Purpose: Alpha-fetoprotein (AFP) is a prognostic marker for hepatocellular carcinoma (HCC). We investigated the prognostic value of AFP levels in patients who achieved complete response (CR) to transarterial chemoembolization (TACE) for HCC. Materials and Methods: Between 2005 and 2018, 890 patients with HCC who achieved a CR to TACE were recruited. An AFP responder was defined as a patient who showed elevated levels of AFP (>10 ng/mL) during TACE, but showed normalization or a >50% reduction in AFP levels after achieving a CR. Results: Among the recruited patients, 569 (63.9%) with naïve HCC and 321 (36.1%) with recurrent HCC after complete resection were treated. Before TACE, 305 (34.3%) patients had multiple tumors, 219 (24.6%) had a maximal tumor size >3 cm, and 22 (2.5%) had portal vein tumor thrombosis. The median AFP level after achieving a CR was 6.36 ng/mL. After a CR, 473 (53.1%) patients experienced recurrence, and 417 (46.9%) died [median progression-free survival (PFS) and overall survival (OS) of 16.3 and 62.8 months, respectively]. High AFP levels at CR (>20 ng/mL) were independently associated with a shorter PFS [hazard ratio (HR)=1.403] and OS (HR=1.284), together with tumor multiplicity at TACE (HR=1.518 and 1.666, respectively). AFP non-responders at CR (76.2%, n=359 of 471) showed a shorter PFS (median 10.5 months vs. 15.5 months, HR=1.375) and OS (median 41.4 months vs. 61.8 months, HR=1.424) than AFP responders (all p=0.001). Conclusion High AFP levels and AFP non-responders were independently associated with poor outcomes after TACE. AFP holds clinical implications for detailed risk stratification upon achieving a CR after TACE.

Purpose: The purpose of this study was to investigate whether routine insertion of peripherally inserted central catheter (PICC) at admission to a hospice-palliative care (HPC) unit is acceptable in terms of safety and efficacy and whether it results in superior patient satisfaction compared to usual intravenous (IV) access. Materials and Methods: Terminally ill cancer patients were randomly assigned to two arms: routine PICC access and usual IV access arm. The primary endpoint was IV maintenance success rate, defined as the rate of functional IV maintenance until the intended time (discharge, transfer, or death). Results: A total of 66 terminally ill cancer patients were enrolled and randomized to study arms. Among them, 57 patients (routine PICC, 29; usual IV, 28) were analyzed. In the routine PICC arm, mean time to PICC was 0.84 days (range, 0 to 3 days), 27 patients maintained PICC with function until the intended time. In the usual IV arm, 11 patients maintained peripheral IV access until the intended time, and 15 patients underwent PICC insertion. The IV maintenance success rate in the routine PICC arm (27/29, 93.1%) was similar to that in the usual IV arm (26/28, 92.8%, p=0.958). Patient satisfaction at day 5 was better in the routine PICC arm (97%, ‘a little comfort’ or ‘much comfort’) compared with the usual IV arm (21%) (p <0.001). Conclusion Routine PICC insertion in terminally ill cancer patients was comparable in safety and efficacy and resulted in superior satisfaction compared with usual IV access. Thus, routine PICC insertion could be considered at admission to the HPC unit.

Purpose: The purpose of this study was to investigate whether routine insertion of peripherally inserted central catheter (PICC) at admission to a hospice-palliative care (HPC) unit is acceptable in terms of safety and efficacy and whether it results in superior patient satisfaction compared to usual intravenous (IV) access. Materials and Methods: Terminally ill cancer patients were randomly assigned to two arms: routine PICC access and usual IV access arm. The primary endpoint was IV maintenance success rate, defined as the rate of functional IV maintenance until the intended time (discharge, transfer, or death). Results: A total of 66 terminally ill cancer patients were enrolled and randomized to study arms. Among them, 57 patients (routine PICC, 29; usual IV, 28) were analyzed. In the routine PICC arm, mean time to PICC was 0.84 days (range, 0 to 3 days), 27 patients maintained PICC with function until the intended time. In the usual IV arm, 11 patients maintained peripheral IV access until the intended time, and 15 patients underwent PICC insertion. The IV maintenance success rate in the routine PICC arm (27/29, 93.1%) was similar to that in the usual IV arm (26/28, 92.8%, p=0.958). Patient satisfaction at day 5 was better in the routine PICC arm (97%, ‘a little comfort’ or ‘much comfort’) compared with the usual IV arm (21%) (p <0.001). Conclusion Routine PICC insertion in terminally ill cancer patients was comparable in safety and efficacy and resulted in superior satisfaction compared with usual IV access. Thus, routine PICC insertion could be considered at admission to the HPC unit.

