Impact of psoas muscle index assessed by a simple measurement method on tolerability and duration of continued treatment with sorafenib in hepatocellular carcinoma patients.

BACKGROUND: In this study, we investigated the impact of simple measurement of psoas muscle index (PMI) on the tolerability of sorafenib treatment of switch from sorafenib to regorafenib. METHOD: This retrospective study enrolled 109 patients with Child-Pugh A hepatocellular carcinoma (HCC) treated with sorafenib. Pretreatment PMI was calculated by measuring and multiplying the greatest anterior/posterior and transverse diameters of the psoas muscles on axial computed tomography images at the L3 vertebral level, and normalizing the sum of bilateral psoas muscle areas by the square of the height in meters. We, then, statistically analyzed the association between PMI and adverse events (AEs) to treatment, tolerability of sorafenib, time to treatment failure (TTF), and prognosis in patients stratified according to PMI. RESULT: Patients were divided into high PMI (n = 41) and low PMI (n = 68) groups based on the cutoff PMI values (men: 7.04 cm2/m2; women: 4.40 cm2/m2) determined by receiver operating characteristic curve analysis to determine sorafenib tolerability. Frequencies of all types of severe AEs were higher in the low PMI group (50.0%) than in the high PMI group (29.3%; P = 0.045). The high PMI group (51.2%) had greater tolerance to sorafenib than the low PMI group (25.0%; P = 0.007). Moreover, in multivariable analysis, PMI was associated with sorafenib tolerability (odds ratio 0.26; P = 0.008) and was a prognostic factor affecting TTF (hazard ratio 1.77; P = 0.021). CONCLUSION: PMI might be a predictive marker of tolerance to treatment and TTF in HCC patients receiving sorafenib treatment.

Possible correlation between increased serum free carnitine levels and increased skeletal muscle mass following HCV eradication by direct acting antivirals.

We aimed to evaluate factors associated with changes in skeletal muscle mass in hepatitis C virus (HCV)-infected patients after treatment with direct-acting antivirals (DAAs). Consecutive HCV-infected patients after treatment with DAA were recruited into the study. Patients who achieved sustained virological response (SVR); and had complete clinical information, preserved serum samples at baseline and SVR48, and skeletal muscle mass evaluations based on the psoas muscle mass index (PMI) on computed tomography at baseline and ≥ 12 months were included. Altogether, 70.7% of patients (41/58) showed increased PMI after DAA therapy, and mean relative PMI was significantly higher after DAA therapy than at baseline. There were no significant associations between baseline clinical factors routinely examined in clinical practice and increased PMI. Among factors reported to be associated with skeletal muscle loss in patients with chronic liver disease, serum zinc levels and total and free carnitine levels increased significantly after DAA therapy and only changes in serum free carnitine levels were significantly associated with an increased PMI (r = 0305, P = 0.020). In conclusion, increased skeletal muscle mass after successful HCV eradication by DAAs was significantly associated with increased serum-free carnitine levels. L-carnitine supplementation may be beneficial in patients with low skeletal muscle mass after DAA.

L-leucine stimulation of glucose uptake and utilization involves modulation of glucose - lipid metabolic switch and improved bioenergetic homeostasis in isolated rat psoas muscle ex vivo.

The antidiabetic effect of l-leucine has been attributed to its modulatory effect on glucose uptake and lipid metabolism in muscles. However, there is a dearth on its effect on glucose metabolism in muscles. Thus, the present study investigated the effect of l-leucine - stimulated glucose uptake on glucose metabolism, dysregulated lipid metabolic pathways, redox and bioenergetic homeostasis, and proteolysis in isolated psoas muscle from Sprague Dawley male rats. Isolated psoas muscles were incubated with l-leucine (30-240 µg/mL) in the presence of 11.1 mMol glucose at 37 ˚C for 2 h. Muscles incubated in only glucose served as the control, while muscles not incubated in l-leucine and/or glucose served as the normal control. Metformin (6.04 mM) was used as the standard antidiabetic drug. Incubation with l-leucine caused a significant increase in muscle glucose uptake, with an elevation of glutathione levels, superoxide dismutase, catalase, E-NTPDase and 5'nucleotidase activities. It also led to the depletion of malondialdehyde and nitric oxide levels, ATPase, chymotrypsin, acetylcholinesterase, glycogen phosphorylase, glucose-6-phosphatase, fructose-1,6-bisphosphatase and lipase activities. There was an alteration in lipid metabolites, with concomitant activation of glycerolipid metabolism, fatty acid metabolism, and fatty acid elongation in mitochondria in the glucose-incubated muscle (negative control). Incubation with l-leucine reversed these alterations, and concomitantly deactivated the pathways. These results indicate that l-leucine-enhanced muscle glucose uptake involves improved redox and bioenergetic homeostasis, with concomitant suppressed proteolytic, glycogenolytic and gluconeogenetic activities, while modulating glucose - lipid metabolic switch.

Prognostic value of preoperative psoas muscle index as a measure of nutritional status in patients with esophageal cancer receiving neoadjuvant therapy.

