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Zentralblatt Fur Chirurgie May 2024One of the most common surgical procedures in infants and children is the repair of an indirect inguinal hernia. This can be carried out by open technique or using...
One of the most common surgical procedures in infants and children is the repair of an indirect inguinal hernia. This can be carried out by open technique or using minimally invasive surgery (MIS). Since 1998, numerous different MIS techniques have been described. Scientifically proven advantages include a shorter operation time for bilateral hernias, along with a lower risk of metachronal, contralateral hernia. Nevertheless, the proportion of inguinal hernias treated using MIS in children in this country is relatively low, at around 8% of all operations. The aim of this synopsis is to describe the different MIS techniques for inguinal hernia repair in children, including their respective advantages and disadvantages.This video compilation shows the spectrum of different techniques for laparoscopic inguinal hernia repair in children. It includes the intracorporeal suturing technique, the incision of the peritoneum, extracorporeal percutaneous techniques, and the cauterisation of the open peritoneal vaginal process in girls.Although minimally invasive inguinal hernia repair in children is technically and scientifically established, it is not yet being widely used. This video manuscript provides an overview of the various techniques, thus facilitating clinical application.
PubMed: 38810959
DOI: 10.1055/a-2329-6806 -
Calcified Tissue International May 2024Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome characterized by hypophosphatemia, bone mineralization disorders with increased risk of fragility...
Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome characterized by hypophosphatemia, bone mineralization disorders with increased risk of fragility fractures, muscle pain, and progressive weakness. TIO has been associated with increased production of the phosphaturic hormone Fibroblast Growth Factor 23 (FGF23) usually by mesenchymal tumors of soft tissue or bone (Phosphaturic Mesenchymal Tumors-PMTs). In rare cases TIO may be observed in association with other malignancies. We report the case of a 66-year-old woman with an occasional diagnosis of both a PMT and an ovarian cancer during the evaluation of TIO. We also systematically review the literature to discover possible correlations between osteomalacia, FGF23 production, and ovarian cancer. Four studies were eligible for the analysis. Two case reports described an association between TIO development and ovarian cancer, whereas the two case-control studies hypothesized a possible correlation between FGF/FGF receptor axis and cancer development. Although it does not provide conclusive evidence regarding the association between TIO and ovarian cancer, this case report highlights the possibility that in the diagnostic workup of suspected TIO, both FGF23-secreting tumors distinct from PMT and tumors unrelated to the clinical presentation of TIO could be identified. This information is important for guiding successful tumor staging and determining the necessity for surgical intervention and/or eventual adjuvant therapy.
PubMed: 38806758
DOI: 10.1007/s00223-024-01231-2 -
Cell Death & Disease May 2024Epithelial-to-mesenchymal transition (EMT) is one of the main causes of peritoneal fibrosis. However, the pathophysiological mechanisms of EMT, specifically its...
Epithelial-to-mesenchymal transition (EMT) is one of the main causes of peritoneal fibrosis. However, the pathophysiological mechanisms of EMT, specifically its relationship with autophagy, are still unknown. This study aimed to evaluate the role of autophagy in transforming growth factor-beta 1 (TGF-β1)-induced EMT in human peritoneal mesothelial cells (HPMCs). Primary cultured HPMCs were treated with TGF-β1 (2 and 5 ng/mL) and changes in autophagy markers and the relationship between autophagy and EMT were evaluated. We also identified changes in EMT- and autophagy-related signaling pathways after autophagy and NADPH oxidase 4 (NOX4) inhibition. TGF-β1 increased the generation of NOX4 and reactive oxygen species (ROS) in HPMCs, resulting in mitochondrial damage. Treatment with GKT137831 (20 μM), a NOX1/4 inhibitor, reduced ROS in the mitochondria of HPMC cells and reduced TGF-β1-induced mitochondrial damage. Additionally, the indirect inhibition of autophagy by GKT137831 (20 μM) downregulated TGF-β1-induced EMT, whereas direct inhibition of autophagy using 3-methyladenine (3-MA) (2 mM) or autophagy-related gene 5 (ATG5) gene silencing decreased the TGF-β1-induced EMT in HPMCs. The suppressor of mothers against decapentaplegic 2/3 (Smad2/3), autophagy-related phosphoinositide 3-kinase (PI3K) class III, and protein kinase B (Akt) pathways, and mitogen-activated protein kinase (MAPK) signaling pathways, such as extracellular signal-regulated kinase (ERK) and P38, were involved in TGF-β1-induced EMT. Autophagy and NOX4 inhibition suppressed the activation of these signaling pathways. Direct inhibition of autophagy and its indirect inhibition through the reduction of mitochondrial damage by upstream NOX4 inhibition reduced EMT in HPMCs. These results suggest that autophagy could serve as a therapeutic target for the prevention of peritoneal fibrosis in patients undergoing peritoneal dialysis.
