Incidence and risk factors for trocar site hernia following laparoscopic cholecystectomy: a long-term follow-up study.

BACKGROUND: The aim of this retrospective study was to assess the incidence of trocar site hernias (TSH) following laparoscopic cholecystectomy (LC) through a long-term follow-up and to elucidate the significance of several technical and patient-related factors. METHODS: A total of 313 patients submitted to LC between 2000 and 2004 were included in our study. The pneumoperitoneum was always performed by means of Hasson's technique at the umbilical site and the operative trocars were positioned using either the American technique or the French technique. Closure of the fascial defect was performed only at the umbilical site. The effects of several variables, including age, gender, size of gallstones, co-existing umbilical hernia, complexity of operation, diabetes, obesity, malnutrition, smoking, and heavy manual work on the development of TSH were assessed by univariate and multivariate models. RESULTS: Thirteen cases of TSH (4.1 %) were detected over a mean follow-up period of 89.8 months (range: 60-128). Of these, 11 (84.6 %) developed at the umbilicus and 2 at the 10 mm subxiphoid site (15.4 %). At univariate and multivariate analysis, gallstones ≥ 2 cm (p = 0.030; OR = 9.95, p = 0.01) and obesity (p = 0.002; OR = 22.93, p < 0.01) were found to increase the likelihood of TSH development. CONCLUSIONS: After long-term follow-up, the incidence of TSH following LC was higher than expected. The insertion of large trocars at the umbilical site plays a key role in the development of TSH. Other conditions such as obesity and large gallstones can be additional risk factors since the umbilical defect must often be widened in these cases.

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.

[Intestinal obstruction due to perforated cecal volvulus. Case report]. / Occlusione intestinale da volvolo perforato del colon destro. Descrizione di caso clinico.

Cecal volvulus is an uncommon cause of large-bowel obstruction. Its developement is due to an abnormal mobility of the ileocecal loop because of lacking attachement of ascending colon. Clinical features are frequently aspecific and should be differentiated from sigmoid volvulus and neoplastic obstruction. Therapy depends on visceral circulatory conditions at the moment of diagnosis. Possible options include endoscopic decompression, cecopexy with or without cecostomy, right colectomy with immediate or delayed anastomosis. The present paper reports the case of cecal volvulus in a 44 year old woman, successfully treated with right colectomy and primary anastomosis.

[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.

Prophylaxis with GM-CSF mouthwashes does not reduce frequency and duration of severe oral mucositis in patients with solid tumors undergoing high-dose chemotherapy with autologous peripheral blood stem cell transplantation rescue: a double blind, randomized, placebo-controlled study.

BACKGROUND: The aim of this study was to evaluate the effectiveness of granulocyte-macrophage colony-stimulating factor (GM-CSF) mouthwashes in the prevention of severe mucositis induced by high doses of chemotherapy. PATIENTS AND METHODS: Ninety consecutive patients affected by solid tumors and undergoing high-dose chemotherapy with autologous peripheral blood stem cell transplantation rescue were randomized to receive placebo versus GM-CSF mouthwash 150 micro g/day. Patients were stratified on the basis of the conditioning treatment and the consequent different risk of severe oral mucositis. Treatment was administered from the day after the end of chemotherapy until the resolution of stomatitis and/or neutrophil recovery. RESULTS: The statistical analyses were intention-to-treat and involved all patients who entered the study. The severity of stomatitis was evaluated daily by the physicians according to National Cancer Institute Common Toxicity Criteria. Both study and control groups were compared with respect to the frequency [30% versus 36%, chi(2) exact test, not significant (NS)] and mean duration (4.8 +/- 4.7 versus 4.4 +/- 2.7 days, t-test, NS) of severe stomatitis (grade > or =3). Oral pain was evaluated daily by patients themselves by means of a 10 cm analog visual scale: the mean (+/- standard error of the mean) maximum mucositis scores were 4.8 +/- 3.5 versus 4.2 +/- 3.5 cm (t-test, NS). Furthermore, 15/46 patients in the study group (33%) and 19/44 patients in the control group experienced pain requiring opioids (chi(2) exact test, NS). CONCLUSION: We did not find any evidence to indicate that prophylaxis with GM-CSF mouthwash can help to reduce the severity of mucositis in the setting of the patients we studied.

Neoadjuvant high dose chemotherapy plus peripheral blood progenitor cells in inflammatory breast cancer: a multicenter phase II pilot study.

