The Role of Diet and Supplements in the Prevention and Progression of COVID-19: Current Knowledge and Open Issues.

A healthy diet and dietary supplements have gained attention as potential co-adjuvants in managing and preventing coronavirus disease 2019 (COVID-19). This paper critically reviews the current evidence regarding the impact of diet and supplements on the prevention and progression of COVID-19. According to available data, a healthy diet and normal weight are considered protective factors. Regarding dietary supplementation, the most robust results from human studies are for vitamin C, which appears to decrease inflammatory markers and suppress cytokine storm. A small, randomized trial showed that a high dose of vitamin D significantly reduced the need for intensive care unit treatment of patients requiring hospitalization for COVID-19. According to retrospective human studies, there is limited evidence for vitamin E and selenium supplements. Animal studies have investigated the effects of green tea and curcumin. Xanthohumol and probiotics, interesting for their antiviral, anti-inflammatory, and immunoregulatory properties, need formal clinical study. In summary, there is promising evidence supporting the role of diet and supplements as co-adjuvants in the treatment of COVID-19. Further studies and properly designed clinical trials are necessary to draw more robust conclusions; however, it is not unreasonable to take a pragmatic approach and promote the use of appropriate diet and supplements to counter the effects of COVID-19, ideally with a mechanism to assess outcomes.

Chromogranin A as a predictor of radiological disease progression in neuroendocrine tumours.

BACKGROUND: Chromogranin A (CgA) is the best established neuroendocrine biomarker. This study was aimed at investigating the prognostic value of CgA as a predictor of radiological disease progression in neuroendocrine tumour (NET) patients. METHODS: Patients with metastatic NETs and evidence of radiological progression (RP) according to RECIST 1.1 were identified from a NET database. Plasma CgA levels were measured 6 and 12 months before RP and at the event of RP. CgA was measured with the Supra-regional-Assay-Service radioimmunoassay (Hammersmith Hospital). RESULTS: A total of 152 patients were evaluated including 91 midgut NETs and 61 pancreatic NETs (PNETs). Of these, 56 were G1 NETs, 65 G2, 10 G3, 21 of unknown histology. For all NETs, there was a positive trend in terms of increase of CgA values 6 months prior to RP compared to 12 months before RP. Subgroup analysis at first episode of RP showed that for PNETs there was evidence of a difference in the median CgA levels. CgA 6 months before RP was 100 pmol/L [interquartile 1 (Q1) =53 and Q3 =286.25 pmol/L) and 12 months before was 52 pmol/L (Q1 =36.25 and Q3 =128 pmol/L), W=52, P=0.48. This observation was not confirmed in midgut NETs, where median CgA 6 months before RP was 389.5 pmol/L (Q1 =131.5 and Q3 =791.5 pmol/L) and 12 months before was 319 pmol/L (Q1 =158 and Q3 =753 pmol/L), W=191, P=0.39]. Low grade tumours (G1) had a median CgA value at 6 months significantly higher than at 12 months [181 (Q1 =56.25, Q3 =624) vs. 149.5 (Q1 =44, Q3 =247.25) pmol/L, W=70, P=0.48]. CONCLUSIONS: CgA seems to have predictive value 6 months prior to RP for PNETs and G1 tumours. Further prospective analyses are needed to enable more definitive conclusions.

Goblet cell appendiceal tumors--management dilemmas and long-term outcomes.

BACKGROUND: Appendiceal Goblet cell tumors (GCTs) are clinically more aggressive, and have a worse outcome than midgut neuroendocrine tumors (mNETs). Guidelines for management of GCTs are limited. METHODS: A retrospective case-study analysis was performed in patients with a diagnosis of GCT, confirmed on histological review. Patients were evaluated clinically, biochemically, and radiologically. RESULTS: 48 patients were identified (TNM stage I-II: 27, stage III: 15, stage IV: 6). Median follow-up was 44 months and was complete in all patients. 68.8% presented with acute appendicitis. 44/48 patients had initial appendectomy, followed by prophylactic right hemicolectomy in 41. 10/48 patients had recurrent disease [median time to recurrence 28 months (range 4-159)]. Of those, 9 received systemic chemotherapy (FOLFOX/FOLFIRI), which was also given in 5/48 patients with disseminated disease at diagnosis. Partial response, stable disease and disease progression was noted in 22%, 22% and 56%, respectively. Adjuvant chemotherapy was also administered in 9/48 patients with stage III disease after right hemicolectomy, however in 3/9 the disease recurred. Median progression/disease-free-survival was 44 months (range 3-159) and overall 5-year survival rate was 41.6%. CONCLUSIONS: The clinical behaviour of GCTs is more similar to colorectal adenocarcinomas than to NETs. A prophylactic right hemicolectomy is recommended to reduce the risk of recurrence. Systemic chemotherapy, using colorectal adenocarcinoma regimens, is indicated for advanced or recurrent disease and has encouraging results. Prospective studies are needed to define the role of adjuvant chemotherapy and the optimal chemotherapy regimen.

