Half of the patients with subepithelial tumors present borderline or pathologic anxiety-distress and carcinophobia: a multicenter cohort study.

BACKGROUND AND AIMS: Minor nonspecific gastrointestinal subepithelial lesions (usually defined by the term 'tumor') are usually associated with a malignant illness and cancer. The aim of this study was to assess anxiety-distress and carcinophobia in patients referred to specialized monographic outpatient clinics for evaluation and treatment of this type of lesion. METHODS: Prospective, multicenter, cohort study. Specific self-reported questionnaires were used to report threatening life-experiences and to assess levels of distress (The Hospital Anxiety and Depression Scale) and cancer-related worries (The Cancer Worry Scale). RESULTS: Forty participants were included and analyzed at baseline. Pathologic and borderline anxiety were detected in 13% (5/40, 95%CI: 4-27%) and 35% (14/40, 95%CI: 21-52%) of participants, respectively, whereas, cancer-related worries (moderate to very high) were observed in 48% (19/40, 95%CI: 32-64%) of participants. Pathologic global distress was identified in 25% (10/40, 95%CI: 13-42%) of subjects. Higher educational level (university studies), a lack of lifetime psychiatric comorbidity and a lack of family history of cancer were associated with less anxiety, global distress and carcinophobia. CONCLUSIONS: Almost half of the patients diagnosed with a minor nonspecific gastrointestinal subepithelial lesion presented anxiety-distress and/or carcinophobia. Specific associations with anxiety-distress reaction and fears were detected.

Epigenetic inactivation of the p53-induced long noncoding RNA TP53 target 1 in human cancer.

Long noncoding RNAs (lncRNAs) are important regulators of cellular homeostasis. However, their contribution to the cancer phenotype still needs to be established. Herein, we have identified a p53-induced lncRNA, TP53TG1, that undergoes cancer-specific promoter hypermethylation-associated silencing. In vitro and in vivo assays identify a tumor-suppressor activity for TP53TG1 and a role in the p53 response to DNA damage. Importantly, we show that TP53TG1 binds to the multifaceted DNA/RNA binding protein YBX1 to prevent its nuclear localization and thus the YBX1-mediated activation of oncogenes. TP53TG1 epigenetic inactivation in cancer cells releases the transcriptional repression of YBX1-targeted growth-promoting genes and creates a chemoresistant tumor. TP53TG1 hypermethylation in primary tumors is shown to be associated with poor outcome. The epigenetic loss of TP53TG1 therefore represents an altered event in an lncRNA that is linked to classical tumoral pathways, such as p53 signaling, but is also connected to regulatory networks of the cancer cell.

Serum micronutrients and prealbumin during development and recovery of chemotherapy-induced peripheral neuropathy.

Chemotherapy-induced peripheral neuropathy (CIPN) is a frequent adverse event. Nutritional status can become impaired in cancer patients, potentially contributing to neuropathy's evolution. Our aim was to evaluate serum micronutrients and prealbumin in a cohort of 113 solid-cancer patients receiving platinum and taxane compounds during the development and recovery of neuropathy, up to 1 year after finishing treatment. CIPN was graded according to Total Neuropathy Score(©) and NCI.CTCv3 at T0 (baseline), T1 (1-3 months), and T12 (12 months) after chemotherapy. CIPN was classified as asymptomatic (< grade 2) or symptomatic (≥2). CIPN recovery was defined as ≥1 grade improvement at T12. Symptomatic CIPN developed in 52% of patients. Symptomatic patients presented a higher increase in TNSc (p < 0.001), in TNSr(©) (p < 0.001), and decrease in sural (p < 0.001) and radial nerve conduction (p < 0.001). No significant differences with any of the micronutrients were observed along T0-T1 period between severity or chemotherapy groups. By T12, symptomatic patients without recovery had a decrease in vitamin E levels (p = 0.019) and prealbumin (p = 0.062) compared with those symptomatic that improved. A correlation between the variation of vitamin E and prealbumin at T0-T1 (r = 0.626, p = 0.001) and T1-T12 (r = 0.411, p = 0.06) was observed. After chemotherapy treatment, the improvement of patients displaying symptomatic neuropathy is related to vitamin E and prealbumin serum levels. Our results suggest that nutritional status can play a role in CIPN recovery.

