False Liver Metastasis by Positron Emission Tomography/Computed Tomography Scan after Chemoradiotherapy for Esophageal Cancer-Potential Overstaged Pitfalls of Treatment.

In patients with esophageal cancer undergoing neoadjuvant chemoradiotherapy (nCRT), subsequent restaging with F-18-fluorodeoxyglucose (18F-FDG) positron emission tomography-computed tomography (PET-CT) can reveal the presence of interval metastases, such as liver metastases, in approximately 10% of cases. Nevertheless, it is not uncommon in clinical practice to observe focal FDG uptake in the liver that is not associated with liver metastases but rather with radiation-induced liver injury (RILI), which can result in the overstaging of the disease. Liver radiation damage is also a concern during distal esophageal cancer radiotherapy due to its proximity to the left liver lobe, typically included in the radiation field. Post-CRT, if FDG activity appears in the left or caudate liver lobes, a thorough investigation is needed to confirm or rule out distant metastases. The increased FDG uptake in liver lobes post-CRT often presents a diagnostic dilemma. Distinguishing between radiation-induced liver disease and metastasis is vital for appropriate patient management, necessitating a combination of imaging techniques and an understanding of the factors influencing the radiation response. Diagnosis involves identifying new foci of hepatic FDG avidity on PET/CT scans. Geographic regions of hypoattenuation on CT and well-demarcated regions with specific enhancement patterns on contrast-enhanced CT scans and MRI are characteristic of radiation-induced liver disease (RILD). Lack of mass effect on all three modalities (CT, MRI, PET) indicates RILD. Resolution of abnormalities on subsequent examinations also helps in diagnosing RILD. Moreover, it can also help to rule out occult metastases, thereby excluding those patients from further surgery who will not benefit from esophagectomy with curative intent.

A modified procedure of T-tube maneuver to treat tracheal total obstruction involving ablative bronchoscopy sparing open surgical intervention.

Objectives: The study objectives were to test an innovative T-tube procedure involving ablative bronchoscopy for the treatment of total airway occlusion and to orchestrate a safe and nontraumatic maneuver to treat intricate subglottic stenosis amenable for substituting the conventional surgical intervention. Methods: This was an uncontrolled single-center cohort study on 1254 patients from January 2001 to June 2021. Patients underwent the modified T-tube procedure treatment for tracheal stenosis. Only 42 patients were included in the study because they had full records for subglottic total occlusion sitting tracheostomy. The ablative bronchoscopy, aided by a fixed suspending laryngoscope, was applied to retunnel their total airway occlusion. T-tube revision and removal were conducted under general anesthesia with laryngeal mask airway aid during follow-up. Results: The primary outcome was 90-day mortality. The secondary outcome was 90-day morbidity. The 42 patients included in the study had a mean age of 52.29 years (range, 9-84 years) with 22 men (52.38%). Their mean length of hospital stay was 13.67 days (range, 2-45 days). Their mean operation time was 73 minutes (range, 43-256 minutes). Their mean length of the tracheal stenosis was 2.8 cm (range, 0.8-6.3 cm). Outcomes were good in 29 patients (69.05%), satisfactory in 10 patients (23.81%), and considered failures in 3 patients (7.14%). A total of 16 patients (38.10%) underwent decannulation, and 3 patients (7.14%) were shifted to a Shiley tracheostomy. All 42 patients had a median follow-up of 6.2 years (range, 1.5-16.3 years). Conclusions: The modified T-tube procedure, which offered both resilience and versatility, improved the conventional technique in treating those patients experiencing total tracheal stenosis and who were unqualified for conventional open surgery.

Feasibility of in situ chondrogenesis for the entire umbilical cord in preliminary preparation for tracheal graft.

BACKGROUND: There remains a scarcity of both autografts and allografts for tracheal transplantation after long-segmental resection. Subsequently, tissue engineering has become a promising alternative for tracheal transplantation, which requires successful in vitro chondrogenesis. METHODS: To optimize the protocol for in situ chondrogenesis using the pig-derived whole Umbilical Cord (UC) as the starting material, it must be performed without using the UC-multipotent stromal cell (MSCs) isolation procedure. Nevertheless, chondrogenic induction is performed under a variety of conditions; with or without TGF-ß1 at different concentrations, and also in combination with either a rotatory or hollow organ bioreactor. The engineered explant sections were analyzed using various histochemical and immunohistochemical stains to assess the expression of chondrocyte markers. Cell viability was determined through use of the APO-BrdU TUNEL assay kit. RESULTS: The results showed that culture conditions induced heterogeneous chondrogenesis in various compartments of the UC. Moreover, explants cultured with 10 ng/ml TGF-ß1 under hypoxic (1% O2) in combination with a bioreactor, significantly enhanced the expression of aggrecan and type II collagen, but were lacking in the production of Glycosaminoglycans (GAGs), as evidenced by alcian blue staining. We speculated that whole segment UCs allowed for the differentiation into premature chondrocytes in our tissue-engineered environments. CONCLUSION: This study has provided exciting preliminary evidence showing that a stem cell-rich UC wrapped around an anatomical tracheal scaffold and implanted in vivo can induce nodes of new cartilage growth into a structurally functional tissue for the repairing of long-segmental tracheal stenosis.