The role of dietary factors in prevention and progression of breast cancer.

BACKGROUND/AIM: Breast cancer (BC) is the leading global cause of cancer-related death in women. There is growing evidence for a role for dietary factors in BC pathophysiology. The aim of the present review was to evaluate the impact of dietary factors in BC risk. MATERIALS AND METHODS: Bibliographical searches were performed in PubMed, using the following terms: "nutrition and breast cancer", "nutrition and breast carcinoma", "dietary factors and breast cancer", "risk factors and breast cancer", "diet and breast cancer, "breast cancer epidemiology", "breast cancer and prevention". RESULTS: Consumption of well-done red meat appears to be associated with increased risk of BC, whereas fish may be protective. Total cholesterol, triglyceride levels and glycaemic load should be monitored and controlled in at risk populations because they may be associated with increased risk of BC, although the exact mechanisms involved are not clear. Alcohol intake should be minimized since it is a risk factor for BC. High intake of polyphenol/phyto-oestrogen -rich food (i.e. flavonoids, soya products), as well as fibres, fruits and vegetables, may have potential protective effects against BC occurrence but the results might vary according to hormonal status. Vitamin D supplements appear protective against BC development and similarly other vitamins and oligo-elements might decrease BC risk, although further large prospective studies are required. CONCLUSION: There exist increasing evidence that dietary factors can play an important role in both the development and prevention of BC. Large randomized clinical and epidemiological studies are required but are difficult to design due to the number of variable factors.

Case report of multimodality treatment for metastatic parathyroid hormone-related peptide-secreting pancreatic neuroendocrine tumour.

AIMS AND BACKGROUND: Hypercalcaemia due to metastatic parathyroid hormone-related peptide-secreting pancreatic neuroendocrine tumour is challenging to manage and requires a multimodality approach. METHODS: We present a case of a woman undergoing liver transplantation for metastatic parathyroid hormone-related peptide-secreting pancreatic neuroendocrine tumour. RESULTS: A young woman with a history of parathyroid hormone-related peptide-secreting pancreatic neuroendocrine tumour (Ki-67 5%) removed in 1998 developed bilobar liver metastases in 2004 and underwent repeated transarterial embolisations of liver tumour and therapy with somatostatin analogue. In view of symptomatic hypercalcaemia refractory to medical therapy, she underwent liver transplantation in 2006. In 2012, follow-up imaging showed a 3-cm hypervascular lesion in the posterior wall of the stomach, which was confirmed on endoscopic ultrasound and on gallium-68-octreotate positron emission tomography scan. A gastric wall resection was performed in February 2013, and biopsies showed a neuroendocrine tumour of intermediate grade (Ki-67 15%). In June 2013, a restaging imaging showed a 2.4 cm lesion in the left breast, which was reported as a primary breast cancer on biopsies, and a 14-mm tissue lesion anterior to the gastric antrum. The patient underwent surgical excision of the breast cancer followed by hormone treatment and radiotherapy. She had surgical removal of the gastric recurrence with adjuvant chemotherapy postoperatively. CONCLUSIONS: Hypercalcaemia related to parathyroid hormone-related peptide-secreting neuroendocrine tumour can be life-threatening, and liver transplantation may be a viable option in case of liver only diffuse neuroendocrine metastases refractory to other therapies. The risk of tumour recurrence remains a significant clinical problem after liver transplantation, and only a few patients might be considered tumour-free 5 years after liver transplantation.

Prostate cancer and the influence of dietary factors and supplements: a systematic review.

