Impact of muscle mass loss on outcomes in advanced or metastatic gastric cancer patients receiving a second-line treatment.

OBJECTIVE: Sarcopenia is a frequent disorder among cancer patients. It commonly leads to muscle mass wasting and poor clinical outcomes, even though it is rarely recognized and often undertreated. The relationship between skeletal muscle depletion and chemotherapy toxicity or postoperative complications is well known. The aim of the present study was to analyze the impact of sarcopenia on clinical outcomes of pretreated metastatic gastric cancer (GC) patients. PATIENTS AND METHODS: 88 pretreated GC patients were retrospectively analyzed. Patients were divided into two groups according to their skeletal mass index (SMI): sarcopenic patients with low SMI (≤39 cm2/m2 for women and ≤55 cm2/m2 for men) and non-sarcopenic patients with normal/high SMI value. The two groups were compared according to outcomes and adverse events. RESULTS: Progression-free survival (PFS) was significantly higher in patients with normal/high SMI than in those with low SMI (6 vs. 3.5 months, respectively; HR 0.52). Similarly, the overall response rate (ORR) was higher in the subgroup with normal/high SMI (41% vs. 20%; p=0.02). Overall survival (OS) was not significantly different, but multivariate analysis demonstrated that both SMI and performance status were associated with OS. In the sarcopenic group, the patients treated in the second line with paclitaxel and ramucirumab regimen showed a better outcome profile. Overall, adverse events (AEs) were more frequent in the group of patients with low SMI (p<0.0001). CONCLUSIONS: Early recognition of sarcopenia may contribute to personalizing second or further lines of treatment in advanced GC and to weigh up the potential risk of serious toxicities.

The Apparent Asymmetrical Relationship Between Small Bowel Bacterial Overgrowth, Endotoxemia, and Liver Steatosis and Fibrosis in Cirrhotic and Non-Cirrhotic Patients: A Single-Center Pilot Study.

Introduction: Gut microbiota are a complex ecosystem harboring our intestine. They maintain human body equilibrium, while their derangement, namely, "dysbiosis", has been associated with several gastrointestinal diseases, such as liver steatosis (NAFLD) and liver cirrhosis. Small intestinal bacterial overgrowth (SIBO) is an example of dysbiosis of the upper gastrointestinal (GI) tract. Aim: The aim of this study is to evaluate the relationship between SIBO and levels of endotoxemia and grade of liver steatosis (LS) and liver fibrosis (LF) in hepatologic patients. Materials and Methods: Consecutive outpatients referred to our hepatology clinic were tested for SIBO by the lactulose breath test (LBT) and peripheral blood levels of endotoxemia; LS grading and LF were assessed by abdominal ultrasound and transient elastography, respectively. Results: Fifty-two consecutive patients (17 with alcohol abuse (4.5 ± 0.8 alcohol units per day), 4 with HCV and 2 with HBV infection, 24 of metabolic origin, 2 of autoimmune origin, and 3 with cholangiopathies; mean age 54.7 ± 8.3 years, 31 F, BMI 24.1 ± 1.1 Kg/m2) and 14 healthy volunteers (HV) (mean age 50.1 ± 4.3 years, 9 F, BMI 23.3 ± 1.1 Kg/m2) were enrolled. SIBO prevalence was significantly higher in cirrhotic (LC) vs. non-cirrhotic (LNC) patients and vs. HV (all, p < 0.05), with a significant positive trend according to Child-Pugh status (all, p < 0.05). SIBO prevalence was not correlated with LS stages (all, p = NS). Consensually, endotoxin levels were significantly higher in LC vs. LNC and vs. HV (all, p < 0.05) and significantly correlated with LF in patients with LC, according to Child-Pugh status (all, p < 0.05). Conclusion: This study shows that SIBO prevalence and relative endotoxin blood levels seem to be significantly associated with the grade of LF vs. LS in LC. SIBO is also present under pre-cirrhotic conditions, but its prevalence seems to correlate with liver disease irreversible derangement.

Nutritional knowledge among a large cohort of Italian students: a cross-sectional study.

