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Background Specific data regarding coronavirus disease 2019 (COVID-19) in patients with neuroendocrine neoplasms (NENs) are lacking. The aim of this study is to describe the characteristics of patients with NENs who tested severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive. Material and methods This is a worldwide study collecting cases of patients with NENs along with a positive nasopharyngeal swab reverse transcriptase-polymerase chain reaction (RT-PCR) test for SARS-CoV-2 between June 1, 2020, and March 31, 2021. Centres treating patients with NENs were directly contacted by the principal investigator. Patients with NENs of any primary site, grade and stage were included, excluding small-cell lung carcinoma and mixed adenoneuroendocrine carcinoma. Results Among 81 centres directly contacted, 88.8% responded and 48.6% of them declined due to lack of cases or interest. On March 31st, 2021, eight recruiting centres enrolled 89 patients. The median age was 64 years at the time of COVID-19 diagnosis. Most patients had metastatic, non-functioning, low-/intermediate-grade gastroenteropancreatic NENs on treatment with somatostatin analogues and radioligand therapy. Most of them had comorbidities. Only 8% of patients had high-grade NENs and 12% were receiving chemotherapy. Most patients had symptoms or signs of COVID-19, mainly fever and cough. Only 3 patients underwent sub-intensive treatment, whereas most of them received medical therapies, mostly antibiotics. In two third of cases, no changes occurred for the anti-NEN therapy. More than 80% of patients completely recovered without sequelae, whereas 7.8% patients died due to COVID-19. Conclusions Patients included in this study reflect the typical NEN population regardless of SARS-CoV-2. In most cases, they overcome COVID-19 without need of intensive care, short-term sequelae and discontinuation of systemic oncological therapy.

Second-line chemotherapy in patients with metastatic gastric cancer (MGC) pre-treated with cisplatin is not a standard option. We studied a combination of irinotecan, fluorouracil and folates.Patients progressive to cisplatin-based chemotherapy were enrolled. Irinotecan 180 mg/m(2), folinic acid 200 mg/m(2), and fluorouracil 400 mg/m(2) were given on day 1, immediately followed by fluorouracil 2,400 mg/m(2) 46 h continuous infusion (simplified FOLFIRI), every 2 weeks.Between June 2002 and May 2003, 28 patients were treated. Median age was 57 years (range 38-68). Most patients had a distal primary (90%), and metastatic disease (71%). Partial response was obtained in six patients (21%, 95% CI 8-41) and stable disease in eight (21%, 95% CI 13-41). Among the six responsive patients three were refractory to docetaxel. At a median follow-up of 2.9 years median time to progression was 4 months (95% CI: 2-5), and median overall survival was 5 months (95% CI 4-9). Toxicity was mild, without treatment-related deaths or life-treating adverse events.Simplified FOLFIRI was moderately active and well tolerated in unselected patients with MGC pre-treated with cisplatin-based chemotherapy. Its role in patients refractory to taxanes is promising and warrants further investigation.

BACKGROUND. Gefitinib, an orally active inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase, combined with chemotherapy, has shown efficacy as second-line treatment for advanced colorectal cancer (CRC). Gefitinib combined with FOLFOX6 (oxaliplatin plus folinic acid and 5-fluorouracil) was tested as a first-line therapy. METHODS. Patients with metastatic EGFR-positive CRC received gefitinib at a dose of 250 mg/day combined with simplified FOLFOX6. Gefitinib was continued as maintenance treatment in nonprogressing patients. Responses were assessed by Response Evaluation Criteria in Solid Tumors (RECIST) criteria and adverse events were assessed with the National Cancer Institute Common Toxicity Criteria (NCI-CTC) scale. RESULTS. A total of 56 patients were recruited. There were 26 men and 30 women, with a median age of 57.5 years. The Eastern Cooperative Oncology Group (ECOG) performance status was as follows: 0 in 39 patients, 1 in 12 patients, and 2 in 5 patients. Thirty-nine patients (69.6%) had stage IV disease at diagnosis, 92.9% had liver involvement, and 46.4% had ≥2 metastatic sites. All patients were evaluated for safety, and 53 were evaluated for response: 40 patients (71.4%; 95% confidence interval [95% CI], 57.8%–82.6%) had complete or partial responses, and 11 patients (19.6%) had stable disease. Median time to progression was 7 months (range, 2.1–33.0 months; 95% CI, 6.2–9.0 months). Radical surgery or thermoablation of metastatic sites was performed in 14 patients (25%). NCI-CTC grade 3–4 events occurred in 36 patients (64.3%): diarrhea in 9 patients (16.1%), and hematologic toxicity in 13 patients (23.2%). Four patients (7.1%) were withdrawn for drug-related adverse events. CONCLUSIONS. The regimen has shown promising efficacy with manageable toxicity as a first-line treatment for patients with advanced CRC. Cancer 2007. © 2007 American Cancer Society.

