N. Di Martino

A phase II study of biweekly oxaliplatin plus infusional 5-fluorouracil and folinic acid (FOLFOX-4) as first-line treatment of advanced gastric cancer patients

The aim of the study was to assess the toxicity and the clinical activity of biweekly oxaliplatin in combination with infusional 5-fluorouracil (5-FU) and folinic acid (FA) administered every 2 weeks (FOLFOX-4 regimen) in patients with advanced gastric cancer (AGC). A total of 61 previously untreated AGC patients were treated with oxaliplatin 85 mg m−2 on day 1, FA 200 mg m−2 as a 2 h infusion followed by bolus 5-FU 400 mg m−2 and a 22 h infusion of 5-FU 600 mg m−2, repeated for 2 consecutive days every 2 weeks. All patients were assessable for toxicity and response to treatment. Four (7%) complete responses and 19 partial responses were observed (overall response rate, 38%). Stable disease was observed in 22 (36%) patients, with progressive disease in the other six (10%) patients. Median time to progression (TTP) and median overall survival (OS) were 7.1 and 11.2 months, respectively. National Cancer Institute Common Toxicity Criteria grade 3 and 4 haematologic toxicities were neutropenia, anaemia and thrombocytopenia in 36, 10 and 5% of the patients, respectively. Grade 3 peripheral neuropathy was recorded in three (5%) patients. FOLFOX-4 is an active and well-tolerated chemotherapy. Response rate (RR), TTP and OS were comparable with those of other oxaliplatin-based regimens, suggesting a role for this combination in gastric cancer.

A multicenter phase II study of induction chemotherapy with FOLFOX-4 and cetuximab followed by radiation and cetuximab in locally advanced oesophageal cancer.

Background:Preoperative chemoradiotherapy (CRT) improves the survival of patients with oesophageal cancer when compared with surgery alone.Methods:We conducted a phase II, multicenter trial of FOLFOX-4 and cetuximab in patients with locally advanced oesophageal cancer (LAEC) followed by daily radiotherapy (180 cGy fractions to 5040 cGy) with concurrent weekly cetuximab. Cytokines levels potentially related to cetuximab efficacy were assessed using multiplex-bead assays and enzyme-linked immunosorbent assay at baseline, at week 8 and at week 17. Primary end point was complete pathological response rate (pCR).Results:In all, 41 patients were enroled. Among 30 patients who underwent surgery, a pCR was observed in 8 patients corresponding to a rate of 27%. The most frequent grade 3/4 toxicity was skin (30%) and neutropenia (30%). The 36-month survival rates were 85 and 52% in patients with pathological CR or PR vs 38 and 33% in patients with SD or PD.Conclusions:Incorporating cetuximab into a preoperative regimen for LAEC is feasible; no correlation between cytokines changes and patient outcome was observed. Positron emission tomography/computed tomography study even if influenced by the small number of patients appears to be able to predict patients outcome both as early and late metabolic response.

Combined videofluoroscopy and manometry in the diagnosis of oropharyngeal dysphagia: examination technique and preliminary experience

