MITO END-3: efficacy of avelumab immunotherapy according to molecular profiling in first-line endometrial cancer therapy.

BACKGROUND: Immunotherapy combined with chemotherapy significantly improves progression-free survival (PFS) compared to first-line chemotherapy alone in advanced endometrial cancer (EC), with a much larger effect size in microsatellite instability-high (MSI-H) cases. New biomarkers might help to select patients who may have benefit among those with a microsatellite-stable (MSS) tumor. PATIENTS AND METHODS: In a pre-planned translational analysis of the MITO END-3 trial, we assessed the significance of genomic abnormalities in patients randomized to standard carboplatin/paclitaxel without or with avelumab. RESULTS: Out of 125 randomized patients, 109 had samples eligible for next-generation sequencing analysis, and 102 had MSI tested. According to The Cancer Genome Atlas (TCGA), there were 29 cases with MSI-H, 26 with MSS TP53 wild type (wt), 47 with MSS TP53 mutated (mut), and 1 case with POLE mutation. Four mutated genes were present in >30% of cases: TP53, PIK3CA, ARID1A, and PTEN. Eleven patients (10%) had a BRCA1/2 mutation (five in MSI-H and six in MSS). High tumor mutational burden (≥10 muts/Mb) was observed in all MSI-H patients, in 4 out of 47 MSS/TP53 mut, and no case in the MSS/TP53 wt category. The effect of avelumab on PFS significantly varied according to TCGA categories, being favorable in MSI-H and worst in MSS/TP53 mut (P interaction = 0.003); a similar non-significant trend was seen in survival analysis. ARID1A and PTEN also showed a statistically significant interaction with treatment effect, which was better in the presence of the mutation (ARID1A P interaction = 0.01; PTEN P interaction = 0.002). CONCLUSION: The MITO END-3 trial results suggest that TP53 mutation is associated with a poor effect of avelumab, while mutations of PTEN and ARID1A are related to a positive effect of the drug in patients with advanced EC.

Impact of surgeon learning curve in minimally invasive radical hysterectomy on early stage cervical cancer patient survival.

Background: Recently, it has been sustained that only surgeons skilled in minimally invasive radical hysterectomy (MI-RH) could provide valuable oncological outcomes in early-stage cervical cancer. Still, literature lacks data correlating surgeon experience with patient survival rate. We aimed to investigate the impact of surgeon training on this rate. Methods: This is a retrospective study of 243 early-stage cervical cancer treated with MI-RH. Multiple regression analyses were undertaken to investigate the impact of the surgeons learning curve, according to the number of MI-RH, on patients prognosis. Results: A steady trend of reduction in disease recurrence risk is associated with increased surgeon experience. The peak of the learning curve was shown at the 19th MI-RH (hazard ratio of disease-free survival: 0.321; 95%CI: 0.140-0.737; p= 0.007). The 3 years disease-free survival that a surgeon could provide to patients is significantly lower at the beginning of his/her learning path comparing to what he/she could guarantee once adequate experience had been achieved (75.4% and 91.6% respectively, p=0.005). Surgeon experience appears to be an independent prognostic factor. Conclusion: The experience that a surgeon can achieve practicing in MI-RH significantly influences oncological outcomes of early-stage cervical cancer patients. Future studies comparing minimally invasive and open surgery should take this into account. It would be advisable that the scientific community precisely establishes the minimum training required in the field of MI-RH for early-stage cervical cancer.

Sensitivity of subject-specific models to Hill muscle-tendon model parameters in simulations of gait.

Subject-specific musculoskeletal (MS) models of the lower extremity are essential for applications such as predicting the effects of orthopedic surgery. We performed an extensive sensitivity analysis to assess the effects of potential errors in Hill muscle-tendon (MT) model parameters for each of the 56 MT parts contained in a state-of-the-art MS model. We used two metrics, namely a Local Sensitivity Index (LSI) and an Overall Sensitivity Index (OSI), to distinguish the effect of the perturbation on the predicted force produced by the perturbed MT parts and by all the remaining MT parts, respectively, during a simulated gait cycle. Results indicated that sensitivity of the model depended on the specific role of each MT part during gait, and not merely on its size and length. Tendon slack length was the most sensitive parameter, followed by maximal isometric muscle force and optimal muscle fiber length, while nominal pennation angle showed very low sensitivity. The highest sensitivity values were found for the MT parts that act as prime movers of gait (Soleus: average OSI=5.27%, Rectus Femoris: average OSI=4.47%, Gastrocnemius: average OSI=3.77%, Vastus Lateralis: average OSI=1.36%, Biceps Femoris Caput Longum: average OSI=1.06%) and hip stabilizers (Gluteus Medius: average OSI=3.10%, Obturator Internus: average OSI=1.96%, Gluteus Minimus: average OSI=1.40%, Piriformis: average OSI=0.98%), followed by the Peroneal muscles (average OSI=2.20%) and Tibialis Anterior (average OSI=1.78%) some of which were not included in previous sensitivity studies. Finally, the proposed priority list provides quantitative information to indicate which MT parts and which MT parameters should be estimated most accurately to create detailed and reliable subject-specific MS models.

