Next-generation sequencing (NGS) of cell-free circulating tumor DNA and tumor tissue in patients with advanced urothelial cancer: a pilot assessment of concordance.

BACKGROUND: Advances in cancer genome sequencing have led to the development of various next-generation sequencing (NGS) platforms. There is paucity of data regarding concordance of different NGS tests carried out in the same patient. METHODS: Here, we report a pilot analysis of 22 patients with metastatic urinary tract cancer and available NGS data from paired tumor tissue [FoundationOne (F1)] and cell-free circulating tumor DNA (ctDNA) [Guardant360 (G360)]. RESULTS: The median time between the diagnosis of stage IV disease and the first genomic test was 23.5 days (0-767), after a median number of 0 (0-3) prior systemic lines of treatment of advanced disease. Most frequent genomic alterations (GA) were found in the genes TP53 (50.0%), TERT promoter (36.3%); ARID1 (29.5%); FGFR2/3 (20.5%), PIK3CA (20.5%) and ERBB2 (18.2%). While we identified GA in both tests, the overall concordance between the two platforms was only 16.4% (0%-50%), and 17.1% (0%-50%) for those patients (n = 6) with both tests conducted around the same time (median difference = 36 days). On the contrary, in the subgroup of patients (n = 5) with repeated NGS in ctDNA after a median of 1 systemic therapy between the two tests, average concordance was 55.5% (12.1%-100.0%). Tumor tissue mutational burden was significantly associated with number of GA in G360 report (P < 0.001), number of known GA (P = 0.009) and number of variants of unknown significance (VUS) in F1 report (P < 0.001), and with total number of GA (non-VUS and VUS) in F1 report (P < 0.001). CONCLUSIONS: This study suggests a significant discordance between clinically available NGS panels in advanced urothelial cancer, even when collected around the same time. There is a need for better understanding of these two possibly complementary NGS platforms for better integration into clinical practice.

European Society of Coloproctology consensus on the surgical management of intestinal failure in adults.

Intestinal failure (IF) is a debilitating condition of inadequate nutrition due to an anatomical and/or physiological deficit of the intestine. Surgical management of patients with acute and chronic IF requires expertise to deal with technical challenges and make correct decisions. Dedicated IF units have expertise in patient selection, operative risk assessment and multidisciplinary support such as nutritional input and interventional radiology, which dramatically improve the morbidity and mortality of this complex condition and can beneficially affect the continuing dependence on parenteral nutritional support. Currently there is little guidance to bridge the gap between general surgeons and specialist IF surgeons. Fifteen European experts took part in a consensus process to develop guidance to support surgeons in the management of patients with IF. Based on a systematic literature review, statements were prepared for a modified Delphi process. The evidence for each statement was graded using Oxford Centre for Evidence-Based Medicine Levels of Evidence. The current paper contains the statements reflecting the position and practice of leading European experts in IF encompassing the general definition of IF surgery and organization of an IF unit, strategies to prevent IF, management of acute IF, management of wound, fistula and stoma, rehabilitation, intestinal and abdominal reconstruction, criteria for referral to a specialist unit and intestinal transplantation.

The prognosis of incurable cachectic cancer patients on home parenteral nutrition: a multi-centre observational study with prospective follow-up of 414 patients.

BACKGROUND: The role of home parenteral nutrition (HPN) in incurable cachectic cancer patients unable to eat is extremely controversial. The aim of this study is to analyse which factors can influence the outcome. PATIENTS AND METHODS: We studied prospectively 414 incurable cachectic (sub)obstructed cancer patients receiving HPN and analysed the association between patient or clinical characteristics and surviving status. RESULTS: Median weight loss, versus pre-disease and last 6-month period, was 24% and 16%, respectively. Median body mass index was 19.5, median KPS was 60, median life expectancy was 3 months. Mean/median survival was 4.7/3.0 months; 50.0% and 22.9% of patients survived 3 and 6 months, respectively. At the multivariable analysis, the variables significantly associated with 3- and 6-month survival were Glasgow Prognostic Score (GPS) and KPS, and GPS, KPS and tumour spread, respectively. By the aggregation of the significant variables, it was possible to dissect several classes of patients with different survival probabilities. CONCLUSIONS: The outcome of cachectic incurable cancer patients on HPN is not homogeneous. It is possible to identify groups of patients with a ≥6-month survival (possibly longer than that allowed in starvation). The indications for HPN can be modulated on these clinical/biochemical indices.

Intraoperative ultrasonography in detecting and assessment of colorectal liver metastases.

