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Cureus Nov 2022Malignant peripheral nerve sheath tumors (MPNST) are a rare form of sarcoma derived from Schwann cells. Major risk factors for development are neurofibromatosis 1 (NF1)...
Malignant peripheral nerve sheath tumors (MPNST) are a rare form of sarcoma derived from Schwann cells. Major risk factors for development are neurofibromatosis 1 (NF1) and prior radiation exposure. Tumor location is highly variable. We present a case of an extremely large MPNST tumor in the anterior mediastinum in a 66-year-old male. To the best of our knowledge, the 20.5 cm tumor is the first of its kind in a patient without clinical signs of NF1 or prior radiation exposure. The localization of this tumor to the anterior mediastinum is rarer, as the most common tumors presenting in this area are thyroid neoplasms, thymomas, teratomas, and lymphomas. The patient's tumor responded to doxorubicin-ifosfamide-mesna-based therapy. The tumor decreased from 20.5 cm to 9.0 cm on subsequent imaging. Thus, this is an interesting and valuable case to learn about the presentation and potential treatments of such a rare pathology.
PubMed: 36514670
DOI: 10.7759/cureus.31299 -
Frontiers in Oncology 2022Hepatic undifferentiated embryonal sarcoma of the liver (UESL) is a rare hepatic malignancy found more commonly in pediatric patients. It has been associated with poor...
Hepatic undifferentiated embryonal sarcoma of the liver (UESL) is a rare hepatic malignancy found more commonly in pediatric patients. It has been associated with poor outcomes in adults and the role and timing of systemic therapy is unclear. There have been very few case reports detailing combination neoadjuvant and adjuvant chemotherapy use for hepatic undifferentiated embryonal sarcoma in adults. In this report, a 22-year-old male admitted with right upper quadrant pain was diagnosed with a 20 x 10 x 10 cm well-circumscribed, highly vascularized hepatic mass in the entirety of the left lobe. Biopsy confirmed the diagnosis of UESL. PET/CT showed no evidence of metastatic disease, and he received four cycles of Doxorubicin and Ifosfamide with demonstrated reduction in size and decrease in PET avidity. He underwent left hepatectomy with periportal lymphadenectomy, cholecystectomy, and partial gastrectomy with negative margins and received adjuvant Doxorubicin, Ifosfamide and Mesna. At 48 months, the patient was alive without evidence of disease. We hereby emphasize the potential advantages of combination chemotherapy and surgical resection in the management of UESL in adults.
PubMed: 36465387
DOI: 10.3389/fonc.2022.1004108 -
Annals of Medicine and Surgery (2012) Nov 2022Spine surgery and spinal fusion surgery are rising. Revision rates following initial surgery are between 8 and 45%. Epidural fibrosis is a common response to spine...
UNLABELLED
Spine surgery and spinal fusion surgery are rising. Revision rates following initial surgery are between 8 and 45%. Epidural fibrosis is a common response to spine surgery for most patients and increases complications in revision surgery. Previous research suggests using MESNA (Sodium 2-mercaptoethane sulfonate) in combination with mechanical blunt dissection safely reduces surgical complications. MESNA is a mucolytic agent which selectively cleaves disulphide bonds involved in the adherence and strength of fibrosis, meaning cutting instruments are not needed. The Chemically Assisted DISSection (CADISS®) System is an optimised non-cutting surgical device, consisting of a reconstitution cartridge for MESNA preparation, irrigated surgical instruments, and a footswitch to control MESNA release. This is the first study to investigate the use of the CADISS® System in revision spine surgery.
METHODS
This was a prospective, open label, observational case study. We enrolled 21 patients for revision spine surgery with the CADISS® System at two Belgium sites. The primary assessment was the number of successful removals of epidural fibrosis without cutting. The amount of MESNA used, total dissection and procedure time were recorded. For secondary criterion, the surgeons assessed global satisfaction, facilitation of dissection, quickness of action, usability, bleeding reduction and visualisation of the cleavage plane using an 11-point Likert scale (0-10). Due to the exploratory nature, no formal statistical analysis was planned. We calculated the percentage and confidence interval of successful procedures, the medians and corresponding interquartile range of the Likert criterion, and the mean (±SD) of the amount of MESNA used, CADISS® dissection time and total procedure time.
