CT-based screening of sarcopenia and its role in cachexia syndrome in pancreatic cancer.

Since computed tomography (CT) is a part of standard diagnostic protocol in pancreatic ductal adenocarcinoma (PDAC), we have evaluated the value of CT for sarcopenia screening in patients with PDAC, intending to expand the diagnostic value of tomographic studies. In our study, we included 177 patients with available CT images. Two groups were formed: Group 1 consisted of 117 patients with PDAC in various locations and stages and Group 2, or the control group, consisted of 60 "nominally healthy" patients with other somatic non-oncological diseases. The body mass index (BMI) was defined as a ratio of patient's weight to the square of their height (kg/m2). CT-based body composition analysis was performed using commercially available software with evaluation of sarcopenia using skeletal muscle index (SMI, cm2/m2). Based on the SMI values, sarcopenia was found in 67.5% of patients (79 out of 117) in the first patient group. It was found more frequently in males (42 out of 56; 75%) than in females (37 out of 61; 60.6%). Additionally, we observed a decrease in muscle mass (hidden sarcopenia) in 79.7% in patients with a normal BMI. Even in overweight patients, sarcopenia was found in 50% (sarcopenic obesity). In patients with reduced BMI sarcopenia was found in all cases (100%). Statistically significant difference of SMI between two groups was revealed for both sexes (p = 0,0001), with no significant difference between groups in BMI. BMI is an inaccurate value for the assessment of body composition as it does not reflect in the details the human body structure. As SMI may correlate with the prognosis, decreased muscle mass- especially "hidden" sarcopenia or sarcopenic obesity- should be reported. The use of CT-based evaluation of sarcopenia and sarcopenic obesity will allow for a better treatment response assessment in patients with cancer cachexia.

Development of a formula to predict parathyroid carcinoma in patients with primary hyperparathyroidism.

BACKGROUND: Cure of parathyroid carcinoma (PC) requires initial en bloc resection, including resection of all tumor-bearing tissue, with hemithyroidectomy and dissection of the central lymph node compartment. Unfortunately, no reliable preoperative criteria have yet been assessed to indicate a high likelihood of PC. Thus, the aim of the present study was to develop a formula to indicate preoperatively the presence of PC. METHODS: A prospective database of 1,363 patients with primary hyperparathyroidism (pHPT) was screened for patients with PC. Age, gender, surgical procedures, laboratory data, and follow-up results were evaluated and compared to a group of patients with benign pHPT. Based on preoperative serum calcium (Ca) and parathyroid hormone (PTH) levels, as well as patients' age at the time of diagnosis, a formula was developed by a multivariate logistic model that estimates the individual risk for PC. RESULTS: Between 1987 and 2008, 19 patients with PC were identified. Ca (3.8 ± 0.3 vs 2.9 ± 0.3 mmo/l; p = 0.0002) and PTH levels (1,250 ± 769 vs 194 ± 204 pg/ml; p = 0.0030) were significantly higher in patients with PC than in those with benign pHPT. Patients with PC were also significantly younger than patients with benign pHPT (48.9 ± 12.1 vs 59.1 ± 13.8 years; p < 0.05). With a ≥5 % probability that a given patient suffered from PC, the sensitivity and specificity to identify the disease were 100 and 30 %, respectively, with the new Ca, PTH, and age based logarithmic formula. CONCLUSIONS: The new logarithmic formula can be used to calculate the individual risk for PC. If the calculated individual risk exceeds 5 %, en bloc resection seems to be justified to provide long-term cure in case of PC.

Genotype-based chemotherapy for patients with gastrointestinal tumors: focus on oxaliplatin, irinotecan, and fluoropyrimidines.

This review aimed to summarize the pharmacogenetic studies of the most commonly used drugs in the chemotherapy of gastrointestinal (GI) tumors: oxaliplatin, irinotecan, and fluoropyrimidines. So far, it has not been possible to develop an effective genotype-based approach for oxaliplatin. More and more evidence is emerging in favor of the fact that the choice of a dose of fluorouracil based on pharmacogenetic testing according to DPYD*2A, can be not only effective but also cost-effective. Additional, well-planned trials of the UGT1A1 genotype-based approach to irinotecan therapy are predicted to reduce adverse drug events in people with the UGT1A1*28/*28 genotypes and improve treatment efficacy in the rest of the patients, which might be cost-effective.

