Hepatocellular Carcinoma Differentiation: Research Progress in Mechanism and Treatment

Hepatocellular carcinoma (HCC) is the most common primary malignant tumor of the liver. Although progress has been made in diagnosis and treatment, morbidity and mortality continue to rise. Chronic liver disease and liver cirrhosis are still the most important risk factors for liver cancer. Although there are many treatments, it can only be cured by orthotopic liver transplantation (OLT) or surgical resection. And the worse the degree of differentiation, the worse the prognosis of patients with liver cancer. Then it can be considered that restoring a better state of differentiation may improve the prognosis. The differentiation treatment of liver cancer is to reverse the dedifferentiation process of hepatocytes to liver cancer cells by means of drugs, improve the differentiation state of the tumor, and restore the normal liver characteristics, so as to improve the prognosis. Understanding the mechanism of dedifferentiation of liver cancer can provide ideas for drug design. Liver enrichment of transcription factors, imbalance of signal pathway and changes of tumor microenvironment can promote the occurrence and development of liver cancer, and restoring its normal level can inhibit the malignant behavior of tumor. At present, some drugs have been proved to be effective, but more clinical data are needed to support the effectiveness and reliability of drugs. The differentiation treatment of liver cancer is expected to become an important part of the treatment of liver cancer in the future.

The praziquantel in preschoolers (PIP) trial: study protocol for a phase II PK/PD-driven randomised controlled trial of praziquantel in children under 4 years of age

Background Over 200 million individuals worldwide are infected with Schistosoma species, with over half of infections occurring in children. Many children experience first infections early in life and this impacts their growth and development; however praziquantel (PZQ), the drug used worldwide for the treatment of schistosomiasis, only has regulatory approval among adults and children over the age of four, although it is frequently used “off label” in endemic settings. Furthermore, pharmacokinetic/pharmacodynamics (PK/PD) evidence suggests the standard PZQ dose of 40 mg/kg is insufficient in preschool-aged children (PSAC). Our goal is to understand the best approaches to optimising the treatment of PSAC with intestinal schistosomiasis. Methods We will conduct a randomised, controlled phase II trial in a Schistosoma mansoni endemic region of Uganda and a Schistosoma japonicum endemic region of the Philippines. Six hundred children, 300 in each setting, aged 12–47 months with Schistosoma infection will be randomised in a 1:1:1:1 ratio to receive either (1) 40 mg/kg PZQ at baseline and placebo at 6 months, (2) 40 mg/kg PZQ at baseline and 40 mg/kg PZQ at 6 months, (3) 80 mg/kg PZQ at baseline and placebo at 6 months, or (4) 80 mg/kg PZQ at baseline and 80 mg/kg PZQ at 6 months. Following baseline treatment, children will be followed up for 12 months. The co-primary outcomes will be cure rate and egg reduction rate at 4 weeks. Secondary outcomes include drug efficacy assessed by novel antigenic endpoints at 4 weeks, actively collected adverse events and toxicity for 12 h post-treatment, morbidity and nutritional outcomes at 6 and 12 months, biomarkers of inflammation and environmental enteropathy and PZQ PK/PD parameters. Discussion The trial will provide valuable information on the safety and efficacy of the 80 mg/kg PZQ dose in PSAC, and on the impact of six-monthly versus annual treatment, in this vulnerable age group. Trial registration ClinicalTrials.gov NCT03640377. Registered on 21 Aug 2018.

Giant cell tumour of hand bones: outcomes of treatment

The purpose of this study was to report the incidence of giant cell tumour of the hand bones in an Asian population, document treatment options and report outcomes of treatment. Of 698 giant cell tumours of bone that underwent surgery between January 2011 and December 2020 at our institute, only 22 (3%) were in the hand. Fourteen occurred in the metacarpals, eight in the phalanges. Fifteen were primary tumours and seven had recurrent disease. Twenty lesions had an associated soft tissue component. Two patients treated for primary disease and one who had been treated for recurrence had local recurrence. Recurrence occurred in two of nine patients treated with curettage, one of three with resection and none of five with ray or digit amputation. Both curettage and resection/amputation are acceptable treatment options for the rare condition of giant cell tumour of bone in the hand, with a need to individualize treatment decisions based on the site and extent of disease to minimize treatment morbidity while maximizing disease control. Level of evidence: IV

A Matched Case Control Study of Surgically and Non-surgically Treated Patent Ductus Arteriosus in Extremely Pre-term Infants

