bluuebunny/crossref_metadata_2025 huggingface dataset:
Preservation of exhaled breath samples for analysis by off-line SESI-HRMS: proof-of-concept study
Authors: Sola-Martínez Rosa A , Zeng Jiafa , Awchi Mo , Gisler Amanda , Arnold Kim , Singh Kapil Dev , Frey Urs , Díaz Manuel Cánovas , de Diego Puente Teresa , Sinues Pablo
Published: November 2023

Secondary electrospray ionization-high resolution mass spectrometry (SESI-HRMS) is an established technique in the field of breath analysis characterized by its short analysis time, as well as high levels of sensitivity and selectivity. Traditionally, SESI-HRMS has been used for real-time breath analysis, which requires subjects to be at the location of the analytical platform. Therefore, it limits the possibilities for an introduction of this methodology in day-to-day clinical practice. However, recent methodological developments have shown feasibility on the remote sampling of exhaled breath in Nalophan® bags prior to measurement using SESI-HRMS. To further explore the range of applications of this method, we conducted a proof-of-concept study to assess the impact of the storage time of exhaled breath in Nalophan® bags at different temperatures (room temperature and dry ice) on the relative intensities of the compounds. In addition, we performed a detailed study of the storage effect of 27 aldehydes related to oxidative stress. After 2 h of storage, the mean of intensity of all m/z signals relative to the samples analyzed without prior storage remained above 80% at both room temperature and dry ice. For the 27 aldehydes, the mean relative intensity losses were lower than 20% at 24 h of storage, remaining practically stable since the first hour of storage following sample collection. Furthermore, the mean relative intensity of most aldehydes in samples stored at room temperature was higher than those stored in dry ice, which could be related to water vapor condensation issues. These findings indicate that the exhaled breath samples could be preserved for hours with a low percentage of mean relative intensity loss, thereby allowing more flexibility in the logistics of off-line SESI-HRMS studies.
On the Boundary Behavior of Mass-Minimizing Integral Currents
Authors: De Lellis Camillo , De Philippis Guido , Hirsch Jonas , Massaccesi Annalisa
Published: November 2023

Let

Σ
\Sigma

be a smooth Riemannian manifold,

Γ
⊂
Σ

\Gamma \subset \Sigma

a smooth closed oriented submanifold of codimension higher than

2
2

and

T
T

an integral area-minimizing current in

Σ
\Sigma

which bounds

Γ
\Gamma

. We prove that the set of regular points of

T
T

at the boundary is dense in

Γ
\Gamma

. Prior to our theorem the existence of any regular point was not known, except for some special choice of

Σ
\Sigma

and

Γ
\Gamma

. As a corollary of our theorem

we answer to a question in Almgren’s Almgren’s big regularity paper from 2000 showing that, if

Γ
\Gamma

is connected, then

T
T

has at least one point

p
p

of multiplicity

1
2

\frac {1}{2}

, namely there is a neighborhood of the point

p
p

where

T
T

is a classical submanifold with boundary

Γ
\Gamma

;

we generalize Almgren’s connectivity theorem showing that the support of

T
T

is always connected if

Γ
\Gamma

is connected;

we conclude a structural result on

T
T

when

Γ
\Gamma

consists of more than one connected component, generalizing a previous theorem proved by Hardt and Simon in 1979 when

Σ
=

R

m
+
1

\Sigma = \mathbb R^{m+1}

and

T
T

is

m
m

-dimensional.
On the completely positive kernels for nonuniform meshes
Authors: Feng Yuanyuan , Li Lei
Published: November 2023

The complete positivity for convolutional kernels is an important property for the positivity property and asymptotic behaviors of Volterra equations. We investigate the discrete analogue of the complete positivity properties, especially for convolutional kernels on nonuniform meshes. Through an operation which we call pseudo-convolution, we introduce the complete positivity property for discrete kernels on nonuniform meshes and establish the criterion for the complete positivity. We then apply our theory to the L1 discretization of time fractional differential equations on nonuniform meshes.
Comparing frailty prevalence between countries: validation of the Global Burden of Disease study Frailty Index (GBD-FI) in the survey of health, ageing and retirement in Europe
Authors: O’Donovan Mark R , Devleesschauwer Brecht , Sezgin Duygu , Liew Aaron , Kabir Zubair , O’Caoimh Rónán
Published: November 2023

Background

Accurate comparable prevalence proportions are required to better understand the epidemiology of frailty. Estimates in many countries are missing or incomparable. The Global Burden of Disease Frailty Index (GBD-FI) applies the deficit accumulation model to generate frailty scores from items available in the Global Burden of Disease study.

Objective

To externally validate the GBD-FI.

Methods

Data were obtained from the Survey of Health Ageing and Retirement in Europe (SHARE). A 20-item modified GBD-FI was compared with established frailty measures: a 70-item frailty index (FI-70), the Clinical Frailty Scale (CFS), Frailty Phenotype (FP) and SHARE-FI. Area under receiver operating characteristic curves (AUC) were fitted to examine diagnostic accuracy for frailty and predictive validity for 2-year mortality.

Results

In total, 31,624 participants aged ≥50 years from 15 countries were included. Frailty prevalence was 22% using the GBD-FI (ranging from 8% in Switzerland to 41% in Poland). The GBD-FI had good to excellent diagnostic accuracy for frailty, irrespective of approach; the AUC ranged from 0.86 (95% confidence interval: 0.85–0.87) measuring frailty using the CFS to 0.94 (0.93–0.94) with the FI-70. The GBD-FI had similar accuracy for 2-year mortality (AUC 0.71, 0.69–0.74) compared with the CFS (0.73; P = 0.186), FP (0.73; P = 0.392) and SHARE-FI (0.70; P = 0.255) but lower than the FI-70 (0.76; P < 0.001).