The impact of sarcopenic obesity on treatment outcomes in gastrointestinal cancer: A systematic review.

BACKGROUND: GI tract cancer includes a broad spectrum of tumors with generally high prevalence and poor prognosis. Over the past decade sarcopenia (skeletal muscle depletion), myosteatosis, sarcopenic obesity were all shown to have a negative prognostic impact in patients with various malignancies. However, the role of sarcopenic obesity (SO) in patients with GI tumors remains controversial. We systematically reviewed data on the prevalence and prognostic impact of SO for patients with GI malignancies, undergoing surgical and/or chemotherapeutical treatment. METHODS: This study was conducted in adherence to the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. PubMed and Cochrane Library were searched for relevant original studies published between January 2008 to December 2020 reporting postoperative morbidity and mortality, long-term survival and toxicity after chemotherapeutical treatment in SO patients with GI cancer. RESULTS: Twenty-two studies comprising 8571 patients were included. The percentage of SO patients ranged from 2.6% to 51%. The association between SO and outcomes of interest was inconsistent because of various cut-offs used to define sarcopenia and obesity. However, SO was significantly associated with the occurrence of major postoperative complications in five studies. In contrast, three studies did not show the impact of SO on postoperative complications. Three studies demonstrated that mortality rate was significantly higher among patients with SO. Five studies of systematic review revealed a statistically significant influence of SO on overall survival in multivariate analysis. However, only in one of them a significant difference was found between SO and DFS. Three studies evaluated toxicity after chemotherapy and all reported statistically significant negative impact of SO. CONCLUSIONS: There is considerable heterogeneity in methods used to define SO in the literature and current data is limited. Standardized terminology and deeper understanding of sarcopenic obesity pathophysiology is needed to further understand the influence of obesity and sarcopenia on the clinical trajectory of patients with GI cancer.

Patient blood management in oncology in the Russian Federation: Resolution to improve oncology care.

There is accumulating evidence that anemia and iron deficiency, thrombocytopenia, blood loss and coagulopathy are independent risk factors for adverse patient outcomes in oncology and other settings. Patient blood management (PBM) aims to address these factors by managing and preserving a patient's blood. PBM improves patient health, but also reduces resource utilization, including use of allogeneic blood components, which is another risk factor for adverse outcomes. Supported by the World Health Organization and endorsed in WHA63.12, PBM is recommended by an increasing number of health authorities and is about to become a new standard of care. In support of the Russian National Long-Term Oncology Strategy 2030 to improve quality of oncological care, and with support from the National Association of Specialists in PBM, the PBM Oncology Working Group of the Russian Federation was created. In July 2020, this Group met to discuss the rationale and need for PBM in Russian oncology care. The Group recommended to include PBM as an integral part of standard oncology treatment pathways and developed a national resolution as a call to action on this matter, which was adopted in August 2020. This article details the rationale behind the resolution, delineates the action required from facilitating stakeholders (government; healthcare providers; educational facilities; research entities/institutions; funders; patient representatives/advocates), and proposes a roadmap for implementation. The generation of local health-economic and outcome data and the development of educational programs will be important in the implementation of PBM to help alleviate the health, social and economic burden of cancer.

Genotype-based chemotherapy for patients with gastrointestinal tumors: focus on oxaliplatin, irinotecan, and fluoropyrimidines.

This review aimed to summarize the pharmacogenetic studies of the most commonly used drugs in the chemotherapy of gastrointestinal (GI) tumors: oxaliplatin, irinotecan, and fluoropyrimidines. So far, it has not been possible to develop an effective genotype-based approach for oxaliplatin. More and more evidence is emerging in favor of the fact that the choice of a dose of fluorouracil based on pharmacogenetic testing according to DPYD*2A, can be not only effective but also cost-effective. Additional, well-planned trials of the UGT1A1 genotype-based approach to irinotecan therapy are predicted to reduce adverse drug events in people with the UGT1A1*28/*28 genotypes and improve treatment efficacy in the rest of the patients, which might be cost-effective.

