What do we know about inflammatory myofibroblastic tumors? - A systematic review.

BACKGROUND: Inflammatory myofibroblastic tumors (IMTs) are rare intermediate-grade neoplasms that have a high recurrence rate after excision and exhibit low metastatic potential. These tumors contain proliferating neoplastic, fibroblastic and myofibroblastic cells, and are also characterized by chronic inflammatory infiltration by lymphocytes, plasma cells, eosinophils, and histiocytes. They belong to the group of inflammatory spindle cell lesions. Some reactive lesions, such as inflammatory pseudotumors, may appear to be IMTs, which makes their differential diagnosis extremely difficult. The aim of this article is to compile the recent information on IMTs to aid in their diagnosis and treatment. METHODS: We reviewed articles published between 2017 and 2021, which were selected from online medical databases. In addition, some earlier articles and latest scientific monographies were analyzed. RESULTS: The terminology used for inflammatory spindle cell lesions seems to be confusing. The terms "inflammatory myofibroblastic tumors" and "inflammatory pseudotumors" are interchangeably used by many scientists. However, a detailed analysis of the development of terminology suggests that the term "inflammatory myofibroblastic tumors" should be used to refer to a neoplastic lesion. CONCLUSIONS: IMTs are rare neoplasms, which have not been investigated in detail due to the difficulty in collecting a large number of cases. Thus, our knowledge about this disease remains unsatisfactory. Recently developed techniques such as next-generation sequencing and computer-aided histopathological diagnosis may be useful in understanding the etiopathology of IMTs, which will help in the selection of the most appropriate therapy for patients.

Adverse Events during Vitreoretinal Surgery under Adequacy of Anesthesia Guidance-Risk Factor Analysis.

Vitreoretinal surgeries require the administration of general anesthesia (GA) in selected groups of patients. The administration of intraoperative rescue narcotic analgesia (IRNA) during GA poses the risk of postoperative nausea and vomiting (PONV). The surgical pleth index (SPI), a crucial component of the adequacy of anesthesia (AoA) guidance of GA, optimizes the intraoperative titration of IRNA. The current analysis evaluated the risk factors for the occurrence of PONV and the oculo-cardiac reflex (OCR) in patients undergoing pars plana vitrectomy (PPV) under AoA guidance. In total, 175 patients undergoing PPV were randomly allocated to receive either GA with SPI-guided IRNA administration using fentanyl alone or in addition to different preoperative analgesia techniques. Any incidence of PONV or OCR was recorded. Obesity, overweight, smoking status, motion sickness, postoperative intolerable pain perception, female gender, fluid challenge and arterial hypertension did not correlate with an increased incidence of PONV or OCR under AoA guidance. Diabetes mellitus, regardless of insulin dependence, was found to correlate with the increased incidence of PONV. The AoA regimen including SPI guidance of IRNA presumably created similar conditions for individual subjects, so no risk factors of the occurrence of PONV or OCR were found, except for diabetes mellitus. We recommend using AoA guidance for GA administration to reduce OCR and PONV rates.

Adequacy of Anesthesia and Pupillometry for Endoscopic Sinus Surgery.

Inadequate intraoperative analgesia causes the deterioration of the condition of the surgical field (CSF) as a result of hemodynamic instability. Analgesia monitors are used to guide remifentanil) infusion to optimize intraoperative analgesia. The main aim of the current randomized controlled trial was to investigate the potential advantages of intraoperative analgesia monitoring using surgical Pleth index (SPI)- or pupillometry (PRD)-guided remifentanil administration for managing the volume of total intraoperative blood loss (TEIBL), CSF, and length of operation (LOP) in comparison with the standard practice in patients undergoing endoscopic sinus surgery (ESS). The 89 patients in our study were grouped as follows: 30 patients were assigned to the general analgesia (GA) group, 31 patients were assigned to the SPI group, and 28 patients were assigned to the PRD group. The speed of remifentanil infusion was accelerated by 50% when SPI, PRD, or BSS were increased by >15 points, >5%, or >2, respectively, in adjacent groups until their normalization. The SPI group showed significantly lower TEIBL in comparison to the GA group (165.2 ± 100.2 vs. 283.3 ± 193.5 mL; p < 0.05) and a higher mean arterial pressure (MAP; 73.9 ± 8 vs. 69.2 ± 6.8 mmHg; p < 0.05). In the PRD group, a shorter LOP compared with the GA group was observed (63.1 ± 26.7 min vs. 82.6 ± 33.1 min; p < 0.05). It was noted that the PRD group had a lower total remifentanil consumption than the SPI group (1.3 ± 1.4 vs. 1.8 ± 0.9 mg; p < 0.05). In ASA I-III patients undergoing ESS, intraoperative monitoring based on state entropy and SPI values can optimize the CSF and reduce TEIBL, whereas monitoring based on state entropy and PRD measurements can optimize the cost effectiveness of anesthetic drugs and the use of the operation room.