Definition of a dynamic laparoscopic model for the prediction of incomplete cytoreduction in advanced epithelial ovarian cancer: proof of a concept.

OBJECTIVE: To develop an updated laparoscopy-based model to predict incomplete cytoreduction (RT>0) in advanced epithelial ovarian cancer (AEOC), after the introduction of upper abdominal surgery (UAS). PATIENTS AND METHODS: The presence of omental cake, peritoneal extensive carcinomatosis, diaphragmatic confluent carcinomatosis, bowel infiltration, stomach and/or spleen and/or lesser omentum infiltration, and superficial liver metastases was evaluated by staging laparoscopy (S-LPS) in a consecutive series of 234 women with newly diagnosed AEOC, receiving laparotomic PDS after S-LPS. Parameters showing a specificity≥75%, PPV≥50%, and NPV≥50% received 1 point score, with an additional one point in the presence of an accuracy of ≥60% in predicting incomplete cytoreduction. The overall discriminating performance of the LPS-PI was finally estimated by ROC curve analysis. RESULTS: No-gross residual disease at PDS was achieved in 135 cases (57.5%). Among them, UAS was required in 72 cases (53.3%) for a total of 112 procedures, and around 25% of these patients received bowel resection, excluding recto-sigmoid resection. We observed a very high overall agreement between S-LPS and laparotomic findings, which ranged from 74.7% for omental cake to 94.8% for stomach infiltration. At a LPS-PIV≥10 the chance of achieving complete PDS was 0, and the risk of unnecessary laparotomy was 33.2%. Discriminating performance of LPS-PI was very high (AUC=0.885). CONCLUSIONS: S-LPS is confirmed as an accurate tool in the prediction of complete PDS in women with AEOC. The updated LPS-PI showed improved discriminating performance, with a lower rate of inappropriate laparotomic explorations at the established cut-off value of 10.

TLEM 2.0 - a comprehensive musculoskeletal geometry dataset for subject-specific modeling of lower extremity.

When analyzing complex biomechanical problems such as predicting the effects of orthopedic surgery, subject-specific musculoskeletal models are essential to achieve reliable predictions. The aim of this paper is to present the Twente Lower Extremity Model 2.0, a new comprehensive dataset of the musculoskeletal geometry of the lower extremity, which is based on medical imaging data and dissection performed on the right lower extremity of a fresh male cadaver. Bone, muscle and subcutaneous fat (including skin) volumes were segmented from computed tomography and magnetic resonance images scans. Inertial parameters were estimated from the image-based segmented volumes. A complete cadaver dissection was performed, in which bony landmarks, attachments sites and lines-of-action of 55 muscle actuators and 12 ligaments, bony wrapping surfaces, and joint geometry were measured. The obtained musculoskeletal geometry dataset was finally implemented in the AnyBody Modeling System (AnyBody Technology A/S, Aalborg, Denmark), resulting in a model consisting of 12 segments, 11 joints and 21 degrees of freedom, and including 166 muscle-tendon elements for each leg. The new TLEM 2.0 dataset was purposely built to be easily combined with novel image-based scaling techniques, such as bone surface morphing, muscle volume registration and muscle-tendon path identification, in order to obtain subject-specific musculoskeletal models in a quick and accurate way. The complete dataset, including CT and MRI scans and segmented volume and surfaces, is made available at http://www.utwente.nl/ctw/bw/research/projects/TLEMsafe for the biomechanical community, in order to accelerate the development and adoption of subject-specific models on large scale. TLEM 2.0 is freely shared for non-commercial use only, under acceptance of the TLEMsafe Research License Agreement.

Sensitivity of subject-specific models to errors in musculo-skeletal geometry.