OBJECTIVE: to assess the clinical value of intraoperative ultrasonography (IOUS) in detecting and assessment of liver metastatic tumours in colorectal cancer patients. METHODS: a study is a retrospective analysis of 388 patients operated on for colorectal carcinoma between 1997 and 2004. In all the patients intraoperative ultrasound was performed. The authors analyzed of sensitivity, specificity, PPV, NPV and accuracy of pre- and intraoperative ultrasonography in detecting and staging of colorectal metastatic lesions. RESULTS: Intraoperative ultrasonography showed the highest sensitivity, specificity and accuracy in both, tumor detection (99.1, 98.5 and 98.9%, respectively) and assessment (95.4, 99.5 and 99.1%, respectively). Overall sensitivity of IOUS was significantly better in detection and staging compared with preoperative ultrasonography 91.1 and 72.2%, respectively). CONCLUSIONS: IOUS should be used as routine diagnostic modality in colorectal cancer patients with hepatic metastases or suspected metastases. Transabdominal ultrasonography cannot be used as the only diagnostic tool in the evaluation of liver lesions, but may be helpful in preoperative screening.

Evaluation of adjuvant chemotherapy irinotecan + 5-fluorouracil + leucovorine in advanced colorectal cancer.

OBJECTIVE: to analyze clinical effectivity of chemotherapy based on Irinotecan, 5-Fluorouracyl and Folinic acid in patients with colorectal carcinoma. METHODS: prospective, randomized, open-label trial in group of 204 patients with advanced colorectal cancer randomized to either chemotherapy with irinotecan+5-FU+leucovorin or supportive care alone (control group) between January 1999--January 2005 was performed. Efficacy and safety of treatment was analysed. RESULTS: Administration of the irinotecan, 5FU, LV regimen to patients with stages II and III significantly improved 5-year survival (81% versus 66% and 66% versus 38%, respectively; p < 0.05). Palliative chemotherapy improved survivals also in stage IV, four patients survived 5 years. Adverse event occurred in 44 of 102 patients (43.1%). CONCLUSIONS: study confirms benefits of irinotecan chemotherapy administered to patients with advanced colorectal cancer. Preliminary data suggests that this chemotherapy regimen should be considered for first-line therapy in the adjuvant and palliative treatment of advanced colorectal cancer.

Laparoscopic colorectal cancer surgery combined with enhanced recovery after surgery protocol (ERAS) reduces the negative impact of sarcopenia on short-term outcomes.

INTRODUCTION: Progressive skeletal muscle loss (sarcopenia) is a negative prognostic factor in patients treated for colorectal cancer. Nevertheless, the clinical impact of those changes in body composition has been analyzed only in patients undergoing open resections. The aim of the study was to assess whether laparoscopy may eliminate the deleterious prognostic impact of sarcopenia and whether the combination with enhanced recovery after surgery (ERAS) protocol may improve postoperative recovery also in sarcopenic patients. METHODS: The study included 124 (73M/51F, mean age 65.9 years) patients undergoing elective laparoscopic colorectal resection for cancer. In all of them 16-item ERAS protocol was applied. The L3 skeletal muscle area identified on a preoperative CT scan was used to calculate skeletal muscle index and assess for sarcopenia and myosteatosis. The entire study group was divided into groups regarding the presence of sarcopenia or myosteatosis. The outcome measures were: length of hospital stay, complication rate and functional recovery parameters. RESULTS: The prevalence of sarcopenia and myosteatosis was 27.4% and 38.7%, respectively. There was no association between the presence of sarcopenia or myosteatosis and postoperative complications. There were also no differences in the length of stay or readmission rates. Functional recovery (time to first flatus, oral diet tolerance and mobilization) was similar regardless of the presence of muscle depletion. CONCLUSIONS: In contrary to traditional surgical approach, laparoscopy can reduce the negative impact of sarcopenia and myosteatosis on treatment results. ERAS protocol does not affect negatively the surgical outcomes in sarcopenic patients, compared to patients without changes in body skeletal mass.

The value of imaging techniques in the staging of pancreatic cancer.

BACKGROUND: The aim of this study was to assess the clinical value of endoscopic ultrasound (EUS) in the staging of pancreatic carcinoma and to compare it to ultrasonography (US) and CT. METHODS: We evaluated 45 patients (21 women and 24 men with a mean age of 62.1 years) who had undergone surgical treatment for pancreatic cancer between 1994 and 2004. Out analysis focused on the overall accuracy, sensitivity, and specificity of routine and Doppler US, CT, and EUS. RESULTS: Endoscopic ultrasound was the most accurate modality for local tumor staging (93.1%), vascular infiltration (90%), and lymph node assessment (87.5%). Routine US was the least accurate (82.5%, 67.5%, and 72.5%, respectively). The accuracy rates for CT and Doppler US were similar (88.1%, 82.5% and 80.0%, respectively). CONCLUSIONS: Endoscopic ultrasound is the most accurate method available to stage pancreatic cancer in the preoperative period. However, the advantage of EUS over CT and US does not justify its routine use due to its high cost, low availability, and invasiveness.

The clinical value of parenteral immunonutrition in surgical patients.