RESULTS
24 fibrosis dissections were performed in 19 patients and 23 were successful (95.8%, CI: 78.9%; 99.9%). The mean amount of MESNA used, mean dissection time and procedure time were 16 ml (±4.94), 16.5 min (±16.1) and 86.3 min (±25.1), respectively. No dural tears were reported. The mean global satisfaction score was 9.0 (8.0-9.0). All other Likert criterion had scores of 8.0 or 9.0, excluding quickness of action, which scored 7.0 (6.0-9.0).
CONCLUSIONS
The CADISS® System in revision spine surgery has potential to effectively reduce dissection complications.
PubMed: 36389182
DOI: 10.1016/j.amsu.2022.104718 -
Surgical Endoscopy Dec 2022The CADISS® system combines the use of a topical formulation of mesna (sodium 2-Mercaptoethane sulfonate) to facilitate selective dissection of pathological and... (Clinical Trial)
Clinical Trial
BACKGROUND
The CADISS® system combines the use of a topical formulation of mesna (sodium 2-Mercaptoethane sulfonate) to facilitate selective dissection of pathological and fibrotic tissues with a non-cutting instrument for a safer dissection. A prospective, multi-site, clinical trial was performed to explore the use of the CADISS® system in laparoscopic cholecystectomy for acute cholecystitis.
METHODS
A total of 15 patients were enrolled at different severity stages of pathology according to Tokyo classification. They were operated on prior to, or after 72 h of, the onset of symptoms. The primary measure was the number of critical dissection steps successfully achieved using the CADISS® system without cutting instruments.
RESULTS
Five patients were operated on before 72 h of symptom onset and ten after. All the dissections were successfully achieved using the CADISS® method. No mortality was recorded. No conversion to open surgery was performed. No bile duct injury was observed. Other endpoints (facilitation of dissection of critical structures, identification of cleavage planes and reduction of risk) had scores of above nine on our Likert scale. Four postoperative serious adverse events including cholangitis, fever, pulmonary embolism and right hepatic artery pseudoaneurysm were reported. However, they seemed to be more related to cholecystitis or local conditions rather than the use of the CADISS® method.
CONCLUSION
This is the first study to investigate the use of the CADISS® System in cholecystectomy. The CADISS® system seemed to facilitate dissection in acute cholecystitis. Encouraging results are reported independently of the severity grade of cholecystitis and the delay in performing the surgery. Even now, laparoscopic cholecystectomy for acute cholecystitis remains a surgical challenge. Techniques that could facilitate this operation and reduce surgical complications may be helpful. Further studies should be conducted to confirm our preliminary results. Trial registration Clinical trials.gov NCT05041686.
Topics: Humans; Acute Disease; Cholecystectomy; Cholecystectomy, Laparoscopic; Cholecystitis; Cholecystitis, Acute; Prospective Studies
PubMed: 36319896
DOI: 10.1007/s00464-022-09616-w -
Communications Biology Oct 2022Methanogens and anaerobic methane-oxidizing archaea (ANME) are important players in the global carbon cycle. Methyl-coenzyme M reductase (MCR) is a key enzyme in methane...
Methanogens and anaerobic methane-oxidizing archaea (ANME) are important players in the global carbon cycle. Methyl-coenzyme M reductase (MCR) is a key enzyme in methane metabolism, catalyzing the last step in methanogenesis and the first step in anaerobic methane oxidation. Divergent mcr and mcr-like genes have recently been identified in uncultured archaeal lineages. However, the assembly and biochemistry of MCRs from uncultured archaea remain largely unknown. Here we present an approach to study MCRs from uncultured archaea by heterologous expression in a methanogen, Methanococcus maripaludis. Promoter, operon structure, and temperature were important determinants for MCR production. Both recombinant methanococcal and ANME-2 MCR assembled with the host MCR forming hybrid complexes, whereas tested ANME-1 MCR and ethyl-coenzyme M reductase only formed homogenous complexes. Together with structural modeling, this suggests that ANME-2 and methanogen MCRs are structurally similar and their reaction directions are likely regulated by thermodynamics rather than intrinsic structural differences.