Subject-specific musculo-skeletal models of the lower extremity are an important tool for investigating various biomechanical problems, for instance the results of surgery such as joint replacements and tendon transfers. The aim of this study was to assess the potential effects of errors in musculo-skeletal geometry on subject-specific model results. We performed an extensive sensitivity analysis to quantify the effect of the perturbation of origin, insertion and via points of each of the 56 musculo-tendon parts contained in the model. We used two metrics, namely a Local Sensitivity Index (LSI) and an Overall Sensitivity Index (OSI), to distinguish the effect of the perturbation on the predicted force produced by only the perturbed musculo-tendon parts and by all the remaining musculo-tendon parts, respectively, during a simulated gait cycle. Results indicated that, for each musculo-tendon part, only two points show a significant sensitivity: its origin, or pseudo-origin, point and its insertion, or pseudo-insertion, point. The most sensitive points belong to those musculo-tendon parts that act as prime movers in the walking movement (insertion point of the Achilles Tendon: LSI=15.56%, OSI=7.17%; origin points of the Rectus Femoris: LSI=13.89%, OSI=2.44%) and as hip stabilizers (insertion points of the Gluteus Medius Anterior: LSI=17.92%, OSI=2.79%; insertion point of the Gluteus Minimus: LSI=21.71%, OSI=2.41%). The proposed priority list provides quantitative information to improve the predictive accuracy of subject-specific musculo-skeletal models.

Studies on the constituents of Cyclanthera pedata fruits: isolation and structure elucidation of new flavonoid glycosides and their antioxidant activity.

The isolation of six flavon glycosides (1-6), among them four new natural compounds (1-4), from the CHCl(3)/MeOH extract of the fruits of Cyclanthera pedata is reported. All of the structures were elucidated by spectroscopic methods, including the concerted application of one-dimensional ((1)H, (1)H TOCSY, (13)C, and (13)C DEPT-NMR) and two-dimensional NMR techniques (DQF-COSY, HSQC, and HMBC). For all of the isolated compounds the antioxidant activity was determined by measuring the free radical scavenging activity, using the Trolox equivalent antioxidant capacity (TEAC) method, and the coupled oxidation of beta-carotene and linoleic acid.

Aspartyl protease inhibitor pepstatin binds to the presenilins of Alzheimer's disease.

Mutations in the presenilin genes PS1 and PS2 cause early-onset Alzheimer's disease by altering gamma-secretase cleavage of the amyloid precursor protein, the last step in the generation of Abeta peptide. Ablation of presenilin (PS) genes, or mutation of two critical aspartates, abolishes gamma-secretase cleavage, suggesting that PS may be the gamma-secretases. Independently, inhibition experiments indicate that gamma-secretase is an aspartyl protease. To characterize the putative gamma-secretase activity associated with presenilins, lysates from human neuroblastoma SH-SY5Y and human brain homogenates were incubated with biotin derivatives of pepstatin, followed by immunoprecipitation of PS and associated proteins, and biotin detection by Western blotting. Precipitation with PS1 antibodies, directed to either N-terminal or loop regions, yielded the same 43 kDa band, of apparent molecular mass consistent with that of full-length PS1, although it may represent an aspartyl protease complexed with PS1. Incubation of cell lysates with pepstatin-biotin, followed by streptavidin precipitation and PS1 Western blotting, revealed PS1 fragments and full-length protein, indicating that pepstatin-biotin bound to both cleaved and uncleaved PS1. Binding could be competed by gamma-secretase inhibitor L-685,458 and could not be achieved with a PS1 mutant lacking the two transmembrane aspartates. Pepstatin-biotin was also shown to bind to PS2. PS1 was specifically absorbed to pepstatin-agarose, with an optimal pH of 6. Binding of pepstatin-biotin to PS1 from lymphocytes of a heterozygous carrier of pathologic exon 9 deletion was markedly decreased as compared to control lymphocytes, suggesting that this PS1 mutation altered the pepstatin binding site.

Identification of Hb Villejuif [beta123(H1)Thr-->Ile] in Southern Italy.