Conclusion

The GBD-FI demonstrated concurrent and predictive validity, suggesting it is a valid measure of frailty. It has the potential to be an efficient, replicable and consistent approach to comparing frailty between countries and regions across time using GBD data.
PLAG1 Rearranged Soft Tissue Tumor in an Adult
Authors: Alkayyali T , Hwang H
Published: November 2023

Introduction/Objective

PLAG1 rearranged soft tissue tumor is a recently described entity in the pediatric population. Less than 10 cases have been reported identifying PLAG1 gene fusions with various gene partners. This tumor is characterized by spindled cells with low cellularity in fibromyxoid stroma, expressing CD34 and desmin. PLAG1 gene fusions have been identified in various other tumors, including lipoblastoma, salivary gland pleomorphic adenoma, myoepithelial tumors, uterine epithelioid and myxoid leiomyosarcomas, and chondroid syringoma. To our knowledge, we report the first case of a PLAG1 rearranged soft tissue tumor in an adult.

Methods/Case Report

A 32-year-old female with no significant medical history presented with a left thigh mass. MRI showed a 9.8 cm mass involving subcutaneous fat and causing marked sartorius muscle displacement. Resection showed a well-circumscribed, spindle cell tumor of low cellularity in a myxo-collagenous stroma. Bland, elongated, and ovoid-shaped spindled cells with occasional punctate nucleoli were seen. No mitoses or necrosis were identified. The tumor cells expressed CD34 and androgen receptors, partially expressed desmin and estrogen receptors, and focally expressed S100. MUC4 and beta-catenin were negative. Next-generation sequencing performed at Mayo Clinic Labs identified UBC::PLAG1 gene rearrangement.

Results (if a Case Study enter NA)

NA

Conclusion

To our knowledge, we describe the first case of PLAG1 rearranged soft tissue tumor in an adult. This case is also unique as the fusion partner gene, UBC, was not previously identified. All other cases reported occurred in those four years of age or younger, with one report in a 15-year-old female. Our patient has had less than six months of follow-up with no recurrence. With few cases reported, and relatively short follow-up periods thus far, the behavior of these tumors remains undetermined.
Angiosarcoma with Osteoclast-Like Giant Cells: A Rare Presentation and Review of Literature
Authors: Belogrivtseva Y , Nobee A , Lazim A , Taraif S
Published: November 2023

Introduction/Objective

Diagnosing angiosarcoma can be challenging, especially in cases with atypical morphology. For the unsuspecting pathologist, some histopathologic features can be misleading, especially when presenting as the predominant component of a tumor or in unusual locations. Herein, we describe an osteoclast-like giant cell-rich angiosarcoma, which initially presented as a groin mass followed by pulmonary metastasis.

Methods/Case Report

A 54-year-old woman presented with a golf ball size mass near her right groin that she noticed 1 year ago. MRI demonstrated a heterogeneous complex mass with solid and cystic components within the right gracilis muscle. Following the diagnosis of poorly differentiated malignant neoplasm on biopsy, the patient underwent wide excision. Histopathologic examination revealed epithelioid to “rhabdoid-like” cells arranged in a fascicular pattern interspersed with osteoclast-like giant cells. Immunohistochemical stains showed tumor cells are positive for vimentin, CD10, CD31 (focal), CD99 (focal), while negative for Desmin, CD34, SMA, AE1AE3, HMB45, ALK1, CD30, S100, and Melan-A. CD68 highlighted only osteoclast-like giant cells. The lesion was diagnosed as undifferentiated pleomorphic sarcoma (UPS). Nine months later, chest CT showed a 1.3 cm lung nodule. The resected nodule was immunohistochemically and morphologically similar to the groin mass, including the presence of osteoclast-like giant cells. In addition, tumor cells were also diffusely positive for ERG and FLI1.

Results (if a Case Study enter NA)

NA

Conclusion

To our knowledge, this is the first report of soft tissue angiosarcoma with osteoclast-like giant cells presenting with lung metastasis. A high index of suspicion for an angiosarcoma in tumors occurring in proximal sites, characterized by epithelioid to “rhabdoid-like” cells, despite the presence of many osteoclast-like giant cells, is crucial to avoid misdiagnosis. Awareness of this histopathologic pattern and diagnostic confirmation with necessary immunohistochemical stains is important to avoid misinterpretation. UPS is essentially a diagnosis of exclusion, which should only be considered following extensive workup to eliminate all other possibilities.
What is the fuss about FUS fused rhabdomyosarcoma?
Authors: Al-kharouf I , Abdo M E , Hamza A , Meyer A R
Published: November 2023

Introduction/Objective

Rhabdomyosarcoma (RMS) is a rare and aggressive soft tissue sarcoma that primarily affects children and adolescents. It arises from primitive mesenchymal cells committed to skeletal muscle differentiation.

Understanding the molecular drivers and genetic alterations underlying RMS is crucial for developing targeted therapies and improving patient outcomes. Recently, a novel fusion event involving the transcription factor CP2-like protein 2 (TFCP2) and fused in sarcoma (FUS) has emerged as a potential oncogenic driver in a subset of RMS cases. This fusion event represents a novel genetic alteration with implications for RMS pathogenesis, diagnosis, and therapeutic strategies.