PurposeDysphagia is a symptom of different pathological conditions characterised by alteration of the swallowing mechanism, which may manifest at different levels. We report our experience in the evaluation of the swallowing mechanism with combined videofluoroscopy and manometric recordings.Materials and methodsFor the combined study, we used a Dyno Compact computerised system (Menfis Biomedical s.r.l., Bologna, Italy) equipped with: (1) graphics card for the management of ultrasonographic or radiological images; (2) A.VI.U.S. dedicated software package, which enables digital-quality recording (PAL/NTSC, composite video or S-Video) of the videofluoroscopy study in AVI format with 320×240 resolution and 25 Hz acquisition frequency. The delay introduced by the process of image digitalisation is in the order of 200 ms, so for analysis purposes, the images can be considered synchronised with the manometric recordings. The videomanometry study was performed with the administration of contrast material either in bolus form or diluted. Data were collected on a specifically designed grid for the evaluation of 46 videofluoroscopic items, of which 34 are derived from the laterolateral view (seven in the oral preparatory phase, 15 in the oral transport phase and 12 in the pharyngeal phase) and 12 in the anteroposterior view (six in the oral preparatory phase and six in the oropharyngeal phase). A positive finding for the individual parameters is expressed in a binary fashion. Manometric evaluation was based on 11 items divided into four major and seven minor criteria.ResultsDynamic videofluoroscopy swallow study combined with concurrent manometry enabled the simultaneous recording of anatomical alterations and the functional data of oropharyngeal pressure, thus providing a picture of the anatomical, biomechanical and physiological conditions of swallowing and the manner of bolus propulsion and transit.ConclusionsAn early and effective diagnosis of oropharyngeal dysphagia means being able to effectively implement appropriate rehabilitation techniques, improve the patient’s quality of life, and minimise the complications associated with swallowing disorders (choking, aspiration pneumonia, malnourishment). Distinction of the anatomical level of dysphagia is not a matter of simple classification; rather, it is essential in that different clinical presentations require different diagnostic strategies, and a precise definition of the anatomical-functional substrate is required to implement the correct therapeutic approach. This study presents the authors’ experience with the use of combined videofluoroscopy and manometry with particular emphasis on the examination technique.RiassuntoObiettivoLa disfagia è un sintomo sotteso da differenti quadri patologici, in cui si verifica un’alterazione del meccanismo deglutitorio, che può estrinsecarsi a vari livelli. Gli autori riportano la loro esperienza nella valutazione del meccanismo della deglutizione mediante l’integrazione diagnostica combinata manometrica e videofluoroscopica.Materiali e metodiPer lo studio combinato è stato impiegato il sistema computerizzato “Dyno Compact” (Menfis Biomedical s.r.l., Bologna, Italia) dotato di: 1) scheda grafica per la gestione di immagini ecografiche o radiografiche; 2) A.VI.U.S. software dedicato, attraverso il quale è possibile registrare in qualità digitale (PAL/NTSC, video composito o S-Video) la videofluoroscopia, in filmati AVI con risoluzione 320×240 e con frequenza di acquisizione di 25 Hz; il ritardo introdotto dal processo di digitalizzazione dell’immagine è dell’ordine dei 200 ms, quindi, ai fini dell’analisi, l’immagine si può considerare sincronizzata con i tracciati pressori. Lo studio VFS è stato effettuato mediante somministrazione di boli adeguati di mezzo di contrasto opportunamente diluito. I dati vengono raccolti su una griglia precostituita per la valutazione di 46 items videofluoroscopici, di cui 34 derivano dallo studio in proiezione latero-laterale (7 in fase buccale, 15 in fase orale e 12 in fase faringea) e 12 dallo studio in proiezione antero-posteriore (6 in fase buccale e 6 in fase orofaringea); la positività ai singoli parametri è espressa in maniera binaria. La valutazione pressoria si basa su 11 sialoritems manometrici, a loro volta divisi in 4 criteri maggiori e 7 minoriRisultatiLa valutazione fluoroscopica dinamica della deglutizione con registrazione video abbinata alla manometria simultanea, ha permesso di registrare contemporaneamente le alterazioni anatomiche correlandole al dato funzionale della pressione orofaringea, consentendo durante la medesima registrazione di valutare la situazione anatomica, biomeccanica e fisiologica della deglutizione e le modalità di propulsione e transito del bolo.ConclusioniFare precocemente una buona diagnosi di disfagia orofaringea significa poter intervenire efficacemente con tecniche riabilitative logopediche, migliorare la qualità di vita del paziente, nonché ridurre al minimo le complicanze che questa comporta (soffocamento, polmonite ab ingestis, malnutrizione). La differenziazione del livello anatomico della disfagia non riveste una semplice categorizzazione, ma è indispensabile in quanto alla diversità di presentazione clinica corrisponde un differente approccio metodologico diagnostico, ed a una precisa definizione del substrato anatomo-funzionale responsabile del sintomo, corrisponde un diverso approccio terapeutico. Gli autori con il presente contributo presentano la loro esperienza nell’impiego della videofluoromanometria ed in particolare la metodologia di conduzione dell’esame.

