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PubMed1995

[Pseudostroke states in elderly patients].

Clinical characteristics of pseudostroke conditions in connection with the nature of somatic pathology, responsible for those conditions, were investigated in 52 patients. According to the character of somatic pathology all the elder patients were divided into 4 groups: myocardial infarction and progressive heart insufficiency, acute lung and heart insufficiency, inflammatory kidney disorders with signs of renal insufficiency, different intoxications. According to the results of macroscopic brain investigation, there were post-ischaemic cysts. Pathogenetic aspects of post-stroke conditions are discussed.

Acute Disease↗
PubMed1998

Induction chemotherapy with docetaxel, cisplatin, fluorouracil, and leucovorin for squamous cell carcinoma of the head and neck: a phase I/II trial.

PURPOSE: A phase I/II trial of docetaxel, cisplatin, fluorouracil (5-FU), and leucovorin (TPFL5) induction chemotherapy for patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS: Twenty-three previously untreated patients with stage III or IV SCCHN and Eastern Cooperative Oncology Group functional status less than or equal to 2 were treated with TPFL5. Postchemotherapy home support included intravenous fluids, prophylactic antibiotics, and granulocyte colony-stimulating factor (G-CSF). Docetaxel dose was escalated to determine the maximum-tolerated dose (MTD). Fifteen patients were treated with three cycles of TPFL5 at MTD. Patients who achieved either a partial response (PR) or complete response (CR) to three cycles of TPFL5 then received definitive twice-daily radiation therapy. Toxicity and clinical and pathologic response to TPFL5 were assessed. RESULTS: Twenty-three patients received a total of 69 cycles of TPFL5. The MTD was determined to be docetaxel 60 mg/m2. Dose-limiting toxicity (DLT) was neutropenia. Additional significant toxicities at MTD were nausea, mucositis, diarrhea, peripheral neuropathy, and sodium-wasting nephropathy. The overall response rate to TPFL5 was 100%, which included 14 of 23 (61%) clinical CRs and nine of 23 (39%) clinical PRs. Primary-site clinical and pathologic CR rates were 19 of 22 (86%) CRs and 20 of 22 (91%) CRs, respectively. Eight patients had less than a CR in the neck to chemotherapy and, therefore, had postradiation neck dissections, four of which were positive for residual tumor. CONCLUSION: TPFL5 is a tolerable induction regimen in patients with good performance status. The DLT is neutropenia with significant mucositis, diarrhea, peripheral neuropathy, and sodium-wasting nephropathy. The high response rates to TPFL5 justify further evaluation of this combination of agents in the context of formal clinical trials.

Adult↗
PubMed2006

Response to intraarterial induction chemotherapy: a prognostic parameter in oral and oropharyngeal cancer.

BACKGROUND: Patients with head and neck cancer and good pathologic response to neoadjuvant systemic induction chemotherapy have a better prognosis for survival than do those with stable or progressive disease. Thus, induction chemotherapy could theoretically help in stratifying further treatment, but toxicity is much too high. The prognostic implication of superselective intraarterial high-dose cisplatin administered by a femoral approach, which has much less toxicity, is not yet known. METHODS: One hundred eighty-seven unselected consecutive patients with previously untreated oral and oropharyngeal squamous cell carcinoma received intraarterial high-dose cisplatin for induction and were assessed for response by visual examination and palpation. This treatment was followed by surgery and adjuvant radiation with concomitant systemic chemotherapy. Omission of a modality depended on individual contraindications and not on preselection. The consequence of omissions has been the constitution of several treatment arms. The overall and disease-free survival in relation to clinical local response after intraarterial induction chemotherapy was calculated using the Kaplan-Meier method. Additional analysis excluded bias caused by stages and treatment arms. RESULTS: Explorative statistics using the log-rank and chi-square tests demonstrated a strong prognostic relevance of response to intraarterial chemotherapy irrespective of stage and treatment. CONCLUSIONS: Our results are encouraging for prospective randomized studies and molecular genetic investigations with intraarterial chemotherapy.

Adult↗
PubMed2000

Expression of interleukin-9 leads to Th2 cytokine-dominated responses and fatal enteropathy in mice with chronic Schistosoma mansoni infections.