OBJECTIVE: Healthy food behavior among adolescents represents a prevention factor for the onset of chronic diseases in adult life and is influenced by the familiar, socio-cultural and physical environment. Good nutritional knowledge plays a key role in ensuring healthy eating, that is adequate food choice and intake. This study aimed to assess the nutritional knowledge of Italian students from three Italian provinces of the Lazio Region (i.e., Rome, Frosinone, Latina) and to investigate its interrelationship with some socio-demographic characteristics (physical activity, parental education, school district city, BMI) of the surveyed subjects. SUBJECTS AND METHODS: Students (n = 2573) were surveyed for their nutritional knowledge through the Italian version of the Moynihan questionnaire and for their socio-demographic characteristics. The relationship between their nutritional knowledge and their socio-demographic characteristics was investigated by univariate and multivariate statistical analyses. RESULTS: Most participants displayed a normal weight (84%), followed by overweight (14%) and underweight (2%) subjects. Most students (44%) practiced physical activity at least twice a week. Most students (75%) reported a high family education level. Sixty percent of the subjects showed inadequate knowledge about healthy nutrition. A significant association (p<0.001) was observed between nutritional knowledge and school district city. CONCLUSIONS: Educational nutrition programs should be promoted to improve nutritional knowledge among young people and reduce the risk of chronic disease development.

Effects of enteral nutrition on patients with pressure lesions: a single center, pilot study.

OBJECTIVE: Protein-energetic malnutrition (PEM) affects prognosis and mortality in elderly patients as an inadequate nutritional status is a risk factor for the development and worsening of pressure sores (PS). We aimed to evaluate the incidence of PEM in outpatients with PS and to study the impact of nutritional support on the stage of PS. PATIENTS AND METHODS: PS patients, divided in a group treated with artificial nutrition (group A) and those fed orally (group B) at home, were consecutively enrolled in the Integrated Home Care program of Ascoli Piceno between June and September 2015. At T0 the patients underwent medical history, nutritional, anthropometric/biochemical parameters assessment, and the staging of the PS. The same assessments and staging of the pressure lesions were performed three months later (T1). RESULTS: Group A (n=25) started from a better nutritional status vs. group B (n=25) at T0, according to MNA assessment. Group A showed a significant improvement of nutritional status correlating with detailed control of nutrients intake and improvement of PS stage (T0 vs. T1, p<0.05). On the other hand, group B showed a significant difference between nutrients intake and nutritional needs that correlated with both malnutrition state increase and worsening of the PS staging (T0 vs. T1, p<0.05). CONCLUSIONS: The present study shows that PEM has a significant prevalence in the elder, in general, and in older people with PS, in particular. A targeted nutritional intake can prevent and help the healing of PS.

Minimal impact of lenvatinib (Lenvima®) on muscle mass in advanced hepatocellular carcinoma and implications for treatment duration. Two cases from the REFLECT study.

OBJECTIVE: Two case reports of advanced unresectable hepatocellular carcinoma (HCC) treated with lenvatinib (Lenvima®) are presented; the drug's effect on muscle loss and duration of treatment are discussed. PATIENTS AND METHODS: Between November 2014 and December 2017, at the Fondazione Policlinico A. Gemelli IRCCS, Rome, Italy, two male patients with advanced HCC enrolled in the lenvatinib arm of the REFLECT trial received the drug over 24 cycles (almost 2 years). We reviewed the clinical charts from baseline, when lenvatinib was started, through 24 months of treatment. The changes in the skeletal mass area (SMA), as assessed by computed tomography (CT) at the third lumbar level (L3), between baseline and month 24 into treatment were recorded. RESULTS: Case 1: SMA decreased by 2.8 cm2 between baseline and month 24 (134 cm2 vs. 131.2 cm2), with a muscle loss of 2.13%. Case 2: SMA decreased by 13 cm2 between baseline and month 24 (133 cm2 vs. 120 cm2), with a muscle loss of 10.83%. CONCLUSIONS: The disease remained stable for over 2.5 years in both patients. A minimal loss of muscle mass was noted at 24 months of treatment. The minimum effect on muscle loss may be correlated with the positive clinical response and the drug's low toxicity. Our findings may help to elucidate the effect of lenvatinib on muscle mass and inform the development of the targeted nutritional support for HCC patients.

