Platelets in liver disease, cancer and regeneration

Although viral hepatitis treatments have evolved over the years, the resultant liver cirrhosis still does not completely heal. Platelets contain proteins required for hemostasis, as well as many growth factors required for organ development, tissue regeneration and repair. Thrombocytopenia, which is frequently observed in patients with chronic liver disease (CLD) and cirrhosis, can manifest from decreased thrombopoietin production and accelerated platelet destruction caused by hypersplenism; however, the relationship between thrombocytopenia and hepatic pathogenesis, as well as the role of platelets in CLD, is poorly understood. In this paper, experimental evidence of platelets improving liver fibrosis and accelerating liver regeneration is summarized and addressed based on studies conducted in our laboratory and current progress reports from other investigators. In addition, we describe our current perspective based on the results of these studies. Platelets improve liver fibrosis by inactivating hepatic stellate cells, which decreases collagen production. The regenerative effect of platelets in the liver involves a direct effect on hepatocytes, a cooperative effect with liver sinusoidal endothelial cells, and a collaborative effect with Kupffer cells. Based on these observations, we ascertained the direct effect of platelet transfusion on improving several indicators of liver function in patients with CLD and liver cirrhosis. However, unlike the results of our previous clinical study, the smaller incremental changes in liver function in patients with CLD who received eltrombopag for 6 mo were due to patient selection from a heterogeneous population. We highlight the current knowledge concerning the role of platelets in CLD and cancer and anticipate a novel application of platelet-based clinical therapies to treat liver disease

Well leg compartment syndrome after surgery for ulcerative colitis in the lithotomy position: A case report

AbstractIntroductionWell leg compartment syndrome (WLCS) is an uncommon and severe complication that occurs after colorectal surgery in the lithotomy position.Presentation of caseThe current patient was a 28-year-old male suffering from ulcerative colitis. He was underwent elective proctectomy, including ileal J pouch formation and anal anastomosis with temporary loop ileostomy. The ileoanal pouch procedure was quite difficult, and during this procedure, the high lithotomy and head down tilt positions were continued for 255min.After the operation, the patient complained of severe cramping pain, swelling and serious tenderness on palpation in both legs. On the first postoperative day, the patient's complaints gradually worsened. The intra-compartmental pressure was measured, and WLCS was diagnosed. Emergency bilateral fasciotomy was performed. Initially, the patient had a sensory deficit and analgesia, however, his sensory disturbance and pain had almost recovered two months after fasciotomy by rehabilitation.DiscussionIn the current case, the important factors associated with the development of WLCS are thought to be a prolonged operative time in which the patient is placed in the high lithotomy position during ileoanal pouch procedure.ConclusionWe would thus like to emphasize that operations for the ileoanal pouch procedure to treat ulcerative colitis have a high potential for inducing WLCS, because it usually requires a prolonged operative time in which the patient remains in the high lithotomy position

Antisense RNA transcripts in the blood may be novel diagnostic markers for colorectal cancer

Numerous genetic studies have been conducted regarding the occurrence of colorectal cancer (CRC) and the prognosis using microarrays. However, adequate investigations into the diagnostic application of microarrays have yet to be performed. The simplicity and accuracy of diagnosis and prognosis tracking are important requirements for its processes, and the use of blood cells for diagnosis is considered to be suitable to meet these requirements. The patients involved in the study were 28 preoperative patients with CRC and 6 healthy individuals who served as controls. RNA was extracted from the blood cells of the patients and analyzed using a sense/antisense RNA custom microarray. In the patients with CRC, the expression levels of 20 sense RNA and 20 antisense RNA species were identified as being significantly altered compared with that of the healthy volunteers (P2.0). Cluster analysis of these RNA species revealed that the top 10 antisense RNAs significantly clustered patients with cancer and healthy individuals separately. Patients with stage I or II CRC exhibited significant changes in the expression levels of 33 sense and 39 antisense RNA species, as compared with healthy volunteers (P2.0). Cluster analysis demonstrated that patients with stage I or II CRC and healthy volunteers formed separate clusters only among the top 20 antisense RNA species. A tracking study of expression levels of haloacid dehalogenase‑like hydrolase domain‑containing 1 (HDHD1) antisense RNA was performed and a significant difference was identified between the CRC and healthy groups revealing that the levels at one week and three months following surgical removal of the cancerous tissue, decreased to almost same levels of the healthy individuals. The results of the current study indicate that HDHD1 antisense RNA may serve as a potential biomarker for the prognosis of CRC