Endoscopic band ligation without resection in selected patients for small and superficial upper gastrointestinal tract lesions.

BACKGROUND AND AIM: The aim of this study was to evaluate the efficacy of endoscopic band ligation (EBL) in carefully selected patients who would benefit from this method of resection. METHODS: Patients with early upper gastrointestinal and small (< 15 mm) lesions treated with EBL (Duette® Multi-Band Mucosectomy) were prospectively recruited and retrospectively analyzed between 2010 and 2015. All cases were discussed in a multidisciplinary cancer committee and it was concluded that, owing to patient conditions, surgery was not possible and that not conducting histology would not change the clinical management. A first endoscopic control with biopsies was planned at 4-8 weeks. If there was no persistence of the lesion, new controls were programmed at 6 and 12 months. RESULTS: The group (n = 12) included 5 esophagus lesions (adenosquamous carcinoma, n = 1; carcinoma squamous, n = 2; adenocarcinoma, n = 2); 4 gastric lesions (high grade dysplasia, n = 1; adenocarcinoma, n = 2; neuroendocrine tumor [NET], n = 1), and 3 duodenal lesions (NETs) (n = 3). The mean tumor diameter was 9.6 ± 2.8 mm (range 4-15). Only one minor adverse event was described. At first follow-up (4-8 weeks), there was 91.6% and 75% of endoscopic and histological remission, respectively. At 6-month follow-up there was 70% of both endoscopic remission and negative biopsies. And at 12 months, there was 100% and 75% of endoscopic and histological remission, respectively. Persisting lesions were T1 cancers. The median follow-up was 30.6 months. CONCLUSION: EBL without resection is an easy and safe technique that should be considered in patients with multiple morbidities and small superficial UGI lesions.

COVID-19 among workers of a comprehensive cancer centre between first and second epidemic waves (2020): a seroprevalence study in Catalonia, Spain.

OBJECTIVES: Patients with cancer are at higher risk for severe COVID-19 infection. COVID-19 surveillance of workers in oncological centres is crucial to assess infection burden and prevent transmission. We estimate the SARS-CoV-2 seroprevalence among healthcare workers (HCWs) of a comprehensive cancer centre in Catalonia, Spain, and analyse its association with sociodemographic characteristics, exposure factors and behaviours. DESIGN: Cross-sectional study (21 May 2020-26 June 2020). SETTING: A comprehensive cancer centre (Institut Català d'Oncologia) in Catalonia, Spain. PARTICIPANTS: All HCWs (N=1969) were invited to complete an online self-administered epidemiological survey and provide a blood sample for SARS-CoV-2 antibodies detection. PRIMARY OUTCOME MEASURE: Prevalence (%) and 95% CIs of seropositivity together with adjusted prevalence ratios (aPR) and 95% CI were estimated. RESULTS: A total of 1266 HCWs filled the survey (participation rate: 64.0%) and 1238 underwent serological testing (97.8%). The median age was 43.7 years (p25-p75: 34.8-51.0 years), 76.0% were female, 52.0% were nursing or medical staff and 79.0% worked on-site during the pandemic period. SARS-CoV-2 seroprevalence was 8.9% (95% CI 7.44% to 10.63%), with no differences by age and sex. No significant differences in terms of seroprevalence were observed between onsite workers and teleworkers. Seropositivity was associated with living with a person with COVID-19 (aPR 3.86, 95% CI 2.49 to 5.98). Among on-site workers, seropositive participants were twofold more likely to be nursing or medical staff. Nursing and medical staff working in a COVID-19 area showed a higher seroprevalence than other staff (aPR 2.45, 95% CI 1.08 to 5.52). CONCLUSIONS: At the end of the first wave of the pandemic in Spain, SARS-CoV-2 seroprevalence among Institut Català d'Oncologia HCW was lower than the reported in other Spanish hospitals. The main risk factors were sharing household with infected people and contact with COVID-19 patients and colleagues. Strengthening preventive measures and health education among HCW is fundamental.