Preoperative CT-based detection of extrapancreatic perineural invasion in pancreatic cancer.

Accuracy for computed tomography (CT) diagnosis of extrapancreatic perineural invasion (EPNI) in pancreatic ductal adenocarcinoma (PDAC), which is a significant cause of recurrence, has not been established. The aim of the study was to evaluate the diagnostic accuracy of CT in detecting EPNI preoperatively in resectable PDAC of the pancreatic head. Retrospective study design was approved by institutional review board. Preoperative CT-series of 46 patients with resectable PDAC were evaluated by two independent observers. Plexus Pancreaticus Capitalis-II (PPC-II) was assessed as this area is more susceptible for EPNI. All patients underwent surgery with dedicated histopathology, which served as the reference standard. Histologically EPNI was confirmed in 63.1%. Sensitivity of MDCT was 93.1% (95% confidence interval (CI) 77.23% to 99.15%), specificity 64.7% (95% CI 38.33% to 85.79%) with area under the curve (AUC) 0.789 for the first observer. Positive predictive value (PPV) was 81.82% (95% CI 70.12% to 89.62%), negative predictive value (NPV-84.62% (95% CI 57.98% to 95.64%) with diagnostic accuracy of 82.61% (95% CI 68.58% to 92.18%). Interobserver agreement showed k-value of 0.893 ([Formula: see text]), which represents very good agreement between observers. Median actual survival in patients without EPNI was 30 months (95% CI 18.284-41.716), in patients with EPNI-13 months (95% CI 12.115-13.885). CT provides sufficient diagnostic information to detect PPC-II invasion in patients with resectable PDAC of the pancreatic head. Preoperative detection of EPNI might be an additional argument to perform neoadjuvant chemotherapy in patients with resectable PDAC. It should be included in preoperative evaluation form of CT-findings.

TYMS 3'-UTR Polymorphism: A Novel Association with FOLFIRINOX-Induced Neurotoxicity in Pancreatic Cancer Patients.

Pancreatic ductal adenocarcinoma (PDAC) is a highly fatal malignancy that has the worst 5-year survival rate of all of the common malignant tumors. Surgery, chemotherapy, and/or chemoradiation remain the main tactics for PDAC treatment. The efficacy of chemotherapy is often compromised because of the substantial risk of severe toxicities. In our study, we focused on identification of polymorphisms in the genes involved in drug metabolism, DNA repair and replication that are associated with inter-individual differences in drug-induced toxicities. Using the microarray, we genotyped 12 polymorphisms in the DPYD, XPC, GSTP1, MTHFR, ERCC1, UGT1A1, and TYMS genes in 78 PDAC patients treated with FOLFIRINOX. It was found that the TYMS rs11280056 polymorphism (6 bp-deletion in TYMS 3'-UTR) predicted grade 1-2 neurotoxicity (p = 0.0072 and p = 0.0019, according to co-dominant (CDM) and recessive model (RM), respectively). It is the first report on the association between TYMS rs11280056 and peripheral neuropathy. We also found that PDAC patients carrying the GSTP1 rs1695 GG genotype had a decreased risk for grade 3-4 hematological toxicity as compared to those with the AA or AG genotypes (p = 0.032 and p = 0.014, CDM and RM, respectively). Due to relatively high p-values, we consider that the impact of GSTP1 rs1695 requires further investigation in a larger sample size.

Russian Consensus on Exo- and Endocrine Pancreatic Insufficiency After Surgical Treatment.

The Russian consensus on exo- and endocrine pancreatic insufficiency after surgical treatment was prepared on the initiative of the Russian Pancreatic Club using the Delphi method. Its goal was to consolidate the opinions of national experts on the most relevant issues of diagnosis and treatment of exo- and endocrine insufficiency after surgical interventions on the pancreas. An interdisciplinary approach is ensured by the participation of leading gastroenterologists and surgeons.