Topics: Humans; Epithelial-Mesenchymal Transition; Transforming Growth Factor beta1; Autophagy; Oxidative Stress; Reactive Oxygen Species; NADPH Oxidase 4; Signal Transduction; Epithelial Cells; Mitochondria; Peritoneum; Pyrazolones; Pyridones
PubMed: 38806451
DOI: 10.1038/s41419-024-06753-z -
Gastric Cancer : Official Journal of... May 2024Cancer immunotherapy aims to unleash the immune system's potential against cancer cells, providing sustained relief for tumors responsive to immune checkpoint inhibitors...
BACKGROUND
Cancer immunotherapy aims to unleash the immune system's potential against cancer cells, providing sustained relief for tumors responsive to immune checkpoint inhibitors (ICIs). While promising in gastric cancer (GC) trials, the efficacy of ICIs diminishes in the context of peritoneal dissemination. Our objective is to identify strategies to enhance the impact of ICI treatment specifically for cases involving peritoneal dissemination in GC.
METHODS
The therapeutic efficacy of anti-PD1, CTLA4 treatment alone, or in combination was assessed using the YTN16 peritoneal dissemination tumor model. Peritoneum and peritoneal exudate cells were collected for subsequent analysis. Immunohistochemical staining, flow cytometry, and bulk RNA-sequence analyses were conducted to evaluate the tumor microenvironment (TME). A Janus kinase inhibitor (JAKi) was introduced based on the pathway analysis results.
RESULTS
Anti-PD1 and anti-CTLA4 combination treatment (dual ICI treatment) demonstrated therapeutic efficacy in certain mice, primarily mediated by CD8 + T cells. However, in mice resistant to dual ICI treatment, even with CD8 + T cell infiltration, most of the T cells exhibited an exhaustion phenotype. Notably, resistant tumors displayed abnormal activation of the Janus Kinase-Signal Transducer and Activator of Transcription (JAK-STAT) pathway compared to the untreated group, with observed infiltration of macrophages, neutrophils, and Tregs in the TME. The concurrent administration of JAKi rescued CD8 + T cells function and reshaped the immunosuppressive TME, resulting in enhanced efficacy of the dual ICI treatment.
CONCLUSION
Dual ICI treatment exerts its anti-tumor effects by increasing tumor-specific CD8 + T cell infiltration, and the addition of JAKi further improves ICI resistance by reshaping the immunosuppressive TME.
PubMed: 38805119
DOI: 10.1007/s10120-024-01514-5 -
Biomedical Reports Jul 2024End-stage kidney disease (ESKD) is the final stage of chronic kidney disease (CKD), in which long-term damage has been caused to the kidneys to the extent that they are...