Methods/Case Report

A 58-year-old female presented with a tender fullness along the right mandibular body. A biopsy performed at an outside institution was notable for a spindle cell neoplasm. She underwent resection of the lesion with pathology demonstrating a predominantly monomorphic spindle cell sarcoma with focal areas of pleomorphism. The lesion was diffusely positive for MyoD1. SOX10, S100, H-caldesmon, SMA, and pan-cytokeratin were negative. H3K27me3 was retained, arguing against malignant peripheral nerve sheath tumor with extensive rhabdomyoblastic differentiation. Break-apart FISH studies for FUS gene were positive. Overall, the findings were those of a recently described RMS variant with rearranged TFCP2 gene with FUS or EWSR1 as the partner gene. The patient later received adjuvant chemotherapy and radiotherapy. Despite that, her restaging scan 12 months later showed rapid progression with involvement of lungs, bone, and local recurrence in the jaw bilaterally.

Results (if a Case Study enter NA)

NA

Conclusion

TFCP2-FUS gene fusion drives an emerging family of RMS with a predilection for the jaws. Recognition of this rare entity can guide personalized therapeutic approaches and improve the prognostic stratification of RMS patients
A Rare Case of Embryonal Rhabdomyosarcoma of Pineal Gland in An Adult Male
Authors: Iqbal S , Raja F , Cai D
Published: November 2023

Introduction/Objective

Rhabdomyosarcoma (RMS), mesenchymal derived tumor, is predominantly diagnosed in the pediatric population but may present at any age. Less than 1% of all adult solid malignant cancers are sarcomas, and rhabdomyosarcoma comprises <0.001% of adult sarcomas. Primary intracranial RMS is rare and has been reported in the cerebrum, cerebellum, brainstem, and the meninges. The occurrence of a primary intracranial RMS arising from the pineal gland is exceedingly rare.

Methods/Case Report

An adult male presented to the ED with complaint of several months of headaches, progressive confusion, forgetfulness and most recently difficulty in finding words. CT scan showed a large mass arising from the pineal gland causing obstructive hydrocephalus. Subsequently, the patient underwent excisional biopsy. The histopathology examination revealed small round basophilic cells and large polygonal cells with large eccentric nuclei and prominent nucleoli, abundant eosinophilic cytoplasm containing globular paranuclear eosinophilic inclusions, characteristic of rhabdoid cells. Immunohistochemical (IHC) showed tumor cells are positive for Desmin, MyoD1, CK8/18, INI1 (hSNF5; SMARCB1) with retained nuclear expression and faint positivity for Synaptophysin and focally positivity for Neurofilament. The tumor cells showed negative staining for Pankeratin, SOX10, Oct4, SALL4, INSM1, LCA AND CD30, which excluded the possibility of Germ cell tumor and Pineoblastoma. The case was finalized as primary malignant neoplasm, consistent with Embryonal Rhabdomyosarcoma of pineal gland.

Results (if a Case Study enter NA)

NA

Conclusion

This case highlights the rare occurrence of rhabdomyosarcoma originating from the pineal gland in an adult male. Morphologic and immunohistochemical findings were consistent with embryonal rhabdomyosarcoma. Since primary rhabdomyosarcoma of the pineal gland is rare, this case contributes to the limited body of literature on such cases. It underscores the importance of considering unusual entities in intracranial tumors. The distinct morphology and the use of IHC aids in diagnosing this rare entity.
Invasive Solid Papillary Carcinoma of breast in an elderly male: a rare entity in an uncommon gender - case report and review of literature
Authors: Poombal F , Khan S , Siddique K
Published: November 2023

Introduction/Objective

Male breast cancers (MBC) account for less than 1% of all breast cancers. Papillary cancers constitute less than 3% of MBCs. Solid papillary carcinoma (SPC) is a rare subtype of papillary cancer with a solid growth pattern associated with fibrovascular cores. SPC is an indolent disease that typically presents in a post- menopausal woman as a central breast mass. Neuroendocrine differentiation, ER/PR positive status and Her-2 neu negative status are characteristic. SPC can be in situ or have invasive components. SPC is a rare entity in men and so far, approximately less than 40 cases of SPC in men have been discussed in literature. Here, we report a rare case of SPC with multiple invasive foci in an elderly male.

Methods/Case Report

An 84-year-old white male presented with a painless mass in his left breast. Excision biopsy revealed Solid Papillary Carcinoma. He subsequently underwent a Left Modified Radical Mastectomy with Left Sentinel Lymph Node Excision. The final histopathology report showed a background of SPC with multiple invasive foci with largest focus measuring 2 mm. Margins were negative and lymph nodes were negative for malignancy. The tumor was ER and PR positive, Her-2 neu negative and had a Ki-67 proliferation index of 42%. Negative IHC staining for Cytokeratin AE1/AE3 confirmed the absence of metastatic epithelial cells in the examined lymph nodes.

Results (if a Case Study enter NA)

N/A

Conclusion

SPC is an uncommon subtype among the papillary lesions of breast. Furthermore, only a few cases of SPC have been reported in men. Despite its rarity, it has a good prognosis and lymph node positivity, distant metastasis and local recurrence are uncommon. However, there is limited data about SPC with invasive components which may behave like other invasive breast lesions leaving management a dilemma for clinicians. We believe this case will add to the scarce existing literature about invasive SPC in men.
Mucocele-like Lesion: To Excise or Not to Excise?
Authors: Roychoudhury S , Al-Refai R , Morrar D , Bendari A , Sham S , Hajiyeva S
Published: November 2023

Introduction/Objective

Mucocele-like lesions (MLLs) are characterized by cystically dilated, mucin-filled ducts, usually associated with rupture and extravasation of mucin into the stroma. The epithelium lining the ducts may be attenuated or show a spectrum of proliferative changes ranging from hyperplasia to atypical hyperplasia to ductal carcinoma in situ (DCIS). Our study aims to evaluate the necessity of excision of pure MLL without atypia diagnosed on core needle biopsy (CNB).