No unanimous consensus has been reached as to the need for routine laparoscopic cholecystectomy (LC) after endoscopic sphincterotomy (ES) for choledocholithiasis in very elderly patients, who are considered as high-risk subjects for surgery.From 1991 through 1997, 170 patients were referred to undergo preoperative ES and routine LC for common bile duct (CBD) stones. The results for 27 patients (age 80 years or older) were compared with those achieved for younger patients. Successively, in a retrospective case-control study, the results for the selected patients were compared with those for 27 very elderly patients who underwent endoscopic retrograde cholangiopancreatography (ERCP), but did not receive LC. The mean follow-up period was 126 months.Octogenarians showed longer surgery time (79 vs 51 min) and postoperative hospital stay (2.8 vs 1.2 days), as well as more early low-grade complications (15% vs 3%), whereas there were no differences in conversion rate or serious complications. Recurrent symptoms or complications developed in 48% of octogenarians not undergoing routine LC, and 30% finally needed surgery. One patient in the control group died after emergency cholecystectomy for acute cholecystitis. The results of surgery were significantly poorer for the control group.Although a "wait-and-see" policy allowed two-thirds of LCs to be avoided in octogenarians, biliary-related events developed for every second patient, often requiring delayed surgery, with poorer results. Sequential treatment (ES followed by elective LC) is a safe procedure for octogenarians, and should be considered as a standard, definitive treatment for cholecystocholedocholithiasis even after the age of 80 years.

Background and aims: To test current systems evaluating for fecal continence after total anorectal reconstruction (TAR) we adapted the incontinence plus evacuation scoring system proposed by the Working Party on Anal Sphincter Replacement (WPASR). Patients and methods: We examined 51 monthly diaries recorded by 14 patients after TAR or at yearly checks (up to 5 years). A form detailing all items and frequencies of the WPASR system was given to 12 patients who assigned a rating to each item in a frequency cell. The mean values of cells were rounded off, and a 0–20 scoring scale was obtained. We corrected the scores using previously defined criteria aimed at complying with an objective rating of severity while preserving the overall patient rating. Diaries were reevaluated by both patient-rated and surgeon-corrected scales, and the correlation was calculated to each other and to Jorge and Wexner's and the Williams et al. systems; correlations between incontinence and evacuation scores were also calculated. Results: The surgeon-corrected system tended to have a lower mean score than the patient-rated one and was strongly correlated with it (r=0.984), a significantly higher mean score than the Jorge and Wexner scale (r=0.893), and a significantly lower mean score than the Williams et al. classification (quadrupled scores; r=0.857). No correlations between incontinence and evacuation were found. Conclusions: Although not validated, the patient-rated, surgeon-corrected adjustment of the WPASR system proved in our patients a reliable instrument for functional assessment. Its consensus administration to any given patient samples requires further research.