Impact of malnutrition on survival and infections among pediatric patients with cancer: a retrospective study.

OBJECTIVE: Recognizing and managing malnutrition among hospitalized children affected by cancer is a rising need. Awareness and consideration of malnutrition among clinicians are still largely insufficient. This can principally be explained by the lack of consciousness and the shortage of easy and objective tools to identify malnutrition status. The aim of this study is to explore the impact of malnutrition on survival and infections among a population of pediatric patients with cancer. PATIENTS AND METHODS: All children aged between 3 and 18 years, newly diagnosed with a malignancy between August 2013 and April 2018, were included in our study. We assessed nutritional risk at diagnosis (with STRONGkids), then we evaluated anthropometric measurements (BMI Z-scores and weight loss), data about survival and number of hospitalization for febrile neutropenia (FN) in the first year after diagnosis. Cut-off values for malnourishment were chosen as BMI Z-score ≤-2.0. RESULTS: One hundred twenty-six pediatric cancer patients were included in the study. At diagnosis 36 pediatric cancer patients (28.6%) were at high risk of malnutrition (STRONGkids 4 or 5), whereas 6 (4.7%) others were malnourished (BMI Z-score≤-2.0). The risk of mortality and the rate of infections (≥3 hospitalizations for FN episodes) were significantly increased by malnutrition and rapid weight loss in the initial phase of treatment (3-6 months after diagnosis). Multivariate analysis confirmed the independent effect of weight loss≥ 5% at 3 months on both survival and infections, and the independent impact of a high risk of malnutrition at diagnosis on infections. CONCLUSIONS: A personalized evaluation of nutritional risk at diagnosis and a close monitoring of nutritional status during the initial phase of treatment are crucial for ensuring a timely and personalized nutritional intervention, which may potentially improve tolerance to chemotherapy and survival, and prevent prolonged hospitalization for infections in childhood cancer patients.

Nutritional support in mitochondrial diseases: the state of the art.

Mitochondrial diseases are a group of rare multisystem disorders characterized by genetic heterogeneity and pleomorphic clinical manifestations. The clinical burden may be heavy for patients and their caregivers. There are no therapies of proven efficacy until now and a multidisciplinary supportive care is therefore necessary. Since the common pathogenic mechanism is the insufficient energy production by defective mitochondria, nutrition may play a crucial role. However, no guidelines are still available. The article reports the current evidence, highlighting nutrition both as support and as therapy. The estimate of nutritional status, energy needs and nutritional behaviors are firstly discussed. Then, we go in-depth on the scientific rationale and the clinical evidence of the use of anti-oxidants and enzyme-cofactors in the clinical practice. In particular, we analyze the role of Coenzyme Q10, Creatine monohydrate, α-lipoic acid, riboflavin, arginine and citrulline, folinic acid, carnitine, vitamin C, K, and E. Every attempt at nutritional intervention should be made knowing patient's disease and focusing on his/her energy and nutrients' requirements. For this reason, clinicians expert in mitochondrial medicine and clinical nutritionists should work together to ameliorate care in these fragile patients.

Impact of patients nutritional status on major surgery outcome.