Adequacy of Anesthesia Guidance for Colonoscopy Procedures.

In patients undergoing colonoscopy procedures (CPs), inadequate dosing of hypnotic drugs (HD) and opioid analgesics (OA) during intravenous sedoanalgesia (ISA) may lead to intraprocedural awareness with recall (IAwR), intraprocedural (IPP) and postprocedural pain (PPP), as well as postoperative nausea and vomiting (PONV). The aim of this study was to evaluate whether the titration of HD and OA based on the observance of changing values of state entropy (SE) and surgical pleth index (SPI) (adequacy of anesthesia-AoA), state entropy alone, or standard practice may reduce the number of adverse events. One hundred and fifty-eight patients were included in the final analysis. The rate of IAwR and IPP was statistically more frequent in patients from the C group in comparison with the AoA and SE groups (p < 0.01 and p < 0.05, respectively). In turn, the rate of PPP, PONV, and patients' and operators' satisfaction with ISA between groups was not statistically significant (p > 0.05). Changes in hemodynamic parameters, demand for HD, and OA were statistically significant, but of no clinical value. In patients undergoing CPs under ISA using propofol and FNT, as compared to standard practice, intraprocedural SE monitoring reduced the rate of IAwR and IPP, with no influence on the rate of PPP, PONV, or patients' and endoscopists' satisfaction. AoA guidance on propofol and FNT titration, as compared to SE monitoring only, did not reduce the occurrence of the aforementioned studied parameters, imposing an unnecessary extra cost.

Preventive Analgesia, Hemodynamic Stability, and Pain in Vitreoretinal Surgery.

Background and Objectives: Although vitreoretinal surgery (VRS) is most commonly performed under regional anaesthesia (RA), in patients who might be unable to cooperate during prolonged procedures, general anaesthesia (GA) with intraprocedural use of opioid analgesics (OA) might be worth considering. It seems that the surgical pleth index (SPI) can be used to optimise the intraprocedural titration of OA, which improves haemodynamic stability. Preventive analgesia (PA) is combined with GA to minimise intraprocedural OA administration. Materials and Methods: We evaluated the benefit of PA combined with GA using SPI-guided fentanyl (FNT) administration on the incidences of PIPP (postprocedural intolerable pain perception) and haemodynamic instability in patients undergoing VRS (p < 0.05). We randomly assigned 176 patients undergoing VRS to receive GA with SPI-guided FNT administration alone (GA group) or with preventive topical 2% proparacaine (topical anaesthesia (TA) group), a preprocedural peribulbar block (PBB) using 0.5% bupivacaine with 2% lidocaine (PBB group), or a preprocedural intravenous infusion of 1.0 g of metamizole (M group) or 1.0 g of paracetamol (P group). Results: Preventive PBB reduced the intraprocedural FNT requirement without influencing periprocedural outcomes (p < 0.05). Intraprocedural SPI-guided FNT administration during GA resulted in PIPP in 13.5% of patients undergoing VRS and blunted the periprocedural effects of preventive intravenous and regional analgesia with respect to PIPP and haemodynamic instability. Conclusions: SPI-guided FNT administration during GA eliminated the benefits of preventive analgesia in the PBB, TA, M, and P groups following VRS.

System for quantitative evaluation of DAB&H-stained breast cancer biopsy digital images (CHISEL).

This study presents CHISEL (Computer-assisted Histopathological Image Segmentation and EvaLuation), an end-to-end system capable of quantitative evaluation of benign and malignant (breast cancer) digitized tissue samples with immunohistochemical nuclear staining of various intensity and diverse compactness. It stands out with the proposed seamless segmentation based on regions of interest cropping as well as the explicit step of nuclei cluster splitting followed by a boundary refinement. The system utilizes machine learning and recursive local processing to eliminate distorted (inaccurate) outlines. The method was validated using two labeled datasets which proved the relevance of the achieved results. The evaluation was based on the IISPV dataset of tissue from biopsy of breast cancer patients, with markers of T cells, along with Warwick Beta Cell Dataset of DAB&H-stained tissue from postmortem diabetes patients. Based on the comparison of the ground truth with the results of the detected and classified objects, we conclude that the proposed method can achieve better or similar results as the state-of-the-art methods. This system deals with the complex problem of nuclei quantification in digitalized images of immunohistochemically stained tissue sections, achieving best results for DAB&H-stained breast cancer tissue samples. Our method has been prepared with user-friendly graphical interface and was optimized to fully utilize the available computing power, while being accessible to users with fewer resources than needed by deep learning techniques.