Methods/Case Report

We retrospectively identified all subsequent in-house CNBs obtained between January 2017- August 2022 with MLLs. We reviewed all CNB slides with the diagnosis containing a “mucocele-like lesion” and assessed radiologic-pathologic concordance. An upgrade was defined as invasive carcinoma and/or DCIS in the excision. The excision slides of all upgraded cases were re-reviewed. Out of ~16000 consecutive CNBs in the study period, 69 CNBs from 69 patients yielded MLL alone, MLL with atypia, or MLL with carcinoma. We excluded 43 CNBs (7 patients with prior/concurrent carcinoma and 36 without excision). The final cohort consisted of 25 CNBs (14 with pure mucocele-like lesions and 11 MLLs with atypia). The CNB targeted mammographic calcifications in 42 cases, and 4 sonographic mass.

Results (if a Case Study enter NA)

Subsequent excision or clinical follow-up was available for 14 pure MLLs—of which one was upgraded. Five excisions showed atypia (4 atypical ductal hyperplasias (ADH) and one atypical lobular hyperplasia (ALH)). Excisions of 11 MLL with atypia yielded 1 case upgraded to DCIS (9.09%, 1/11) and seven excisions showed atypia (5 ADH, 1 ALH, and 1 flat epithelial atypia). DCIS in an upgraded case was in an area with biopsy site changes. There was no upgrade to invasive carcinoma in either group. Among the 36 MLLs excluded from the study due to not having excision available for review, twelve were followed up with interval radiology and showed either stable lesions or no residual calcifications.

Conclusion

There was one case with upgrade of pure MLLs in our series. Clinicoradiological surveillance can be considered in a patient without prior/current carcinoma in pathological-radiological concordant CNB diagnosis of pure MLL.
Primary pericardial angiosarcoma with pleural metastasis: an unusual clinical presentation
Authors: Han F , Osmani M , Rashidbaigi A , Lazzaro R
Published: November 2023

Introduction/Objective

Primary pericardial angiosarcoma is an uncommon, aggressive cardiac neoplasm that arises from the endothelial cells of blood vessels. It typically affects middle-aged men and has a poor prognosis due to early metastasis. Unfortunately, there are currently no established guidelines or effective treatments for this rare malignancy. The purpose of this case study is to emphasize the significance of recognizing the unspecific presentations of pericardial angiosarcoma and ensuring timely diagnosis and appropriate treatment.

Methods/Case Report

A 56-year-old male presented with recurrent pericardial effusion and exudative pleural effusion. The radiologic studies showed a thickened pericardium with right-sided pericardial effusion and a large right- sided pleural effusion. Resected partial pericardium and parietal pleura showed the presence of epithelioid to spindled cells that formed solid sheets and vascular structures filled with numerous red blood cells. The tumor cells were cytologically malignant, with angulated shapes and hyperchromatic nuclei, and showed extensive invasion into the surrounding connective tissue. Mitotic figures were variably visualized, and there was abundant hemorrhage.

Immunohistochemical analysis of the lesional cells showed positivity for ERG, CD31, Factor VIII, and retention of Methylthioadenosine phosphorylase (MTAP) and BRCA1-associated protein 1 (BAP1), while they were negative for WT1, calretinin, claudin-4, and p40. Based on the morphology and immunoprofile, a diagnosis of high grade angiosarcoma was rendered, and the patient underwent chemotherapy. The overall survival of the patient was 8 months to date.

Results (if a Case Study enter NA)

NA

Conclusion

Prompt diagnosis of pericardial angiosarcoma is crucial, as nonspecific symptoms may lead to misdiagnosis, such as in this case where the patient was initially diagnosed with pericarditis. Video-assisted thoracic surgery and histologic analysis are necessary to reach a correct diagnosis, which ensures appropriate treatment, as a delayed diagnosis can worsen the prognosis and even lead to death.
Undetected Exogenous Insulin Administration in a Child: Assessment of Assay Limitations and Impact on the Practice of Laboratory Medicine
Authors: Najar A , Wu A H , Lynch K L , Akarca F G , Barbati Z
Published: November 2023

Introduction/Objective

The development of new synthetic insulin analogues over the past few decades has significantly impacted the management of hypoglycemia. However, accurately measuring these analogues presents challenges due to variable cross-reactivity with many insulin assays. Failure to consider cross-reactivity may lead to the misdiagnosis of exogenous insulin administration.

Methods/Case Report

A 13-year-old female with a history of type 1 DM was presented to an outside hospital emergency department with symptoms indicative of hypoglycemia. Multiple child protective services (CPS) referrals are noted. The patient had experienced several episodes of hypoglycemia over the prior week with blood glucose in the 30-40 mg/dL range. There were no associated symptoms of diarrhea, emesis, or fatigue. The patient was transferred to a pediatric hospital were preliminary investigations indicated abnormally low blood glucose levels with low insulin and C-peptide levels. Further evaluation was initiated to determine the underlying cause of these episodes and to ensure appropriate adjustments in insulin dosing and regimen. Initially, the Elecsys insulin assay (Roche Diagnostics) was utilized to quantify insulin levels which shows a low cross-reactivity for insulin lispro and glargine. To validate the hypothesis of an undetected exogenous insulin overdose, blood samples were sent to another laboratory employing The Advia Centaur insulin assay (Siemens) which exhibits a higher cross-reactivity for insulin lispro and glargine (89%-143%, respectively), indicating a higher recognition and measurement sensitivity for these insulin analogues. The analysis using this assay revealed significantly elevated insulin levels, corroborating the presence of an insulin overdose. The sample at the time of presentation at the outside hospital was confirmed to be 434.1 mU/L. A sample collected 17 hours later had an insulin level of 23.5 mU/L.

