Hilar Cholangiocarcinoma with Synchronous Metastases to Breast and Skeletal Muscle: A Case Report and Literature Review

Hilar cholangiocarcinoma has been reputed as a slow growth tumor in the past. Skeletal muscle is one of the most unusual sites of metastasis from any malignancy. We report herein a case of hilar cholangiocarcinoma with synchronous metastases to skeletal muscle and breast, and review the literature. The patient was a 48-year-old woman who presented with jaundice and weight loss. An inoperable hilar cholangiocarcinoma was diagnosed. She was treated with a combination of endoscopic plastic stent biloiary drainage and three-dimensional conformal radiotherapy （3DCRT）. Good response was achieved. Ten months later, she exhibited with a painful metastatic mass in the muscle rectus femoris of left thigh and a painless mass in the left breast. She underwent operation to relieve the pain, but died from liver failure after 8 months. The literature only offers isolated cases of cholangiocarcinoma with distant metastases, of which the common sites were cervical lymph node, bone, and portal venous system. Most patients were presented with multiple metastases with extensive local disease.

Effect of nutritional counselling on hepatic,muscle and adipose tissue fat content and distribution in non-alcoholic fatty liver disease

AIM： To assess the effectiveness of the current UK clinical practice in reducing hepatic fat （IHCL）.METHODS： Whole body MRI and IH MRS were obtained, before and after 6 mo nutritional counselling, from liver, soleus and tibialis muscles in 10 subjects with non-alcoholic fatty liver disease （NAFLD）.RESULTS： A 500 Kcal-restricted diet resulted in an average weight loss of 4% （-3.4 kg,） accompanied by significant reductions in most adipose tissue （AT） depots, including subcutaneous （-9.9%）, abdominal subcutaneous （-10.2%） and intra-abdominal- AT （-11.4%）. Intramyocellular lipids （IMCL） were significantly reduced in the tibialis muscle （-28.2%）. Decreases in both IHCL （-39.9%） and soleus IMCL （-12.2%） content were also observed, although these were not significant. Several individuals showed dramatic decreases in IHCL, while others paradoxically showed increases in IHCL content. Changes in body composition were accompanied by improvements in certain liver function tests： serum aspartate aminotransferase （AST） and alanine aminotransferase （ALT）. Significant correlations were found between decreases in IHCL and reductions in both intra-abdominal and abdominal subcutaneous AT. Improvements in liver function tests were associated with reductions in intra-abdominal AT, but not with changes in IHCL. CONCLUSION： This study shows that even a very modest reduction in body weight achieved through lifestyle modification can result in changes in body fat depots and improvements in LETs.

Glycogen storage diseases: New perspectives

Glycogen storage diseases （GSD） are inherited metabolic disorders of glycogen metabolism. Different hormones, including insulin, glucagon, and cortisol regulate the relationship of glycolysis, gluconeogenesis and glycogen synthesis. The overall GSD incidence is estimated 1 case per 20000-43000 live births. There are over 12 types and they are classified based on the enzyme deficiency and the affected tissue. Disorders of glycogen degradation may affect primarily the liver, the muscle, or both. Type I a involves the liver, kidney and intestine （and I b also leukocytes）, and the clinical manifestations are hepatomegaly, failure to thrive, hypoglycemia, hyperlactatemia, hyperuricemia and hyperlipidemia. Type Ilia involves both the liver and muscle, and lib solely the liver. The liver symptoms generally improve with age. Type IV usually presents in the first year of life, with hepatomegaly and growth retardation. The disease in general is progressive to cirrhosis. Type Ⅵ and Ⅳ are a heterogeneous group of diseases caused by a deficiency of the liver phosphorylase and phosphorylase kinase system. There is no hyperuricemia or hyperlactatemia. Type Ⅺ is characterized by hepatic glycogenosis and renal Fanconi syndrome. Type Ⅱ is a prototype of inborn lysosomal storage diseases and involves many organs but primarily the muscle. Types V and Ⅶ involve only the muscle.