Objective: To determine a meta-analytical definition of the discriminant power of Ranson's signs in the prediction of acute pancreatitis severity and outcome, and of their information content, also compared with clinical judgment. Data Sources: Two hundred eleven studies since 1974, reporting any predictive system for acute pancreatitis (MEDLINE by various Medical Subject Headings in MEDLARS, Current Contents, Medscape, Virtual Hospital, and other on-line medical services). Study Selection: One hundred ten studies reporting clinical use of Ranson's signs were retained. A quality index was calculated for each study. A selection was made according to inclusion criteria, separately for prediction of severity (19 studies; group S) and prognosis (10 studies; group P). Six other studies reporting clinical judgment results were also selected (group C). Data Extraction: Sensitivity and specificity values were extracted. Effect sizes were calculated and summarized by the inverse variance-weighted method. Categorical models were studied by analysis of variance. Publication bias was sought by correlation test and analysis of variance. Summary receiver operating characteristic curves were drawn, and the corresponding false-positive rate (FPR) and true-positive rate were calculated for each group. From the total true-positive rate and FPRs, the probabilities of illness for positive and negative results were calculated, for severe pancreatitis prevalence from 0 to 1. Last, the area below the curve and the ratio between this and that of the "perfect test" were calculated as a measurement of information content. Data Synthesis: Ranson's signs demonstrated poor discriminant power in both predictions: "d" values were 1.200 (95% confidence interval, 1.083-1.318) and 1.302 (95% confidence interval, 1.046-1.559), respectively. The lack of homogeneity in group S (Q = 58.737; p = .0000032) can be explained by the presence of three outliers. The summary curves showed, for low FPRs, a higher sensitivity of clinical judgment; Ranson's signs reached useful sensitivity only for high FPRs. No differences between groups in the area below the information content curves were found. Conclusions: Ranson's signs showed a poor predictive power. The information content did not differ from that of clinical judgment.

Purpose Complete surgical resection is the standard treatment for localized breast phyllodes tumors. Post-surgical treatments are still a matter of debate. We carried out an overview of the literature to investigate the clinical outcome of patients with phyllodes tumor. A retrospective analysis of mono-institutional series has been included as well. Methods We reviewed all the retrospective series reported from 1951 until April 2012. We analyzed cases treated at our institution from 1999 to 2010. Results Eighty-three articles (5530 patients; 1956 malignant tumors) were reviewed. Local recurrences were independent of histology. Distant recurrences were more frequent in the malignant tumors (22%). A total of 172 phyllodes tumors were included in the retrospective analysis. Discussion Prognosis of phyllodes tumors is excellent. There are no convincing data to recommend any adjuvant treatment after surgery. Molecular characterization may well provide new clues to permit identification of active treatments for the rare poor prognosis cases.

Background: Vatalanib (PTK787/ZK 222584) inhibits a few tyrosine kinases including KIT, platelet-derived growth factor receptors (PDGFRs) and vascular endothelial growth factor receptors (VEGFRs). We report efficacy and safety results of vatalanib in advanced gastrointestinal stromal tumour (GIST) resistant to imatinib or both imatinib and sunitinib. Patients and methods: Forty-five patients whose metastatic GIST had progressed on imatinib were enrolled. Nineteen (42.2%) patients had received also prior sunitinib. Vatalanib 1250 mg was administered orally daily. Results: Eighteen patients (40.0% 95% confidence interval (CI), 25.7–54.3%) had clinical benefit including 2 (4.4%) confirmed partial remissions (PR; duration, 9.6 and 39.4 months) and 16 (35.6%) stabilised diseases (SDs; median duration, 12.5 months; range, 6.0–35.6+ months). Twelve (46.2%) out of the 26 patients who had received prior imatinib only achieved either PR or SD compared with 6 (31.6%, all SDs) out of the 19 patients who had received prior imatinib and sunitinib (P=0.324). The median time to progression was 5.8 months (95% CI, 2.9–9.5 months) in the subset without prior sunitinib and 3.2 (95% CI, 2.1–6.0) months among those with prior imatinib and sunitinib (P=0.992). Vatalanib was generally well tolerated. Conclusion: Vatalanib is active despite its narrow kinome interaction spectrum in patients diagnosed with imatinib-resistant GIST or with imatinib and sunitinib-resistant GIST.

Background: Ifosfamide and doxorubicin combination is an active regimen for patients with advanced soft tissue sarcomas (STS) but is burdened by high toxicity. A phase II trial was designed to assess the activity of continuous infusion ifosfamide and doxorubicin combination. Patients and Methods: Thirty-four chemotherapy-naive patients with advanced STS were treated with ifosfamide (13 g/m2/12 days as continuous infusion) and doxorubicin (75 mg/m2 on day 8) every 28 days with granulocyte colony-stimulating factor. Results: The major toxicity was hematological: grade 3/4 neutropenia, anemia and thrombocytopenia occurred in 63, 30 and 12% of patients, respectively. The disease control rate was 68% and the median time to progression was 7.1 months. Among leiomyosarcomas, 2 partial responses and 4 stable diseases were observed. Conclusions: Our study confirms that the ifosfamide and doxorubicin combination has a very low non-hematological toxicity profile. This regimen attained a high disease control rate with moderate activity. Further investigation into leiomyosarcoma is warranted.

