General Aspects of Primary Cancer Prevention.

BACKGROUND: Cancer is the second leading cause of death worldwide next to cardiovascular diseases. Despite the advancement in screening, early diagnosis, and development in treatment technology in last several decades, cancer incidence overall, particularly that of gastrointestinal (GI) cancers, is far from being controlled, and is expected to increase worldwide. SUMMARY: Although numerous preclinical and population-based clinical studies have already made important progress in restraining the overall cancer incidence and mortality, the full potential of preventive strategy is still far from being realized, and remains at an early stage. There are several major challenges regarding this issue, and one of the crucial challenges is to maintain the balance between risks and benefits. As a result of past investments, primary prevention nowadays include the integration of various activities such as lifestyle changes to reduce risk, screening to detect early lesions, vaccines and preventive therapies aimed to actively interrupt the carcinogenic pathway. Long-term aspirin use seems to have the largest potential effect on the general population on cancer incidence and mortality overall, especially GI cancers. Helicobacter pylori eradication reduces the risk for gastric cancer and is advocated regardless of the symptoms and stage of disease. Metformin and statins are promising in cancer prevention in patients with type 2 diabetes. Vitamin D supplementation is promising in the prevention of colorectal adenoma recurrence. Key Message: However, additional studies are warranted to establish the potential of various agents and to identify more specific and highly targeted new agents for chemoprevention in digestive oncology.

Beating the odds: efficacy and toxicity of dihydropyrimidine dehydrogenase-driven adaptive dosing of 5-FU in patients with digestive cancer.

AIMS: 5-FU is the backbone of most regimens in digestive oncology. Administration of standard 5-FU leads to 15-30% of severe side effects, and lethal toxicities are regularly reported with fluoropyrimidine drugs. Dihydropyrimidine dehydrogenase (DPD) deficiency is a pharmacogenetic syndrome responsible for most cases of life-threatening toxicities upon 5-FU intake, and pre-treatment checking for DPD status should help to reduce both incidence and severity of side effects through adaptive dosing strategies. METHODS: We have used a simple method for rapidly establishing the DPD phenotype of patients with cancer and used it prospectively in 59 routine patients treated with 5-FU-based therapy for digestive cancers. No patient with total DPD deficiency was found but 23% of patients exhibited poor metabolizer phenotype, and one patient was phenotyped as profoundly deficient. Consequently, 5-FU doses in poor metabolizer patients were cut by an average 35% as compared with non deficient patients (2390 ± 1225 mg vs. 3653 ± 1371 mg, P < 0.003, t-test). RESULTS: Despite this marked reduction in 5-FU dosing, similar efficacy was achieved in the two subsets (clinical benefit: 40 vs. 43%, stable disease: 40 vs. 37%, progressive disease: 20% in both subsets, P = 0.893, Pearson's chi-square). No difference in toxicities was observed (P = 0.104, Fisher's exact test). Overall, only 3% of early severe toxicities were recorded, a value markedly lower than the 15-30% ones usually reported with 5-FU. CONCLUSIONS: This feasibility study shows how simplified DPD-based adaptive dosing of 5-FU can reduce sharply the incidence of treatment-related severe toxicities while maintaining efficacy as part of routine clinical practice in digestive oncology.

Updates in Diagnosis and Endoscopic Management of Cholangiocarcinoma.

Cholangiocarcinoma (CCA) is an adenocarcinoma originating from the epithelial cells of the bile ducts/hepatocytes or peribiliary glands. There are three types of cholangiocarcinoma: intrahepatic, perihilar and distal. CCA represents approximately 3% of the gastrointestinal malignancies. The incidence of CCA is higher in regions of the Eastern world compared to the Western countries. There are multiple risk factors associated with cholangiocarcinoma such as liver fluke, primary sclerosing cholangitis, chronic hepatitis B, liver cirrhosis and non-alcoholic fatty liver disease. Endoscopy plays an important role in the diagnosis and management of cholangiocarcinoma. The main endoscopic methods used for diagnosis, biliary drainage and delivering intrabiliary local therapies are endoscopic retrograde cholangiopancreatography and endoscopic ultrasound. The purpose of this review is to analyze the current data found in literature about cholangiocarcinoma, with a focus on the actual diagnostic tools and endoscopic management options.

[Implementation of pharmaceutical consultations in digestive oncology in a teaching hospital: one-year outcomes]. / Mise en place de consultations pharmaceutiques d'initiation en oncologie digestive dans un centre hospitalo-universitaire : bilan à un an.