OBJECTIVES: It has been reported that preoperative nutritional status in some gastrointestinal cancers has a significant effect on postoperative prognosis. However, there are few reports on esophageal cancer, especially for esophageal cancer patients who have undergone neoadjuvant therapy and surgery. Psoas muscle index (PMI) is widely known as an index for assessing preoperative nutritional status, and has recently been reported for its prognostic value in many malignancies. The aim of this study was to investigate and evaluate the clinical results in our hospital using the PMI method. METHODS: We retrospectively investigated esophageal cancer in patients (clinical stage II or III) who underwent neoadjuvant therapy and surgical treatment (R0 cases) from January 2008 to December 2015. Applicable 63 cases were entered accordingly. In our hospital, nutritional supplements are used for nutritional management during preoperative adjuvant therapy, and these are administered to patients who have difficulty ingesting nutrition by feeding tube or total parenteral nutrition. The target value for nutritional supplement administration was 36 kcal/kg. Taking into account that chemotherapy for esophageal cancer was being performed using Harris-Benedict's basal energy expenditure (25 kcal/kg), we multiplied by 1.44 (active factor; 1.2, stress factor; 1.2) and set 36 kcal/kg as a guide. PMI was evaluated before neoadjuvant therapy and before surgery. We defined sarcopenia by PMI of the third lumbar vertebra (L3) by a computed tomography (CT) examination using 3-dimensional image analysis software, <6.36 for men and <3.92 for women, and investigated the effect of each on prognosis. RESULTS: The prevalence of sarcopenia decreased from 74.6% (47 of 63) to 69.84% (44 of 63) during the pretherapeutic to preoperative period (P = 0.691), suggesting improved nutritional status. Regarding PMI divided by cutoff value for each sex (the cutoff value was the PMI mean value -2 SD [6.36 cm2 m2 for men and 3.92 cm2/m2 for women] of healthy individuals <50 y of age, which was reported as a standard for low skeletal muscle mass in Japanese individuals), there was an improvement observed in the preoperative compared to pretherapeutic period, but it was not obtained as a significant difference (pretherapeutic PMI; 0.87 ± 0.06 [mean ± SD], preoperative PMI; 0.89 ± 0.06 [mean ± SD], P = 0.18). In overall survival (OS) and disease-free survival (DFS), there was no significant difference in the short-term results with and without sarcopenia in the pretherapeutic group (both OS and DFS, P = 0.17). There was a significant difference with and without sarcopenia in the preoperative group in terms of OS and DFS (OS, P = 0.045; DFS, P = 0.043), which was short term due to nutritional intervention during preoperative adjuvant therapy. It was suggested that the results would be improved. CONCLUSIONS: Improving nutritional status before surgery was shown to improve short-term prognosis in patients with esophageal cancer. It is hence suggested that it is important to maintain or improve nutritional status by intervention from the time of neoadjuvant therapy.

Psoas/iliacus muscle invasion from mucinous appendiceal neoplasm. Radiologic appearance and outcome of treatment in 3 patients.

BACKGROUND: Mucinous appendiceal neoplasms have a pattern of metastases that is different from the other gastrointestinal cancers. The first site for cancer dissemination is the peritoneal space surrounding the primary tumor and this is followed by increasingly extensive peritoneal spread. Invasion of the psoas and iliacus muscle is an unusual phenomenon. METHOD: From a prospective database of appendiceal mucinous neoplasms treated by cytoreductive surgery (CRS) and perioperative hyperthermic chemotherapy (HIPEC), patients with psoas muscle invasion were reviewed. Their clinical features and treatments were tabulated. RESULTS: Three patients with ages 33, 60, and 63 were identified. Two patients had disease progression into the psoas muscle 33 and 95 months after CRS plus HIPEC. One had dissecting mucinous tumor into psoas, iliacus and quadratus lumborum muscle at the time of diagnosis of the appendiceal mucinous neoplasm. All three survived at least five years from their initial treatment. CONCLUSION: Despite the fact that mucinous tumor invasion was outside the peritoneal cavity, long term benefit from psoas muscle resection with a mucinous appendiceal neoplasm is possible and resection possibly with HIPEC should be considered.

Modulatory effects of Caralluma fimbriata extract against high-fat diet induced abnormalities in carbohydrate metabolism in Wistar rats.