End-stage kidney disease (ESKD) is the final stage of chronic kidney disease (CKD), in which long-term damage has been caused to the kidneys to the extent that they are no longer able to filter the blood of waste and extra fluid. Peritoneal dialysis (PD) is one of the treatments that remove waste products from the blood through the peritoneum which can improve the quality of life for patients with ESKD. However, PD-associated peritonitis is an important complication that contributes to the mortality of patients, and the detection of bacterial pathogens is associated with a high culture-negative rate. The present study aimed to apply a metagenomic approach for the bacterial identification in the PD effluent (PDE) of patients with CKD based on 16S ribosomal DNA sequencing. As a result of this investigation, five major bacteria species, namely , , , and , were observed in PDE samples. Taken together, the findings of the present study have suggested that this metagenomic approach could provide a greater potential for bacterial taxonomic identification compared with traditional culture methods, suggesting that this is a practical and culture-independent alternative approach that will offer a novel preventative infectious strategy in patients with CDK.
PubMed: 38800037
DOI: 10.3892/br.2024.1790 -
International Journal of Surgery Case... Jul 2024Ingested foreign bodies fail to pass spontaneously through the gastrointestinal tract in about 20 % of the cases and result in complications in about 1 % of the cases....
INTRODUCTION
Ingested foreign bodies fail to pass spontaneously through the gastrointestinal tract in about 20 % of the cases and result in complications in about 1 % of the cases. One of the complications is the migration of the foreign body to the adjacent structure.
CASE PRESENTATION
A 25-year-old female lady presented to our hospital with a 15-cm-long coilable and insulated electrical wire foreign body in her abdomen, which extended from the descending colon to the right upper quadrant abdominal wall. Intra-abdominally, the object was located in the general peritoneum without penetrating the bowel or vascular structure. It was complicated by an abdominal wall abscess without any collection in the general peritoneum. The foreign body was then successfully retracted from the abdomen through a right upper quadrant incision without any complications thereafter.
CLINICAL DISCUSSION
The uncomplicated passage of foreign bodies through the gastrointestinal tract largely depends on the types of objects. Sharp, elongated objects are more likely to be arrested in the bowel commonly at the point of acute angulation and narrowing. The stacked foreign body may then result in different complications, including penetration and migration of the object. Migration of an insulated electrical wire to the anterior abdominal wall, which we encountered, is extremely rare and can pose a difficulty and dilemma in deciding on management options.
CONCLUSION
For an externally accessible, migrated intra-abdominal foreign body that does not result in peritonitis and is confirmed to be located out of the bowel, an exploratory laparotomy could be avoided.
PubMed: 38796941
DOI: 10.1016/j.ijscr.2024.109794 -
The Journal of Surgical Research Jul 2024Ovarian metastases from gastrointestinal cancers such as colorectal cancer, also known as Krukenberg tumors (KTs), present unique challenges in management due to...
INTRODUCTION
Ovarian metastases from gastrointestinal cancers such as colorectal cancer, also known as Krukenberg tumors (KTs), present unique challenges in management due to diagnostic uncertainty, decreased responsiveness to systemic therapies compared to other sites of metastasis, and associated debilitating symptomatology. Thus, we sought to characterize our institutional outcomes in metastatic colorectal cancer (mCRC) patients with KTs.
METHODS
A retrospective single-institution study was performed identifying adult, female patients from 2012 to 2021 with a diagnosis of mCRC. Patient demographics and clinicopathologic characteristics were collected and analyzed. Descriptive statistics, univariate and multivariable analyses, and Kaplan-Meier survival analyses were performed.
RESULTS
Of 235 mCRC patients, 45 (19.1%) had KTs, 41 (91.1%) of whom had KTs in conjunction with other metastatic sites. Other initial sites of metastasis included the liver (n = 93, 39.6%), lung (n = 28, 11.9%), and peritoneum (n = 18, 7.7%). In the KT cohort, the median age was 48 y, 53.3% were non-Hispanic White, 100% had microsatellite stable tumors, 33.3% had Kristen Rat Sarcoma Virus (KRAS) mutations, and 6.7% had V-raf Murine Sarcoma Viral Oncogene Homolog B (BRAF) mutations. Fifty five point six percent of KT patients underwent cytoreductive surgery (CRS), 24.4% underwent palliative debulking, and 20% underwent no surgical intervention. Reasons for not undergoing CRS were disease-related (n = 14, 70%), due to poor performance status (n = 1, 5%), or both (n = 5, 25%). Five-year overall survival was 48.2% in KT patients who underwent CRS. Poor tumor grade was an independent predictor of mortality (hazard ratio 10.69, 95% confidence interval 1.20-95.47, P = 0.03).