Perioperative trastuzumab, capecitabine and oxaliplatin in patients with HER2-positive resectable gastric or gastro-oesophageal junction adenocarcinoma: NEOHX phase II trial.

INTRODUCTION: Perioperative chemotherapy improves overall survival (OS) and disease-free survival (DFS) compared with surgery alone in patients with resectable gastric adenocarcinoma (GA) or gastro-oesophageal junction adenocarcinoma (GEJA). The addition of trastuzumab to chemotherapy improves outcomes in patients with HER2-positive advanced gastric cancer (GC), and we aimed to explore its role in the perioperative setting. MATERIAL AND METHODS: This Spanish, multicentre, open-label phase II trial evaluated the efficacy and toxicity of perioperative capecitabine, oxaliplatin and trastuzumab (XELOX-T) in patients with HER2-positive resectable GA or GEJA. The primary end-point was 18-months DFS; and secondary end-points included pathological complete response (pCR) rate, R0 resection rate, OS and toxicity (NCT01130337). RESULTS: Thirty-six patients were included. After three cycles of preoperative treatment, 14 patients (38% of the intention-to-treat population) had partial response and 18 (50%) had stable disease. Surgery was performed in 31 patients: 28 (90%) had R0 resection, three (9.6%) had a pCR and three (9.6%) died due to surgical complications. A total of 24 patients received post-operative XELOX-T, 22 of whom completed trastuzumab maintenance. Main grade III/IV toxicities included diarrhoea (33%), nausea and vomiting (8%). After a median follow-up of 24.1 months, 18-month DFS was 71% (95% confidence interval [CI], 53-83%); and an update after 102 months of follow-up showed a median OS of 79.9 months and a 60-month OS of 58% (95% CI, 40-73%). CONCLUSIONS: These data suggest that perioperative XELOX-T in patients with HER2-positive GA and GEJA is feasible and active. Further investigation in randomised studies is warranted.

[Surgical treatment of pancreatic adenocarcinoma using cephalic duodenopancreatectomy (Part 2). Long term follow up after 204 cases]. / Tratamiento quirúrgico del adenocarcinoma pancreático mediante duodenopancreatectomía cefálica (parte 2). Seguimiento a largo plazo tras 204 casos.

INTRODUCTION: Surgery is the accepted treatment in adenocarcinoma of the head of the pancreas; however, the long-term survival continues to be low. The aim of this study is to define prognostic factors of long-term survival after cephalic duodenopancreatectomy due to pancreatic adenocarcinoma. MATERIAL AND METHODS: We have collected data on the treatment of adenocarcinoma of the head of the pancreas (ADHP) by means of a cephalic duodenopancreatectomy (CDP) performed n the Bellvitge University Hospital (Barcelona) from 1991 to 2007. RESULTS: A total of 204 CDP due to ADHP were performed. The histology showed that the resected tumour was larger than 3cms in 70 cases, with lymphatic infiltration in 73%, perineural invasion in 89%, and lymphatic involvement in 89%. More than 15 lymph nodes were resected in 120 patients. A total of 113 (60%) patients received adjuvant treatment after surgery. There were 148 (73%) deaths, of which 55 (27%) were alive at closure. The actual mean survival was 2.54 years (95% CI; 2.02-3.07) and an actuarial survival at 5 years of 13.55% (95% CI; 7.69-19.41). The study of mortality risk factors showed that, female gender, absence of peri-operative transfusion (p=0.003), the resection of more than 15 lymph nodes during the operation (P=0.004), and the administration of adjuvant treatment (p=0.004) had a better long-term prognosis. The multivariate analysis showed that transfusion and gender were the most significant variables. CONCLUSIONS: Surgery of head of the pancreas adenocarcinoma must include an adequate lymphadectomy, and must be performed with a low morbidity and without the need of a peri-operative transfusion.

Antiangiogenic effect of gemcitabine following metronomic administration in a pancreas cancer model.