Mice infected with Schistosoma mansoni develop Th2 cytokine-mediated granulomatous pathology that is focused on the liver and intestines. In this study, transgenic mice constitutively expressing IL-9 were infected with S. mansoni and the outcome of infection was determined. Eight weeks after infection, transgenic mice with acute infections had a moderate increase in Th2 cytokine production but were overtly normal with respect to parasite infection and pathological responses. Transgenic mice with chronic infections died 10 weeks after infection, with 86% of transgenic mice dead by week 12 of infection, compared to 7% mortality in infected wild-type mice. Stimulation of mesenteric lymph node cells from infected transgenic mice with parasite antigen elicited elevated interleukin-4 (IL-4) and IL-5 production and reduced gamma interferon and tumor necrosis factor alpha production compared to the responses in wild-type mice. Morbid transgenic mice had substantial enlargement of the ileum, which was associated with muscular hypertrophy, mastocytosis, eosinophilia, goblet cell hyperplasia, and increased mucin expression. We also observed that uninfected transgenic mice exhibited alterations in their intestines. Although there was hepatic mastocytosis and eosinophilia in infected transgenic mice, there was no hepatocyte damage. Death of transgenic mice expressing IL-9 during schistosome infection was primarily associated with enteropathy. This study highlights the pleiotropic in vivo activity of IL-9 and demonstrates that an elevated Th2 cytokine phenotype leads to death during murine schistosome infection.

Animals↗
PubMed1998

Potent suppression of IL-12 production from monocytes and dendritic cells during endotoxin tolerance.

Endotoxin tolerance, the down-regulation of a subset of endotoxin-driven responses after an initial exposure to endotoxin, may provide protection from the uncontrolled immunological activation of acute endotoxic shock. Recent data suggest, however, that the inhibition of monocyte/macrophage function associated with endotoxin tolerance can lead to an inability to respond appropriately to secondary infections in survivors of endotoxic shock. IL-12 production by antigen-presenting cells is central to the orchestration of both innate and acquired cell-mediated immune responses to many pathogens. IL-12 has also been shown to play an important role in pathological responses to endotoxin. We therefore examined the regulation of IL-12 during endotoxin tolerance. Priming doses of lipopolysaccharide ablate the IL-12 productive capacity of primary human monocytes. This suppression of IL-12 production is primarily transcriptional. Unlike the down-regulation of TNF-alpha under such conditions, the mechanism of IL-12 suppression during endotoxin tolerance is not dependent upon IL-10 or transforming growth factor-beta, nor is IL-12 production rescued by IFN-gamma or granulocyte-macrophage colony-stimulating factor. Of note, human dendritic cells also undergo endotoxin tolerance, with potent down-regulation of IL-12 production. Endotoxin tolerance-related suppression of IL-12 production provides a likely mechanism for the anergy seen during the immunological paralysis which follows septic shock.

Cells, Cultured↗
PubMed2001

Preoperative chemotherapy for resectable thoracic esophageal cancer.