Surgical management of advanced gastric cancer: An evolving issue

Worldwide, gastric cancer represents the fifth most common cancer and the third leading cause of cancer deaths. Although the overall 5-year survival for resectable disease was more than 70% in Japan due to the implementation of screening programs resulting in detection of disease at earlier stages, in Western countries more than two thirds of gastric cancers are usually diagnosed in advanced stages reporting a 5-year survival rate of only 25.7%. Anyway surgical resection with extended lymph node dissection remains the only curative therapy for non-metastatic advanced gastric cancer, while neoadjuvant and adjuvant chemotherapies can improve the outcomes aimed at the reduction of recurrence and extension of survival. High-quality research and advances in technologies have contributed to well define the oncological outcomes and have stimulated many clinical studies testing multimodality managements in the advanced disease setting. This review article aims to outline and discuss open issues in current surgical management of advanced gastric cancer.

Search for compensation postures with videofluoromanometric investigation in dysphagic patients affected by amyotrophic lateral sclerosis

PurposeThis study was undertaken to verify the effectiveness of compensatory postures, suggested on the basis of the type of dysphagia identified at videofluoromanometric (VFM) investigation to ensure safe oropharyngeal transit.Materials and methodsEighty-one patients with amyotrophic lateral sclerosis (ALS) underwent speech therapy assessment and VFM investigation of the swallowing process. In the event of altered transit, penetration or aspiration of contrast material into the airways, compensation postures for correction of the swallowing disorder were suggested and verified during VFM examination.ResultsIn 37 patients, contrast agent transport was preserved and safe; in 19, we observed penetration of the contrast agent into the laryngeal inlet without aspiration; in 24, there was aspiration (four preswallowing, eight intraswallowing, nine postswallowing, three mixed), whereas in one patient no transit was seen. Penetration without aspiration was resolved by coughing or throat clearing; aspiration was resolved in 13 patients by assuming the chin-tuck posture and in six by rotating the head; in five patients, it was not resolved. A hyperextended head posture proved to be effective to resolve lack of transit.ConclusionsBy correlating morphological with functional data, VFM enables one not only to precisely characterise the dysphagic disorder but also to identify the most appropriate compensation posture for each patient and verify its effectiveness.RiassuntoObiettivoScopo del nostro lavoro è stato verificare l’efficacia delle posture di compenso, ipotizzate in base alle caratteristiche del disturbo disfagico individuato con videofluoromanometria (VFM), per garantire il transito orofaringeo in sicurezza.Materiali e metodiSono stati inclusi 81 pazienti affetti da sclerosi laterale amiotrofica (SLA) e sottoposti ad un protocollo di valutazione logopedia ed esame VFM della deglutizione. In caso di transito alterato, penetrazione o aspirazione del mezzo di contrasto (MdC) nelle vie aeree, sono state ipotizzate e verificate durante l’esame VFM posture di compenso per la correzione del disturbo deglutitorio.RisultatiIn 37 pazienti il transito del MdC era conservato e sicuro, in 19 abbiamo osservato penetrazione del MdC in aditus laringeo senza aspirazione, in 24 aspirazione (4 pre-deglutitoria, 8 intra-deglutitoria, 9 post-deglutitoria, 3 mista), in 1 non era presente transito. La penetrazione senza aspirazione è stata risolta con un colpo di tosse o col raclage sostenuto; l’aspirazione è stata risolta in 13 pazienti con la postura a capo flesso, in 6 col capo ruotato, in 5 non è stata risolta. Per l’assenza di transito è risultata efficace la postura a capo iperesteso.ConclusioniLa VFM, correlando il dato morfologico a quello funzionale, permette di caratterizzare con precisione il disturbo disfagico ed ipotizzare le posture di compenso più idonee al singolo caso e verificarne l’efficacia.

Complete response to preoperative chemoradiation and survival in esophageal cancer: a pooled analysis of three single-institution phase II trials.

This pooled analysis was performed using individual patient data from three phase II trials that included on the whole 113 esophageal cancer treated preoperatively with chemoradiotherapy (CRT), in order to analyze the efficacy and survival outcomes according to the achievement of the pathologic complete response (pCR). Thirty-nine patients were treated with 5-fluorouracil/cisplatin and RT (40 Gy), 33 patients received paclitaxel/cisplatin weekly during weeks 1-6 with and RT (46 Gy), 41 patients were treated with induction bio-chemotherapy with cetuximab and FOLFOX-4 followed by concomitant cetuximab and RT of 50.4 Gy. One hundred and two out of 113 resected patients were included in the survival analysis. The median overall survival (OS) time for the whole population was 21.5 months. The 12, 24, and 36 months OS rates were 85.4, 45.2, and 33%, respectively. The difference in survival probability between patients with pCR and patients with partial response or stable disease after treatment was significant (P= 0.0002, hazard ratios = 0.21, 95% CI 0.18-0.60). On multivariate analysis, the pathologic response and histology were the only covariates independently associated with OS (P= 0.0157 and P= 0.0212, respectively). In our series, complete responder patients had a significant longer survival probability after treatment when compared to patients with partial response or stable disease.