Gemcitabine shows a marked antitumor effect as a result of its cytotoxic action toward proliferative cells. In this article, we aim to investigate the potential antitumor and antiangiogenic effect of gemcitabine following a metronomic schedule that involves the regular administration of cytotoxic drugs at doses lower than standard treatment. In vitro results showed that human endothelial cells are more sensitive to gemcitabine (IC(50) 3 nmol/L) than pancreatic tumor cells (IC(50) 20 nmol/L). For in vivo studies, we used an orthotopic implantation model of human pancreatic carcinoma in nude mice. Gemcitabine was administered i.p. following a low-dose schedule (1 mg/kg/d for a month) and compared with the conventional schedule (100 mg/kg days 0, 3, 6, and 9 postimplantation). Metronomic treatment effect on established tumor was equivalent to standard administration. The measure of CD31 endothelial marked area allowed us to show an in vivo antiangiogenic effect of this drug that was further enhanced by using metronomic administration. This effect correlated with an induction of thrombospondin-1, a natural inhibitor of angiogenesis. Our results allow us to hypothesize that, in addition to a direct antiproliferative or cytotoxic antiendothelial cell effect, a secondary effect involving thrombospondin-1 induction might provide an explanation for the specificity of the effects of metronomic gemcitabine treatment.

Does gastric conditioning decrease the incidence of cervical oesophagogastric anastomotic leakage? / ¿Puede el acondicionamiento gástrico disminuir la incidencia de dehiscencia anastomótica esofagogástrica cervical?

INTRODUCTION: Oesophageal reconstruction by gastroplasty with cervical anastomosis has a higher incidence of dehiscence. The aim of the study is to analyse the incidence of anastomotic leakage in patients undergoing gastroplasty with cervical anastomosis following angiographic ischaemic conditioning of the gastric conduit. METHODS: Prospective analysis of patients who underwent gastric conditioning two weeks prior to oesophageal reconstruction, from January 2001 to January 2014. The conditioning was performed by angiographic embolization of the left and right gastric artery, and splenic artery. The main variable analysed was the incidence of anastomotic leakage in patients undergoing gastroplasty with cervical anastomosis. Secondary variables analysed were the result of the conditioning, complications arising from that procedure and in the postoperative period, and mean length of postconditioning and postoperative hospital stay. RESULTS: Gastric conditioning was indicated in 97 patients, with neoplasia being the most frequent aetiology motivating the oesophageal reconstruction (76%). 96 procedures were successfully carried out, arterial embolization was complete in 80 (83%). The morbidity rate was 13%, with no mortality. Postoperative morbidity was 45%; the most frequent complications associated with the surgery were respiratory problems. Six (7%) patients experienced cervical fistula, and all received conservative treatment. The rate of postoperative mortality was 7%. CONCLUSIONS: In our serie the incidence of anastomotic leakage in patients undergoing gastroplasty with cervical anastomosis following angiographic ischaemic conditioning is 7%. Angiographic ischaemic conditioning is a procedure with acceptable morbidity.

A phase II Study Evaluating Combined Neoadjuvant Cetuximab and Chemotherapy Followed by Chemoradiotherapy and Concomitant Cetuximab in Locoregional Oesophageal Cancer Patients.