Results (if a Case Study enter NA)

NA

Conclusion

This case study highlights the critical issue of undetected insulin overdose in a child and emphasizes the limitations of the initial insulin assay employed. Improving assay sensitivity and reliability will enhance patient care and safety. This case study reminds clinicians and laboratory professionals of the need for ongoing quality assurance and vigilance in their practices.
Adiponectin/resistin evaluation is a gold biomarker for monitoring CVD in patients with metabolic syndrome
Authors: Abdelmonem M , Alawssi Y , Ahmed K , Alqaisi K , Wasim H , Abdelmageed M
Published: November 2023

Introduction/Objective

Introduction: Various studies have tried correlating specific inflammatory markers with metabolic syndrome. Serum adiponectin levels can serve as a biomarker that predicts metabolic syndrome development. Resistin is another adipose-tissue-derived hormone capable of promoting insulin resistance because it increases the reserve of triglycerides in the muscle and the liver rather than the adipose tissue.

Methods/Case Report

Objectives: To investigate the role of the adiponectin/resistin ratio in monitoring CVD in Jordanian adults with metabolic syndrome.

Methods

Eighty subjects were randomly selected from individuals who attended two clinical laboratories for routine checks during the period between January 2021 and March 2021. Forty-two participants had metabolic syndrome, while the other 38 represented the healthy group. Resistin and adiponectin were evaluated using the ELISA method, while the adiponectin/resistin ratio was calculated. Lipid profile, glucose and body mass index (BMI) were measured for all metabolic syndrome patients and healthy control ones.

Results (if a Case Study enter NA)

Results: Plasma resistin levels were significantly higher in metabolic syndrome patients than in healthy controls (p = 0.04), while no significance was found regarding adiponectin (p = 0.07). In contrast, the adiponectin/resistin ratio was highly significant (p < 0.001). Resistin had shown a negative correlation with HDL (r= -0.33), whereas adiponectin was inversely correlated with LDL (r= -0.33) and LDL/HDL ratio (r= -0.34). Adiponectin/resistin ratio positively correlated with HDL (r= 0.45). The multiple linear regression analysis results revealed the predictive potential of adiponectin and resistin when used in different models for CVD risks using HDL as a risk factor. However, the results revealed that only the third model, which included the adiponectin/resistin ratio, was expected to have a higher CVD risk after controlling for the other predictors in the same model.

Conclusion

The studied metabolic syndrome markers might have an essential role in detecting cardiovascular events. It can be concluded that resistin can be used to evaluate the CVD risks. Furthermore, we found that the adiponectin/resistin ratio is the best marker in predicting CVD events in metabolic syndrome patients compared to other markers, including adiponectin and resistin alone.
The Diagnostic Performance of Serum Hyaluronic Acid and Collagen III in Differentiating Liver Fibrosis in HCV-Induced Patients
Authors: Abdelmonem M , Abdelmageed M , Wasim H , Eldaly R , Saleh Abdelfattah M
Published: November 2023

Introduction/Objective

Chronic liver diseases may lead to inflammation and progressive scarring, causing irreversible hepatic damage (cirrhosis). To avoid the complications of liver puncture biopsy, Collagen III and Hyaluronic acid are studied as non-invasive markers of liver fibrosis in chronic liver diseases.

Aim of the work: Discovering the diagnostic role of serum Hyaluronic acid and Collagen III in liver fibrosis associated with chronic HCV patients.

Methods/Case Report

The study was performed on 118 patients with liver fibrosis associated with chronic HCV (60 males and 58 females) and 50 age-matched healthy subjects (27 males and 23 females). Liver function tests were measured, including ALT, AST, [AST/ ALT] ratio, albumin, total bilirubin, and platelets counts. APRI was also calculated as [AST/ (upper limits of normal)/ platelets count 109/L]×100. Serum levels of Collagen III (ng/ml) and hyaluronic acid (µg/L) were determined. Plotted receiver-operating characteristic (ROC) curves were used to assess and compare the diagnostic accuracy of biomarkers.

Results (if a Case Study enter NA)

The area under ROC curve of collagen III in discriminating liver fibrosis in patients associated with chronic HCV infection and healthy ones was 0.805; P< 0.0001. The Sensitivity and Specificity were 62% and 96%, respectively. While the area under ROC curve of hyaluronic acid in discriminating liver fibrosis patients associated with chronic HCV infection from healthy volunteers was 0.832; P < 0.0001. The Sensitivity and Specificity were 72% and 94%, respectively. Also, there was no significant correlation between levels of collagen III and hyaluronic acid; (r=0.01 & P=0.714).

