Frequency of Body Weight Loss is an Independent Prognostic Factor of First-Line Treatment Outcomes in Metastatic Colorectal Cancer.

One of the main features of wasting in cancer is an involuntary weight loss which is most pronounced in gastrointestinal tract tumors and leads to worse clinical outcomes. The aim of this study is to analyze the frequency of body weight loss (FBWL) as an additional prognostic factor in the treatment of patients with metastatic colorectal cancer (mCRC).In this observational, single-center study, data were retrieved for 236 patients treated for mCRC. FBWL was defined as a percent of change in weight divided by weeks of therapy. Patients were stratified into two groups according to the median of FBWL which equaled to the loss of 0.05%/week. Patients who lost >0.05%/week (N = 116) had shorter progression-free survival (PFS) in the first-line treatment, then the ones who lost <0.05%/week (N = 120); 28.3 vs 46.3 weeks, respectively. Cox regression model showed that FBWL and sidedness were significant predictors of PFS, while age, sex and ECOG were not. Significantly more patients with stable weight were also eligible for second-line treatment. In conclusion, stabilization of body weight is important and independent predictor of longer PFS in first-line therapy of patients with mCRC.

Leukocytoclastic vasculitis associated with sorafenib treatment for hepatocellular carcinoma.

Small-vessel vasculitis is an uncommon diagnosis associated with many causes, including certain medication. Characteristic findings are immune complex deposition, vessel wall damage, and erythrocyte extravasation. We present a case of a 77-year-old man with advanced hepatocellular carcinoma who was treated with sorafenib. Twenty days post introduction to sorafenib, the patient experienced high fever and painful purpura on the lower limbs. The results of the skin biopsy confirmed the diagnosis. More extensive diagnostics was undertaken, which excluded other possible causes of vasculitis and infectious disease. Following a full recovery, after the steroid treatment was completed, sorafenib has been continued until the progression of the carcinoma. This is the second described case of hepatocellular carcinoma associated with sorafenib treatment and leukocytoclastic vasculitis. Sorafenib is a potential cause of vasculitis, and clinicians should bear in mind to differentiate it from hand-foot skin reaction, which is a common side effect of multikinase inhibitors. The result of our assessment is important considering that vasculitis requires more specific diagnostic procedures, treatment, and often drug discontinuation.

LEUKOCYTAPHERESIS IN THE MANAGEMENT OF SEVERE STEROID-DEPENDENT ULCERATIVE COLITIS.

Ulcerative colitis (UC) is a multifactorial disease of unknown precise etiology and immunopathogenesis. Peripheral blood granulocytes and monocytes/macrophages are the major sources of cytokines, which regulate inflammation. Leukocytapheresis (LCAP) is a method where blood is processed by apheresis system that removes lymphocytes and plasma before being returned to the body. We report the first case in Croatia where we used LCAP in the treatment of a patient with severe steroid-dependent UC. After 12 LCAP procedures, good clinical response was obtained and there were no significant adverse side effects noticed. The patient remained in clinical remission over two years in which he underwent regular follow ups at outpatient clinic. Over a 10-year follow-up period after LCAP, the patient had only occasional clinical symptoms of disease activity. The clinical course was complicated with the development of metastatic colorectal carcinoma, which points to the importance of regular disease monitoring rather than the increased risk of malignant disease after LCAP. Patients with UC are a demanding group of patients that warrant the search for novel treatment strategies other than conventional pharmacological therapies. Although LCAP is still not a common treatment modality in our daily practice, data from recent studies suggest it to be an effective and safe procedure in the management of active UC patients.

Step-Up versus Open Approach in the Treatment of Acute Necrotizing Pancreatitis: A Case-Matched Analysis of Clinical Outcomes and Long-Term Pancreatic Sufficiency.