OBJECTIVE: Surgery is a major stress factor that activates several inflammatory and catabolic pathways in man. An appropriate nutritional status allows the body to react properly to this stressor and recover in a faster and more efficient manner. On the other hand, malnutrition is related to a worse surgery outcome and to a higher prevalence of comorbidities and mortality. The aims of this study were to evaluate the nutritional status of patients undergoing major surgery and investigate the potential correlation between malnutrition and surgical outcomes. PATIENTS AND METHODS: Mini Nutritional Assessment (MNA) and global clinical examination (including biochemical parameters and comorbidities existence) were undertaken in 50 consecutive patients undergoing major surgery. Patients' clinical conditions were re-evaluated at 3 and 6 days after surgery, recording biochemical parameters and systemic and/or wound-related complications. RESULTS: A compromised nutritional status was present in more than half (54%) of patients (malnutrition in 10% and risk of malnutrition in 44% of patients, respectively). Females were slightly more at risk of malnutrition (48% vs. 41%, p=NS, females vs. males) and clearly malnourished (14% vs. 7%, p<0.05, females vs. males). Age was an independent risk factor for malnutrition and within the elders' group (> 80 years old) 16.70% of patients was diagnosed with malnutrition and 58.3% was at risk of malnutrition. Systemic complications were registered in all patients both at 3 and 6 days after surgery. However, well-nourished and at-risk of malnutrition patients had earlier complications that only partially resolved within six days after the operation. Malnourished patients showed fewer complications at the 3rd post-surgery follow-up day but had a worse outcome six days after surgery. CONCLUSIONS: Older age and but not female sex are independent risk factors for malnutrition development in patients undergoing major surgery. More interestingly, more than half of patients with an impaired nutritional status presented a less appropriated stress response to surgery. These data suggest that nutritional status assessment may be important to recognize patients at potential risk of surgical complications and that early nutritional interventions must be promptly arranged.

Imaging assessment of portal venous system: pictorial essay of normal anatomy, anatomic variants and congenital anomalies.

The purpose of this pictorial essay is to describe anatomic variants and congenital anomalies of portal venous system and related liver parenchymal alterations. The imaging findings of some of these entities have been previously described in other articles, however this work encompasses all congenital anomalies of portal venous system with attention to their features on various imaging modalities; in particular we illustrated with detailed pictures all the main portal vein variants, congenital extra- and intra-hepatic porto-systemic venous shunts and portal vein aneurysm. Variants of portal branches and intrahepatic portosystemic shunts are quite uncommon, however, when present, they should be recognized before performing surgery or interventional procedures. Congenital absence of the portal vein is an important finding as the complete loss of portal perfusion predisposes the liver to focal or diffuse hyperplastic or dysplastic changes. Portal vein aneurysm is a rare clinical entity that can affect intra- and extra-hepatic portal branches; although usually asymptomatic, thrombosis can occur. Awareness of congenital variants of portal venous system among radiologists should allow a more confident diagnosis and permit an accurate planning of surgical procedures and percutaneous interventions; identification of portal system anomalies also suggest an accurate evaluation of associated hepatic parenchymal anomalies such as nodular regenerative hyperplasia, focal nodular hyperplasia (FNH), and adenomas with high risk of malignant transformation.

Clinical tools to assess nutritional risk and malnutrition in hospitalized children and adolescents.

Malnutrition in children and adolescents may be underestimated during hospital stay. In western countries, children were often hospitalized for acute or chronic diseases that are not necessarily related to malnutrition. However, acute or chronic injuries may hamper nutritional status, prolonging recovery after admission and consequently length of hospital stay. Several methods and techniques are known to investigate malnutrition in children, even if their use is not widespread in clinical practice. Many of these are simple and easy to perform and could be useful to a better management of every kind of illness. In this review, we will focus on clinical tools necessary to reveal a nutritional risk at admission and to assess nutritional status in hospitalized children and adolescents.

A peculiar case of diffuse hemangiomatosis of the left hepatic lobe in an asymptomatic adult patient: case report and literature review.

We report a rare case of diffuse hepatic hemangiomatosis (DHH) of the left hepatic lobe coexistent with giant hepatic hemangioma and without extra-hepatic involvement in an asymptomatic adult patient. Liver hemangiomas are the most common benign liver tumors. However, DHH without extra-hepatic involvement has rarely been reported in adults. Furthermore, giant hepatic hemangioma coexistent with DHH is even uncommon, although an association between hemangiomatosis and giant hepatic hemangiomas may be supposed. In this peculiar case, we observed an exclusive and widespread involvement of the left hepatic lobe with a sharp boundary between normal and altered liver parenchyma running along Cantlie's line.

Nutritional support in acute pancreatitis: from physiopathology to practice. An evidence-based approach.