BACKGROUND: Prostate cancer is the second most common cause of cancer worldwide after lung cancer. There is increasing evidence that diet and lifestyle plays a crucial role in prostate cancer biology and tumourigenesis. Prostate cancer itself represents a good model of cancer in which to look for chemopreventive agents due to the high disease prevalence, slowly progressive nature, and long latency period. Dietary agents have gained considerable attention, often receiving much publicity in the media. AIM: To review the key evidence available for potential chemopreventive nutrients. METHODS: The methodology for this review involved a PubMed search from 1990 to 2013 using the key-words "diet and prostate cancer", "nutrition and prostate cancer", "dietary factors and prostate cancer", "prostate cancer epidemiology", "prostate cancer prevention", "prostate cancer progression". RESULTS: Red meat, dietary fat and milk intake should be minimised as they appear to increase the risk of prostate cancer. Fruit and vegetables and polyphenols may be preventive in prostate cancer, but further studies are needed to draw more solid conclusions and to clarify their role in patients with an established diagnosis of prostate cancer. Selenium and vitamin supplements cannot be advocated for the prevention of prostate cancer and indeed higher doses may be associated with a worse prognosis. There is no specific evidence regarding benefits of probiotics or prebiotics in prostate cancer. CONCLUSIONS: From the wealth of evidence available, many recommendations can be made although more randomised control trials are required. These need to be carefully designed due to the many confounding factors and heterogeneity of the population.

Liver transplantation for unresectable neuroendocrine tumor liver metastases.

BACKGROUND: Liver transplantation (LT) is performed in selected patients with neuroendocrine hepatic metastases. Survival benefit and the risk of tumor recurrence after LT, also exacerbated by immunosuppressive therapy, remain important clinical issues. Whether patients with particular types of neuroendocrine tumors (NET) benefit more than others is unclear. METHODS: Bibliographical searches were performed in PubMed for the terms "liver transplantation and neuroendocrine tumors," "liver transplant and neuroendocrine tumors," "liver transplantation and immunosuppressive therapy," "tumor recurrence." RESULTS: Promising results have been reported for LT for NET metastases with 5-year survival of up to 90 % in patients with well-differentiated gastroenteropancreatic NETs, but only few patients are free of tumor 5 years after LT. Better outcomes have been reported for gastrointestinal tumors than for pancreatic NETs for both survival and risk or recurrence after LT. Selection criteria for LT are limited and include the 2007 Milan Criteria and the 2012 European Neuroendocrine Tumor Society guidelines, including: well-differentiated NET (Ki-67 <10 %), age <55 years, absence of extrahepatic disease, primary tumor removed before transplantation, stable disease for at least 6 months before LT, and <50 % liver involvement. CONCLUSIONS: LT might be considered in carefully selected patients. The risk of tumor recurrence remains a significant clinical problem after LT, but data focused on immunosuppression issue are lacking, and there are no currently approved strategies for prevention of recurrence or follow-up protocols. Further studies are needed to define universally accepted inclusion criteria, reliable predictors of better outcome, and optimal timing for LT.

Nutrition and pancreatic cancer.

BACKGROUND: Pancreatic cancer is the fourth leading cause of cancer death in men and women. Prognosis is poor with a 5-year survival rate of less than 5%. As there is no effective screening modality, the best way to reduce morbidity and mortality due to pancreatic cancer is by effective primary prevention. AIM: To evaluate the role of dietary components in pancreatic cancer. MATERIALS AND METHODS: Bibliographical searches were performed in PubMed using the terms "pancreatic cancer", together with "nutrition", "diet", "dietary factors", "lifestyle", "smoking", "alcohol" and "epidemiology". RESULTS: Fruits (particularly citrus) and vegetable consumption may be beneficial. The consumption of whole grains has been shown to reduce pancreatic cancer risk and fortification of whole grains with folate may confer further protection. Red meat, cooked at high temperatures, should be avoided, and replaced with poultry or fish. Total fat should be reduced. The use of curcumin and other flavonoids should be encouraged in the diet. There is no evidence for benefit from vitamin D supplementation. There may be benefit for dietary folate. Smoking and high Body Mass Index have both been inversely associated with pancreatic cancer risk. CONCLUSION: The lack of randomized trials and the presence of confounding factors including smoking status, physical activity, distance of habitat from the equator, obesity, and diabetes may often result in inconclusive results. There is evidence to encourage the use of whole grain in the staple diet and supplementation within the diet of folate, curcumin and other flavanoids. Carefully designed randomized trials are required to further elucidate these important matters.