Background/Objectives: Acute necrotizing pancreatitis (ANP) with secondary infection of necrotic tissue is associated with a high rate of complications and mortality. The optimal approach is still debatable, but the minimally invasive modality has gained great attention in the last decade as it follows the principle of applying minimal surgical trauma to achieve a satisfying therapeutic objective. We compared clinical outcomes between the step-up approach (SUA) and open necrosectomy (ON) in the treatment of acute necrotizing pancreatitis. Methods: A prospective cohort study over the period of 2011-2021 in a university teaching hospital was performed. Results of 99 consecutive patients with ANP who required surgical/radiological intervention were collected. A case match analysis (2:1) was performed, and the final groups comprised 40 patients in the OA group and 20 patients in the SUA group. Demographic, clinicopathologic, and treatment data were reviewed. Results: Baseline characteristics and disease severity were comparable between the two groups. The patients from the SUA group had a significantly lower morbidity rate and rate of pancreatic insufficiency. Death occurred in 4 of 20 patients (20%) in the SUA group and in 11 of 40 patients (27.5%) in the ON group (risk ratio with the step-up approach, 0.72; 95% confidence interval, 0.26 to 1.99; p = 0.53). Conclusions: A minimally invasive step-up approach provides comparable outcomes to open necrosectomy in the treatment of ANP with infected pancreatic necrosis. While mortality and hospital stay were comparable between the groups, morbidity and pancreatic insufficiency were significantly lower in the SUA group. Further studies on a larger number of patients are required to define the place of SUA in the modern treatment of ANP.

Successful resection of hepatocellular cancer not amenable to Milan criteria and durable complete remission induced by systemic polichemotherapy after development of metastases - should we think about revising the current treatment guidelines in selected patients?

OBJECTIVES: To refresh clinical diagnostic and therapeutic dilemmas in patients presenting with hepatocellular cancer (HCC) and to report a rare success of systemic polichemotherapy in metastatic HCC. METHODS: Case report of a patient with successfully resected HCC although initially deemed inoperable according to current guidelines, and who was successfully treated by systemic polichemotherapy after development of metastatic disease, resulting in a sustained complete remission. RESULTS: We describe a 71-year-old female with HCC initially treated by atypical liver resection, although not amenable to initial surgery according to current treatment guidelines, which resulted in 6 months disease-free interval. After development of pulmonary metastases, the patient was treated by systemic polichemotherapy, due to local unavailability of novel biologic agents. After 3 months of chemotherapy biochemical remission was confirmed, and after 10 months of active treatment complete radiological remission was verified according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria, now exceeding 9 months in duration. CONCLUSION: There is an increasing body of evidence that criteria for surgical interventions in HCC should be revised and expanded, and our case is an example of such an approach. Although novel biologic therapies are not widely available in all regions of the world due to their cost, currently there are no hard recommendations for use of chemotherapy in such areas. Since this is a large problem in clinical practice, we conclude that chemotherapy should be offered to selected patients of good performance status if novel agents are unavailable.

Paraneoplastic stiff person syndrome associated with colon cancer misdiagnosed as idiopathic Parkinson's disease worsened after capecitabine therapy.

OBJECTIVES: To refresh clinical diagnostic dilemmas in patients presenting with symptoms resembling to those of parkinsonism, to report rare association of colon cancer and paraneoplastic stiff person syndrome (SPS), and to draw attention on the possible correlation of capecitabine therapy with worsening of paraneoplastic SPS. METHODS: Case report of the patient with paraneoplastic SPS due to colon cancer that was misdiagnosed as idiopathic Parkinson's disease (iPD), whose symptoms worsened after beginning adjuvant capecitabine chemotherapy. RESULTS: We describe a 55-year-old woman with subacute onset of symmetrical stiffness and rigidity of the truncal and proximal lower limb muscles that caused lower body bradykinesia, gait difficulties, and postural instability. Diagnose of iPD was made and levodopa treatment was initiated but failed to provide beneficial effect. Six months later, colon cancer was discovered and the patient underwent surgical procedure and chemotherapy with capecitabine thereafter. Aggravation of stiffness, rigidity, and low back pain was observed after the first chemotherapy cycle and capecitabine was discontinued. Furthermore, levodopa was slowly discontinued and low dose of diazepam was administered which resulted in partial resolution of the patient's symptoms. CONCLUSION: Paraneoplastic SPS is rare disorder with clinical features resembling those of parkinsonian syndrome and making the correct diagnosis remains a challenge. The diagnosis of parkinsonian syndrome should be re-examined if subsequent examinations discover an associated malignant process. Although it remains unclear whether the patients with history of SPS are at the greater risk for symptoms deterioration after administration of capecitabine, clinicians should be aware of capecitabine side effects because recognition and appropriate management can prevent serious adverse outcomes.