Effects of rhubarb on isolated gastric muscle strips of guinea pigs

AIM:To study the effects of rhubarb (dried root of Rheum officinale Baill.) on contractile activity of isolated gastric muscle strips of guinea pigs and its possible mechanism. METHODS: A total of 48 guinea pigs were killed to remove the whole stomach. Then, the stomach was opened and the mucosal layer was removed. Parallel to the circular fibers, muscle strips were cut from the body. Each isolated gastric muscle strip was suspended in a tissue chamber containing 5 mL Krebs solution, constantly warmed by water jacket at 37℃ and bubbled continuously with a mixed gas of 950 mL/L O2 and 50 mL/L CO2. After being incubated for 1 h with 1 g tension, rhubarb of varied concentrations (1%, 2%, 7%, 20% and 70%) was added cumulatively into the tissue chamber at intervals of 2 min. Atropine (10-6 mol/L) or isoptin (5x10-8 mol/L) or hexamethonium (10-5 mol/L) was given 2 min before the administration of rhubarb. The isometrical response was measured with an ink-writing recorder. RESULTS: Rhubarb dose dependently increased the resting tension of gastric body circular muscle (CM) (r = 0.726, P<0.05). Atropine (r= 0.829, A:0.05), isoptin (r= 0.764, A;0.05) and hexamethonium (r = 0.797, P<0.05) did not affect its action in a dose-related manner. Atropine apparently reduced the increasing action of 1%, 3%, 10%, 30% and 100% rhubarb on the resting tension of gastric body CM. Isoptin inhibited the effect of 10%, 30% and 100% rhubarb on the resting tension of gastric body CM. Hexamethonium reduced the increasing action of 1%, 10%, 30% and 100% rhubarb on the resting tension of gastric body CM. Rhubarb increased the contractile frequency of CM of body. While atropine, isoptin and hexamethonium did not inhibit the contractile frequency of gastric body CM in comparison with rhubarb at the same concentration, rhubarb at the highest concentration (100%) decreased the mean contractile amplitude of gastric body CM. Atropine, isoptin and hexamethonium did not affect the mean contractile amplitude of gastric body CM compared to rhubarb at the same concentration. CONCLUSION: Rhubarb has exciting actions on isolated gastric smooth muscle strips of guinea pig. The exciting action of rhubarb is partly mediated via cholinergic M receptor, cholinergic N receptor and L-type calcium channel.

Experimental gastric dysrhythmias and its correlation with in vivo gastric muscle contractions

AIM： To study the direct correlation between gastric dysrhythrnias and in vivo gastric muscle tone. METHODS： Five healthy dogs were implanted with 4 pairs of electrodes along the greater curvature, with a strain gauge （SG） being sutured parallel to the distal electrodes （2 cm above the pylorus）. Intravenous vasopressin was given to induce gastric dysrhythrnia. The percentage of regular slow waves and SG energy were calculated. RESULTS： （1） the regularity of gastric rnyoelectric activity （GMA） was reduced during and after infusion of vasopressin; （2） SG energy was significantly decreased during the infusion of vasopressin; （3） the decrease in SG energy was well correlated with the reduction in GMA regularity; （4） SG energy was negatively correlated with bradygastria and tachygastria. CONCLUSION： Vasopressin inhibits gastric contractions and impairs gastric slow waves; gastric dysrhythrnias are associated with the reduced antral muscle contractions, and are indicative of antral hypornotility.