BACKGROUND: Carcinoma of the esophagus is a relatively uncommon but lethal cancer that continues to kill over 90% of its victims within 5 years. Surgery is the treatment of choice for most localized esophageal cancer patients. However, despite curative resection, the 5-year survival rate ranges from 15% to 39%. The failure of surgery to cure clinically localized esophageal cancer is because of the advanced state of the disease before symptoms occur, high frequency of lymph node involvement, and the common occurrence of submucosal spread and extension to surrounding structures. Preoperative chemotherapy has been used in an attempt to decrease tumour activity, increase resectability, and improve disease-free and overall survival. A number of studies have investigated whether preoperative chemotherapy followed by surgery leads to an improvement in cure rates, but the individual reports have not been encouraging. The role of preoperative chemotherapy in the treatment of resectable thoracic esophageal cancer remains undefined. OBJECTIVES: The objective of this review is to determine the role of preoperative chemotherapy on overall survival and/or quality-of-life for patients with resectable thoracic esophageal carcinoma. SEARCH STRATEGY: Trials were identified by searching the Cochrane Controlled Trials Register (Issue 2 - 2000), MEDLINE (1966 - 2000), EMBASE (1988 - 2000) and CancerLit (1993 - 2000). The references of all identified studies, review articles, and standard textbooks were examined. Members of the Cochrane UGPD Group and experts in the oncology field were contacted and asked to supply details of any outstanding clinical trials and relevant unpublished materials. There were no language restrictions. The searches were updated in June 2000. The clinical trial registers of the National Cancer Institute and the Radiation Therapy Oncology Group were consulted for ongoing trials. SELECTION CRITERIA: Types of studies Studies (published or unpublished) that randomised patients with potentially resectable carcinoma of the esophagus (of any histologic type) to chemotherapy or no chemotherapy before surgery were included in this review. Studies were excluded if they were not truly randomised (phase I or II trials), earlier versions of updated trials, if other treatment modalities (e.g. radiotherapy, hyperthermia) were used, or if there was not a surgery alone control arm. Types of participants The participants consisted of patients with potentially resectable thoracic esophageal carcinoma (of any histologic type). Trials involving patients with carcinoma of the cervical esophagus were excluded. Types of interventions Trials that compared chemotherapy before surgery (esophagectomy) with surgical resection alone (esophagectomy). Types of outcome measures The primary outcome was death at yearly intervals. Morbidity (complications), and quality-of-life were secondary outcomes. DATA COLLECTION AND ANALYSIS: Overall mortality at yearly intervals was determined by extracting the total number of patients randomised to the treatment and control groups and the number of deaths in each group. All analyses were carried out on intention-to-treat that is patients were analyzed according to their allocated treatment, irrespective of whether they received that treatment. Mortality at 1, 2, 3, 4 and 5 years were used as endpoints of clinical relevance. If survival numbers at the specified time intervals were not given, they were estimated from the published survival curves. The number of deaths in the treatment groups (preoperative chemotherapy plus surgery) was compared to the number of deaths in the control groups (surgery alone). Treatment modalities as well as patient demographics and characteristics and side-effects were also recorded. Trials meeting the inclusion criteria were evaluated by two independent reviewers using the Jadad method MAIN RESULTS: A total of 14 randomised controlled trials and 1 meta-analysis of preoperative chemotherapy versus surgery alone for esophageal carcinoma were identified to be potentially eligible for review. This review is based on 7 randomised trials and 1653 patients. At 1 year the Peto odds ratio based on the fixed-effects models showed no difference in mortality between preoperative chemotherapy and surgery alone (OR = 1.03). At 2 years there was a 20% significant decrease in mortality for preoperative chemotherapy (OR = 0.80; 95% C.I. 0.65 to 0.99) but the results were not robust. The results at 3, 4, and 5 years found odds ratios tending to favour preoperative chemotherapy, but wide confidence intervals that included 1. None of the published trials reported on quality-of-life outcomes. There appeared to be an increased risk of morbidity with chemotherapy. REVIEWER'S CONCLUSIONS: The results of this review suggest that there is no strong evidence to recommend preoperative chemotherapy in the treatment of surgically resectable carcinomas of the thoracic esophagus. (ABSTRACT TRUNCATED)

Antineoplastic Agents↗
PubMed1994

Genetic resistance to parasitic disease: particularly of resistance in ruminants to gastrointestinal nematodes.

There is substantial variation among individuals in susceptibility to a wide variety of parasitic diseases and part of this variation in susceptibility is due to genetic factors. The challenge now is to determine the best methods of using the variation to improve our understanding of parasitic infection and to reduce the ravages of parasitic disease. Scientific and commercial applications will depend upon the type of genetic variation. Variation among breeds can be easily exploited by a policy of breed substitution. Variation within a breed can be exploited by selective breeding to improve resistance to infection or to disease, but more work is needed to develop selection indices which are acceptable to livestock breeders. Identifying genes which contribute to the variation in resistance provides a better understanding of the mechanisms of resistance but more work is needed to determine if such genes, alone or in combination, account for a sufficient proportion of the variation in resistance to allow marker assisted selection. A comparison of responses in susceptible and resistant stock provides a powerful tool to distinguish among protective, irrelevant and pathological responses. These themes have been illustrated by three studies of gastrointestinal nematode infections in ruminants.

Animals↗
PubMed1999

Monitoring response to treatment in liver tumours.

New imaging techniques offer better ways of measuring response to treatment and remain central to the formal assessment of response in clinical trials and routine clinical practice. Increasing tumour size is consistently associated with progressive disease. However, there is evidence that the designation 'partial response', as determined by conventional imaging techniques, may not always accurately reflect the degree of treatment-induced tumour necrosis. Thus, responses classified as partial on imaging grounds have, in some cases, been shown to be complete pathological responses after surgical resection, implying that residual tumour and necrotic/fibrotic tumour remnants cannot always be accurately distinguished by imaging. In this situation, serological tumour markers such as alphafetoprotein may be useful in measuring the true degree of response. While radiological imaging is likely to remain the main method of assessing response in phase II trials of drugs for the treatment of liver cancer, it may in some instances be useful to apply additional parameters such as alphafetoprotein level.