Hb Villejuif [beta123(H1)Thr-->Ile] is a silent and asymptomatic variant described in 1989 in an 87-year-old woman of French origin suffering from coincidental polycythemia vera. This paper reports the second observation of Hb Villejuif in three related subjects from Montesarchio, Southern Italy. All routine techniques for hemoglobin analysis yielded normal results with the exception of a slight increase in the Hb A2 value. The occurrence of a variant beta-globin was rapidly assessed by liquid chromatography mass spectrometric analysis and the abnormal chain purified by high performance liquid chromatography. The amino acid replacement Thr-->Ile at beta123 was determined by tandem electrospray mass spectrometric analysis of the tryptic digest of the variant beta chain. The corresponding DNA mutation was established as C-->T at the second position of codon 123 (ACC-->ATC) by polymerase chain reaction amplification techniques.

Primary intraosseous verrucous carcinoma developing from a maxillary odontogenic cyst: case report.

Primary intraosseous carcinoma (PIOC) is an extremely rare lesion, almost always occurring in cranial bones. The origin of this tumor, specific to the maxillae, is associated with the cells of the epithelial rests of Malassez. Among the histotypes which can be included in these neoplasms, verrucous carcinoma is of particular interest due to its rarity: only a single case has been reported to date. After a short survey of the literature, the authors describe a directly observed case of verrucous carcinoma arising from a maxillary odontogenic cyst.

Low-dose monitored mitotane treatment achieves the therapeutic range with manageable side effects in patients with adrenocortical cancer.

Eight patients with adrenocortical cancer were treated with low doses of mitotane (2-3 g daily) while monitoring drug plasma levels. When the mitotane concentrations reached the therapeutic range (defined as mitotane plasma levels between 14-20 microg/mL), a dose reduction was performed to avoid toxicity. Thereafter, the mitotane dose was tailored according to plasma levels. A progressive increase in plasma mitotane concentrations was observed during treatment, and a highly significant linear correlation was found between plasma drug levels and the total mitotane dose. The therapeutic threshold was reached in all patients after 3-5 months and a total mitotane dose of 283-387 g/days (median, 363). The duration of treatment was 8-40 months (median, 9). Toxicity was manageable in all but one patient, who discontinued treatment. It is therefore possible to design a standard low dose schedule, e.g. 3 g/daily for about 3-4 months with following dose adjustments guided by the monitoring of plasma mitotane levels. This approach is able to provide therapeutic mitotane concentrations and limit the unwanted effects. The present data provide a rationale to change the approach to mitotane treatment in patients with adrenocortical carcinoma from high dose to low dose regimens.

Lipocalins of boar salivary glands binding odours and pheromones.

Large amounts of an odorant-binding protein have been isolated from submaxillary glands of mature male pig. This polypeptide molecule is sex-specific, being absent in females. On electrophoretic gels under denaturing conditions it migrated as a broad band with an apparent molecular mass of around 20 kDa. Electrospray mass spectrometry revealed the presence of three main components, whose mass differences are not interpretable as result of any common post-translational modifications, indicating the presence of distinct polypeptide chains. N-terminal Edman degradation yielded a single sequence of 29 amino acids. It includes the lipocalin signature (-G-X-W-) and shows clear homology with a subclass of odorant-binding proteins present in mouse saliva, nasal mucus and urine. The purified protein still retained small ligands tightly bound; among them 5alpha-androst-16-en-3-one and 5alpha-androst-16-en-3alpha-ol, both known sex pheromones for the pig, were identified. The protein also binds 2-isobutyl-3-methoxypyrazine, a good ligand for most odorant-binding proteins, with a dissociation constant of 5 microM.

In vitro reactivity of the antineoplastic drug carmustin and acrolein with model peptides.

The in vitro interaction of the antineoplastic drug 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU) and acrolein with model peptides has been investigated in order to provide a detailed description of their electrophilic reactivity towards biological macromolecules. Following incubation with these substances, the modified species were separated by HPLC and identified by fast atom bombardment mass spectrometry, whereas the reactive amino acids within the peptide structure were assigned by tandem mass spectrometry. Incubation with BCNU led essentially to the formation of an N-terminal carbamoyl derivative that slowly decomposed to form three isomeric structures and a very minor ethylated adduct. Alkylation with acrolein gave rise to a mixture of different adducts due to the reaction of both the double bond and the carbonyl group. Two species containing intramolecular cross-links were also observed. These results constitute the prerequisite for in vitro and in vivo studies on the modification of haemoglobin in patients following treatment with antineoplastic drugs.

Enhancement of calcyclin gene RNA expression in squamous cell carcinoma of the oral mucosa, but not in benign lesions.