Reactive Oxygen Species in Skin Repair, Regeneration, Aging, and Inflammation

As the most important and largest surface barrier, the skin provides a necessary protection to the organism from the external factors, including chemical, biological, and physical irritation, injury, and others. External environmental irritants or their metabolites are inherent oxidants and/or directly or indirectly drive the production of various reactive oxidants, reactive oxygen species (ROSs), owing to the redox imbalances. ROSs, the most common free oxygen radicals, participate in a series of physiological and pathological skin processes. Here, we discussed the role of oxidative events in injury, repair, photoaging, and cutaneous disease development. Intrinsic and extrinsic factors lead to the skin barrier damage, which leads to the disequilibrium in oxidant and antioxidant balance and induces excessive ROS production. The underlying mechanisms include DNA damage, MAPK/AP-1, NF-κB, and JAK/STAT-signaling pathways, apoptosis and autophagy, and autoimmune reaction of melanocytes and keratinocytes. The skin employs a number of antioxidant agents to protect the oxidative balance, such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), ascorbic acid, and tocopherols. The results presented here indicate that antioxidant treatments may be effective when applied in the therapy of cutaneous diseases where oxidative stress plays a prominent pathogenic role

Novel functions of platelets in the liver

Platelets contain not only proteins needed for hemostasis but also many growth factors that are required for organ development, tissue regeneration, and repair. Thrombocytopenia, which is frequently observed in patients with chronic liver disease (CLD) and cirrhosis, is due to various causes, such as decreased thrombopoietin production and accelerated platelet destruction caused by hypersplenism; however, the relationship between thrombocytopenia and hepatic pathogenesis and the role of platelets in CLD are poorly understood. Thus, in this paper, the experimental evidence for platelets improving liver fibrosis and accelerating liver regeneration is summarized and addressed based on studies conducted in our laboratory and current progress reports from other investigators. Platelets improve liver fibrosis by inactivating hepatic stellate cells to decrease collagen production. The level of intracellular cAMP is increased by adenosine through its receptors on hepatic stellate cells, thereby resulting in inactivation of these cells. Adenosine is produced by degradation of adenine nucleotides, which are stored in abundance within the dense granules of platelets. The regenerative effect of platelets in the liver consists of three mechanisms: a direct effect on hepatocytes, a cooperative effect with liver sinusoidal endothelial cells, and a collaborative effect with Kupffer cells. Based on these experiments, a clinical trial suggested that the increase in platelets induced by platelet transfusion improved liver function in patients with CLD in a clinical setting.We highlight the current knowledge concerning the role of platelets in CLD and expect to open a novel avenue for application of these clinical therapies to treat liver disease

Pubic osteomyelitis after surgery for perforated colonic diverticulitis with fecal peritonitis: A case report

IntroductionPubic osteomyelitis is a rare type of suppurative osteomyelitis. Early diagnosis of pubic osteomyelitis is difficult, and prolonged inflammation results in progressive bone degradation, severe pelvic pain and a wide-based gait.Presentation of caseWe report the case of an 82-year-old woman who was admitted to a previous hospital with severe abdominal pain caused by a perforated colonic diverticulum with fecal peritonitis. She underwent an emergency operation and a postoperative wound infection occurred. Despite treatment of the infection, purulent exudate was discharged for three months and she gradually showed a gait disturbance.CT and MRI revealed that pubic symphysis showed osteolysis and there was severe inflammation around the wound. After administration of appropriate antibiotics, an operation, which included the removal of a fistula, debridement of sequestra and lavage of the abscess cavity, was performed. The inflammation improved promptly after the operation, and the patient was discharged on postoperative day 27 without any complications.DiscussionPubic osteomyelitis does not show the findings of typical acute suppurative osteomyelitis and hematological findings are nonspecific. It is important for early diagnosis to consider the risk factors of pubic osteomyelitis during examination.ConclusionWe would emphasize that a definitive diagnosis by CT and MRI and appropriate antimicrobial therapy combined with surgical treatment are important for pubic osteomyelitis