Effect of preoperative chemoradiotherapy on outcome of patients with locally advanced esophagogastric junction adenocarcinoma—a pilot study

BACKGROUND To date, few studies of preoperative chemotherapy or chemoradiotherapy (crt) in gastroesophageal junction (gej) cancer have been statistically powered; indeed, gej tumours have thus far been grouped with esophageal or gastric cancer in phase iii trials, thereby generating conflicting results. METHODS We studied 41 patients affected by locally advanced Siewert type i and ii gej adenocarcinoma who were treated with a neoadjuvant crt regimen [folfox4 (leucovorin-5-fluorouracil-oxaliplatin) for 4 cycles, and concurrent computed tomography-based three-dimensional conformal radiotherapy delivered using 5 daily fractions of 1.8 Gy per week for a total dose of 45 Gy], followed by surgery. Completeness of tumour resection (performed approximately 6 weeks after completion of crt), clinical and pathologic response rates, and safety and outcome of the treatment were the main endpoints of the study. RESULTS All 41 patients completed preoperative treatment. Combined therapy was well tolerated, with no treatment-related deaths. Dose reduction was necessary in 8 patients (19.5%). After crt, 78% of the patients showed a partial clinical response, 17% were stable, and 5% experienced disease progression. Pathology examination of surgical specimens demonstrated a 10% complete response rate. The median and mean survival times were 26 and 36 months respectively (95% confidence interval: 14 to 37 months and 30 to 41 months respectively). On multivariate analysis, TNM staging and clinical response were demonstrated to be the only independent variables related to long-term survival. CONCLUSIONS In our experience, preoperative chemoradiotherapy with folfox4 is feasible in locally advanced gej adenocarcinoma, but shows mild efficacy, as suggested by the low rate of pathologic complete response.

Search for compensation postures with videofluoromanometric investigation in dysphagic patients affected by amyotrophic lateral sclerosis@@@Ricerca delle posture di compenso della disfagia con videofluoromanometria nella sclerosi laterale amiotrofica

PurposeThis study was undertaken to verify the effectiveness of compensatory postures, suggested on the basis of the type of dysphagia identified at videofluoromanometric (VFM) investigation to ensure safe oropharyngeal transit.Materials and methodsEighty-one patients with amyotrophic lateral sclerosis (ALS) underwent speech therapy assessment and VFM investigation of the swallowing process. In the event of altered transit, penetration or aspiration of contrast material into the airways, compensation postures for correction of the swallowing disorder were suggested and verified during VFM examination.ResultsIn 37 patients, contrast agent transport was preserved and safe; in 19, we observed penetration of the contrast agent into the laryngeal inlet without aspiration; in 24, there was aspiration (four preswallowing, eight intraswallowing, nine postswallowing, three mixed), whereas in one patient no transit was seen. Penetration without aspiration was resolved by coughing or throat clearing; aspiration was resolved in 13 patients by assuming the chin-tuck posture and in six by rotating the head; in five patients, it was not resolved. A hyperextended head posture proved to be effective to resolve lack of transit.ConclusionsBy correlating morphological with functional data, VFM enables one not only to precisely characterise the dysphagic disorder but also to identify the most appropriate compensation posture for each patient and verify its effectiveness.RiassuntoObiettivoScopo del nostro lavoro è stato verificare l’efficacia delle posture di compenso, ipotizzate in base alle caratteristiche del disturbo disfagico individuato con videofluoromanometria (VFM), per garantire il transito orofaringeo in sicurezza.Materiali e metodiSono stati inclusi 81 pazienti affetti da sclerosi laterale amiotrofica (SLA) e sottoposti ad un protocollo di valutazione logopedia ed esame VFM della deglutizione. In caso di transito alterato, penetrazione o aspirazione del mezzo di contrasto (MdC) nelle vie aeree, sono state ipotizzate e verificate durante l’esame VFM posture di compenso per la correzione del disturbo deglutitorio.RisultatiIn 37 pazienti il transito del MdC era conservato e sicuro, in 19 abbiamo osservato penetrazione del MdC in aditus laringeo senza aspirazione, in 24 aspirazione (4 pre-deglutitoria, 8 intra-deglutitoria, 9 post-deglutitoria, 3 mista), in 1 non era presente transito. La penetrazione senza aspirazione è stata risolta con un colpo di tosse o col raclage sostenuto; l’aspirazione è stata risolta in 13 pazienti con la postura a capo flesso, in 6 col capo ruotato, in 5 non è stata risolta. Per l’assenza di transito è risultata efficace la postura a capo iperesteso.ConclusioniLa VFM, correlando il dato morfologico a quello funzionale, permette di caratterizzare con precisione il disturbo disfagico ed ipotizzare le posture di compenso più idonee al singolo caso e verificarne l’efficacia.