Histopathology of laboratory-reared Nothobranchius fishes: Mycobacterial infections versus neoplastic lesions.

Short-lived killifishes of the genus Nothobranchius Peters, 1868 (Cyprinodontiformes) are considered promising model organisms for biomedical research on ageing and tumorigenesis. We conducted histopathological analysis of 411 adult individuals from three Nothobranchius species to study details on spontaneous age-related neoplastic lesions. Light microscopy based on H&E and toluidine blue-stained sections revealed (a) non-proliferative liver changes with pronounced vacuolation of hepatocytes; (b) proliferation of kidney haemopoietic tissue contributing to excretory system damage; (c) proliferation of splenic mononuclear haemoblasts accompanied by reduced erythropoiesis; (d) proliferation of mononuclear cell aggregates in the liver parenchyma; and (e) rare occurrence of hepatocellular adenomas. Ziehl-Neelsen (ZN) staining revealed that the proliferative lesions are a host defence response to mycobacterial infections manifested by activation of the mononuclear phagocytic system and atypical granulomatous inflammatory reaction. 16S rRNA analysis identified three species of Mycobacterium in our samples. Our findings turn attention to lesions which mimic neoplasms by their gross appearance and question the light microscopic interpretation of lesions unless differential ZN staining is included. Beyond the limitations of our morphological approach, the intensity of mycobacterial infections is a challenging opportunity for research into the molecular-genetic background of the mononuclear phagocytic system reaction in Nothobranchius killifish.

Safety profile of autologous hematopoietic stem cell mobilization and transplantation in patients with systemic sclerosis.

Autologous hematopoietic stem cell transplantation (AHSCT) is thought to be effective therapeutic approach in patients with poor prognosis systemic sclerosis; however, the toxicity remains a challenge. Between years 2003 and 2016, we enrolled 18 patients with systemic sclerosis at median age at transplant of 52 years (range 24-68). The median duration of disease before AHSCT was 14 months (range 2-85). Peripheral blood stem cells were mobilized with cyclophosphamide (CY) and granulocyte colony-stimulating factor. Conditioning regimen included CY (200 mg/kg) and alemtuzumab (median dose, 60 mg) [n = 11], melphalan (MEL; 140 mg/m2) and alemtuzumab [n = 2], CY and rabbit anti-thymocyte globulin (rATG; 7.5 mg/kg) [n = 4], and CY alone (n = 1). Four deaths occurred early after transplant. There were three males and one female at median age at death of 51 years (range 24-68). The AHSCT-related deaths have been observed on days + 1, + 4, + 9, and + 15 after procedure. The causes of death included bilateral pneumonia followed by multi-organ failure in three patients and myocardial infarction in one. Three patients expired late during post-transplant follow-up, after 5, 21, and 42 months. The causes of death were disease progression in two patients and sudden heart attack in one. Eleven patients are alive after median follow-up after AHSCT of 42.0 months (range 0-95). Before proceeding to AHSCT in systemic sclerosis, there is a strong need to optimize patient selection to reduce toxicity. The administration of alemtuzumab should be avoided due to high risk of life-threatening infectious complications.

Comparison of the manual, semiautomatic, and automatic selection and leveling of hot spots in whole slide images for Ki-67 quantification in meningiomas.

Background. This paper presents the study concerning hot-spot selection in the assessment of whole slide images of tissue sections collected from meningioma patients. The samples were immunohistochemically stained to determine the Ki-67/MIB-1 proliferation index used for prognosis and treatment planning. Objective. The observer performance was examined by comparing results of the proposed method of automatic hot-spot selection in whole slide images, results of traditional scoring under a microscope, and results of a pathologist's manual hot-spot selection. Methods. The results of scoring the Ki-67 index using optical scoring under a microscope, software for Ki-67 index quantification based on hot spots selected by two pathologists (resp., once and three times), and the same software but on hot spots selected by proposed automatic methods were compared using Kendall's tau-b statistics. Results. Results show intra- and interobserver agreement. The agreement between Ki-67 scoring with manual and automatic hot-spot selection is high, while agreement between Ki-67 index scoring results in whole slide images and traditional microscopic examination is lower. Conclusions. The agreement observed for the three scoring methods shows that automation of area selection is an effective tool in supporting physicians and in increasing the reliability of Ki-67 scoring in meningioma.