Introduction: There are still uncertainties about the timing and indication for surgical ligation of patent ductus arteriosus (PDA) in pre-term infants, where lower gestational age (GA) usually is predictive for surgical treatment.Objective: Our aim was to assess differences in clinical characteristics and outcomes between surgically treated and matched non-surgically treated PDA in extremely pre-term infants.Methods: All extremely pre-term infants born 2010–2016 with surgically treated PDA (Ligated group; n = 44) were compared to non-surgically treated infants (Control group; n = 44) matched for gestational age (+/−1 week) and time of birth (+/−1 month). Perinatal parameters, echocardiographic variables, details of pharmacological PDA treatment, morbidity, and mortality were assessed.Result: Mean GA and birthweight were similar between the Ligated group (24+5 ± 1+3 weeks and 668 ± 170 g) and the Control group (24+5 ± 1+3 weeks and 704 ± 166 g; p = 1.000 and p = 0.319, respectively). Infants in the Ligated group had larger ductal diameters prior to pharmacological treatment, and lack of diameter decrease and PDA closure after treatment (p = 0.022, p = 0.043 and 0.006, respectively). Transfusions, post-natal steroids and invasive respiratory support were more common in the Ligated group. Except for a higher incidence of severe bronchopulmonary dysplasia (BPD) in the Ligated group there were no other differences in outcomes or mortality between the groups.Conclusion: Early large ductal diameter and reduced responsiveness to pharmacological treatment predicted the need for future surgical ligation in this matched cohort study of extremely pre-term infants where the effect of GA and differences in treatment strategies were excluded. Besides an increased incidence of severe BPD in the Ligated group, no other differences in morbidity or mortality were detected.

Risk of urinary morbidity associated with photoselective vaporization of the prostate (PVP) in prostate cancer patients undergoing a combined radiotherapy regimen consisting of dynamic adaptive radiotherapy (DART) and brachytherapy boost.

231 Background: Recent studies have shown PVPs to be associated with diminished perioperative and postoperative complications compared to transurethral resection of the prostate (TURP) for benign prostatic hyperplasia (BPH). This is the first study to evaluate the timing of PVP intervention and post-treatment morbidity related to a combined regimen of DART and Pd-103 brachytherapy for treatment of prostate cancer. Methods: Between 12/05 and 04/20, 51 consecutive patients underwent Greenlight Laser (GLL) or Olympus Plasma Button (OPB) PVP after DART (median dose: 45 Gy) and before Pd-103 brachytherapy (median dose: 90 Gy). 27 patients received GLL PVP and 24 patients received OPB PVP. Peripheral seed loading designs were utilized to achieve optimal urethral sparing. The time from DART to PVP ranged from 1 to 81 days (median: 18 days). For 12 patients, the interval between DART and PVP was ≤7 days. The time from PVP to seed implant ranged from 0 to 55 days (median: 18 days). For 13 patients, the interval between PVP and implant was ≤7 days. American Urological Association (AUA) symptom scores were compiled prior to PVP and on the last post-brachytherapy follow-up. Post-implant follow-up ranged from 6 months to 15 years (median: 6.4 years). Results: No patient experienced post-implant urinary retention or incontinence. Morbidity was limited to RTOG grade 1-2 symptoms, with the exception of one patient who experienced protracted dysuria, which was identified to be secondary to a pre-existing prostate anomaly (steep urethral curvature). Only that patient required dilation for urethral stricture. AUA scores improved or remained the same in 43 of 51 patients. Only 1 patient of the remaining 8 experienced an increase in AUA > 8 points. Conclusions: In our experience, there have been remarkably few adverse urinary sequelae following Pd-103 implantation in patients with prior PVP and DART. In contrast to TURPs, PVPs are safe even with short intervals between DART and brachytherapy. Based upon these results, pre-implant PVP is preferred, rather than PVPs or TURPs in the post-implant setting.