Gastrointestinal manifestations in myotonic muscular dystrophy

Myotonic dystrophy （MD） is characterized by myotonic phenomena and progressive muscular weakness. Involvement of the gastrointestinal tract is frequent and may occur at any level. The clinical manifestations have previously been attributed to motility disorders caused by smooth muscle damage, but histologic evidence of alterations has been scarce and conflicting. A neural factor has also been hypothesized. In the upper digestive tract, dysphagia, heartburn, regurgitation and dyspepsia are the most common complaints, while in the lower tract, abdominal pain, bloating and changes in bowel habits are often reported. Digestive symptoms may be the first sign of dystrophic disease and may precede the rnusculo-skeletal features. The impairment of gastrointestinal function may be sometimes so gradual that the patients adapt to it with little awareness of symptoms. In such cases routine endoscopic and ultrasonographic evaluations are not sufficient and targeted techniques （electrogastrography, manornetry, electromyography, functional ultrasonography, scintigraphy, etc.） are needed. There is a low correlation between the degree of skeletal muscle involvement and the presence and severity of gastrointestinal disturbances whereas a positive correlation with the duration of the skeletal muscle disease has been reported. The drugs recommended for treating the gastrointestinal complaints such as prokinetic, antidyspeptic drugs and laxatives, are mainly aimed at correcting the motility disorders. Gastrointestinal involvement in MD remains a complex and intriguing condition since many important problems are still unsolved. Further studies concentrating on genetic aspects, early diagnostic techniques and the development of new therapeutic strategies are needed to improve our management of the gastrointestinal manifestations of MD.

Symptoms relieved after tumor removal in a case of dermatomyositis associated with hepatocellular carcinoma:case report and literature review

A case of dermatomyositis associated with hepatocellular carcinoma is reported in a 43-year-old man,in which removal of the tumor resulted in great improvement of dermatomyositis.The patient had shown aggravating symptoms of dermatomyositis including manifestations of typical skin rashes and muscle weakness six months before he came to our hospital.He had no history of drug allergy and took no medicine in these days.When first visiting the dermatological clinic,he complained of discomforts in skin and muscle manifestation and was diagnosed as having dermatomyositis.At the same time,A CT scan discovered a resectable liver tumor in the right lobe.Then he came to our hospital and asked for surgical treatment.Removal of the tumor resulted in great improvement of dermatomyositis and recurrence of liver tumor was followed by resumption of dermatomyositis.

Sources of calcium in agonist-induced contraction of rat distal colon smooth muscle in vitro

AIM: To study the origin of calcium necessary for agonist-induced contraction of the distal colon in rats.METHODS: The change in intracellular calcium concentration ([Ca2+]i) evoked by elevating external Ca2+ was detected by fura 2/AM fluorescence. Contractile activity was measured with a force displacement transducer. Tension was continuously monitored and recorded using a Powerlab 4/25T data acquisition system with an ML110 bridge bioelectric physiographic amplifier.RESULTS: Store depletion induced Ca2+ influx had an effect on [Ca2+]i. In nominally Ca2+-free medium, the sarco-endoplasmic reticulum Ca2+-ATPase inhibitor thapsigargin (1 μmol/L) increased [Ca2+]i from 68 to 241 nmol/L, and to 458 (P < 0.01) and 1006 nmol/L (P < 0.01), respectively, when 1.5 mmol/L and 3.0 mmol/L extracellular Ca2+ was reintroduced. Furthermore, the change in [Ca2+]i was observed with verapamil (5 μmol/L), La3+ (1 mmol/L) or KCl (40 mmol/L) in the bathing solution. These channels were sensitive to La3+ (P < 0.01), insensitive to verapamil, and voltage independent. In isolated distal colons we found that in normal Krebs solution, contraction induced by acetylcholine (ACh) was partially inhibited by verapamil, and the inhibitory rate was 41% (P < 0.05). On the other hand, in Ca2+-free Krebs solution, ACh induced transient contraction due to Ca2+ release from the intracellular stores. The transient contraction lasted until the Ca2+ store was depleted. Restoration of extracellular Ca2+ in the presence of atropine produced contraction, mainly due to Ca2+ influx. Such contraction was not inhibited by verapamil, but was decreased by La3+ (50 μmol/L) from 0.96 to 0.72 g (P < 0.01). CONCLUSION: The predominant source of activator Ca2+ for the contractile response to agonist is extracellular Ca2+, and intracellular Ca2+ has little role to play in mediating excitation-contraction coupling by agonists in rat distal colon smooth muscle in vitro. The influx of extracellular Ca2+ is mainly mediated through voltage-, receptor- and store-operated Ca2+ channels, which can be used as an alternative to develop new drugs targeted on the dysfunction of digestive tract motility.