BACKGROUND AND OBJECTIVES: With the introduction of combined modality therapy, approximately 30% of patients with inflammatory breast cancer (IBC) are alive and free of disease at 5 years, but the lack of control of systemic disease continues to be the main reason for treatment failure. The importance of the response to primary chemotherapy and, in particular, complete tumor regression after primary chemotherapy have previously been described to be among the most reliable prognostic factors along with the dose intensity of doxorubicin. DESIGN AND METHODS: To evaluate pathologic response rate and toxicity of neoadjuvant high dose chemotherapy (HDCT) with autologous peripheral blood progenitor cell (PBPC) support in patients affected by IBC, 21 patients were enrolled in a study in which it was planned that they would receive 4 courses of epirubicin 150 mg/m(2) plus granulocyte colony-stimulating factor (G-CSF) as induction and mobilizing chemotherapy. Patients with non-progressive disease were intended to receive 2 consecutive courses of a combination of high doses of mitoxantrone 40 mg/m(2) , thiotepa 500 mg/m(2) and cyclophosphamide 200 mg/kg as a conditioning regimen. RESULTS: PBPC collection was successful in 20/21 patients. Twelve patients received a single course of HDCT, whereas 7/20 patients underwent a double procedure. At a median follow up of 48 months, 20/21 patients were evaluable for toxicity and 19/21 for response. At surgery 4/19 patients (21%) had no evidence of viable tumor cells in the breast and in axillary nodes, while 4 (21%) and 11 patients (58%) had microscopic and macroscopic disease, respectively. Eight patients have relapsed (35%) so far at a median of 16 months (9-54) from diagnosis. Eleven patients remain alive without evidence of disease. Five out of 20 patients experienced severe cardiotoxicity with congestive heart failure (CHF) which was responsible for the only treatment-related death. INTERPRETATION AND CONCLUSIONS: This neoadjuvant HDCT regimen seems to be very effective in terms of objective responses, but we observed a high rate of cardiotoxicity and only a few patients were able to receive the two planned courses of high dose chemotherapy.

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.

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.

New high-performance liquid chromatographic method for the detection of picolinic acid in biological fluids.

A HPLC method is described to quantify picolinic acid in milk, blood serum and tissue culture supernatant. The method requires very little sample preparation because acid precipitation allows total recovery of picolinic acid. High specificity and sensitivity were obtained using ion-pair chromatography on a C18 reversed-phase column with tetrabutylammonium hydrogen sulfate as ion pairing reagent. We describe the conditions for the automated testing of multiple samples and for the detection of L-tryptophan and L-kynurenine together with picolinic acid. This system will be utilized to elucidate the relationship between picolinic acid production and human disease. Furthermore, we provide the first evidence of picolinic acid in human blood serum.

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.

Relationships between total CD34+ cells reinfused, CD34+ subsets and engraftment kinetics in breast cancer patients.

BACKGROUND AND OBJECTIVE: The aim of the present study was to evaluate the correlation between the number of CD34+ cells transfused and the duration of hypoplasia, and the relationship between various CD34+ subsets (CD34+/33-; CD34+/38-; CD34+/ HLA-DR-; CD34+/Thy-1+) and engraftment kinetics in a series of patients with breast cancer treated with high doses of thiotepa and melphalan. DESIGN AND METHODS: We treated 42 consecutive patients: 19 in an adjuvant context (>= 4 positive axillary nodes) and 23 for metastatic disease. A combination of thiotepa 600 mg/m(2) and melphalan 140-160 mg/m(2) was administered as the conditioning regimen. All patients received peripheral blood progenitor cells (PBPC) and growth factors for hematopoietic rescue. RESULTS: In univariate analysis, we found a significant relationship between the number of CD34+ cells reinfused and the time to hematologic recovery and the duration of hospital stay. We observed an inverse correlation between the number of CD34+ cells reinfused and the units of platelets transfused. Cox multivariate analysis confirmed that the number of CD34+ cells reinfused is the most effective predictor of time to hematologic recovery. CFU-GM resulted to be a better predictor of the duration of hospitalization. INTERPRETATION AND CONCLUSIONS: We found a significant relationship between the number of PBPC reinfused and the time to hematologic recovery after high doses of thiotepa and melphalan. In our experience, the numbers of subsets of CD34+ cells infused did not give compared additional information to that provided by the total number of CD34+ cells infused.

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.

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.

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.

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.

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.

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.

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.

[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.