% of cases in the pre-H2-antagonist period and 95.8% in the post-H2-antagonist period. Two patients from the first period were subjected to gastroduodenal resection. In no patient of the second period was further ulcer therapy necessary. In patients of the first period, oesophagogastroduodenoscopy evidenced duodenal ulcer in one case and erosive duodenitis in two cases; erosive duodenitis was present in one patient of the second period. The choice of rafia would appear to be a valid one. Follow-up after a longer period should provide confirmation.

Chemoembolization in liver malignant involvement. Experiences on 17 cases.

INTRODUCTION: Liver invasion is the major cause of organ failure in patients with primary liver cancer and metastatic large bowel cancer. Furthermore it causes high morbidity in many other carcinomas. The normal liver presents a double circulation: 75% from portal circulation and 25% from hepatic artery. In malignant primary and secondary lesions the blood support is given by hepatic artery. Antineoplastic drugs mixed to selectively injecting embolic particles, such as polyvinyl alcohol and gelatin powder (Gelfoam), can be injected to infarct tumors and to obtain a therapeutical advantage. Chemoembolization using an emulsion of Lipiodol ultra-fluid (LUF) and drugs is a recent tool in liver regional therapy. LUF has been shown to be taken up hepatocellular carcinoma and retained for a long period of time in the tumor bed. Chemoembolization causes massive shrinkage due to ischemia and increasing the local drug intensity and drug exposure. Our study reports the results of multi-agents chemoembolization (MACHEM) in 17 patients bearing massive liver involvement. MATERIAL AND METHODS: From January 1988 we treated 17 patients (5 HCCs, 7 large bowell carcinomas, 1 gastric cancer, 1 ocular melanoma, 1 pancreas, 1 soft tissue sarcoma, 1 carcinoid) using a transfemoral approach to cannulate the celiac axis and then the hepatic artery. The catheter was advanced into the vessel responsible for the majority of the tumor blood supply and a mixture of Gelfoam, radiopaque contrast media, followed by chemotherapy (mitomycin 10 mg/sqm, cisplatin 20 mg/sqm, epirubicin 20 mg/sqm) mixed to LUF was injected until vascular stasis occurred. After chemoembolization, analgesics and anti-pyretics were administered. Liver function tests were monitored daily. RESULTS: Objective tumor regression was observed in 11 out 15 full evaluable patients; the median duration of survival was 9.5 months. Within 8 weeks shrinkage, due to development of necrosis, appeared in the tumors. One patient with high levels of 5-HIAA due to carcinoid, demonstrated more than 75% decreasing in urinary excretion. In 6 patients out 8 with CEA elevation a clear reduction was documented as well in 2 HCCs out 5 with alfa-fetoprotein elevation. DISCUSSION: The palliation of HCC and metastatic liver disease have been extremely disappointing. Systemic chemotherapy produces in HCC a response rate of no more than 20% and does not increase the median survival. Venook obtained 24% of PRs and liquefaction in 35 out 50 HCC treated with chemoembolization. Some results have been also demonstrated in the treatment of metastatic liver tumors by Carrasco, Daniels and Modiano. Moertel stressed that chemoembolization could be incorporated in the initial management of carcinoid. Because of the difference in chemoembolization protocols it is difficult to compare the relative efficacy of this tool, although encouraging response rates have been reported in palliation of bulky tumors. In our study Gelfoam given before LUF and antineoplastic agents mixture produce a distal arteriolar occlusion and this would facilitate the migration of the polychemotherapy emulsion toward the tumor. Our MACHEM program has been shown to have significant activity even in heavily pretreated patients with an acceptable toxicity. We conclude that hepatic arterial chemoembolization will be improved by mean of better combination of chemotherapy with embolizing agents in well selected patients.

[Teicoplanin in the prevention of wound infections in major ambulatory surgery]. / La teicoplanina nella profilassi delle infezioni della ferita in chirurgia ambulatoriale maggiore.

Wound infection is a frequent complication and is related to various parameters: type of surgery, patient's age, nutritional status, associated diseases, length of surgery and hospital stay, use of prosthesis and drainage and finally surgeon's ability. The frequency of wound infection is reported between 1.5%-5.1% after "clean surgery" and the greatest source of microbial contamination is due to GRAM positive cocci either aerobic or anaerobic. The Authors present their experience of ultra short-term prophylaxis with Teicoplanin in 375 patients undergoing major ambulatory surgery. Median age was 49 years (15-87 ys); patients over 65 years were 22%. Hernias of the abdominal wall and varicose veins represent the diseases most commonly operated on. In 30% of the cases the patients selected for major ambulatory surgery were in II and III classes according to the standards of the American Society of Anaesthesiologists (A.S.A.). The ultra short-term prophylaxis with Teicoplanin was administered as follows: 400 mg, i.v., thirty minutes pre-operatively. The operations were performed under local or loco-regional anaesthesia. The choice of Teicoplanin was based on the strong bactericidal activity on GRAM positive cocci, including the methicillin-resistant Staphylococcus aureus infections, and on the long activity of the drug. The results were considered according to the American College of Surgeons scheme: no wound infection was observed and excellent local and general drug's tolerance were noticed. Ultra short-term prophylaxis in ambulatory surgery was chosen for the following reasons: large use of prosthesis, major risk of sepsis in older patients and at last for a badly accepted infective complications in outpatient surgery.