The current literature does not provide unequivocal data on prognostic factors in conservative management of fecal incontinence. Moreover, the physiopathologic effects of pelvic floor rehabilitation on anorectal function are not well understood. Our aim is to identify some prognostic parameters and assess their effects on anorectal physiology of biofeedback therapy plus anal electrostimulation for fecal incontinence. We studied prospectively 45 consecutive adult patients with fecal incontinence treated at our institution with biofeedback plus electrostimulation. The outcome parameter was modification of the Wexner Incontinence Score (WIS) at the end of treatment. In addition, we studied the modifications of anorectal manometry and the rectal sensitivity threshold after treatment. At univariate analysis, age, the pretreatment WIS, and the pretreatment resting and maximum squeeze pressures were correlated with the clinical outcome. Patients showed a significant reduction in the rectal sensitivity threshold but no significant change in manometric parameters after treatment. We identify good sphincter function and mild to moderate symptomatology as favorable prognostic factors in biofeedback and anal electrostimulation therapy. Improvement in rectal sensitivity can be implicated in symptomatic improvement. The impossibility of correlating the clinical results with the effects on anorectal physiology suggests a nonspecific effect of conservative treatment.

Background: despite the fact that the combination of gemcitabine (GCB) and docetaxel shows an increased benefit for disease-free survival and overall survival compared to GCB alone in patients with soft-tissue sarcoma, GCB mono-chemotherapy should be considered as a preferable option with respect to the combination because of its lower toxicity profile and the possibility of it being administered continuously for a long time period. Case report: we report a clinical case of a woman with advanced high-grade uterine leiomyosarcoma, refractory to ifosfamide, doxorubicin and trabectedin, who experienced a sustained and progressive response to GCB alone. Conclusions: GCB given as mono-chemotherapy can obtain long-lasting tumour control in patients heavily pre-treated with various chemotherapeutic regimes for uterine LMS and should be considered as a possible option for this subset of patients.

Aims To report the outcomes of anorectal reconstruction by electrostimulated graciloplasty as part of abdominoperineal resection, on data prospectively collected over 10 years. Patients and methods Twenty-three abdominoperineal resections were associated to coloperineal pull through, double graciloplasty and loop abdominal stoma. Fifteen patients also received an implantable pulse generator, either for unsatisfactory result after external-source intermittent electrostimulation and biofeedback (five cases) or during graciloplasty (10 cases). Follow-up was to a maximum of 10 years. Functional outcome was followed up in sixteen patients who underwent stoma takedown. Results Mean actuarial survival at 5 years was 72.3%. Satisfactory results (score≤8) occurred in 75% of patients (three without and 13 with stimulator) in the early stages, decreasing to 57% at 1 year and gradually increasing up to 100% at 5 years and over. Conclusions Total anorectal reconstruction yields a good functional outcome over time. Thus, despite, and because of, a high complication rate and a great drain on resources, it should be considered a suitable procedure only for selected, strongly motivated patients.

Surgical and functional results after abdominoperineal resection and total anorectal reconstruction by electrostimulated gracilis muscle transposition are still poorly documented. This study prospectively evaluated surgical and functional outcome over time in our patients. Twenty-three patients underwent abdominoperineal resection, coloperineal pullthrough, double graciloplasty, and loop abdominal stoma. Temporary external-source intermittent electrostimulation, biofeedback training, and selective delayed stimulator implantation to improve unsatisfactory results were carried out in the first 13 patients (1st series); thereafter (2nd series) the stimulator was implanted during graciloplasty. Surgical and oncological results were followed up in all patients. Functional results were evaluated in 16 patients who underwent abdominal stoma takedown, eight in each of the two series, by anomanometry (up to 1 year) and our own 0–20 scoring system (up to 8 years from initial surgery). The rate of major and minor postoperative complications was 21.7% and 65%, respectively. Continuous electrostimulation proved effective on resting anal pressure. Early clinical assessments showed satisfactory functional results (considered as having a score ≤8) in all first-group patients, including five who had stimulator support, and in one-half of second-group patients. After impairment (at least 2 points) at 1 year in five patients, four of whom were from the first group, all functional results improved and became satisfactory from 5 years on (1st series) and from 4 years on (2nd series). Despite marked morbidity the high rate of good results, which improved over time, suggests that total anorectal reconstruction is worth being performed as part of abdominoperineal resection in well-selected patients with a strong motivation to avoid a permanent colostomy.