Acute Pancreatitis (AP) is a potentially fatal syndrome, associated with a hyper-catabolic state as well as early and late complications that may lead to multi-organ failure and death. Clinical researches produced in recent years suggest that acute pancreatitis may benefit from early oral or enteral nutrition. Nevertheless, many clinicians still believe erroneously that fasting - particularly in the early phase - may reduce AP complications and mortality. The goal of our review is to demonstrate that such false belief may harm the patients and that the whole management paradigm must change, adopting a more rational, evidence-based approach. First, we will describe AP physiopathology and the clinical assessment of its severity. Then we will discuss evidence-based data supporting early oral or enteral nutrition in AP. Finally, we will offer some practice recommendations as regards nutritional support.

Transarterial chemoembolization with degradable starch microspheres (DSM-TACE): an alternative option for advanced HCC patients? Preliminary results.

OBJECTIVE: To assess safety, feasibility and effectiveness of transarterial chemoembolization with degradable-starch-microspheres (DSM-TACE) in the treatment of patients with advanced hepatocellular carcinoma (HCC) dismissing or ineligible for multikinase-inhibitor chemotherapy administration (Sorafenib) due to unbearable side effects or clinical contraindications. PATIENTS AND METHODS: Six consecutive advanced HCC patients dismissing Sorafenib because of unbearable side effects or worsened clinical conditions were enrolled in our prospective single-center pilot study. DSM-TACE was performed via a lobar approach, based on extent and distribution of the disease (1 treatment session for every lobe involved, with a 2-week interval in case of bilobar disease). Tumor response based on mRECIST criteria was evaluated on MD-CT performed at 1 month after "complete treatment" and every 3 months thereafter. RESULTS: Eleven treatments were performed, and technical success was achieved in all patients. No intra/peri-procedural death/major complications occurred. No signs of liver failure or systemic toxicity were detected. At one month follow-up, 5 partial responses (83.3%) and 1 progression disease (16.6%) with an overall disease control (ODC) of 83.3% were observed. In two patients with ODC and residual viable tumor higher than 50%, a repeated DSM-TACE treatment was performed. During the mean follow-up of 11 months (range: 4-14 months), an ODC of 66.6% was obtained. Progression-free survival was 5.5 months with a cumulative 6-month and 1-year overall survival rates of 83.3% and 66.6%, respectively. CONCLUSIONS: DSM-TACE seems to be a promising option for advanced HCC patients ineligible for Sorafenib administration or dismissing it due to progressive disease or unbearable side effects.

From small nodule to overt HCC: a multistep process of carcinogenesis as seen during surveillance.

BACKGROUND: Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death in the world. Despite many diagnostic and therapeutic tools are now available to improve survival and reduce its recurrence, prognosis is closely conditioned by the time of diagnosis. Surveillance and early diagnosis are crucial for a successful therapy. We report a clinical case from the HCC archive of the Hepatocatt meetings held in Ge-melli Hospital (Catholic University of Rome). The case describes a tumor progression in a multistep process from a small liver nodule to overt HCC and its management by a multidisciplinary team.

Isolation and characterization of CD133+ cell population within human primary and metastatic colon cancer.

BACKGROUND: "Cancer stem cells" (CSC) have been identified as a minority of cancer cells responsible for tumor initiation, maintenance and spreading. Although a universal marker for CSC has not yet been identified, CD133 has been proposed as the hallmark of CSC in colon cancer. The aim of our study was to assess the presence of a CD133+ cell fraction in samples of colon cancer and liver metastasis from colon cancer and evaluate their potential as tumor-initiating cells. METHODS: Tissue samples from 17 colon cancers and 8 liver metastasis were fragmented and digested using collagenase. Cell suspensions were characterized by flow cytometry using anti-CD133, CD45 and CD31 antibodies. CD133+ cells were also isolated by magnetic cell sorting and their tumor-initiating potential was assessed versus the remaining CD133- fraction by soft-agar assay. RESULTS: Our results confirmed the existence of a subset of CD133+ tumor cells within human colon cancers. Interestingly, CD133+ cells were detectable in liver metastasis at a higher percentage when compared to primary tumors. Soft-agar assay showed that CD133+ cell fraction was able to induce larger and more numerous colonies than CD133-cells. CONCLUSION: Our findings data that the CD133+ colon cancer cells might play an important role in both primary tumors as well as in metastatic lesions thus warranting further studies on the role(s) of this subset of cells in the metastatic process.