The First-Year Follow-Up of a Cleft Lip and Palate Patient Treated With Nasoalveolar Molding (NAM)

The objectives of pre-surgical orthopedics are to allow surgical repair with minimal tension of the involved tissues and less restriction to the craniofacial growth. The aim of this study was to evaluate the benefits of nasoalveolar model (NAM) as a pre-operative therapy in a patient with bilateral cleft lip and palate followed by labioplasty and palatoplasty. A 15-day-old patient underwent orthopedic treatment with NAM. After pre-operative treatment, retraction of the pre-maxilla was observed with reduction of the fissure. Due to the successful effects of NAM treatment the patient had a one-step surgery for lip correction. Six months later, due to lip pressure the fissure was further decreased. After six months, the patient underwent palatoplasty. Both surgeries contributed to the remaining closure of the fissure, which were reduced by half compared to the end of pre-operative treatment. The uses of NAM as a pre-operative treatment approached the alveolar segments, centralized the pre-maxilla, decreased the cleft palate resulting in a marked improvement of the arch and provide superior surgical results. In addition, it allows the primary repair of the patient’s lip with asymmetric bilateral fissure in only one-step surgery; in consequence, it will reduce treatment morbidity and decrease cost of treatment.

Management modalities of isolated liver injury in blunt abdominal trauma

Background: The liver is one of the most commonly injured organ in blunt abdominal trauma. Management of liver injury due to blunt abdominal trauma has been dramatically evolved in recent years. Dramatic change from operative management to non-operative management has improved survival in these patients, becoming the standard of care for most liver injuries.Methods: A retrospective study of the patients admitted with the diagnosis of isolated liver injury due to blunt abdominal trauma between 2013-2018. Data collected of 30 patients of isolated liver injury who either treated conservative management of operative management. Variable analyzed included demographic data, mechanism of injury, associated injury, conservative treatment, operative treatment, morbidity, mortality, and hospital stay.Results: A total of 30 patients were analyzed of isolated liver injury due to blunt abdominal trauma, 27 patient sustained minor liver injury (grade I, II and III), whereas 3 patients had major liver injury (grade IV, V and VI). 25 cases due to road traffic accident and 5 cases were due to falls from a height. 27 patients with American Association for the surgery of trauma grade I, II, III and 2 patients with grade IV, V managed conservatively, surgical intervention required in 1 patient with grade V, mortality occurred in 1 patient out of 29 who were treated conservatively.Conclusions: Isolated liver injury is common in the blunt abdominal trauma patient. Most of the patients with the liver injury with hemodynamically stable treated conservatively. Only a few of them require surgical management if they are hemodynamically unstable.

Poisoning by Brachiaria spp. in various lamb breeds at increasing levels of supplementation during growth

ABSTRACT: The study evaluate the frequency of poisoning by Brachiaria spp. at the rearing, growth and termination stages in various lamb breeds at increasing supplementation levels. Forty-five lambs were used in the growth phase in pastures of Brachiaria spp. with a history of having induced poisoning. The lambs were distributed in nutritional treatments: lambs receiving mineral supplementation (MS), energy/protein supplementation (EPS) at 0.8% of body weight (bw), EPS at 1.6% bw and EPS at 2.4% bw. The lambs were allotted two flocks (F1 and F2) of 21 and 24 lambs each. Clinical signs of poisoning were observed in all treatments. All MS lambs died. The frequency of poisoning were highest in the 0.8% EPS and 1.6% EPS treatments. All lambs in the 2.4% EPS treatment recovered. F1 lambs had a higher frequency of poisoning than F2 lambs regardless of nutritional treatment. Morbidity rates for the F1 and F2 lambs were 52.3 and 16.7%, respectively. Supplementation was not sufficient to decrease the frequency of poisoning in lambs at the termination stage, which was dependent on the genetic origin of the lambs. EPS of 2.4% bw treatment, was an efficient nutritional strategy to minimize the effects of poisoning in lambs fed on Brachiaria spp.

Neuroblastoma in a Neonate: A Case Report

Neuroblastoma represents approximately 6 to 10 percent of childhood cancers, yet is one of the most common solid tumors observed in neonates; approximately 700 cases are reported in the United States each year. Neuroblastoma occurs secondary to oncogene mutations that cause abnormal proliferation of neural crest cells and tumor formation anywhere along the spinal cord. Visible manifestations include a blueberry rash and subcutaneous skin nodules. Common histologic findings include multifocal, small, round, blue cell tumors. Cytogenetics testing differentiates aggressive versus nonaggressive forms of neuroblastoma. Treatment ranges from supportive care to surgery and chemotherapy; targeted molecular therapies and immunotherapy offer opportunity to individualize treatment. Morbidity and mortality are contingent upon age at diagnosis and genetic abnormalities. Neonatal clinicians must establish and maintain active knowledge of the current science pertaining to this neoplasm to assist in early identification and timely initiation of medical management. This article presents a case report and comprehensive discussion of the state of the science on metastatic familial (congenital) neuroblastoma.