After presentation of the historical background of graciloplasty for anorectal reconstruction, after abdominoperineal excision of the anorectum for cancer, and illustration of pathophysiological bases, techniques and results of“dynamic” graciloplasty, a 6-year experience is reported with twenty-one patients submitted to primary total anorectal reconstructions and temporary loop abdominal ileo- or colostomy.

PURPOSE: The aim of this study was to describe and discuss the anosphincter-restoring procedure adopted in an adult patient with rectal cancer, affected by anorectal atresia and rectovestibular fistula not previously treated. METHODS: After anterior resection and transverse dissection of the rectovaginal septum, a straight double-staple low colorectal anastomosis was performed. A subcutaneous tunnel was extended from the inter-rectovaginal space, surrounding the pseudoanal orifice. The tunnel housed a left gracilis muscle arranged counter-clockwise and connected to an implanted stimulator. The vaginal and anorectal flaps were sutured longitudinally, thereby spacing out the two orifices and creating an anorectal angle. A temporary loop right colostomy was performed. RESULTS: The postoperative course was uneventful. After continuous electrostimulation training and colostomy takedown, the patient had improved continence (stimulator on) and normal defecation (stimulator off). CONCLUSIONS: The solution described seemed a suitable alternative to a pull-through procedure, which would have involved a colocutaneous anastomosis and the loss of the anorectal sensory function. Any previous anal transposition or pull-through procedures would have prevented the saving of the pre-existing “anus,” because of the interruption of the residual mesenteric vascular supply to the anorectal remnant secondary to mesorectal excision.

Summary Background Paclitaxel is a plant product highly active in numerous cancers, but anaphylactic-like hypersensitivity reactions with it have been reported in about 28% of patients receiving the drug. Thirty to sixty minutes are needed to give a standard premedication with steroids and diphenhydramine, leading to patients and nurses’ discomfort and stealing time from other infusional treatments. Patients and methods Eighty-nine patients with advanced NSCLC never pre-treated with taxanes, received paclitaxel followed by gemcitabine on days 1, 8, 15 q4wks. Premedication consisted of prednisone 25 mg/os on day 0 and hydrocortisone plus clorfenamina maleato given intravenous on day 1 by a 15 min infusion immediately before paclitaxel administration. Results Hypersensitivity reactions occurred in 3/341 (0.8%) cycles. In all three cases we observed severe dyspnoea and bronchospasm, that required treatment discontinuation but one was probably due to gemcitabine and another had a protracting time after premedication. Conclusions A 15-min premedication infusion administered immediately before paclitaxel appeared to be highly effective in patients treated with 1 h-infusion paclitaxel.

PURPOSE: The aim of the present study is to demonstrate further reconstruction of a double-gracilis anorectal neosphincter that had been destroyed because of a severe postoperative perineal infection, with necrosis of the distal part of the muscles. METHOD: Each residual gracilis muscle was split longitudinally into two branches, which surrounded the neorectum, one posteriorly and the other one anteriorly, so as to perform a perineorectal double sling. RESULT: Owing to a poor functional result, continence was achieved only by the support of an implantable pulse generator. CONCLUSION: This technique seemed to permit the optimum use of the contractile potential of the residual gracilis muscles, which did not show evidence of defunction-related or ischemia-related fibrosis.

e13072 Background: Extrapulmonary rapidly progressive neuroendocrine carcinomas (NECs) clinically resemble a small cell lung cancer (SCLC), where carboplatin has been reported as active as cisplati...