BACKGROUND: Pre-operative chemoradiotherapy using a 5-fluorouracil (5-FU)/cisplatin backbone is widely used to improve surgical outcomes in locoregional oesophageal cancer patients, despite a non-negligible failure rate. OBJECTIVE: We evaluated intensification of this approach to improve patient outcomes by adding cetuximab to induction 5-FU/cisplatin/docetaxel (TPF) and to chemoradiotherapy in a phase II study. PATIENTS AND METHODS: Between November 2006 and April 2009, 50 patients with stage II-IVa squamous cell carcinoma (SCC) or adenocarcinoma of the oesophagus or gastro-oesophageal junction initiated three TPF/cetuximab cycles. Six weeks later, patients with response or stabilisation initiated 6 weeks of cisplatin/cetuximab/radiotherapy, followed by surgery. The primary objective was the clinical complete response (cCR) rate after induction therapy plus chemoradiotherapy in intent-to-treat patients. RESULTS: Thirty-eight patients were evaluable after chemoradiotherapy, 84% of whom showed disease control. Six patients (12%) achieved a cCR, with a 54% overall response rate. Twenty-seven patients underwent surgery, 11 of whom (22%; nine SCC, two adenocarcinoma) had a pathological CR (41%). Fifteen patients were alive after a median follow-up of 23.2 months. Median progression-free survival was 12.2 months (95% confidence interval [CI] 1.7-22.8). Median overall survival was 23.4 months (95% CI 12.2-36.6) and was significantly longer among the 22 patients with complete resection than in the five patients without (42.1 vs. 24.9 months; p = 0.02, hazard ratio: 3.6, 95% CI 1.1-11.6). The toxicity profile was acceptable. CONCLUSIONS: Neoadjuvant cetuximab/TPF followed by chemoradiotherapy in locoregional oesophageal carcinoma patients is feasible and offers a modest response rate in this trial. The results of combining trimodality neoadjuvant treatment with cetuximab are consistent with the literature. Registration: The study is registered at ClinicalTrials.gov (NCT00733889).

Correction to: A Phase II Study Evaluating Combined Neoadjuvant Cetuximab and Chemotherapy Followed by Chemoradiotherapy and Concomitant Cetuximab in Locoregional Oesophageal Cancer Patients.

Errors were subsequently identified in the article and the following corrections should be noted.

Clinical relevance of histologic subtypes in locally advanced esophageal carcinoma treated with pre-operative chemoradiotherapy: Experience of a monographic oncologic centre.

BACKGROUND: Locally advanced esophageal carcinoma (LAEC) represents less than 30% of all diagnosed esophageal carcinoma worldwide. The standard of care for resectable tumours consists of preoperative chemoradiotherapy (CRT) followed by surgery. Despite the curative intent, the prognosis is still poor mainly due to relapse. A multidisciplinary approach is required in order to optimize the therapeutic strategy and follow-up. Differences in outcomes between the two main histological subtypes, adenocarcinoma (ADC) and squamous cell carcinoma (SCC), have been reported. Nevertheless, the heterogeneity in trials design and data available have hampered the achievement of clear conclusions. The purpose of this study is to report the outcomes from a cohort of patients with LAEC treated with a multidisciplinary approach and to remark the differences observed between the two main histologic subtypes and their clinical implications. METHODS: We retrospectively reviewed 100 patients diagnosed with LAEC that were treated with preoperative CRT at our institution and integrated centres. Histopathological characteristics and toxicities during treatment were recorded. Patterns of recurrence at the first relapse were analysed. Survival curves were plotted using the Kaplan Meier method and multivariate Cox proportional hazards models were used. RESULTS: Among the patients who received preoperative CRT, 83% underwent surgery. The median overall survival (mOS) was 31.7 months, 26.9 months for ADC and 45.5 for SCC (p-value = 0.33). In the multivariate Cox regression analysis, ypN+ was the only factor that negatively influenced in OS (OR = 4.1, p-value = 0.022). Patterns of recurrence differed according to histologic subtype. Distant relapse was more frequent in ADC (62%), whereas locoregional relapse was higher in SCC (50%) (p-value = 0.027). Second line therapeutic strategies could be offered to 50% of those patients who relapsed. CONCLUSIONS: Differences in outcomes and recurrence pattern could be observed between the two main histologic subtypes of LAEC. A better molecular characterization, adapted therapeutic regimens and follow up strategies should be adopted in order to improve survival of these patients.

Detection of occult breast cancer cells by amplification of CK19 mRNA by reverse transcriptase-polymerase chain reaction: role of surgical manipulation.