Biomarkers, Tumor↗
PubMed2005

Conditioned medium from keloid keratinocyte/keloid fibroblast coculture induces contraction of fibroblast-populated collagen lattices.

BACKGROUND: Keloid scars represent a pathological response to cutaneous injury. Overproliferation of fibroblasts and overproduction of collagen characterize these abnormal scars. The pathology of these scars remains poorly understood. The role of epithelial-mesenchymal interactions in keloid pathogenesis and scar contracture has recently been explored. OBJECTIVES: To test our hypothesis that epithelial-mesenchymal interactions play a major role in modulating keloid scar contracture. METHODS: A coculture model was employed wherein keloid and normal keratinocytes were cocultured with keloid or normal fibroblasts, and the conditioned media from day 5 cocultures were collected to study the effect of the paracrine secretions on contraction of an in vitro fibroblast-populated collagen lattice (FPCL) model. RESULTS: Keloid keratinocyte/keloid fibroblast coculture conditioned media brought about increased contraction of the collagen lattice compared with non-cocultured conditioned media. When keloid fibroblasts populated the collagen lattice, significantly increased lattice contraction was induced compared with lattices populated by normal fibroblasts. The addition of antitransforming growth factor (TGF)-beta neutralizing antibody to the conditioned media produced an attenuation of the contraction of the FPCLs. When keloid and normal fibroblasts were cultured on chamber slides and treated with conditioned media from coculture and non-coculture series, immunohistochemical analysis demonstrated an increased expression of alpha-smooth muscle actin (a marker for fibroblast differentiation into myofibroblasts) in fibroblasts exposed to conditioned media from coculture. CONCLUSIONS: These data indicate that epithelial-mesenchymal interactions are likely to play a major role in scar contracture and scar pathogenesis, and underscore the role of TGF-beta1 as a key player in keloid pathogenesis.

Actins↗
PubMed2005

Prognostic significance of tumor regression after preoperative chemoradiotherapy for rectal cancer.

PURPOSE: We assessed the impact of tumor regression grading (TRG) and its value in correlation to established prognostic factors in a cohort of rectal carcinoma patients treated by preoperative chemoradiotherapy (CRT). PATIENTS AND METHODS: TRG was evaluated on surgical specimens of 385 patients treated within the preoperative CRT arm of the CAO/ARO/AIO-94 trial: 50.4 Gy was delivered, fluorouracil was given in the first and fifth week, and surgery was performed 6 weeks thereafter. TRG was determined by the amount of viable tumor versus fibrosis, ranging from TRG 4 when no viable tumor cells were detected, to TRG 0 when fibrosis was completely absent. TRG 3 was defined as regression more than 50% with fibrosis outgrowing the tumor mass, TRG 2 was defined as regression less than 50%, and TRG 1 was defined basically as a morphologically unaltered tumor mass. We performed an initially unplanned, hypothesis-generating analysis with respect to the prognostic value of this TRG system. RESULTS: TRG 4, 3, 2, 1, 0 was found in 10.4%, 52.2%, 13.8%, 15.3%, and 8.3% of the resected specimens, respectively. Five-year disease-free survival (DFS) after CRT and curative resection was 86% for TRG 4, 75% for grouped TRG 2 + 3, and 63% for grouped TRG 0 + 1 (P = .006). On multivariate analysis, the pathologic T category and the nodal status after CRT were the most important independent prognostic factors for DFS. CONCLUSION: In this exploratory analysis, complete (TRG 4) and intermediate pathologic response (TRG 2 + 3) suggested improved DFS after preoperative CRT. TRG assessment should be implemented in pathologic evaluation and prospectively validated in further studies.

Adenocarcinoma↗
PubMedDate not supplied

The combination of epirubicin plus docetaxel as neoadjuvant chemotherapy in locally-advanced breast cancer.