Topics: Archaea; Mesna; Oxidoreductases; Methane
PubMed: 36266535
DOI: 10.1038/s42003-022-04057-6 -
Cancer Reports (Hoboken, N.J.) Nov 2022Ewing sarcoma (ES), the second most common malignant bone tumor after osteosarcoma in the second decade, occurs in 0.9% of cases as the primary non-sacral form.
BACKGROUND
Ewing sarcoma (ES), the second most common malignant bone tumor after osteosarcoma in the second decade, occurs in 0.9% of cases as the primary non-sacral form.
CASE
A 20-years-old male presented with acute paraparesis of bilateral lower limb and numbness following initial back pain for the last 6 months. Magnetic resonance imaging (MRI) of the lumbar spine revealed a 4 cm enhancing soft tissue mass at the L4/L5 vertebra extending into the spinal canal with compression of the thecal sac. The computed tomography (CT) of the chest, abdomen, and pelvis revealed aggressive lytic lesions in the L4 spinous process with soft tissue extension into the spinal canal with no other site of distant metastasis. He was treated with IV steroids (Injection dexamethasone 10 mg IV followed by 4 mg tablet dexamethasone q6h; subsequently tapered off). A core needle biopsy showed a small, round blue cell neoplasm, (suggestive of a primitive neuroectodermal) stained positive for CD99 and vimentin stain. The diagnosis of ES lumbar spine was made which was treated with surgical resection with an appropriate margin measuring 8 × 4.5 × 2.5 cm with decompression and L4/5 laminectomies, which had a negative margin in the surgical pathology report. Concomitant local radiotherapy and chemotherapy [cycles of vincristine 2 mg/m , adriamycin/doxorubicin 75 mg/m , cyclophosphamide 1200 mg/m (VDC) with mesna rescue alternating with cycles of ifosfamide 1800 mg/m and etoposide 100 mg/m (IE)] was started. The motor strength was regained gradually with preserved spine biomechanics and oncological control with no recurrence in 2-year follow-ups.
CONCLUSIONS
The presentation of lumbar ES can vary from local pain and swelling to acute paraparesis. Timely diagnosis and treatment with multimodal therapy, namely, steroids for acute spinal cord compression and surgery with chemoradiotherapy for ES can improve spinal biomechanics and oncological control.
Topics: Humans; Male; Young Adult; Adult; Sarcoma, Ewing; Bone Neoplasms; Neoplasms, Second Primary; Spine; Paraparesis; Dexamethasone
PubMed: 36193025
DOI: 10.1002/cnr2.1725 -
Current Opinion in Otolaryngology &... Dec 2022The management of paediatric patients with cholesteatoma is complex, as the disease process is more aggressive in children than adults. New technologies and practice... (Review)
Review
PURPOSE OF REVIEW
The management of paediatric patients with cholesteatoma is complex, as the disease process is more aggressive in children than adults. New technologies and practice adaptations currently help optimize the surgical management and monitoring of these challenging patients.
RECENT FINDINGS
Several options of surgical management are available and are associated with equal if not improved outcomes. Technologic advancements in endoscopic ear surgery, the discovery of chemical-assisted dissection of cholesteatoma and advanced imaging protocols have enabled surgeons to better care for patients with this complex disease process.
SUMMARY
The advances in endoscopic ear surgery, the discovery of Mesna as a chemically assisted dissection agent to improve recidivism rates and the use of specific diffusion-weighted MRI protocols enable the otologic surgeon to better care for these paediatric patients.
Topics: Adult; Child; Humans; Cholesteatoma, Middle Ear; Treatment Outcome; Otologic Surgical Procedures; Mesna; Diffusion Magnetic Resonance Imaging
PubMed: 36165030
DOI: 10.1097/MOO.0000000000000850 -
Proceedings of the National Academy of... Sep 2022Mercaptoethane sulfonate or coenzyme M (CoM) is the smallest known organic cofactor and is most commonly associated with the methane-forming step in all methanogenic...