De novo cartilage growth after implantation of a 3-D-printed tracheal graft in a porcine model.

BACKGROUND: Experiments were conducted on the assumption that vivid chondrogenesis would be boosted in vivo following previously preliminary chondrogenesis in a mesenchymal stem cell (MSC)-rich entire umbilical cord (UC) in vitro. METHODS: Virtual 3-D tracheal grafts were generated by using a profile obtained by scanning the native trachea of the listed porcine. Although the ultimate goal was the acquisition of a living specimen beyond a 3-week survival period, the empirical results did not meet our criteria until the 10th experiment, ending with the sacrifice of the animal. The categories retrospectively evolved from post-transplant modification due to porcine death using 4 different methods of implantation in chronological order. For each group, we collected details on graft construction, clinical outcomes, and results from both gross and histology examinations. RESULTS: Three animals died due to tracheal complications: one died from graft crush, and two died secondary to erosion of the larger graft into the great vessels. It appeared that the remaining 7 died of tracheal stenosis from granulation tissue. Ectopic de novo growth of neocartilage was found in three porcine subjects. In the nearby tissues, we detected neocartilage near the anastomosis containing interim vesicles of the vascular canals (VCs), perichondrial papillae (PPs) and preresorptive layers (PRLs), which were investigated during the infancy of cartilage development and were first unveiled in the tracheal cartilage. CONCLUSIONS: 3-D-printed anatomically precise grafts could not provide successful transplantation with stent-sparing anastomosis; nonetheless, de novo cartilage regeneration in situ appears to be promising for tracheal graft adaptability. Further graft refinement and strategies for managing granulated tissues are still needed to improve graft outcomes.

Quantitative structure-activity relationships for the pre-steady state acetylcholinesterase inhibition by carbamates.

4-Nitrophenyl-N-substituted carbamates (1) are characterized as pseudosubstrate inhibitors of acetylcholinesterase. The first step is formation of the enzyme-inhibitor tetrahedral intermediate with the inhibition constant (Ki), the second step is formation of the carbamyl enzyme with the carbamylation constant (kc), and the third step is hydrolysis of the carbamyl enzyme with decarbamylation constant (kd). According to pre-steady state kinetics the Ki step is divided further into two steps: (1) formation of the enzyme-inhibitor complex with the dissociation constant (KS) and (2) formation of the enzyme-inhibitor tetrahedral intermediate from the complex with the equilibrium constant (k2/k-2). Since the inhibitors are protonated in pH 7.0 buffer solution, the virtual dissociation constant (KS') of the enzyme-protonated inhibitor complex can be calculated from the equation, -log KS'=-log KS-pKa + 14. The -logKS, -log KS', log k2, and log k-2 values are multiply linearly correlated with the Jave equation (log(k/k0)=rho*sigma* + deltaEs + psi pi). For -log KS'-sigma*-Es)pi-correlation, the rho* value of -0.4 indicates that the enzyme-protonated inhibitor complexes have more positive charges than the protonated inhibitors, the delta value of 0.44 suggests that the bulkily substituted inhibitors lessen the reaction due to the difficulty of the inhibitors to enter the narrow enzyme active site gorge, and the psi value of 0.27 implies that the inhibitors with hydrophobic substituents accelerate the inhibitors entering the active site gorge of the enzyme. For log k2/k-2,-sigma*-Es-pi-correlation, the rho* value of 1.1 indicates that the enzyme-protonated inhibitor tetrahedral intermediates have more negative charges than the enzyme-protonated inhibitor complexes, the delta value of 0.15 suggests that the bulkily substituted inhibitors are difficult to bind into a small acyl binding site of the enzyme, and the psi value of -0.3 implies that the inhibitors with hydrophobic substituents resist binding to the hydrophilic acyl binding site of the enzyme.