Oral cancer is a neoplasm with some known causes. Proliferation genes are significant among its few pathogenetic and prognostic factors. Calcyclin is a cell-cycle-related gene, the function of which is still unclear. Its expression and that of Haras and histone-H3 have been investigated in an assessment of their pathogenetic role in squamous cell carcinoma. RNA extracted from the pathological and normal mucosa of patients with squamous cell carcinoma (SCC) and benign lesions was reverse transcribed and amplified by the polymerase chain reaction (PCR). The expression of all three genes in the pathological mucosa was enhanced in SCC only. This suggests that they may be involved in its pathogenesis and provides another parameter for the differentiation of malignant and benign lesions.

[Rokitamycin in odontostomatology. Controlled study of doses]. / Rokitamicina in odontostomatologia. Studio controllato tra dosi.

BACKGROUND: Rokitamycin is a semisynthetic macrolide with a lactonic ring with 16 atoms, showing anti-bacterial action at concentrations near to MIC. A controlled clinical study is carried out, in parallel groups, whose aim was to assess the therapeutic action and safety of two dosage schemes of rokitamycin, in the short term treatment (5 days) of acute infective processes of odontostomatological origin. METHODS: Twenty patients (14 males, 6 females) were recruited for the trial, suffering from alveolitis, abscess, phlegmon, sialadenitis and suppurating cysts. The patients were divided in a randomized fashion into two groups: 10 patients were treated orally with 800 mg/day and 10 with 1200 mg/day. Rokitamycin was supplied in 400 mg tablets. RESULTS: The 5 days of treatment with rokitamycin determined the complete resolution of the infective process, with eradication of the germs originally isolated, all belonging to the Streptococcus genus. Clinical efficacy was evident by the third day of treatment, with a prompt improvement of symptoms (functional limitation, pain, tumefaction) and the return of body temperature to within normal limits, in a totally superimposable fashion between the two groups. Safety was excellent with both doses, with no side effects observed. CONCLUSIONS: The results of the study show that treatment with rokitamycin in the short term, at the usual dosage of 800 mg/day, is a valid therapeutic scheme in infective processes in odontostomatology.

Structural characterization by mass spectrometry of hemoglobin adducts formed after in vivo exposure to methyl bromide.

A mass spectrometric procedure is described for the structural study of the adducts formed in human hemoglobin by in vitro exposure of erythrocytes to the alkylating agent methyl bromide using different protein to reagent ratios. Peptide mapping by HPLC and tandem mass spectrometry allowed location of methylated amino acids within the protein sequence. A prominent reactivity of several nucleophilic side chains in human hemoglobin subunits was observed, which was modulated by the concentration of the alkylating agent. Cysteine residues, the main reactive sites, were fully methylated in hemoglobin exposed to a 10-fold excess of methyl bromide, differently from other residues, including histidines, showing a heterogeneous pattern of methylation that was largely directed by their environment. No evidence of methylation was found at the heme proximal histidines beta92 and alpha87. A more selective methylation was obtained when the ratio methyl bromide: hemoglobin was lowered to about 1:1. In this last case only specific residues were reactive. Among them, the N-terminal amino group of both alpha- and beta-globins, cysteine 104 in the alpha-chain and cysteine 93 (not cysteine 112) in the beta-chain, indicating a different accessibility to reaction of the sulfhydryl groups on the protein chain. Thus hemoglobin side chains are selectively modified and the degree of modification at each site is a function of the position of the single amino acid residue within the protein quaternary structure, raising the possibility that alterations of structure and functional properties of human hemoglobin following exposure to alkylating agents may be mediated through such covalent protein modifications. The results obtained demonstrate the usefulness of the analytical approach for the characterization of hemoglobin adducts with methyl bromide or similar compounds, which can constitute the basis for biomonitoring of human exposure.

Oxidative structural modifications of low density lipoprotein in homozygous familial hypercholesterolemia.