15076 Background: thalidomide has been reported to have anti-angiogenic properties and therefore has been studied in several hypervascularized cancers. We evaluated the effect of thalidomide on progression-free survival (PFS) and several surrogate markers of angiogenesis in patients (pts) with advanced hepatocellular carcinoma (HCC). Methods: from June 2005 to November 2006, 19 out of the foreseen 24 HCC pts were treated with oral thalidomide 200 mg/day continuously. All of them had cytological/histological diagnosis of HCC, with no indication for curative treatment. Prior treatment was allowed. Six-month PFS was the main clinical endpoint. Perfusion parameters (Blood Flow -BF-, Blood Volume -BV-, Permeability Surface -PS-, and Mean Transit Time -MTT-) were measured with perfusion Computed Tomography (CTp). Circulating endothelial cells (CEC), progenitor cells (CEP), and apoptotic CECs, were measured by flow cytometry. Results: Eleven pts were HCV-positive and 4 HBV-positive. Eighteen had cirrhosis (80% Child-Pugh A). Five pts had extra-hepatic metastases. The maximum CLIP value was 3, in 5 pts. Six-month PFS was 41%. Constipation and somnolence were the most common G2–3 toxicities, occurring in 50% and 18% of pts, respectively. Three pts stopped treatment because of toxicity (one oedema, one neurotoxicity, and one suspect intratumoral bleeding). Baseline BF and BV of HCC were significantly higher (p No significant financial relationships to disclose.

4119 Background: EGFR-overexpression reported in colorectal cancer, justifies use of EGFR inhibitors. We conducted a phase II study (ESMO 2005) in ACC with the aim to assess efficacy of gefitinib plus oxaliplatin containing regimen. Main biological objective was to assess serum EGFR extra-cellular binding domain as surrogate marker of tyrosine-kinase inhibition and as predictor of outcome. Methods: 57 patients with EGFR-positive ACC,received gefitinib 250 mg/day combined with simplified FOLFOX-6 for at least 4 cycles,for a maximum of 10 courses.In not progressive disease, gefitinib was continued as maintenance treatment. Tumour assessment by RECIST criteria was performed at baseline and every 4 cycles.Serum EGFR extracellular binding-domain was evaluated by quantitative enzyme-linked immunoadsorbent.Serum EGFR as predictive factor was evaluated both taking into account the basal value only,and the whole EGFR pattern over time.The analyses were performed by logistic and Cox’s regression model with time-dependent covariate respectively;both models included centre, gender,age and site of primary tumours as adjusting factors. Results: Serum samples for EGFR were obtained at baseline and at every assessment.During mono-therapy phase the patients with serum samples decreased. Over treatment,34 patients reported a CR or PR as best objective response (BOR),while 9 patients showed SD or PD. Higher serum EGFR was associated to BOR both at baseline and over time.This result was confirmed by a similar analysis,which considered the whole EGFR profile,instead of the basal value only. Conclusions: Serum EGFR at baseline can be considered a significant predictor for the BOR.This observation is in line with data reported on lung cancer (Gregorc V, 2004).Although the EGFR trend over time seems to confirm the basal difference,this result should be taken with caution,due to the little number of cases reporting EGFR values besides the basal one. [Table: see text] No significant financial relationships to disclose.

3659 Background: The orally active epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, gefitinib (IRESSA) shows promising activity in several tumor types. Preclinical studies suggest gefitinib has synergistic activity in combination with oxaliplatin in colorectal cancer (CRC) cells. This Phase II multicenter study evaluated gefitinib combined with FOLFOX-6 as first-line treatment in patients (pts) with EGFR-positive advanced CRC. Methods: Pts received gefitinib 250 mg/day combined with simplified FOLFOX-6 every 2 weeks for ≥8 weeks in order to be evaluable for response. Treatment was continued until progressive disease (PD), unacceptable toxicity, or withdrawal. Pts with clinical benefit after up to a maximum of 10 courses could continue gefitinib monotherapy. Tumor assessment (CT scan) by RECIST was made at baseline and every 4 cycles. All adverse events (AEs) were assessed by NCI-CTC. Serum EGFR was evaluated at baseline and every assessment. Results: 47/49 pts met the entry criteria: 21 ...