INTRODUCTION: The announcement of a cancer diagnosis is traumatic for the patient. In France, an announcement system has been in place, providing medical time for announcement and treatment proposal, nursing time for support, without including the pharmacist. In order to improve management of patients treated with intravenous anticancer drugs, we set up introductory pharmaceutical consultations in digestive oncology. The aims were to assess the situation one year after the introduction of these consultations, and to assess their contribution. METHODS: When a patient was diagnosed with digestive cancer and receiving intravenous treatment, a pharmaceutical initiation consultation was scheduled. Indicators of activity (number of consultations, average duration, average preparation time and various delays) and results (number and type of pharmaceutical interventions, patient satisfaction) were collected in order to assess activity. RESULTS: Forty-seven pharmaceutical initiation consultations were carried out. The average duration of the consultations was 39.3minutes. Consultations were carried out on average 12.1 days after the medical consultation and 9.6 days before the first chemotherapy treatment. Twenty-nine patients responded to the satisfaction questionnaire. All were satisfied, and the majority of patients said they had improved their knowledge of cancer treatment. DISCUSSION: This activity enables us to review with patients essential aspects of their care, such as implanting an implantable chamber catheter, anti-cancer treatment and managing potential side effects and improve their self-care skills.

Do Clinical Trials Meet Current Care Needs? Views of Digestive Oncology Specialists in Galicia (Spain) Using the Delphi Method.

Background: In recent years, abundant scientific evidence has been generated based on clinical trials (CT) in the field of oncology. The general objective of this paper is to find out the extent to which decision making is based on knowledge of the most recent CT. Its specific objectives are to pinpoint difficulties with decision making based on the CT performed and find out the motivations patients and clinicians have when taking part in a CT. Methodology: Combined, prospective study, based on the Delphi method. A lack of correspondence between the people who take part in CT and patients who come for consultation has been identified. A need for training in analysing and interpreting CT has also been identified and a lack of trust in the results of CT financed by the pharmaceutical industry itself has been perceived. Conclusions: There is a difficulty in selecting oncological treatment due to the lack of correspondence between the patients included in the CT and patients seen in consultation. In this process, real world data studies may be highly useful, as they may provide this group with greater training in interpreting CT and their results.

Digestive Oncology in the COVID-19 Pandemic Era.

INTRODUCTION: Since the rise of the COVID-19 pandemic there has been widespread concern regarding the possible delay in the diagnosis/treatment of cancer patients. We aimed to assess the impact of the COVID-19 pandemic on the diagnosis, treatment, and outcome of patients with digestive cancer. METHODS: This was a retrospective study including patients with an inaugural digestive cancer diagnosis discussed for the first time at our center during the weekly digestive oncology reunion (DOR) meeting. The study group was enlisted from March to August 2020, and a control group was sourced from the equivalent period of 2018. Patients with a previous digestive cancer diagnosis/discussion in the DOR were excluded. The following data were collected: demographics, referral origin, tumor staging, first DOR discussion timing, treatment, and outcome. RESULTS: A total of 235 patients were included: 107 in the study group (65.4% male, mean age 71.59 years); 128 in the control group (54.7% male, mean age 68.16 years). The mean number of clinical discussions per week was higher in 2018 (13.65 vs. 10.67, p = 0.040), without a difference in the mean number of patients discussed for the first time (inaugural diagnosis) between groups (p = 0.670). In the 2020 study group, more patients were referred to DOR from the emergency room (ER), fewer from the outpatient clinic/hospital wards (p < 0.001), and more were referred after urgent surgery (p = 0.022). There was no difference in the mean waiting time from diagnosis to first DOR discussion (p = 0.087). Tumor staging in colorectal, gastric, and esophageal cancer was not significantly different between the groups (p = 0897, p = 0.168, and p = 0.717). More patients in the study group presented with stage IV pancreatic cancer (p = 0.043). There was no difference in the time span from DOR until the beginning of neoadjuvant chemotherapy (p = 0.680) or elective surgery (p = 0.198), or from surgery until adjuvant chemotherapy (p = 0.396). Also, there was no difference in 30-day mortality from the first DOR date between the groups (p = 0.742). CONCLUSION: During the COVID-19 era there was a reduced number of clinical discussions in the DOR, but the number of debated patients with an inaugural digestive cancer diagnosis was similar. In the study group more patients were referred to DOR from the ER, and were referred after urgent surgery, suggesting a delayed demand for clinical attention. Study group patients were not significantly affected by the pandemic regarding timely DOR discussion, beginning of treatment, or 30-day mortality, reflecting the maintenance of the quality of care for digestive cancer patients.