Background: Multiple system atrophy (MSA) is a sporadic neurodegenerative disease characterized by various combinations of parkinsonism, cerebellar ataxia, autonomic dysfunction and pyramidal signs. Two clinical subtypes are recognized: MSA with predominant cerebellar ataxia (MSA-C) and MSA with predominant parkinsonism (MSA-P). The aim of this study was to compare pathological features between MSA-C and MSA-P. Methods: Two autopsy confirmed cases with MSA were included from the Pusan National University Hospital Brain Bank. Case 1 had been clinically diagnosed as MSA-C and case 2 as MSA-P. The severity of neuronal loss and gliosis as well as the glial and neuronal cytoplasmic inclusions were semiquantitatively assessed in both striatonigral and olivopontocerebellar regions. Based on the grading system, pathological phenotypes of MSA were classified as striatonigral degeneration (SND) predominant (SND type), olivopontocerebellar degeneration (OPC) predominant (OPC type), or equivalent SND and OPC pathology (SND=OPC type). Results: Both cases showed widespread and abundant α-synuclein positive glial cytoplasmic inclusions in association with neurodegenerative changes in striatonigral or olivopontocerebellar structures, leading to the primary pathological diagnosis of MSA. Primary age-related tauopathy was incidentally found but Lewy bodies were not in both cases. The pathological phenotypes of MSA were MSA-OPC type in case 1 and MSA-SND=OPC type in case 2. Conclusions Our data suggest that clinical phenotypes of MSA reflect the pathological characteristics.

Purpose: Thrombocytopenia (platelet count <150×103 /μL) is associated with poor outcomes in various critical illness settings. However, the prognostic value of platelet count in patients with cardiogenic shock (CS) remains unclear. Materials and Methods: We enrolled 1202 patients between January 2014 and December 2018 from a multicenter retrospective– prospective cohort registry of CS. Clinical characteristics and treatment outcomes were compared between the patients with and without thrombocytopenia. Results: At presentation with CS, 244 (20.3%) patients had thrombocytopenia. The patients with thrombocytopenia had lower blood pressure, hemoglobin level, and worse liver and renal functions compared to the patients without. During hospitalization, the patients with thrombocytopenia had more frequent gastrointestinal bleeding (10.5% vs. 3.8%, p=0.009), sepsis (8.3% vs. 2.6%, p=0.013), requirement of renal replacement therapy (36.5% vs. 18.9%, p<0.001), requirement of mechanical ventilation (65.2% vs.54.4%, p=0.003), longer intensive care unit stay (8 days vs. 4 days, p<0.001), and thirty-day mortality (40.2% vs. 28.5%, p<0.001) compared to those without. In addition, the platelet count was an independent predictor of 30-day mortality (per 103 /µL decrease; adjusted hazard ratio: 1.002, 95% confidence interval: 1.000–1.003, p=0.021). Conclusion Thrombocytopenia at CS presentation was associated with worse clinical findings, higher frequencies of complications, and longer stay at the intensive care unit. Also, thrombocytopenia was independently associated with increased 30-day mortality.(Clinical trial registration No. NCT02985008).