Nasogastric tube syndrome induced by an indwelling long intestinal tube

The nasogastric tube (NGT) has become a frequently used device to alleviate gastrointestinal symptoms. Nasogastric tube syndrome (NTS) is an uncommon but potentially life-threatening complication of an indwelling NGT. NTS is characterized by acute upper airway obstruction due to bilateral vocal cord paralysis. We report a case of a 76-year-old man with NTS, induced by an indwelling long intestinal tube. He was admitted to our hospital for treatment of sigmoid colon cancer. He underwent sigmoidectomy to release a bowel obstruction, and had a long intestinal tube inserted to decompress the intestinal tract. He presented acute dyspnea following prolonged intestinal intubation, and bronchoscopy showed bilateral vocal cord paralysis. The NGT was removed immediately, and tracheotomy was performed. The patient was finally discharged in a fully recovered state. NTS be considered in patients complaining of acute upper airway obstruction, not only with a NGT inserted but also with a long intestinal tube

Indocyanine green fluorescence-navigated laparoscopic metastasectomy for peritoneal metastasis of hepatocellular carcinoma: a case report

BackgroundIndocyanine green (ICG) can selectively accumulate in primary hepatocellular carcinoma (HCC) and its extrahepatic metastases. ICG fluorescence imaging is an extremely sensitive intraoperative tool for detecting HCC foci and can be used to detect impalpable tumors in laparoscopic surgery. Here, we report a case of a 75-year-old man who underwent peritoneal metastasis resection of HCC using a laparoscopic near-infrared imaging system and ICG fluorescence-navigated surgery.Case presentationA 75-year-old man was referred to our department for peritoneal metastasis resection of HCC. Two years before admission, he had undergone transarterial embolization and segmentectomy of segment 6 with open surgery for ruptured HCC. Computed tomography revealed a 12-mm peritoneal metastatic lesion on the abdominal wall near the cut surface of the liver. No other metastases were observed; resection of the solitary metastasis was scheduled. ICG (0.5 mg/kg body weight) was intravenously injected, 72 h preoperatively. An endoscopic, ICG near-infrared fluorescence imaging system revealed clear green fluorescence, indicating peritoneal metastasis of HCC on the abdominal wall. The tumor was resected with adequate surgical margin by partially resecting the liver and diaphragm, followed by histological confirmation as peritoneal metastasis of HCC. No recurrence was observed after 12 months of follow-up.ConclusionsICG fluorescence can be useful in laparoscopic surgery for identifying peritoneal metastasis

Thrombocytopenia after liver transplantation: Should we care?

Transient thrombocytopenia is a common phenomenon after liver transplantation. After liver transplantation (LT), platelet count decreases and reaches a nadir on postoperative days 3-5, with an average reduction in platelet counts of 60%; platelet count recovers to preoperative levels approximately two weeks after LT. The putative mechanisms include haemodilution, decreased platelet production, increased sequestration, medications, infections, thrombosis, or combination of these processes. However, the precise mechanisms remain unclear. The role of platelets in liver transplantation has been highlighted in recent years, and particular attention has been given to their effects beyond hemostasis and thrombosis. Previous studies have demonstrated that perioperative thrombocytopenia causes poor graft regeneration, increases the incidence of postoperative morbidity, and deteriorates the graft and decreases patient survival in both the short and long term after liver transplantation. Platelet therapies to increase perioperative platelet counts, such as thrombopoietin, thrombopoietin receptor agonist, platelet transfusion, splenectomy, and intravenous immunoglobulin treatment might have a potential for improving graft survival, however clinical trials are lacking. Further studies are warranted to detect direct evidence on whether thrombocytopenia is the cause or result of poor-graft function and postoperative complications, and to determine who needs platelet therapies in order to prevent postoperative complications and thus improve post-transplant outcomes