The present study was aimed to evaluate the modulatory effects of hydroalcoholic extract of Caralluma fimbriata (CFE) by assaying the activities of key enzymes of carbohydrate metabolism and changes in glycogen content (liver and muscle) in high-fat (HF) diet-induced diabetic rats. In vitro glucose uptake studies were carried out in both psoas muscle and adipose tissue. The inhibitory effect of the extract on α-amylase was determined in in vitro studies. Male Wistar rats of body weight around 180g were divided into five groups (n=8), two of these groups were fed with standard pellet diet and the other three groups were fed with HF- (60%) diet. CFE (200mg/kg body weight/day) was administered through oral route to each group of standard pellet diet rats and HF-fed rats and Metformin (Met) (20mg/kg body weight/day) was administered through oral route to HFD+Met group for 90 days. At the end of the experimental period, biochemical parameters related to glycogen content in liver and muscle, and intestinal disaccharidases like maltase, sucrase and lactase were assayed. Alterations in the activities of enzymes of glucose metabolism (hexokinase, phosphorfructoki nase, pyruvate kinase, glucose-6-phosphatase, fructose-1,6-bisphosphatase, and glucose-6-phosphate dehydrogenase), intestinal disaccharidases and glycogen content as observed in the high fat diet-fed rats were prevented with CFE/Met administration. From this study, we observed that CFE/Met could significantly restore the levels of glycogen in liver and muscle and key enzymes of carbohydrate metabolism to near normal in groups-HFD+CFE and HFD+Met. The skeletal muscle of HF-diet fed rats showed degenerative changes of muscle myofibers with fat deposition. These changes were attenuated in the HFD group treated with CFE/Met and retained their normal structure appearance. It can be concluded from these results that CFE might be of value in reducing the alterations related to carbohydrate metabolism under high calorie diet consumption.

Psoas syndrome: a frequently missed diagnosis.

Psoas syndrome is an easily missed diagnosis. However, it is important to consider this condition as part of the differential diagnosis for patients presenting with low back pain--particularly for osteopathic physicians, because patients may view these practitioners as experts in musculoskeletal conditions. The authors describe the case of a 48-year-old man with a 6-month history of low back pain that had been attributed to "weak core muscles." The diagnosis of psoas syndrome was initially overlooked in this patient. After the correct diagnosis was made, he was treated by an osteopathic physician using osteopathic manipulative treatment, in conjunction with at-home stretches between office treatments. At his 1-month follow-up appointment, he demonstrated continued improvement of symptoms and a desire for further osteopathic manipulative treatment.

Acquired haemophilia complicated with gastrointestinal bleeding and spontaneous iliopsoas muscle haematoma in a woman with chronic C hepatitis under treatment with pegylated IFN alpha 2a and ribavirin.

Acquired haemophilia A is a very rare (1-2 cases per million people) but often life-threatening haemorrhagic disorder characterized by antibodies directed against coagulation factor VIII. We report the case of a 55-year old woman under treatment with Pegylated alpha 2a interferon (IFN) and Ribavirin for chronic viral C hepatitis, who developed a progressive severe haemorrhagic syndrome diagnosed as acquired haemophilia based on supplementary laboratory data (prolonged activated partial thromboplastin time, extremely low factor VIII level - 1%, high titre of factor VIII inhibitor - 30 Bethesda U/ml).The onset was insidious, about three months before presenting to our unit. Antiviral therapy had been stopped three weeks before current admission. Emergency intensive treatment included: haemostatic agents - rFVII (Novoseven), FEIBA (Factor VIII Inhibitor Bypassing Activity), vitamin K, adrenostazin, cryoprecipitate, fresh frozen plasma, as well as immunosuppressive therapy (high dose corticotherapy and cyclophoshamide), immunoglobulins (Humaglobin), prophylactic PPI and antibiotics. The evolution was slowly favourable with the remission of the haemorrhagic syndrome and regression of the iliopsoas muscle haematoma. Clinicians should be aware that acquired forms of haemophilia do exist, representing a rare diagnosis and a therapeutic challenge. To our knowledge, this is the first reported case of acquired haemophilia in Romania, in a patient with chronic viral C hepatitis under antiviral treatment.

Effect of psoas training on postmenopausal lumbar bone loss: a 3-year follow-up study.

The present study completed a previous randomized trial that demonstrated the protective effect of 1-year psoas training on lumbar bone loss in postmenopausal women. Computerized tomography had been carried out at the beginning (CT1) and at the end (CT2) of this trial. In the present study, 67 women having completed the first trial were asked to practice psoas exercises (60 hip flexions in sitting position with a 5 kg weight on the knee) for 2 additional years with a third CT control at the end of this period (CT3). The aim of this complementary study was to assess the compliance rate and long-term effect on bone of daily psoas muscle training over a longer period. Twenty-one women performed this daily psoas training for 3 years from CT1 to CT3, and 14 acted as controls during the same period. Fourteen women were controls during the first year (from CT1 to CT2) but practiced psoas training during the following 2 years (from CT2 to CT3). Four women were psoas trained during the first year (from CT1 to CT2) and subsequently crossed over to the control group for the last 2 years. The compliance rate was 42%, with an attendance rate of 88%. The lumbar bone loss was lower in the 21 women trained over the 3 years (-3.26 +/- 28.45 mg/cm3) than in the 14 untrained women (-16.79 +/- 8.51 mg/cm3) (P = 0.02). The bone loss was not significantly reduced between the two periods of the study in the 12 women having been controls from CT1 to CT2 and having crossed over to the active training group from CT2 to CT3. Psoas training may be effective against lumbar bone loss. We conclude that specific training may play a contributing role in the preventive strategy to avoid osteoporosis.