BACKGROUND: The pain-relief properties of tricyclic antidepressants can be attributed to several actions. Recent observations suggest that adenosine is involved in the antinociceptive effect of amitriptyline. The A3 adenosine receptor (A3AR) is the only adenosine subtype overexpressed in inflammatory and cancer cells. This study was performed to investigate the role of A3AR in the anti-nociceptive effect of amitriptyline. METHODS: Spinal nerve-ligated neuropathic pain was induced by ligating the L5 and L6 spinal nerves of male Sprague-Dawley rats. The neuropathic rats were randomly assigned to one of the following three groups (8 per group): a neuropathic pain with normal saline group, a neuropathic pain with amitriptyline group, and a neuropathic pain with amitriptyline and 3-ethyl-5-benzyl- 2-methyl-4-phenylethynyl-6-phenyl-1,4-(±)-dihydropyridine-3,5-dicarboxylate (MRS) group. Amitriptyline or saline was administered intraperitoneally and 3-ethyl-5-benzyl-2-methyl-4-phenylethynyl-6-phenyl-1,4-(±)-dihydropyridine-3,5-dicarboxylate (MRS-1191), an A3AR antagonist, was injected subcutaneously immediately before amitriptyline administration. The level of extracellular signal-regulated kinase P44/42 (ERK1/2), cyclic AMP response element-binding protein (CREB), and proinflammatory cytokines were assessed using immunoblotting or reverse-transciption polymerase chain reaction. RESULTS: Amitriptyline increased the mechanical withdrawal threshold of the neuropathic rats. The level of phospho-ERK1/2 and phospho-CREB proteins, and proinflammatory cytokines produced by spinal nerve ligation were significantly reduced by amitriptyline administration. However, the use of MRS-1191 before amitriptyline administration not only reduced the threshold of mechanical allodynia, but also increased the signaling protein and proinflammatory cytokine levels, which were reduced by amitriptyline. CONCLUSIONS: The results of this study suggest that the anti-nociceptive effect of amitriptyline involves the suppression of ERK1/2 and CREB signaling proteins, and A3AR activation also affects the alleviation of the inflammatory response.
Adenosine ; Amitriptyline ; Animals ; Antidepressive Agents, Tricyclic ; Cyclic AMP Response Element-Binding Protein ; Cytokines ; Humans ; Hyperalgesia ; Immunoblotting ; Ligation ; Male ; Neuralgia ; Phosphotransferases ; Polymerase Chain Reaction ; Rats ; Rats, Sprague-Dawley ; Receptors, Purinergic P1 ; Spinal Nerves

We present a case of spontaneous rupture of hepatocellular carcinoma with poor liver function managed by transcatheter arterial embolization (TAE). The patient's bilirubin level was 2.1 mg/dL, albumin level was 2.4 g/dL, and prothrombin time international normalized ratio was 2.1. In addition, the patient had also developed a large number of ascites. The tumor was supplied by the right renal capsular artery, as observed on angiography. With successful TAE, no hepatic failure occurred. We believe TAE can be a safe and effective treatment option, even in patients with poor liver function, if tumors are supplied only by extrahepatic collateral vessels.
Angiography ; Arteries ; Ascites ; Bilirubin ; Carcinoma, Hepatocellular ; Humans ; International Normalized Ratio ; Liver ; Liver Failure ; Prothrombin Time ; Rupture, Spontaneous