Conclusion

Collagen III and Hyaluronic acid can identify patients with liver fibrosis with a detection rate of 62% and 72%, respectively. So, both biomarkers are considered powerful non-invasive methods in discriminating and diagnosing liver fibrosis in chronic HCV patients.
Pioglitazone as a Treatment Option for Ataxia-Telangiectasia
Authors: Shackelford R , Tahir M
Published: November 2023

Introduction/Objective

The ataxia-telangiectasia mutated (ATM) gene product regulates cell cycle checkpoints, the cellular redox state, and DNA break repair. ATM loss causes the rare disorder ataxia-telangiectasia (A-T), characterized by progressive ataxia, telangiectasias, immune dysfunction, and an elevated cancer risk. The clinical course of A-T is relentless, causing death by the early twenties.

Methods/Case Report

A-T cells show extreme sensitivity to oxidants and ionizing radiation, impaired glutathione (GSH) synthesis, genomic instability, poor cell cycle checkpoint initiation, and increased reactive oxygen species. A-T cells also show unusual iron responses, with iron chelators increasing A-T cell growth, oxidant exposure resistance, and genomic stability, while labile iron exerts toxic effects not seen in ATM wild-type cells. Since GSH is dysregulated in A-T cells and much of the cellular iron is bound up in iron-sulfur clusters, we examined the cellular sulfur pool in A-T cells with and without an ATM expression vector, and in ATM wild-types cells. Free hydrogen sulfide and protein- bound sulfide levels were unchanged with ATM expression. However, iron-sulfur clusters (the acid-labile sulfur faction) were low in the A-T cells and dramatically increased with ATM expression. ATM expression also increased the expression of NFS1, NFU1, and several mitochondrial complex I iron-sulfur proteins. As NFS1 and NFU1 play central roles in the synthesis of iron-sulfur clusters, and ATM expression increases these clusters, our data reveals a role for ATM in iron metabolism. Interestingly, the type II diabetes drug pioglitazone increased the acid-labile sulfur and protein bound sulfur factions in both cell types. It also increased the A-T cell reduced GSH, cell viability following oxidative stress, and decreased oxidative stress-induced double-stranded DNA break formation.

Results (if a Case Study enter NA)

Our finding that pioglitazone increased both cellular acid-labile and protein-bound sulfur fractions, indicates that these sulfur pools may be a therapeutic target for some type II diabetes drugs. Our data also indicates that pioglitazone may have value in treating A-T

Conclusion

We propose that pioglitazone could be a promising A-T treatment drug. More clinical research and trials are needed to determine the potential advantages and side effects of using pioglitazone in A-T.
Clinicopathological features of superficial esophageal squamous cell carcinomas in patients without history of smoking and drinking
Authors: Tateishi Y , Fukuchi T , Hirasawa K , Okudela K , Nakanishi Y , Inayama Y , Nemoto T , Oyama T , Maeda S
Published: November 2023

Introduction/Objective

Cigarette smoking and drinking are the major causative risk factors for esophageal squamous cell carcinoma (ESCC). ESCCs in patients without history of smoking and drinking account for approximately 5% of all ESCCs. Clinicopathological features of superficial ESCCs in patients without history of smoking and drinking have not been well investigated.

The aim of this study is to clarify the clinicopathological features of superficial ESCCs in patients without history of smoking and drinking.

Methods/Case Report

A multicenter study including 12 leading institutions of the Japan Research Society of Early Esophageal Cancer and Chromoendoscopy was conducted. Clinical data and pathological features of 108 superficial ESCCs in endoscopic submucosal dissection (ESD) specimens of 102 patients without history of smoking and drinking (NSND group) were reviewed. For comparison, clinicopathological features of 767 superficial ESCCs in ESD specimens of 544 patients with history of smoking and drinking (SD group) were also reviewed. Clinicopathological features including age, sex, synchronous/metachronous cancer, gastroesophageal reflux disease (GERD), tumor size, tumor site, macroscopic type, Lugol-voiding lesion (LVL), invasion depth, and lymphovascular invasion were analyzed in both NSND group and SD group. LVLs were graded according to the number of LVLs in preoperative endoscopic examination (grade A, no lesions; B, 1 – 9 lesions; C, more than 9 lesions).

Results (if a Case Study enter NA)

The univariate analysis revealed that female predominance (95.1% vs. 11.6%, p<0.001), absence of synchronous/metachronous cancer (81.4% vs. 60.8%, p<0.001), grade A LVLs (74.5% vs.

6.6%, p<0.001), presence of GERD (42.2% vs. 18.0%, p<0.001), tumor location at the posterior wall (58.3% vs. 47.5%, p<0.005), and 0-IIa macroscopic type (14.8% vs. 3.0%, p<0.001) were significantly more frequently observed in NSND group than SD group.

Conclusion

ESCCs in patients without history of smoking and drinking are characterized by female predominance, absence of synchronous/metachronous cancer, grade A LVLs, presence of GERD, tumor location at the posterior wall, and 0-IIa macroscopic type.
The Biologic Diversity of Colorectal Carcinoma (CRC) is Present in the Early Stage: Quantitative Analysis of Malignant Polyps
Authors: Chand M T , Stashek K , Furth E E , Tondon R , Al Zeer A
Published: November 2023

Introduction/Objective

Risk factors in malignant polyps to predict recurrence in T1 colorectal carcinoma (CRC) include depth of invasion, margin status, lymphovascular invasion, tumor differentiation and budding. However, the effect of other factors, such as tumor volume and tumor cellularity, are not well studied. We quantitatively, using image analysis, determined the strength and interdependence of the depth of invasion, margin status, tumor volume and tumor cell density on the probability of having residual adenocarcinoma on resection and long term patient outcomes.