BACKGROUND & AIM: To analyze the clinical impact and cost-effectiveness of parenteral immunonutrition (PN). METHODS: Prospective clinical trial of a group of 105 patients operated on for gastric carcinoma between 2001-2003. During the postoperative period, patients were randomly allocated to one of three groups: standard PN (A), PN + glutamine (B) and PN + omega-3-FA (C). The rate and type of complications, hepatic and renal function, cost and treatment tolerance in all groups were analyzed. RESULTS: Postoperative complications were observed in 11 patients (36.6%) in group A, in 7 (23.3%) in B and in 8 (26.6%) in C. The most common complication was pneumonia. Prealbumin concentration and TLC increased faster in groups B and C. The length of hospital stay was significantly shorter in the immunonutrition groups. The cost of PN was highest in C group, while cost of hospital stay was longer in A. CONCLUSIONS: Immunostimulating parenteral nutrition helps to reduce the number of infectious complications, improves the function of the immune system, and has no influence on surgical complications, hepatic and renal function and protein synthesis. The cost of immunostimulating treatment based on omega-3-unsaturated fatty acids is higher than standard.

Diagnostic criteria for malnutrition - An ESPEN Consensus Statement.

OBJECTIVE: To provide a consensus-based minimum set of criteria for the diagnosis of malnutrition to be applied independent of clinical setting and aetiology, and to unify international terminology. METHOD: The European Society of Clinical Nutrition and Metabolism (ESPEN) appointed a group of clinical scientists to perform a modified Delphi process, encompassing e-mail communications, face-to-face meetings, in group questionnaires and ballots, as well as a ballot for the ESPEN membership. RESULT: First, ESPEN recommends that subjects at risk of malnutrition are identified by validated screening tools, and should be assessed and treated accordingly. Risk of malnutrition should have its own ICD Code. Second, a unanimous consensus was reached to advocate two options for the diagnosis of malnutrition. Option one requires body mass index (BMI, kg/m(2)) <18.5 to define malnutrition. Option two requires the combined finding of unintentional weight loss (mandatory) and at least one of either reduced BMI or a low fat free mass index (FFMI). Weight loss could be either >10% of habitual weight indefinite of time, or >5% over 3 months. Reduced BMI is <20 or <22 kg/m(2) in subjects younger and older than 70 years, respectively. Low FFMI is <15 and <17 kg/m(2) in females and males, respectively. About 12% of ESPEN members participated in a ballot; >75% agreed; i.e. indicated ≥7 on a 10-graded scale of acceptance, to this definition. CONCLUSION: In individuals identified by screening as at risk of malnutrition, the diagnosis of malnutrition should be based on either a low BMI (<18.5 kg/m(2)), or on the combined finding of weight loss together with either reduced BMI (age-specific) or a low FFMI using sex-specific cut-offs.

The value of modern ultrasonographic techniques and computed tomography in detecting and staging of pancreatic carcinoma.

OBJECTIVE: to assess the clinical value of ultrasonographic methods and computed tomography in diagnosing and staging pancreatic carcinoma. METHODS: prospective clinical trial of 140 patients (64 women and 77 men; mean age 59,6) operated on for pancreatic carcinoma between 2000 and 2004. In each case helical CT, routine-, color- and power Doppler and 3-D USG were performed to detect and stage cancer. Analyses of accuracy, sensitivity, specificity, PPV and NPV of ultrasonographic methods and CT were made. RESULTS: 3-D USG showed the best accuracy of local staging (T): 95.6%. CT was the most accurate in lymph node assessment: 91.3%. The accuracy of CT, 3-D USG and power-Doppler at detecting vascular infiltration was 93.1%. CONCLUSIONS: diagnostic accuracy of modern ultrasound techniques is comparable to helical CT in detecting and staging pancreatic carcinoma. USG is recommended due to the relatively low cost, non-invasiveness and availability of the procedure.

[Nutritional therapy and the immune system]. / Leczenie zywieniowe a uklad odpornosciowy.

Malnutrition is one of the consequences of chronic and neoplastic diseases. Therefore the attention has been paid recently to the most appropriate nutritional therapy in order to reduce the number of postoperative complications, mortality rates and the length of hospitalisation. Administered nutritional substances should cover basic and calorific demands. However it was observed that malnutrition leads to the state of immunosuppression. Several studies were carried out using potentially immunostimulating substances e.g. nucleotides, some of amino acids, vitamins and trace elements or unsaturated fatty acids, in addition to the nutritional support. The authors are presenting a review of the current state of knowledge and data from clinical trials on the immunostimulating role of the nutritional components.

Double-blind pilot-study on the efficacy of enzyme therapy in advanced colorectal cancer.

All tested variables showed a tendency in favor for Wobe-Mugos E therapy as addition to standard therapy. Enzymes improve the quality of life by reducing cancer disease typical symptoms, they reduce side effects of chemo-/radiotherapy and they have a potential of prolonging life (preliminary data only).