CONCLUSIONS
Almost 90% of our patient cohort with KTs from mCRC experience additional sites of metastasis. Around half of KT patients who underwent CRS were alive at 5 y.
Topics: Humans; Female; Middle Aged; Retrospective Studies; Colorectal Neoplasms; Krukenberg Tumor; Adult; Aged; Ovarian Neoplasms; Kaplan-Meier Estimate; Treatment Outcome; Cytoreduction Surgical Procedures; Proto-Oncogene Proteins B-raf
PubMed: 38795557
DOI: 10.1016/j.jss.2024.04.030 -
Journal of Personalized Medicine May 2024Acral amelanotic melanomas (AAMs), a rare subset of melanomas located on acral sites such as the palms, soles, and subungual areas, are diagnostically challenging due to... (Review)
Review
BACKGROUND
Acral amelanotic melanomas (AAMs), a rare subset of melanomas located on acral sites such as the palms, soles, and subungual areas, are diagnostically challenging due to their lack of typical pigmentation and often benign clinical appearance. Misdiagnosis is common, leading to delays in treatment and potentially worse outcomes. This systematic review aims to synthesise evidence on cases of AAM initially misdiagnosed as other conditions, to better understand their clinical and epidemiological characteristics, diagnostic pitfalls, and management strategies.
METHODS
A comprehensive search of the MEDLINE/PubMed, EMBASE, and SCOPUS databases was conducted up to March 2024. Case reports and small case series of AAMs initially misdiagnosed as other conditions were included. Data on patient demographics, clinical presentation, and diagnostic methods were collected and analyzed.
RESULTS
Of the 152 records identified, 26 cases from 23 articles met the inclusion criteria. A demographic analysis revealed that the gender distribution appears to be perfectly balanced, with an age range of 38 to 91 years. Misdiagnoses included non-healing ulcers or traumatic lesions (37.5%), benign proliferative lesions (29.2%) and infectious lesions (20.8%). The foot was the most affected site (53.8%). Notably, a histological evaluation was performed in 50% of cases involving the upper extremities, in contrast to only 7.1% of cases involving the foot and 0% of cases of the heel. This discrepancy suggests a reluctance to perform biopsies in the lower extremities, which may contribute to a higher misdiagnosis rate in these areas.
CONCLUSIONS
The underutilization of biopsy in the diagnosis of lower extremity lesions contributes significantly to the misdiagnosis and delay in treatment of AAMs. Especially when the clinical assessment and dermoscopy are inconclusive, biopsies of suspicious lesions are essential. Immunohistochemistry and markers such as PRAME are critical in differentiating melanoma from other malignancies such as clear cell sarcoma. This review highlights the need for increased vigilance and a proactive diagnostic approach to increase early detection rates and improve prognostic outcomes.
PubMed: 38793100
DOI: 10.3390/jpm14050518 -
Journal of Personalized Medicine Apr 2024Isolated limb hyperthermic-antiblastic perfusion (ILP) was the most effective local treatment for advanced in-transit melanoma, but the advent of modern effective...
BACKGROUND
Isolated limb hyperthermic-antiblastic perfusion (ILP) was the most effective local treatment for advanced in-transit melanoma, but the advent of modern effective immunotherapy (IT), such as immune checkpoint inhibitors, has changed the treatment landscape.