Gut microbiota and obesity.

The human gut hosts more than 100 trillion microorganisms, encompassing thousands of species. In adults, Bacteroidetes and Firmicutes are the most prevalent phyla. Experimental data in animal and observational studies in obese patients suggest that obesity is associated with substantial changes in the composition and metabolic function of the gut microbiota. The initial findings linked obesity with the decreased relative proportion of Bacteroidetes to Firmicutes. There are some authors who suggest that probiotics and prebiotics can modulate obesity-host metabolism in obesity and obesity-related disorders.

The effectiveness of nab-paclitaxel plus gemcitabine and gemcitabine monotherapy in first-line metastatic pancreatic cancer treatment: A real-world evidence.

Pancreatic cancer is one of the most lethal malignancies with a rise in mortality rates. FOLFIRINOX and nab-paclitaxel plus gemcitabine demonstrated a survival benefit compared to gemcitabine alone. Both protocols are now considered the standard of first-line treatment with no significant difference between them, primarily based on observational studies. Although new therapeutic options have emerged recently, the prognosis remains poor. We conducted a retrospective single-center study on 139 patients treated for metastatic pancreatic adenocarcinoma (mPDAC) with gemcitabine monotherapy (Gem) or nab-paclitaxel + gemcitabine (Nab-P/Gem) in the first line. The aim of our study was to evaluate the effectiveness in terms of overall survival (OS) and progression-free survival (PFS) as well as the influence of patient and disease characteristics on outcomes. Nab-P/Gem resulted in OS of 13.87 months compared to 8.5 months in patients receiving Gem. The same trend was achieved in PFS, 5.37 versus 2.80 months, respectively, but without reaching statistical significance. Furthermore, the 6-month survival in the Nab-P/Gem group was also higher, 78.1% versus 47.8%. In terms of survival, the group of elderly patients, patients of poorer performance, with higher metastatic burden and liver involvement, benefited the most from combination therapy. In our analysis ECOG performance status (p.s.), previous primary tumor surgery, and liver involvement were found to be independent prognostic factors. The addition of nab-paclitaxel to gemcitabine resulted in a significant improvement in the OS of patients with mPDAC. Subgroup analysis demonstrated that patients with some unfavorable prognostic factors benefited the most.

[Croatian guidelines for nutrition in the elderly, part II--clinical nutrition]. / Hrvatske smjernice za prehranu osoba starije dobi, dio II--klinicka prehrana.

Malnutrition and sarcopenia are frequent in the hospitalized and institutionalized elderly. They have negative consequences on morbidity, mortality, function and quality of life. Enteral and parenteral nutrition are valid options in the malnourished elderly, both in the hospital and at home. Elderly patients share most indications and complications with adult patients, even though more focus needs to be put on function and quality of life than on mortality. In these guidelines we discuss the indications and special considerations of enteral and parenteral nutrition in geriatric patients as well as guidelines for clinical nutrition in three common pathologies in the elderly: decubital ulcers, dysphagia and dementia.

Ten years of Croatian national guidelines for use of eicosapentaenoic acid and megestrol acetate in cancer cachexia syndrome - Evaluation of awareness and implementation among Croatian oncologists.