Tissue engineering for neuromuscular disorders of the gastrointestinal tract

The digestive tract is designed for the optimal processing of food that nourishes all organ systems.The esophagus,stomach,small bowel,and colon are sophisticated neuromuscular tubes with specialized sphincters that transport ingested food-stuffs from one region to another.Peristaltic contractions move ingested solids and liquids from the esophagus into the stomach;the stomach mixes the ingested nutrients into chyme and empties chyme from the stomach into the duodenum.The to-and-fro movement of the small bowel maximizes absorption of fat,protein,and carbohydrates.Peristaltic contractions are necessary for colon function and defecation.

Non-alcoholic fatty liver disease connections with fat-free tissues: A focus on bone and skeletal muscle

The estimates of global incidence and prevalence of non-alcoholic fatty liver disease(NAFLD) are worrisome, due to the parallel burden of obesity and its metabolic complications. Indeed, excess adiposity and insulin resistance represent two of the major risk factors for NAFLD; interestingly, in the last years a growing body of evidence tended to support a novel mechanistic perspective, in which the liver is at the center of a complex interplay involving organs and systems, other than adipose tissue and glucose homeostasis. Bone and the skeletal muscle are fat- free tissues which appeared to be independently associated with NAFLD in several cross-sectional studies. The deterioration of bone mineral density and lean body mass, leading to osteoporosis and sarcopenia, respectively, are age-related processes. The prevalence of NAFLD also increases with age. Beyond physiological aging, the three conditions share some common underlying mechanisms, and their elucidations could be of paramount importance to design more effective treatment strategies for the management of NAFLD. In this review, we provide an overview on epidemiological data as well as on potential contributors to the connections of NAFLD with bone and skeletal muscle.

Alveolar Rhabdomyosarcoma of the Laryngohypopharynx： A Case Report

Introduction Rhabdomyosarcoma is one of the most commonly seen soft-tissue sarcomas in children and teenagers, approximately accounting for half of all soft-tissue sarcomas. The tumor is usually found in head and neck, four limbs and urogenital system. However, the tumor orig- inating from the laryngohypopharynx is rare. In 2008, a patient with alveolar rhabdomyosarcoma of the laryngohypopharynx was admitted to our hospital. Clinical information of the disease was reported as follows, and clinicopathologic features and current therapeutic principle were discussed and summarized in combination with the review of literature, to facilitate the diagnosis and treatment of the patients with rhabdomyosarcoma of the laryngohypopharynx in future.

Acute myopathy associated with liver cirrhosis

AIM： Many cirrhotic patients have muscular symptoms and rhabdomyolysis. However, myopathy associated with liver cirrhosis has not been established as a disease entity. We evaluated the clinical significance of acute myopathy associated with liver cirrhosis. METHODS： We retrospectively reviewed the medical records of 5440 cirrhotic patients who had been admitted to Gyeongsang National University Hospital from August 1997 to January 2003. Among these, 99 developed acute myopathies, and they were analyzed with respect to clinical and laboratory parameters, and outcomes. RESULTS： The Child-Pugh classification at the time of myopathy onset was A in 3（3.1%） cases, B in 33（33.3%）, and C in 63 （63.6%）. Infection was identified as the most predisposing factor to myopathy. Fifty percent of 18 idiopathic cases who were tested for influenza antibody were positive. Forty-two of the 99 cases were complicated by acute renal failure, and 25 （59.5%） of these expired. Apart from 6 cases lost to follow-up, 64 of 93 recovered, giving a mortality rate of 31.2%. Mortality was higher in Child-Pugh class C than in B or A. CONCLUSION： Acute myopathy can develop as a serious complication in liver cirrhosis. Its frequency, severity and mortality depend on underlying liver function, and are higher in decompensated liver cirrhosis. Influenza should be considered as an etiologic factor in idiopathic cases. It is proposed that acute myopathy associated with liver cirrhosis be called ＇hepatic myopathy; and that careful monitoring for hepatic myopathy is necessary in the patients with advanced liver cirrhosis.