Patients with homozygous familial hypercholesterolemia (FH), as a result of the increased levels and prolonged residence time of low density lipoprotein (LDL) in plasma, have a strong tendency toward accumulation of LDL-cholesterol in the arterial wall, causing premature atherosclerosis. This phenomenon may enhance per se the physiological degradation of both protein and lipid component of LDL, which be more susceptible to oxidative damage induced by oxygen radicals. It is well known that LDL may undergo oxidative modification before being taken up by macrophages which are then transformed into foam cells. It has been suggested that platelet-activating factor (PAF) may play an important role in atherogenesis and PAF catabolism is known to be mediated by serum acetylhydrolase, an enzyme that is normally associated with LDL. Thus, the present study was designed to investigate the structural properties of LDL, including acetylhydrolase activity, in homozygous FH as compared to normolipidemic subjects before and after xanthine/xanthine oxidase-mediated oxidation. We studied 8 homozygous FH patients matched with 8 normolipidemic volunteers. Lipids of LDL fraction were extracted and verified by thin layer chromatography (TLC) analysis. Fatty acids were methylated and injected into a gas chromatograph/mass spectrometer. Vitamin E in LDL was determined by high performance liquid chromatography (HPLC). As an index of susceptibility of LDL to oxidative modifications, the formation of lipid-conjugated dienes was continuously monitored at 234 nm. Lipid peroxidation was also evaluated from the amount of both lipid peroxides (LPO) and malonyldialdehyde (MDA) content. Apolipoprotein (apo) B-100 on LDL was carried on polyacrylamide and agarose gel electrophoresis. In the homozygous FH patients, the relative content of cholesteryl ester was slightly increased. Interestingly, the relative amount of arachidonic acid (20:4) was constantly increased in each lipid fraction in homozygous FH patients. The amount of vitamin E was not significantly different in the patient group from that in the control group. However, LDL from patients carried lower levels of vitamin E (nmol/mg LDL) than controls (2.7 +/- 0.4 vs. 2.9 +/- 0.3 P = NS). The results shows that lag time (min) was decreased (82 +/- 19 vs. 111 +/- 21; P < 0.05) and the maximal rate of diene production and total diene production was increased in homozygous FH patients. Mean levels of MDA were similar in both groups before oxidation, but levels after initiation of oxidation were significantly higher in the patient group. In contrast, mean levels of LPO were already higher in patients before oxidation (58 vs. 27 nmol/mg of protein; P < 0.05), and after initiation of oxidation were also significantly higher at each time points. When oxidized LDL was run on a polyacrylamide gel, an extensive apo B-100 fragmentation replaced by lower molecular mass fragments ranging from 45,000 to 205,000 m.wt., was observed only in LDL from homozygotes. Relative LDL agarose gel mobility shows that LDL from patients migrated higher than LDL of controls. Finally acetylhydrolase activity associated with LDL in patients was significantly reduced as compared to controls. Thus, in homozygous FH patients, LDL appeared more susceptible to oxidation in vitro; the indices for LDL oxidizability were all significantly different from those of controls. This phenomenon might be due to prolonged residence time of LDL in these patients, as suggested from high basal LPO levels and lower vitamin E levels carried by LDL. This hypothesis may explain together with the high content of arachidonic acid, the enhanced susceptibility of LDL from homozygous FH patients to oxidative damage.

[Eosinophilic granuloma of the maxillary bone. Review of the literature and report of a case of mandibular location in an HIV-positive patient]. / Granuloma eosinofilo delle ossa mascellari. Revisione della letteratura e presentazione di un caso di localizzazione mandibolare in paziente HIV positivo.

Following a short review of the literature, the authors report a case of an eosinophilic granuloma in bone in an immunodepressed patient (manifest AIDS) suffering from chronic hepatitis B and C. The possible link between the viral infection and immunodepression and the pathology in question in then discussed.

[Benign tumors of epithelial origin of the salivary glands. The authors' own experience and cases]. / Tumori benigni di origine epiteliale delle ghiandole salivari. Esperienza e casistica personale.

Following a review of the most recent literature on benign tumours of the salivary glands of epithelial origin, the paper illustrates an up-to-date classification of these tumours in anatomical and pathological terms. The author's personal clinical experience in 50 cases of major and minor salivary glands operated during the period between 1985 and 1991.

[Verrucous carcinoma of the oral cavity. Personal experience with combined chemo-surgical treatment]. / Carcinoma verrucoso del cavo orale. Esperienze personali sul trattamento chemio-chirurgico integrato.

Following an introduction regarding the anatomo-pathological and clinical aspects of verrucous carcinoma of the oral cavity, the authors review several recent reports concerning the prognosis and treatment of this tumour and its possible evolution. This is followed by a wide-ranging discussion of the differing opinions put forward by various researchers regarding the possible role of radiotherapy and in particular the high risk of triggering off latent forms and provoking the differentiated and more aggressive forms of carcinoma. The authors then illustrate their experience of integrated chemo-surgical treatment, excluding radiotherapy, administered over the past six years to patients who were brought to their attention suffering from this form of carcinoma.