INTRODUÇÃO: Desde o início da pandemia por COVID-19, desenvolveu-se a preocupação com o possível atraso no diagnóstico/tratamento dos doentes oncológicos. O nosso objetivo foi avaliar o impacto da pandemia no diagnóstico, tratamento e prognóstico dos doentes com cancro digestivo. MÉTODOS: Estudo retrospetivo, incluindo doentes com diagnóstico inaugural de cancro digestivo, discutidos pela primeira vez na reunião semanal de oncologia digestiva (ROD) do nosso hospital, de Março-Agosto 2020 (grupo de estudo) e do período equivalente de 2018 (grupo controlo). Excluídos doentes com diagnóstico prévio de cancro digestivo/discussão prévia na ROD. Colheram-se: dados demográficos, origem da referenciação, estadio tumoral ao diagnóstico, data da primeira discussão na ROD, tratamento e prognóstico. RESULTADOS: Incluídos 235 doentes, 107 no grupo de estudo (65.4% homens, idade média 71.59), 128 no grupo controlo (54.7% homens, idade média 68.16). Número médio de discussões clínicas semanais na ROD foi superior em 2018 (13.65 vs. 10.67, p = 0.040). Sem diferença estatisticamente significativa no número de doentes discutidos pela primeira vez na ROD (diagnóstico inaugural) entre os grupos (p = 0.670). Mais doentes referenciados à ROD do Serviço de Urgência (SU) em 2020, menos a partir do ambulatório/ enfermaria (p < 0.001) e mais doentes referenciados após cirurgia urgente em 2020 (p = 0.022). Sem diferença entre os dois grupos no tempo médio de espera desde diagnóstico até a primeira discussão na ROD (p = 0.087). O estadio tumoral do cancro colorretal, gástrico e esofágico não foi significativamente diferente nos dois grupos (p = 0897, p = 0.168 e p = 0.717). Mais doentes apresentaram cancro pancreático em estadio IV no grupo de estudo (p = 0.043). Sem diferença no tempo desde ROD até início de quimioterapia neoadjuvante (p = 0.680) ou cirurgia eletiva (p = 0.198), nem da cirurgia até quimioterapia adjuvante (p = 0.396). Sem diferença na mortalidade aos 30 dias após primeira discussão na ROD nos dois grupos (p = 0.742). CONCLUSÃO: Durante a pandemia, o número de discussões clínicas na ROD foi inferior, mas o número de doentes com diagnóstico inaugural de cancro digestivo foi semelhante. No grupo de estudo, mais doentes foram referenciados à ROD do SU e mais após cirurgia urgente, sugerindo maior demora dos doentes para procurar atenção médica. Em 2020, os doentes não foram significativamente afetados pela pandemia relativamente à discussão atempada na ROD, início de tratamento ou mortalidade aos 30 dias, refletindo a manutenção da qualidade do suporte clínico aos doentes com cancro digestivo.

Chemotherapy use in end-of-life digestive cancer patients: a retrospective AGEO observational study.

BACKGROUND: The use of chemotherapy (CT) near the end-of-life (EOL) is an important issue in oncology since it could degrade quality of life. CT near EOL is still poorly studied, with no dedicated study in gastrointestinal (GI) cancer patients. AIM: To analyze in GI cancer patients the factors associated with the use of CT within 3- and 1-month before patients' death. METHODS AND PARTICIPANTS: All consecutive patients who died from a GI cancer in 10 French tertiary care hospitals during 2014 were included in this retrospective study. Clinical, demographical and biological data were collected and compared between patients receiving or not CT within 3- and 1-month before death. Variables associated with overall survival (OS) was also determined using of univariate and multivariate analyses with a Cox model. RESULTS: Four hundred and thirty-seven patients with a metastatic GI cancer were included in this study. Among them, 293 pts (67.0%) received CT within 3-months before death, and 121 pts (27.7%) received CT within 1-month before death. Patients receiving CT within 3-months before death were significantly younger (median age: 65.5 vs 72.8 years, p < 0.0001), with a better PS (PS 0 or 1: 53.9 vs 29.3%, p < 0.0001) and a higher albumin level (median: 32.8 vs 31.0 g/L, p = 0.048). Similar results were found for CT within 1 month before death. Palliative care team intervention was less frequent in patients who received CT in their last month of life (39.7% vs 51.3%, p = 0.02). In multivariate analysis, median OS from diagnosis was shorter in the group receiving CT within 1-month before death (HR = 0.59; 95% CI [0.48-0.74]). CONCLUSION: In GI-cancer patients, CT is administered within 3- and 1-month before death, in two and one third of patients, respectively. Patients receiving CT within 1-month before death, had more aggressive disease with poor OS. Palliative care team intervention was associated with less administration of CT in the last month of life. These results highlight the need to better anticipate the time to stop CT treatment in the end-of-life and the importance of an active collaboration between oncology and palliative care teams.

Oral therapies in digestive oncology (Review).