Autoantibody profiles in autoimmune hepatitis and chronic hepatitis C identifies similarities in patients with severe disease

To determine how the auto-antibodies (Abs) profiles overlap in chronic hepatitis C infection (CHC) and autoimmune hepatitis (AIH) and correlate to liver disease.METHODSLevels of antinuclear Ab, smooth muscle antibody (SMA) and liver/kidney microsomal-1 (LKM-1) Ab and markers of liver damage were determined in the sera of 50 patients with CHC infection, 20 AIH patients and 20 healthy controls using enzyme linked immunosorbent assay and other immune assays.RESULTSWe found that AIH patients had more severe liver disease as determined by elevation of total IgG, alkaline phosphatase, total serum bilirubin and serum transaminases and significantly higher prevalence of the three non-organ-specific autoantibodies (auto-Abs) than CHC patients. Antinuclear Ab, SMA and LKM-1 Ab were also present in 36% of CHC patients and related to disease severity. CHC cases positive for auto-Abs were directly comparable to AIH in respect of most markers of liver damage and total IgG. These cases had longer disease duration compared with auto-Ab negative cases, but there was no difference in gender, age or viral load. KLM-1+ Ab CHC cases showed best overlap with AIH.CONCLUSIONAuto-Ab levels in CHC may be important markers of disease severity and positive cases have a disease similar to AIH. Auto-Abs might have a pathogenic role as indicated by elevated markers of liver damage. Future studies will unravel any novel associations between these two diseases, whether genetic or other.

Prevalence and impact of musculoskeletal pain in Japanese gastrointestinal endoscopists:A controlled study

AIM:To examine the frequency and prevention of musculoskeletal pain in Japanese gastrointestinal endoscopists and non-endoscopist physicians.METHODS:Questionnaires were sent to 275 endoscopists and 173 non-endoscopists working in Hiroshima University Hospital and its affiliated hospitals.RESULTS:The completed questionnaires were returned by 190(69%)endoscopists and 120(69%)non-endoscopists.The frequency of pain in the hand and wrist,and especially the left thumb,was significantly higher in endoscopists than in non-endoscopists(17%vs 6%,P=0.004).Using multivariate analysis,the only significant factor associated with this pain was the age of the endoscopist(odds ratio 2.77,95%confidence interval,1.23-6.71,P=0.018).Interestingly,endoscopists had made significantly fewer modifications to their endoscopic practices than non-endoscopists(12%vs 33%,P <0.0001)to prevent pain.CONCLUSION:Pain in the hand and wrist may be endoscopy-related.However,endoscopists made little modifications in practice to prevent such pain.More attention to prevention appears necessary.

Pancreatic metastasis of leiomyosarcoma in the right thigh:A case report

Pancreatic tumors are primary in most of the cases. Pancreatic metastases associated with other primary malignancies, especially pancreatic metastasis of leiomyosarcoma, are uncommon. A 66-year-old woman underwent surgical resection of malignant mesenchymoma （70% osteosarcoma and 30% leiomyosarcoma） in the right thigh. In the postoperative period, a pancreatic mass was identified radiologically by abdominal computed tomography. Pylorus-preserving pancreaticoduodenectomy was performed. The surgical specimen revealed leiomyosarcoma metastasized to the pancreas. A metastatic nodule on the remnant pancreatic tail was discovered 9 mo after the first pancreatic resection, and distal pancreatectomy was performed. Cases of pancreatic metastasis from leiomyosarcoma are extremely rare, especially when the tumor was resectable. We report here a unique case of pancreatic metastasis from a leiomyosarcoma in the dght thigh that had been treated surgically.