BACKGROUND: To assess if surgical manipulation increases peripheral blood cancer cells dissemination in early stage (I and II) breast cancer patients. PATIENTS AND METHODS: We analyzed 64 patients using RT-PCR for cytokeratin-19 as a marker for peripheral blood breast cancer cell dissemination. Peripheral blood was obtained at 4 different time-points (24 hours before and after surgery, one week and one month later). RESULTS: RT-PCR was positive in 14 (24%) out of 59 evaluable patients. Circulating cells were detected in 4 out of 14 patients before surgery (7%) while in the remaining 10, the positivity was observed after surgery (17%). The percentage of patients with occult breast cancer cells increased significantly after surgery (p = 0.01). CONCLUSION: 1) 7% of early breast cancer patients had circulating tumor cells before surgery. 2) After surgery tumor cells were detected in 17% of patients. 3) Surgery significantly increased the presence of occult breast cancer cells. 4) The clinical significance of occult breast cancer cells should be tested within a larger clinical trial trying to assess their role as an independent prognostic factor.

Phase II trial of induction irinotecan-cisplatin followed by concurrent irinotecan-cisplatin and radiotherapy for unresectable, locally advanced gastric and oesophageal-gastric junction adenocarcinoma.

PURPOSE: The prognosis of patients with unresectable M0 gastric cancer remains very poor. We performed a phase II trial to explore the efficacy and toxicity of induction irinotecan-cisplatin (IC) followed by concurrent irinotecan-cisplatin and radiotherapy (IC/RT) in this setting. METHODS AND MATERIALS: Patients with unresectable M0 gastric (GC) or oesophageal-gastric junction (EGJC) adenocarcinomas were treated with two courses of IC (irinotecan, 65 mg/m(2); cisplatin, 30 mg/m(2) on days 1 and 8 every 21 days) followed by IC/RT (daily radiotherapy-45 Gy-with concurrent IC: irinotecan, 65 mg/m(2), and cisplatin, 30 mg/m(2), on days 1, 8, 15, and 22). Resectability was reassessed after this treatment, and surgical resection was performed if feasible. The primary endpoint was the R0 resection rate after induction treatment. RESULTS: Seventeen patients were included in the study (EGJC: 6; GC: 11). An R0 resection was achieved in only 5 patients (29%), and according to the design of the trial (Simon's optimal two-stage) accrual of patients was terminated after the first stage. No patient died during IC, whereas 3 patients (24%) died during IC/RT and one of 5 resected patients (20%) died during the first 30 days after resection. The median survival was 10.5 months, and the actuarial 2-year survival rate was 27%. CONCLUSIONS: Induction IC followed by IC/RT showed poor efficacy and significant toxicity in patients with unresectable GC/EGJC.

Phase II trial of preoperative irinotecan-cisplatin followed by concurrent irinotecan-cisplatin and radiotherapy for resectable locally advanced gastric and esophagogastric junction adenocarcinoma.

PURPOSE: To determine in a Phase II trial whether preoperative irinotecan-cisplatin (IC) followed by concurrent IC therapy and radiotherapy (IC/RT) improved outcome in patients with resectable, locally advanced gastric adenocarcinoma (GC) or esophagogastric junction cancer (EGJC). PATIENTS AND METHODS: Patients with resectable Stage II-IV, M0 GC or EGJC made up the study population. The primary endpoint was pathologic complete response (pCR). Two courses of IC (irinotecan, 65 mg/m(2); cisplatin, 30 mg/m(2) on Days 1 and 8 every 21 days) were given. Patients without progression then received IC/RT, consisting of daily radiotherapy (45Gy) with concurrent IC (irinotecan, 65 mg/m(2); cisplatin, 30 mg/m(2) on Days 1, 8, 15, and 22). Surgical resection was performed, if feasible, 5-8 weeks after the end of radiotherapy. RESULTS: Twenty-three patients were included in the study: 10 with EGJC and 13 with GC. Two patients (9%) achieved pCR. The incidences of Grade 3-4 toxicities were as follows: IC: neutropenia 35% (febrile 13%), anemia 22%, diarrhea 22%, emesis 8%; IC/RT: neutropenia 52% (febrile 5%), asthenia 19%, anemia 9%, emesis 9%, diarrhea 5%, cardiotoxicity 5%. No patients died during IC or IC/RT. R0 resection was achieved in 15 patients (65%). Median survival was 14.5 months, and the actuarial 2-year survival rate was 35%. CONCLUSIONS: Preoperative IC followed by IC/RT resulted in moderate response and resection rates with mild toxicity in patients with GC and EGJC.