BACKGROUND: The purpose of this study was to evaluate the activity and toxicity of epirubicin plus docetaxel as neoadjuvant chemotherapy for locally advanced breast cancer. PATIENTS AND METHODS: In this single-center, phase II trial, twenty-one patients with locally advanced breast cancer (T>3 cm or N>1) received epirubicin (70 mg/m2) and docetaxel (60 mg/m2) on Day 1 of each cycle for up to 6 cycles. RESULTS: Clinically complete responses (CR) were observed in 5 patients and partial responses were observed in 14 patients. The clinical response rate was 90.5% (95% confidence interval, 78.0-99.9). Eleven patients (52.4%) underwent breast conserving surgery. Pathological response evaluation revealed 2 CR (9.5%). Grade 4 neutropenia was recorded in 81.0% of the patients and febrile neutropenia occurred in 1 patient. CONCLUSION: The combination of epirubicin plus docetaxel was an active and well-tolerated treatment for locally-advanced breast cancer.

Adult↗
PubMedDate not supplied

[Electrophysiological analysis of various brain stem reflexes in multiple sclerosis].

An electrophysiological study of "blink reflex" and "jaw reflex" was carried out on 20 sicilian patients with "definited" Multiple Sclerosis. The R1 component of the "blink reflex" was abnormal in 13 patients on 20 (65%), the R2 component in 8 patients on 20 (40%). Considering together the R1 and R2 responses, the abnormal percentage was 75%. The "jaw reflex" showed abnormal responses in 5 patients on 20 (25%). Considering both the "blink reflex" and "jaw reflex", the pathological percentage was 75%, in order that no patients had isolated changes of the "jaw reflex". The simultaneous study of the two reflexes does not increase the probability to prove pathological responses. The frequency of the clinically silent brain-stem lesions in our patients was not substantially different from that showed by other authors on different populations.

Adolescent↗
PubMed1998

[What does the Babinski sign have to offer 100 years after its description?].

One hundred years after its description, the Babinski sign remains a faithful and precise indicator of dysfunction in the pyramidal tract. Unlike a normal plantar reflex, which is a local reflex (S1), the Babinski sign is an integral part, though with its own specificity and thus value, of the defense reflectivity of the lower limbs. It should be triggered, preferably in the lateral region of the foot, by a non-painful stimulation. The characteristic response is a dorsal flexion of the greater toe by recruitment of the extensor hallucis. The pathological response is related to a dysfunction involving a precise fraction of the pyramidal tract (van Gijn. 1996), responsible for a monosynaptic stimulation of the extensor hallucis motor neurons, but also, via interneurons, for inhibition of the extensor hallucis. Its relationship with defense reflexes is certain (Walshe, etc.) put quite complex. We refer here to the "fanning" sign or Babinski "equivalents", plantar areflexia, peripheral "pseudo-Babinski", responses obtained by stimulating the plantar aspect of the foot in the newborn, and to global hyperflexion. We also discuss the role of the Lundberf dorsal reticulospinal tract.

Brain Diseases↗
PubMedDate not supplied

Nonneoplastic lung responses induced in experimental animals by exposure to poorly soluble nonfibrous particles.

The intent of this article is to review the comparative nonneoplastic pathological responses (inflammation, fibrosis, and epithelial proliferation) of rats, hamsters, mice, and monkeys to low-toxicity dusts (TiO(2), carbon black, talc, coal-mine dust, and diesel particulate). The paucity of information on some of these comparisons and the important information on other dusts (e.g., silica) that illuminate this question have necessitated inclusion of a number of papers that go beyond these nontoxic dusts.

Air Pollutants↗
PubMed1986

Cellular control of abscess formation: role of T cells in the regulation of abscesses formed in response to Bacteroides fragilis.

Although abscesses are a major sequela of infection, little is known about which cellular events initiate and which prevent this pathologic response. These studies are the first to indicate a role for T cells in the important pathogenic process of abscess development and also in immunity to abscesses induced by Bacteroides fragilis. We have shown that T cells initiate the formation of abscesses in mice after i.p. challenge with B. fragilis. These T cells bear both Ly-1 and Ly-2 surface markers. Nude mice (which have been shown by others to have T cell or T cell precursors) are also able to form abscesses. Cyclophosphamide-treated mice (with depressed T cell function) were not capable of developing abscesses. Reconstitution with normal or nude mouse spleen cells restored this ability. However, reconstitution with anti-Thy-1.2-treated, anti-Ly-1, or anti-Ly-2-treated spleen cells (or a mixture of the two cell populations) failed to allow abscess formation after bacterial challenge. Immunity to abscesses caused by B. fragilis requires two T cells. The first Ly-1-2+ T cell has an IJ surface marker and has been shown to release a small m.w. soluble factor (ITF) that is antigen specific. Immunity to abscesses, however, depends on the interaction of ITF with a second Ly-1-2+ T cell, demonstrated in reconstitution experiments with nude mice. The data presented document a critical role for T cells in abscess induction and suggest the existence of a suppressor-like T cell circuit in immunity to abscesses.