BACKGROUND & AIMS: Cancer cachexia (CC) syndrome and anorexia-cachexia syndrome are common terms used to describe changes in metabolism with increased inflammatory activity and can progressively develop through various stages such as pre-cachexia; cachexia; and refractory cachexia. Therefore in year 2007 Croatian guidelines for use of eicosapentaenoic acid and megestrol acetate in cancer cachexia syndrome were published. Aim of this study was to assess the awareness and implementation of Croatian guidelines for use of eicosapentaenoic acid (EPA) and megestrol acetate (MA) into clinical practice among Croatian oncologists approximately 10 years after the publication, but also to point out the importance of adequate recognition and treatment of CC. METHODS: Survey with questions was designed to assess the awareness and implementation of Croatian guidelines for use of EPA and MA into clinical practice and was distributed among all Croatian oncologists in secondary and tertiary hospital centers. Survey was conducted in January 2011 (40 months following release of the guidelines), February 2013 and June 2018, and were formed in a way of yes/no answers. Additional multiple choice questions that focus on the implementation of guidelines were added in June 2018. RESULTS: A total of 128 oncologists completed a questionnaire. There was no statistically significant difference in follow up period (2011-2018) of percentage of oncologists that are familiar with Croatian guidelines for use of EPA and MA in CC, percentage of oncologists in which Croatian national guidelines changed their approach in treating patients with CC syndrome and proportion of oncologists that are using MA, enteral nutrition formulas with EPA or their combination. Most of the oncologists 38% (N = 44) are using >2.2 g of EPA per day. Nutritional support is prescribed in 25-50% of patients by 42% (N = 48) of oncologists and most of the oncologists (35%, N = 41) start with nutritional support when a body mass loss is >5%. Oncologists mostly recommend patients to use nutritional support during 1 year or more (43%, N = 49) or two months to 1 year (42%, N = 48). Compliance of patients with malignant diseases for using nutritional support was mostly evaluated as medium (69%, N = 60). CONCLUSIONS: Results have shown that majority of oncologists who filled the questionnaire believe that the Croatian national guidelines for use of EPA and MA in CC syndrome changed their approach in treating patients with CC, but also that there are several targeted issues that can be significantly improved. The awareness of and adherence to national guidelines was maintained at high level even 11 years after the guidelines were published.

Fluorouracil, leucovorin and irinotecan combined with intra-arterial hepatic infusion of drug-eluting beads preloaded with irinotecan in unresectable colorectal liver metastases: side effects and results of a concomitant treatment schedule. Clinical investigation.

AIM: Safety evaluation of concomitant systemic chemotherapy and liver chemoembolization in patients with colorectal cancer. PATIENTS AND METHODS: Seven patients with metastases confined to the liver were included and stratified into two groups, depending of dosage of systemic chemotherapy. The first group received systemic chemotherapy (FOLFIRI) with 20% dose reduction, and the second group received the full dose of the same chemotherapy. In both groups, chemoembolization of liver metastases with drug-eluting bead irinotecan (DEBIRI) was performed following the application of systemic chemotherapy. The toxicity profiles of the two groups were compared. RESULTS: Of the 7 patients included, 4 received the reduced systemic chemotherapy dose and 3 received the full chemotherapy dose. DEBIRI was performed in all 7 patients. The main toxicities observed in the reduced chemotherapy dose group were leukopenia (25%), anorexia (75%), diarrhea (25%), vomiting (25%), right upper abdominal quadrant pain (100%) and elevated serum amylase level (25%). Main toxicities observed in the full chemotherapy dose group were anorexia (66.6%), vomiting (33.3%), right upper abdominal quadrant pain (100%), and elevated serum amylase level (66.6%). There were no significant differences between the two groups ( P = 0.78541). CONCLUSIONS: Patients with isolated liver metastases from a colorectal primary can safely be treated with DEBIRI chemoembolization and a full dose of systemic chemotherapy (FOLFIRI).