Methods/Case Report

Endoscopic mucosal resection (EMR) specimens of polyps with T1 CRC were identified by retrospective search of the pathology database over a 14-year period (01/01/2008 to 05/05/2022). Depth of invasion, distance of tumor to margin, tumor volume (defined by the invasive area comprising the tumor cells and associated others cells) and cellularity (number of adenocarcinoma cells/area) were measured using Aperio eSlide Manager Leica Biosystems Imaging, Inc. The depth of invasion was measured from the muscularis mucosa. Available outcome data was collected from subsequent segmental resection and oncology consultations and imaging from the patient charts.

Results (if a Case Study enter NA)

22 patients of malignant polyps with EMR were identified; 11 patients underwent subsequent resection with residual tumor in 4 and lymph node metastasis in 1. Follow-up period was from 3 to 12 yrs, with recurrence in none. The median tumor cellularity was 2712 cells/mm2 with SD 1421 cells/mm2 and was similar in residual versus non residual tumors with no correlation with LVI. Distance of tumor (um) from deep margin was measured in 20 cases and by Receiver Operator Characteristic analysis and calculation of the area under the curve (AUC) was a good test of residual tumor (AUC = 0.88) while depth of invasion was not a good test (AUC =0.5). Tumor volume and adenocarcinoma cells/area were not correlated; however, interestingly, tumor volume and depth of invasion were linearly correlated (p<0.001).

Conclusion

The distance of tumor to the margin is a better predictor for residual cancer than depth of invasion. The linear correlation of tumor volume and depth of invasion implies the same shape of invasion which is interestingly independent of tumor cellularity. This finding further strengthens the hypothesis that cancer associated cells in the tumor microenvironment are important in driving the biological behavior of malignant polyps.
Unusual Cause of Small bowel Intussusception
Authors: Abdo M E , Sami F I , Hamza A
Published: November 2023

Introduction/Objective

Intussusception is uncommon in adults. When it occurs it is usually secondary to a mass lesion. The purpose of this report is to highlight an unusual cause of intussusception.

Methods/Case Report

A 48-year-old female presented with right lower abdominal pain, nausea, vomiting, and bloating. She didn’t have a bowel movement in 3-4 days. CT of the abdomen and pelvis demonstrated long segment small bowel intussusception in the right abdomen with a lead point mass. The patient subsequently underwent surgical resection. Grossly the specimen consisted of a 30cm segment of small bowel remarkable for two mucosal nodules measuring 1.9 cm and 1.0 cm in greatest dimension. Microscopically the nodules were composed of sheets of discohesive epithelioid cells with marked nuclear pleomorphism and prominent nucleoli, underlying the normal mucosa. Immunohistochemical studies revealed that the tumor cells to be positive for SOX-10 and MART-1and negative for pan-cytokeratin and DOG1. Diagnosis of malignant melanoma was rendered.

Results (if a Case Study enter NA)

NA

Conclusion

Intussusception due to malignant / metastatic melanoma is rare but should be on the differential for patients with symptoms of small bowel obstruction and intussusception with a lead point mass.
Loss of α-smooth muscle actin immunostaining is not a useful marker for functional impairment: a comparison from patients with and without small bowel motility disorder
Authors: Collins K , González I A , Idrees M T , Saeed O A , Gupta A , Wo J M
Published: November 2023

Introduction/Objective

Prior studies have reported the loss α-smooth muscle actin (α-SMA) immunostaining in the inner circular layer of the muscularis propria in small bowel motility disorder cases, but this remains controversial with conflicting data. In this study we aimed to characterize the immunoreactivity of α-SMA expression in the muscularis propria of the small intestine, specifically jejunum, in patients with and without small bowel motility disorder.

Methods/Case Report

A total of 28 samples of transmural proximal jejunum biopsies from adult patients with small bowel motility disorder by manometric and/or radiologic testing and 47 control tissues were evaluated. The controls were full thickness, longitudinal tissue sections from segmental resections performed due to trauma from gunshot wound (n= 30), multi-visceral transplant for neoplasms (n= 4), liver failure with concurrent portal vein thrombosis (n= 9), and isolated intestinal transplant for Crohn disease (n= 4). Immunostaining for α-SMA was performed with appropriate controls to confirm the presence of staining in the circular and longitudinal muscle layers of the muscularis propria in each sample and recorded as retained or diminished.

Results (if a Case Study enter NA)

In the small bowel motility disorder and control cases, 43% (12/28) and 62% (29/47) of the cases showed no or minimal α-SMA expression in the inner circular layer with peripheral accentuation (p = 0.113), respectively. The remaining small bowel motility disorder cases (16/28, 57%) and the control group (18/47, 38%) showed retained expression of α-SMA in both layers of the muscularis propria.

Conclusion

Loss or diminished α-SMA expression in the inner circular layer of muscularis propria is present in similar frequency in cases with and without small bowel motility disorder and does not correlate with impairment of function.
Primary Renal Well Differentiated Neuroendocrine Neoplasm with Nodal Metastasis Possibly Originating from A Teratoma
Authors: Lazim A , Hennawy R
Published: November 2023

Introduction/Objective

Well differentiated neuroendocrine tumors (WDNETs) of the kidney are extremely rare and are aggressive tumors with higher rate of metastasis, even those with low proliferative rates. Primary WDNET arising in a renal teratoma is an exceedingly rare entity.