Abscess↗
PubMed2006

A haplotype of the methylenetetrahydrofolate reductase gene predicts poor tumor response in rectal cancer patients receiving preoperative chemoradiation.

OBJECTIVE: The objective of the present study was to evaluate whether germline methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms as well as polymorphisms in the thymidylate synthase gene promoter, namely the variable number tandem repeat polymorphism (TS VNTR) and the intrarepeat G to C single nucleotide polymorphism (TS SNP), are predictive markers of tumor regression in rectal cancer patients following preoperative chemoradiotherapy. BASIC METHODS: Blood samples from 125 patients with primary adenocarcinoma of the mid-low rectum who received 5-fluorouracil-based chemotherapy and external beam radiotherapy (median dose 48.4 Gy), 125 patients (women n=45, men n=80; median age 60 years, range 31-79 years) were genotyped. Response to preoperative treatment was evaluated employing the Tumor Regression Grade criteria. On the basis of the pathologic response, patients were classified as responders (TRG 1-2, n=48) and non-responders (TRG 3-5, n=74). Three patients were excluded because of insufficient data. MAIN RESULTS: Among the polymorphic variants examined, the MTHFR 677T-1298A haplotype was, upon univariate analysis, the only variable found associated with tumor regression (P=0.004). Moreover, at multivariate analysis, the MTHFR 677T-1298A haplotype was an independent predictor of tumor regression. Patients not carrying the MTHFR 677T-1298A haplotype (odds ratio 0.29, 95% confidence interval 0.13-0.64, P=0.002) displayed a higher response rate than patients with the MTHFR 677T-1298A haplotype. CONCLUSIONS: Unlike TS VNTR and SNP polymorphisms, MTHFR 677T-1298A haplotype in genomic DNA has the potential to be a predictive marker of tumor response in rectal cancer patients submitted to preoperative chemoradiotherapy.

Adenocarcinoma↗
PubMed1996

Isolated limb perfusion with high-dose tumor necrosis factor-alpha in combination with interferon-gamma and melphalan for nonresectable extremity soft tissue sarcomas: a multicenter trial.

PURPOSE: To determine the efficacy of isolated limb perfusion (ILP) with tumor necrosis factor-alpha (TNF) in combination with interferon-gamma (IFN) and melphalan as induction therapy to render tumors resectable and avoid amputation in patients with nonresectable extremity soft tissue sarcomas (STS). PATIENTS AND METHODS: Among 55 patients with 30 primary and 25 recurrent sarcomas, there were 48 high-grade and seven grade 1 sarcomas (very large, recurrent, or multiple). The composition of this series of patients is unusual: 13 patients (24%) had multifocal primary sarcomas or multiple recurrent tumors; tumors were very large (median, 18 cm); and nine patients (16%) had known systemic metastases. IFN was administered subcutaneously on the 2 days before ILP with TNF, IFN, and melphalan. A delayed marginal resection of the tumor remnant was usually performed 2 to 3 months after ILP. RESULTS: A major tumor response was seen in 87% of patients and rendered the sarcomas resectable in most cases. Clinical response rates were as follows: 10 (18%) completes responses (CRs), 35 (64%) partial responses (PRs), and 10 (18%) no change (NC). Final outcome was defined as follows by clinical and pathologic response: 20 (36%) CRs, 28 (51%) PRs, and seven (13%) NC. Limb salvage was achieved in 84% (follow-up duration, 20+ to 50+ months). In 39 patients, resection of the tumor remnant (n = 31) or of two to eight tumors (n = 8) after ILP was performed; local recurrence developed in five (13%). When no resection was performed (multiple tumors or systemic metastases), local recurrences were frequent (five of 16), but limb salvage was often achieved as patients died of systemic disease. Regional toxicity was limited and systemic toxicity minimal to moderate with no toxic deaths. Histology showed hemorrhagic necrosis; angiographies showed selective destruction of tumor-associated vessels. CONCLUSION: ILP with TNF, IFN, and melphalan is a safe and highly effective induction biochemotherapy procedure that can achieve limb salvage in patients with nonresectable extremity STS. TNF is an active anticancer drug in humans in the setting of ILP.

Adolescent↗