Targeted therapy and oral chemotherapy indications are increasing in the realm of digestive oncology. Oral intake of cancer agents is sometimes compulsory (no i.v. equivalent) or is preferred by the patient or the physician. Although oral chemotherapy facilitates the treatment of oncology patients, the treatment diversity, risk of pharmaceutical interactions and monitoring of side effects are potentially challenging and need to be fully acknowledged by the physician. We offer here a literature review of the indications, doses, side effects and monitoring of every oral therapy indicated in Digestive Oncology. We suggest a prescription algorithm including therapeutic education by the physician or a trained nurse, and pharmaceutical counseling.

The effectiveness of intravenous iron for iron deficiency anemia in gastrointestinal cancer patients: a retrospective study.

BACKGROUND: Knowledge of the role of intravenous iron without the use of additional erythropoietic stimulating agents in anemic cancer patients is limited. This study evaluated the effect of ferric carboxymaltose (FCM) in a group of digestive oncology (DIO) patients and aimed to differentiate therapy response according to different types of iron deficiency (ID) anemia. METHODS: In this retrospective study, we identified DIO patients who were receiving FCM and had eligible baseline and follow-up hemoglobin (Hb) levels that did not require red blood cell transfusion. Subgroup analyses examined adequately versus inadequately treated patients and low (<100 µg/L) vs. high (>100 µg/L) baseline ferritin levels. Inadequate treatment was defined as administration of an insufficient dose of FCM, based on the modified Ganzoni formula. RESULTS: A total of 414 patients were receiving FCM, of whom 41 were excluded because of transfusion and another 70 because of unknown or inadequate baseline iron status. Thus, the study group consisted of 303 patients. Follow-up serum levels were evaluated after a median of 4 weeks. Overall, the median change between baseline and follow-up Hb was 0.5 (interquartile range [IQR]: -0.1-1.6) g/dL. No significant difference in this change was found between the adequately and inadequately dosed groups. The median change in Hb was significantly greater in the low baseline ferritin group than in the high baseline ferritin group: 1.2 (IQR: 0.3-2.2) vs. 0.4 (IQR: -0.3-1.4) g/dL, respectively; P=0.004. CONCLUSIONS: Intravenous administration of iron in DIO patients with ID anemia leads to a significant increase in Hb. Moreover, differentiating between the types of ID anemia based on ferritin levels could be applied to predict therapy response, although better biomarkers are needed.

Oncological emergencies associated with gastrointestinal tumors.

Oncological emergencies are defined as acute life-threatening conditions in cancer patients either as a result of the malignancy or as a result of its treatment. In this review, we focus on oncological emergencies associated with gastrointestinal tumors. They can be categorized by their system of origin as hematologic, neurologic or metabolic. Furthermore, we discuss mechanical emergencies such as intestinal obstruction and vena cava superior syndrome as well as acute gastrointestinal bleeding and pulmonary embolism. The patients' performance status as well as prognosis are essential during decision making for optimal treatment.

Current practices in management of hepatocellular carcinoma in India: results of an online survey.

BACKGROUND: Prior to INASL guidelines, there were no Indian guidelines for management of hepatocellular carcinoma (HCC) in India. The guidelines given by other societies like AASLD, EASL etc are not uniform and not tailored for Indian patients. Hence management practices for HCC in India largely depended on physicians' individual preferences. This survey aimed to study current practices in management of HCC in India. METHODS: An online survey was conducted from the platform of a survey portal (www.surveymonkey.com), from December 2012 to April 2013. Invitation to participate in the survey was sent to 1383 doctors of India who were expected to be involved in management of patients of HCC. The survey was of 10 min duration and consisted of questions on how the respondents diagnosed and managed patients of HCC. RESULTS: Three hundred and seventy-seven doctors answered the survey questions (72% gastroenterologists, 95% working in India). The important points which emerged from the survey are following: (i) The incidence of HCC is increasing in India; (ii) The most common etiologic agent is Hepatitis B responsible for 43% cases; (iii) Only 14% patients present in early stage when curative treatment is possible (BCLC-A); (iv) 90% of these respondents screen for HCC when they first evaluate a cirrhotic patient; (v) While following a patient of cirrhosis most respondents screen for HCC by ultrasound and AFP at every 6 months to 1 year; and (vi) Most (82%) respondents follow some international guideline for staging and treatment of HCC. The respondents also suggested that there is a need for spreading awareness about HCC in public as well as in medical fraternity, and there is a need for a national registry of HCC. CONCLUSIONS: This is the first survey on management practices on HCC. With the publication of the INASL guidelines on HCC, the diagnosis and treatment of HCC will be more uniform and protocol based. Further such surveys should be carried out at periodic interval to track increasing awareness and better management practices for HCC in India.