Reproducibility of serial creatinine excretion measurements in peritoneal dialysis

AIMTo test whether muscle mass evaluated by creatinine excretion （EXCr） is maintained in patients with end-stage kidney disease （ESKD） treated by peritoneal dialysis （PD）, we evaluated repeated measurements of EXCr in a PD population.METHODSOne hundred and sixty-six PD patients （94 male, 72 female） receiving the same PD dose for the duration of the study （up to approximately 2.5 years） had repeated determinations of total （in urine plus spent dialysate） 24-h EXCr （EXCr T） to assess the adequacy of PD by creatinine clearance. All 166 patients had two EXCr T determinations, 84 of the 166 patients had three EXCr T determinations and 44 of the 166 patients had four EXCr T measurements. EXCr T values were compared using the paired t test in the patients who had two studies and by repeated measures ANOVA in those who were studied three or four times.RESULTSIn patients who were studied twice, with the first and second EXCr T measurements performed at 9.2 ± 15.2 mo and 17.4 ± 15.8 mo after onset of PD, respectively, EXCr T did not differ between the first and second study. In patients studied three times and whose fnal assessment occurred 24.7 ± 16.3 mo after initiating PD, EXCr T did not differ between the first and second study, but was significantly lower in the third study compared to the frst study. In patients who were studied four times and whose fourth measurement was taken 31.9 ± 16.8 mo after onset of PD, EXCr T did not differ between any of the studies. The average EXCr T value did not change signifcantly, with the exception of the third study in the patients studied thrice. However, repeated determinations of EXCr T in individuals showed substantial variability, with approximately 50% of the repeated determinations being higher or lower than the first determination by 15% or more.CONCLUSIONThe average value of EXCr T remains relatively constantfor up to 2.5 years of follow-up in PD patients who adhereto the same PD schedule. However, repeated individualEXCr T values vary considerably in a large proportion ofthe patients. Further studies are needed to evaluatethe clinical signifcance of varying EXCr T values and thestability of EXCr T beyond 2.5 years of PD follow-up.

Unexplainable development of a hydatid cyst

Echinococcosis is a cyclozoonosis characterized by cystic lesions usually situated inside or outside the liver. We discuss the case of a 77-year-old woman with a recurrent hydatidosis with a cyst arising from the liver, growing through the lateral right abdomen wall, and reaching the subcutaneous tissue of the lumbar region. In the literature, rare subcutaneous or muscular Iocalizations of hydatid cysts are described, however, there is no mention of a cyst growing over the abdominal wall muscles, shaped like an hourglass, partially in the liver and partially in the subcutaneous tissue, as in our case. We have not found any pathogenetic explanation for this growth pattern which is not typical of the biological behaviour of a hydatid cyst.

Sarcopenia is associated with Framingham risk score in the Korean population： Korean National Health and Nutrition Examination Survey （KNHANES） 2010-2011

Background Sarcopenia is a risk factor for metabolic disorders and cardiovascular disease, but the association between sarcopenia and cardiovascular risk factors according to age and obesity status in the general population remains unknown. We thus investigated these associations in the Korean population. Methods We included 8,958 and 8,518 subjects from the fifth Korean National Health and Nutrition Examination Survey （KNHANES） （from 2010 and 2011, respectively）. The study was restricted to participants 〉 20 years old who had completed the health examination survey, including whole body dual-energy X-ray absorptiometry scans. After exclusion, 7,366 subjects （3,188 men, 4,178 women） were included in our final analysis. Age was categorized according to three age groups （20-39, 40-59, mad 〉 60 years）, and subjects were catego- rized according to their sarcopenic and obesity status. Cardiovascular risk was assessed with Framingham risk score （FRS）. Results The sarco- penic obese group had a higher FRS than the non-sarcopenic obese group, which had a higher FRS than the non-sarcopenic non-obese group. Age-wise, the 20-39 year-old group showed a non-significant association between sarcopenia and FRS. In the 40-59 year-old group, regardless of obesity status, sarcopenic subjects had a higher FRS than non-sarcopenic subjects. In the 〉 60 year-old group, sarcopenic subjects had a higher FRS than non-sarcopenic subjects for the non-obese group. Conclusions Sarcopenia was associated with cardiovascular disease and may be an early predictor of its susceptibility in both elderly and middle-aged subjects. Thus, management of sarcopenia is necessary to prevent cardiovascu- lar disease.