Methods/Case Report

Herein, we describe a case with a primary WDNET and possible mature cystic teratoma of the right kidney of a 22-year old male who presented with an epigastric/right upper quadrant abdominal pain. Abdominal MRI identified a 4.4cm isointense mass in the mid-lower pole of the right kidney within renal sinus. Robotic assisted partial nephrectomy was performed. Grossly, the 56gm excised mass is well circumscribed with tan- brown friable homogeneous cut surface. Histologically, tumor cells show round to oval nuclei with speckled chromatin and calcifications. The tumor metastasized to two hilar lymph nodes. The tumor is positive for AE1/AE3, vimentin, synaptophysin, CD99, INI-1 (SMARCB1), FLI-1, and chromogranin. While negative for CK7, CK20, PAX-8, CD10,

WT-1, CEA, and CDX-2. Ki-67 is 2% and the mitotic count is < 1 per 10 HPF. The histology and immunoprofile are consistent with WDNET. No pathogenic fusions detected on Next Generation Sequencing (NGS) targeting RNA and DNA panels. Adjacent to the tumor, there is a cystic structure lined by intestinal mucosa positive for CDX2.

Results (if a Case Study enter NA)

N/A

Conclusion

Neuroendocrine cells are not identified in the normal parenchyma of the kidney, while noted in adjacent intestinal mucosa raising the possibility that renal WDNET is arising from mature renal teratoma.
Ultrasound-MRI Fusion Prostate Biopsy: Experience from a Cancer Center in the Midwest
Authors: Al-Kharouf I , Sami F I , Abdo M E , Hamza A
Published: November 2023

Introduction/Objective

Majority of literature with few exceptions suggests ultrasound-magnetic resonance imaging (MRI) fusion biopsy of prostate to be superior in diagnosing cancer compared to systematic transrectal ultrasonographic (TRUS) biopsy. However, it is highly dependent on the expertise of the person performing the biopsy and comes at a higher cost. The purpose of this study is a to evaluate the effectiveness of ultrasound-MRI fusion prostate biopsy at our institution.

Methods/Case Report

All prostate biopsies received at our institution from January to December 2022 were included. Data such as patient age, presence of region of interest (ROI) biopsy, presence of cancer in any core, presence of cancer in ROI core, total number of cores with cancer, highest Gleason score in ROI core, and highest Gleason score in other cores were collected.

Results (if a Case Study enter NA)

A total of 448 consecutive cases were identified. Of these 214 (47.8%) were transrectal ultrasonographic and 234 (52.2%) were ultrasound-MRI fusion biopsies. Mean age of patients with TRUS biopsy was 64.3±8.6 years and mean age of patients with MRI-guided biopsy was 65.4±6.9 years, a statistically comparable population (p-value 0.001). Among TRUS cases, 133 (62.1%) had tumor. Among ultrasound-MRI fusion cases, 169 (72.2%) had tumor.

Among ultrasound-MRI fusion cases with tumor, 31 had cancer only in ROI core, 55 had cancer only in other cores and 83 had cancer in ROI core as well as at least one additional non-ROI core. Among 83 cases with tumor in ROI as well as non-ROI cores, 12 had higher Gleason score in ROI core, 18 had higher Gleason score in non-ROI core and in 53 cases the Gleason score in ROI core and highest Gleason score in any of the other positive cores were equal.

Conclusion

In our experience ultrasound-MRI fusion biopsy improves cancer detection; however, it does not improve the rate of detection of higher-grade cancer.
INCIDENTAL BLADDER MELANOSIS WITH CHRONIC CYSTITIS
Authors: Asad M , Vidhun R , Okby N
Published: November 2023

Introduction/Objective

Melanosis is a black or brown discoloration due to melanin deposition in the skin or on the mucosa of body organs such as conjunctiva, lips, mouth, genitalia, colon, and rectum. For example, melanosis coli is associated with chronic laxative use. However, melanosis on the bladder mucosa is an extremely rare, incidental, and benign finding which is commonly associated with bladder cancer or melanoma. We report an unusual case of incidental bladder melanosis with chronic cystitis in a patient diagnosed with bladder cancer.

Methods/Case Report

A 77-year-old male current smoker presented for a follow-up of recurrent bladder cancer (high-grade T1 Transitional Cell Carcinoma, TCC) diagnosed in 2016 with currently no symptoms. His past medical history included high blood pressure, papillary thyroid carcinoma status post thyroid lobectomy, and Type 2 diabetes mellitus. He had completed two cycles of treatment of Bacillus Calmette-Guerin (BCG) and BCG/Interferon for 6 weeks each. He had multiple transurethral bladder resections and biopsies in the past which revealed invasive high- grade papillary urothelial carcinoma, not invading muscularis propria. A recent computerized tomography scan of the abdomen and pelvis revealed diffuse bladder wall thickening and trabeculation along the dome and posterior urinary bladder. His lab workup including urinalysis, complete blood count, and chemistry were within normal limits. This time, the patient underwent urinary bladder midline and back wall cystoscopic biopsies and transurethral resection of the right lateral wall. The biopsies showed mild chronic cystitis with melanosis, however, the resection showed non- invasive high-grade papillary urothelial carcinoma.

Results (if a Case Study enter NA)

NA

Conclusion

Bladder melanosis has been reported less than 25 times in the literature worldwide. The etiology of melanosis is still unknown. No specific symptoms or treatment guidelines have been established for bladder melanosis so far due to decreased number of cases reported and therefore, reduced follow-up surveillance.

Nonetheless, the general behavior of bladder melanosis alone seems to be benign. To the best of our knowledge, this is the first report of bladder melanosis with chronic cystitis. Further studies are required to establish the association of bladder melanosis with chronic cystitis and to probe its clinicopathologic course, and implications.