Ricerca delle posture di compenso della disfagia con videofluoromanometria nella sclerosi laterale amiotrofica

PurposeThis study was undertaken to verify the effectiveness of compensatory postures, suggested on the basis of the type of dysphagia identified at videofluoromanometric (VFM) investigation to ensure safe oropharyngeal transit.Materials and methodsEighty-one patients with amyotrophic lateral sclerosis (ALS) underwent speech therapy assessment and VFM investigation of the swallowing process. In the event of altered transit, penetration or aspiration of contrast material into the airways, compensation postures for correction of the swallowing disorder were suggested and verified during VFM examination.ResultsIn 37 patients, contrast agent transport was preserved and safe; in 19, we observed penetration of the contrast agent into the laryngeal inlet without aspiration; in 24, there was aspiration (four preswallowing, eight intraswallowing, nine postswallowing, three mixed), whereas in one patient no transit was seen. Penetration without aspiration was resolved by coughing or throat clearing; aspiration was resolved in 13 patients by assuming the chin-tuck posture and in six by rotating the head; in five patients, it was not resolved. A hyperextended head posture proved to be effective to resolve lack of transit.ConclusionsBy correlating morphological with functional data, VFM enables one not only to precisely characterise the dysphagic disorder but also to identify the most appropriate compensation posture for each patient and verify its effectiveness.RiassuntoObiettivoScopo del nostro lavoro è stato verificare l’efficacia delle posture di compenso, ipotizzate in base alle caratteristiche del disturbo disfagico individuato con videofluoromanometria (VFM), per garantire il transito orofaringeo in sicurezza.Materiali e metodiSono stati inclusi 81 pazienti affetti da sclerosi laterale amiotrofica (SLA) e sottoposti ad un protocollo di valutazione logopedia ed esame VFM della deglutizione. In caso di transito alterato, penetrazione o aspirazione del mezzo di contrasto (MdC) nelle vie aeree, sono state ipotizzate e verificate durante l’esame VFM posture di compenso per la correzione del disturbo deglutitorio.RisultatiIn 37 pazienti il transito del MdC era conservato e sicuro, in 19 abbiamo osservato penetrazione del MdC in aditus laringeo senza aspirazione, in 24 aspirazione (4 pre-deglutitoria, 8 intra-deglutitoria, 9 post-deglutitoria, 3 mista), in 1 non era presente transito. La penetrazione senza aspirazione è stata risolta con un colpo di tosse o col raclage sostenuto; l’aspirazione è stata risolta in 13 pazienti con la postura a capo flesso, in 6 col capo ruotato, in 5 non è stata risolta. Per l’assenza di transito è risultata efficace la postura a capo iperesteso.ConclusioniLa VFM, correlando il dato morfologico a quello funzionale, permette di caratterizzare con precisione il disturbo disfagico ed ipotizzare le posture di compenso più idonee al singolo caso e verificarne l’efficacia.

The laparoscopic Nissen fundoplication is a safe and effective treatment of the pathological acid and bile gastroesophageal reflux in the elderly

Aim The influence of age in the choice of treatment for gastroesophageal reflux disease (GERD) is still debated. In summary, although the laparoscopic antireflux surgery is generally undertaken with some hesitation in the elderly and the total fundoplication is considered an obstacle in presence of defective peristaltic activity, some authors recently showed good clinical outcome and low morbidity in the older GERD patients treated by laparoscopic 360° fundoplication.