Mercaptoethane sulfonate or coenzyme M (CoM) is the smallest known organic cofactor and is most commonly associated with the methane-forming step in all methanogenic archaea but is also associated with the anaerobic oxidation of methane to CO in anaerobic methanotrophic archaea and the oxidation of short-chain alkanes in species. It has also been found in a small number of bacteria capable of the metabolism of small organics. Although many of the steps for CoM biosynthesis in methanogenic archaea have been elucidated, a complete pathway for the biosynthesis of CoM in archaea or bacteria has not been reported. Here, we present the complete CoM biosynthesis pathway in bacteria, revealing distinct chemical steps relative to CoM biosynthesis in methanogenic archaea. The existence of different pathways represents a profound instance of convergent evolution. The five-step pathway involves the addition of sulfite, the elimination of phosphate, decarboxylation, thiolation, and the reduction to affect the sequential conversion of phosphoenolpyruvate to CoM. The salient features of the pathway demonstrate reactivities for members of large aspartase/fumarase and pyridoxal 5'-phosphate-dependent enzyme families.
Topics: Anaerobiosis; Archaea; Bacteria; Coenzymes; Euryarchaeota; Mesna; Methane; Oxidation-Reduction; Phosphates
PubMed: 36037354
DOI: 10.1073/pnas.2207190119 -
Viruses Aug 2022Flavivirus infections, such as those caused by dengue and West Nile viruses, emerge as new challenges for the global healthcare sector. It has been found that these two...
Flavivirus infections, such as those caused by dengue and West Nile viruses, emerge as new challenges for the global healthcare sector. It has been found that these two viruses encode ion channels collectively termed viroporins. Therefore, drug molecules that block such ion-channel activity can serve as potential antiviral agents and may play a primary role in therapeutic purposes. We screened 2839 FDA-approved drugs and compounds in advanced experimental phases using three bacteria-based channel assays to identify such ion channel blockers. We primarily followed a negative genetic screen in which the channel is harmful to the bacteria due to excessive membrane permeabilization that can be relieved by a blocker. Subsequently, we cross-checked the outcome with a positive genetic screen and a pH-dependent assay. The following drugs exhibited potential blocker activities: plerixafor, streptomycin, tranexamic acid, CI-1040, glecaprevir, kasugamycin, and mesna were effective against dengue virus DP1. In contrast, idasanutlin, benzbromarone, 5-azacytidine, and plerixafor were effective against West Nile Virus MgM. These drugs can serve as future antiviral therapeutic agents following subsequent in vitro and in vivo efficacy studies.
Topics: Antiviral Agents; Dengue; Hematopoietic Stem Cell Mobilization; Heterocyclic Compounds; Humans; Viroporin Proteins; West Nile Fever; West Nile virus
PubMed: 36016372
DOI: 10.3390/v14081750 -
Cancer Reports (Hoboken, N.J.) Oct 2022Leiomyosarcoma (LMS) is an aggressive soft tissue sarcoma that is derived from smooth muscles. Ifosfamide is in use for advanced metastatic LMS.
BACKGROUND
Leiomyosarcoma (LMS) is an aggressive soft tissue sarcoma that is derived from smooth muscles. Ifosfamide is in use for advanced metastatic LMS.
CASE
A-44-years old woman with a chief complaint of pain in the epigastric area, itching, coughing, nausea, and vomiting was referred to the emergency department. Her medical history was LMS. She had taken Ifosfamide and mesna in her last chemotherapy. Seventy percent of her liver and her left kidney were removed 4 years ago to prevent the progress of the disease. Because of the increase in the level of creatinine and urea in the initial laboratory report, a Shaldon catheter was inserted for the patient, and she was under emergency dialysis for 3 h. In addition, during the six-day hospitalization period, dialysis was done two times. Finally, the patient was discharged with improved clinical tests accompanied by a twice-weekly dialysis order.
CONCLUSION
Ifosfamide is metabolized into chloroacetaldehyde, which can cause acute kidney injury. Recovery from acute kidney injury may not always be perfect and can lead to some degree of chronic kidney disease. Opposite to hemorrhagic cystitis, mesna is not effective in preventing ifosfamide's nephrotoxicity and N-acetylcysteine may be effective in the prevention of this nephrotoxicity.
Topics: Acetylcysteine; Acute Kidney Injury; Creatinine; Female; Humans; Ifosfamide; Leiomyosarcoma; Mesna; Urea
PubMed: 35830327
DOI: 10.1002/cnr2.1666