Risk factors for the development and progression of carcinoid heart disease.

The development of valvular heart disease in patients with carcinoid syndrome is thought to be related to the secretion of vasoactive substances by a tumor. We sought to identify modifiable risk factors for the development of carcinoid heart disease because this may help define strategies to attenuate the disease process. Two hundred fifty-two patients with carcinoid syndrome were prospectively followed with serial echocardiograms at 6-month intervals. Clinical characteristics, biochemical markers, and radiologic markers were measured at set intervals. An echocardiographic scoring system was applied. Patients were defined as having progression of carcinoid heart disease if the echocardiographic score increased by ≥25%. After a median follow-up of 29 months, 44 patients developed carcinoid heart disease or had progression of existing valvular dysfunction. At time of progression of carcinoid heart disease compared to the previous 6 months, there was a significant increase in median levels of 5-hydroxyindoleacetic acid (5-HIAA; 791 vs 460.5 µmol/24 hours) and flushing episodes (4.5 vs 2 episodes per day). Independent predictors of the development or progression of carcinoid heart disease were a 5-HIAA level ≥ 300 µmol/24 hours and ≥ 3 episodes of flushing per day. 5-HIAA levels of ≥ 300 to 599, 600 to 899, and > 900 µmol/24 hours conferred 2.74, 3.16, and 3.40 times the risk of progression of carcinoid heart disease, respectively. In conclusion, a 5-HIAA level ≥ 300 µmol/24 hours and ≥ 3 flushing episodes per day are predictors of the development or progression of carcinoid heart disease.

Usefulness of N-terminal pro-brain natriuretic peptide as a biomarker of the presence of carcinoid heart disease.

We sought to investigate whether N-terminal pro-brain natriuretic peptide (NT-pro-BNP) can be used as a biomarker for the detection of carcinoid heart disease (CHD); 200 patients with carcinoid syndrome were screened for CHD using transthoracic echocardiography. A carcinoid score was formulated to quantify severity of CHD. NT-pro-BNP was measured in all patients before echocardiography. Patients were categorised into New York Heart Association class. CHD was present in 39 patients (19.5%). NT-pro-BNP was significantly higher in those with CHD (median 1,149 pg/ml) than in those without CHD (median 101 pg/ml, p <0.001). The sensitivity and specificity of NT-pro-BNP at a cut-off level of 260 pg/ml for detection of CHD were 0.92 and 0.91, respectively. NT-pro-BNP positively correlated both with carcinoid score (r = 0.81, p <0.001) and New York Heart Association class (p <0.001). The number of patients screened to diagnose 1 case of CHD decreased from 5.1 to 1.4. In conclusion, NT-pro-BNP seems to be an excellent biomarker of CHD. A high negative predictive value may allow it to provide a screening test for CHD.

Analysis of 150 patients with carcinoid syndrome seen in a single year at one institution in the first decade of the twenty-first century.

Carcinoid heart disease (CHD), reported in 50% to 70% of patients with carcinoid syndrome, is thought to be related to the production of 5-hydroxytryptamine by the tumor. The development of new therapeutic modalities designed to reduce tumor hormone production may have altered the development of CHD. Currently, echocardiography is performed when clinical suspicion of CHD exists. The aim of this study was to establish the prevalence of CHD in the setting of modern treatment regimens and delineate whether a screening program for CHD is needed. One hundred fifty patients with carcinoid syndrome were screened for CHD by transthoracic echocardiography. The functional status of patients was classified according to New York Heart Association class. Thirty patients (20%) were found to have CHD. Of those with CHD, 14 (47%) had left- and right-sided valvular lesions. Patent foramen ovale was present in all patients with left-sided CHD. Forty-three percent of patients were in New York Heart Association class I, 40% in class II, 13% in class III and 3% in class IV. Eight patients (27%) with moderate or severe valvular lesions were in class I. Thirty-seven percent of patients with CHD had no physical signs. In conclusion, the presence of symptoms or abnormalities on clinical examination has a low sensitivity for the presence of CHD. Therefore, screening with echocardiography, even in patients who are asymptomatic, should be advocated.