BACKGROUND: The pain-relief properties of tricyclic antidepressants can be attributed to several actions. Recent observations suggest that adenosine is involved in the antinociceptive effect of amitriptyline. The A3 adenosine receptor (A3AR) is the only adenosine subtype overexpressed in inflammatory and cancer cells. This study was performed to investigate the role of A3AR in the anti-nociceptive effect of amitriptyline. METHODS: Spinal nerve-ligated neuropathic pain was induced by ligating the L5 and L6 spinal nerves of male Sprague-Dawley rats. The neuropathic rats were randomly assigned to one of the following three groups (8 per group): a neuropathic pain with normal saline group, a neuropathic pain with amitriptyline group, and a neuropathic pain with amitriptyline and 3-ethyl-5-benzyl- 2-methyl-4-phenylethynyl-6-phenyl-1,4-(±)-dihydropyridine-3,5-dicarboxylate (MRS) group. Amitriptyline or saline was administered intraperitoneally and 3-ethyl-5-benzyl-2-methyl-4-phenylethynyl-6-phenyl-1,4-(±)-dihydropyridine-3,5-dicarboxylate (MRS-1191), an A3AR antagonist, was injected subcutaneously immediately before amitriptyline administration. The level of extracellular signal-regulated kinase P44/42 (ERK1/2), cyclic AMP response element-binding protein (CREB), and proinflammatory cytokines were assessed using immunoblotting or reverse-transciption polymerase chain reaction. RESULTS: Amitriptyline increased the mechanical withdrawal threshold of the neuropathic rats. The level of phospho-ERK1/2 and phospho-CREB proteins, and proinflammatory cytokines produced by spinal nerve ligation were significantly reduced by amitriptyline administration. However, the use of MRS-1191 before amitriptyline administration not only reduced the threshold of mechanical allodynia, but also increased the signaling protein and proinflammatory cytokine levels, which were reduced by amitriptyline. CONCLUSIONS The results of this study suggest that the anti-nociceptive effect of amitriptyline involves the suppression of ERK1/2 and CREB signaling proteins, and A3AR activation also affects the alleviation of the inflammatory response.

We aimed to compare fentanyl, remifentanil and dexmedetomidine with respect to hemodynamic stability, postoperative pain control and achievement of sedation at the postanesthetic care unit (PACU). In this randomized double-blind study, 90 consecutive total laparoscopic hysterectomy patients scheduled for elective surgery were randomly assigned to receive fentanyl (1.0 µg/kg) over 1 minute followed by a 0.4 µg/kg/hr infusion (FK group, n = 30), or remifentanil (1.0 µg/kg) over 1 minute followed by a 0.08 µg/kg/min infusion (RK group, n = 30), or dexmedetomidine (1 µg/kg) over 10 minutes followed by a 0.5 µg/kg/hr infusion (DK group, n = 30) initiating at the end of main procedures of the operation to the time in the PACU. A single dose of intravenous ketorolac (30 mg) was given to all patients at the end of surgery. We respectively evaluated the pain VAS scores, the modified OAA/S scores, the BIS, the vital signs and the perioperative side effects to compare the efficacy of fentanyl, remifentanil and dexmedetomidine. Compared with other groups, the modified OAA/S scores were significantly lower in DK group at 0, 5 and 10 minutes after arrival at the PACU (P < 0.05), whereas the pain VAS and BIS were not significantly different from other groups. The blood pressure and heart rate in the DK group were significantly lower than those of other groups at the PACU (P < 0.05). DK group, at sedative doses, had the better postoperative hemodynamic stability than RK group or FK group and demonstrated a similar effect of pain control as RK group and FK group with patient awareness during sedation in the PACU. (World Health Organization registry, KCT0001524).
Blood Pressure ; Dexmedetomidine* ; Double-Blind Method ; Fentanyl* ; Heart Rate ; Hemodynamics* ; Humans ; Hysterectomy ; Ketorolac ; Pain, Postoperative* ; Vital Signs

Approximately 15% of patients with frontotemporal dementia (FTD) have co-occurring motor neuron disease (MND). FTD-MND cases have frontotemporal lobar degeneration (FTLD)-transactive response DNA-binding protein (TDP) pathology, which is divided into four subtypes (types A, B, C, and D) based on the morphological appearance, cellular location, and distribution of the abnormal TDP inclusions and dystrophic neurites. We report a patient with FTD-MND whose pathological diagnosis was FTLD-TDP type B. This is the first documented autopsy-confirmed case of FTD-MND in Korea.
Autopsy* ; Diagnosis ; Frontotemporal Dementia* ; Frontotemporal Lobar Degeneration ; Humans ; Korea ; Motor Neuron Disease* ; Motor Neurons* ; Neurites ; Pathology