Comparing Western and Eastern criteria for sarcopenia and their association with survival in patients with pancreatic cancer.

BACKGROUND & AIMS: Sarcopenia and cachexia are associated with pancreatic cancer and serve as important adverse prognostic factors. Body composition can be analyzed by routine computed tomography (CT) for cancer staging and has been used to study many types of cancer. The CT measurements are robust, but the diagnostic criteria for sarcopenia vary among different studies. Age, sex and race are important factors that affect muscle and fat masses. This study aimed to analyze the effect of different sarcopenia diagnostic criteria on the prognosis of patients with pancreatic cancer. METHODS: Patients with newly diagnosed pancreatic cancer at National Taiwan University Hospital between October 2013 and October 2016 were retrospectively reviewed in this study. Body composition was assessed using cross-sectional CT images to calculate the total skeletal muscle (TSM) index. The concordance and interobserver variability of the TSM measurements were evaluated using both the Western criteria and the Eastern criteria. Kaplan-Meier analyses and the Cox proportional hazard ratio with two different diagnostic criteria for sarcopenia were used to compare the effect on overall survival (OS). RESULTS: A total of 146 patients with pancreatic cancer were enrolled. The TSM index measured by the Western institute was highly correlated with that measured by the Eastern institute (r = 0.953, p < 0.001). The prevalence of sarcopenia in the patient group at baseline was 66.4% (97/146) by the Western criteria and 11.0% (16/146) by the Eastern criteria, and only low agreement was found between the Western and Eastern criteria (Kappa value = 0.028, p = 0.149). Patients who were sarcopenic by the Western criteria showed no significant difference in OS versus those who were not sarcopenic (p = 0.807). However, patients who were sarcopenic by the Eastern criteria showed a significant difference in OS versus those who were not sarcopenic in a univariate analysis (p = 0.008) and multivariate analysis after adjustment for AJCC stage (p = 0.014). CONCLUSIONS: Our study demonstrates that different diagnostic criteria may result in different diagnoses and that sarcopenia is an important poor prognostic factor for pancreatic cancer when appropriate diagnostic criteria are selected.

Reliability and validity of the new VikingSlice software for computed tomography body composition analysis.

BACKGROUND/OBJECTIVES: Body composition assessment by computed tomography (CT) is increasingly used for diagnostic and prognostic purposes in various patient groups. This study aimed to compare the reliability and validity of a newly in-house developed segmentation software VikingSlice against a commercial software (SliceOMatic) for quantification of adipose tissue and skeletal muscle cross-sectional areas (CSA). SUBJECTS/METHODS: Fifty abdominal CT sets from chronic pancreatitis patients were analyzed (mean age 49, range 27-84 years; 38 males). Soft tissue CSAs at level of 4th lumbar vertebra were assessed by measuring standard Hounsfield unit threshold definitions with both softwares. Analysis with VikingSlice included automatic segmentation of interested region with subsequent manual corrections. Analysis with SliceOMatic included manual segmentation of each area. Same investigator measured CSAs using both programs. Inter-observer reliability of CSAs measurements with VikingSlice were assessed by comparing results from two independent investigators. Measurements were compared using the intra-class correlation coefficient (ICC), coefficient of variation (CV), Jaccard index and Bland-Altman analyses. RESULTS: The inter-observer reliability of VikingSlice was excellent (CV 3.4-15.4%, ICC 0.979-0.999, Jaccard index 0.68-0.98). Validity was high (CV 1.6-10.2%, ICC 0.950-0.997) for measurements by SliceOmatic and VikingSlice. The findings were supported in the Bland-Altman plots. The reliability study had small average differences with means of soft tissue compartments in range -2.29 cm2 to 1.56 cm2; average differences between both softwares were -1.28 cm2 to 0.31 cm2. CONCLUSIONS: The in-house developed software VikingSlice was fast and showed good reliability that is comparable with commercial software in its utility to estimate adipose tissue and skeletal muscle CSAs.