METHODS
This study evaluated the role of the association between ILP and IT in the treatment of locally advanced unresectable melanoma, particularly in relation to modern systemic therapies. We analyzed 187 consecutive patients who were treated with ILP (melphalan or melphalan associated with TNF-alpha) for advanced melanoma at the Veneto Institute of Oncology of Padua (Italy) and the Padua University Hospital (Italy) between June 1989 and September 2021. Overall survival (OS), disease-specific survival (DSS), local disease-free survival (local DFS) and distant disease-free survival (distant DFS) were evaluated. Local toxicity was classified according to the Wieberdink scale and surgical complications according to the Clavien-Dindo classification. Response to locoregional therapy was evaluated during follow-up according to the RECIST 1.1 criteria (Response Evaluation Criteria in Solid Tumor).
RESULTS
A total of 99 patients were treated with ILP and 88 with IT + ILP. The overall response rate was 67% in both groups. At 36 months, OS was 43% in the ILP group and 61% in the ILP + IT group ( = 0.02); DSS was 43% in the ILP group and 64% in the ILP + IT group ( = 0.02); local DFS was the 37% in ILP group and 53% in the ILP + IT group ( = 0.04); and distant DFS was 33% in the ILP group and 35% in the ILP + IT group ( = 0.40). Adjusting for age and lymph node involvement, receiving ILP + IT was associated with improved OS ( = 0.01) and DSS ( = 0.007) but not local DFS ( = 0.13) and distant DFS ( = 0.21).
CONCLUSIONS
Our findings confirm the synergy between ILP and IT. ILP remains a valuable loco-regional treatment option in the era of effective systemic treatments. Further studies are needed to establish the optimal combination of loco-regional and systemic treatments and address the best timing of this combination to obtain the highest local response rate.
PubMed: 38793023
DOI: 10.3390/jpm14050442 -
Medicina (Kaunas, Lithuania) Apr 2024The impact of positive peritoneal cytology has been a matter of controversy in early-stage endometrial cancer for several years. The latest staging systems do not take... (Meta-Analysis)
Meta-Analysis Review
The impact of positive peritoneal cytology has been a matter of controversy in early-stage endometrial cancer for several years. The latest staging systems do not take into consideration its presence; however, emerging evidence about its potential harmful effect on patient survival outcomes suggests otherwise. In the present systematic review and meta-analysis, we sought to accumulate current evidence. Medline, Scopus, the Cochrane Central Register of Controlled Trials CENTRAL, Google Scholar and Clinicaltrials.gov databases were searched for relevant articles. Effect sizes were calculated in Rstudio using the meta function. A sensitivity analysis was carried out to evaluate the possibility of small-study effects and p-hacking. Trial sequential analysis was used to evaluate the adequacy of the sample size. The methodological quality of the included studies was assessed using the Newcastle-Ottawa scale. Fifteen articles were finally included in the present systematic review that involved 19,255 women with early-stage endometrial cancer. The Newcastle-Ottawa scale indicated that the majority of included studies had a moderate risk of bias in their selection of participants, a moderate risk of bias in terms of the comparability of groups (positive peritoneal cytology vs. negative peritoneal cytology) and a low risk of bias concerning the assessment of the outcome. The results of the meta-analysis indicated that women with early-stage endometrial cancer and positive peritoneal cytology had significantly lower 5-year recurrence-free survival (RFS) (hazards ratio (HR) 0.26, 95% CI 0.09, 0.71). As a result of the decreased recurrence-free survival, patients with positive peritoneal cytology also exhibited reduced 5-year overall survival outcomes (HR 0.50, 95% CI 0.27, 0.92). The overall survival of the included patients was considerably higher among those that did not have positive peritoneal cytology (HR 12.76, 95% CI 2.78, 58.51). Positive peritoneal cytology seems to be a negative prognostic indicator of survival outcomes of patients with endometrial cancer. Considering the absence of data related to the molecular profile of patients, further research is needed to evaluate if this factor should be reinstituted in future staging systems.
Topics: Humans; Female; Endometrial Neoplasms; Survival Rate; Neoplasm Staging; Peritoneum; Cytodiagnosis; Cytology
PubMed: 38792916
DOI: 10.3390/medicina60050733