Abstract
Colorectal carcinoma (CRC) is associated with significant morbidity and mortality worldwide. Cytokeratins (CKs) are widely expressed in various types of carcinomas, whereas in CRC it is ...usually CK7 − and CK20 + . A subset of CRCs is CK7 + . This study aims to determine the prevalence of CK7 expression in CRC and its impact on overall survival. We analyzed 300 randomly selected surgically treated CRC cases using paraffin embedded tumor tissue samples and evaluated CK7 and CK20 expression using the tissue microarray method. Tumors with positivity > 10% and > 25% of tumor cells were considered CK7 and CK20 positive, respectively. Expression of both CKs and several clinical-pathological variables (stage, grade, laterality, mismatch-repair/MMR status) were evaluated using patient follow up data (Kaplan–Meier analysis of cancer-specific survival (CSS)). Significant results include shorter CSS (restricted mean 4.98 vs. 7.74 years,
P
= 0.007) and 5-year survival (29.4% vs. 64.6%,
P
= 0.0221) in CK7 + tumors compared to CK7 − tumors, respectively; without significant association with grade, stage or right-sided location. These results were significant in a multivariate analysis. CK20 + tumors are more frequently MMR-proficient and left-sided. MMR-deficient tumors are more frequently right-sided and had longer survival. CK7 expression, right-sided location (rmean CSS 6.83 vs. 8.0 years,
P
= 0.043), MMR-proficiency (rmean CSS 7.41 vs. 9.32 years,
P
= 0.012), and UICC stages III + IV (rmean CSS 6.03 vs. 8.92 years,
P
< 0.001) of the tumor correlated with negative prognostic outcomes, whereas the most significant results concern stage and CK7 positivity. The result concerning negative prognostic role of CK7 differs from those obtained by several previous studies focused on this topic.
Undifferentiated carcinoma with osteoclast-like giant cells (UCOGC) of the pancreas is a rare malignancy regarded as a subvariant of pancreatic ductal carcinoma (PDAC) characterized by variable ...prognosis. UCOGC shows a strikingly similar spectrum of oncogenic DNA mutations to PDAC. In the current work, we analyzed the landscape of somatic mutations in a set of 13 UCOGC cases via next-generation sequencing (NGS). We detected a spectrum of pathogenic or likely pathogenic mutations similar to those observed in PDAC following previously published results (10
, 9
, 4
, and 1
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,
,
,
,
,
,
, and
). Our results support the theory that UCOGC is a variant of PDAC, despite its unique morphology; however, a UCOGC-specific genomic signature as well as predictive markers remain mainly unknown. Programmed death ligand 1 (PD-L1) status remains an important predictive marker based on previous studies.
Pancreatic carcinoma remains one of the leading cancer-related causes of death worldwide and is generally characterized by a dismal prognosis and limited potential for oncologic treatment. A rare ...subvariant of pancreatic cancer, undifferentiated carcinoma with osteoclast-like giant cells (UCOGC), has an unpredictable prognosis according to many previous studies, with unexpectedly long survival in individual cases. In this study, we collected, retrospectively, 13 cases of well-documented UCOGCs and performed immunohistochemistry focused on the expression of the programmed death-ligand 1 (PD-L1) and several other potential therapeutic and predictive markers (PanTRK, p53, MSH2, PMS2, and the number of tumor-infiltrating lymphocytes), to explore their correlation with the follow-up of the patients. As a control group, we examined 24 cases of conventional pancreatic ductal adenocarcinoma (PDAC). In our results, PanTRK was negative in all 24 cases. P53 did not show any significant differences between UCOGCs and PDACs, and the entire cohort was MSH2, MLH1, PMS2, and MSH6 positive. Significant differences were present in the analysis of PD-L1: UCOGCs were found to express PD-L1 significantly more frequently and have a higher number of tumor-infiltrating lymphocytes than PDAC. The expression of PD-L1 was related to significantly shorter survival in patients with UCOGC and in the entire cohort. Patients with PD-L1 negative UCOGCs displayed surprisingly long survival in comparison to PD-L1 positive UCOGCs and PDACs (both PD-L1+ and PD-L1−). We compared our results with previously published data, and, after statistical analysis, we were able to identify PD-L1 as an effective prognostic marker of UCOGC and suggest a strong need for a clinical trial of immune checkpoint immunotherapy in patients with advanced PD-L1 positive UCOGC.
Colorectal carcinoma (CRC) is a disease that causes significant morbidity and mortality worldwide. To improve treatment, new biomarkers are needed to allow better patient risk stratification in terms ...of prognosis. This study aimed to clarify the prognostic significance of colonic-specific transcription factor special AT-rich sequence-binding protein 2 (SATB2), cytoskeletal protein cytokeratin 7 (CK7), and immune checkpoint molecule programmed death-ligand 1 (PD-L1). We analyzed a cohort of 285 patients with surgically treated CRC for quantitative associations among the three markers and five traditional prognostic indicators (i.e., tumor stage, histological grade, variant morphology, laterality, and mismatch-repair/MMR status). The results showed that loss of SATB2 expression had significant negative prognostic implications relative to overall survival (OS) and cancer-specific survival (CSS), significantly shortened 5 years OS and CSS and 10 years CSS in patients with CRC expressing CK7, and borderline insignificantly shortened OS in patients with PD-L1 + CRC. PD-L1 showed a significant negative impact in cases with strong expression (membranous staining in 50-100% of tumor cells). Loss of SATB2 was associated with CK7 expression, advanced tumor stage, mucinous or signet ring cell morphology, high grade, right-sided localization but was borderline insignificant relative to PD-L1 expression. CK7 expression was associated with high grade and SATB2 loss. Additionally, a separate analysis of 248 neoadjuvant therapy-naïve cases was performed with mostly similar results. The loss of SATB2 and CK7 expression were significant negative predictors in the multivariate analysis adjusted for associated parameters and patient age. In summary, loss of SATB2 expression and gain of CK7 and strong PD-L1 expression characterize an aggressive phenotype of CRC.
Undifferentiated or anaplastic thyroid carcinoma (ATC) is rare and one of the most aggressive human malignancies. The tumor is usually voluminous and fast-growing and mostly affects older women. The ...most common sites of distant metastases are the lungs, brain, and bones. Herein, we describe the case of a 66-year-old woman with a history of bilateral breast carcinoma and ATC, who presented with an acute abdomen and subsequently died. At autopsy, an isolated metastasis of ATC in the small intestine leading to bowel perforation was found. Moreover, there was adenocarcinoma in the descending colon. The review of extra-abdominal malignancies metastasizing to bowel and coincidence of breast and thyroid carcinoma is included.
The paper gives the detailed information about a newly developed plasma system applicable for conductive target non-thermal plasma indirect treatment. High voltage microsecond duration pulses ...delivered in the kHz range are used to ignite a discharge in a glass funnel vessel flushed with argon and equipped with a needle electrode. An air dielectric barrier discharge (DBD) can subsequently be generated if a grounded grid is set a few millimeters apart from the thin glass plate constituting the funnel base, in the funnel-DBD setup. Thus, this air DBD operates with its powered electrode consisting in the transient argon streamer discharge spreading inside the funnel and over the glass plate. This “plasma electrode DBD” is characterized using time-resolved ICCD imaging together with voltage and current probes. This work reports for the first time the funnel-DBD proof of concept operation and its potentialities for large surface decontamination. Argon and air plasma temporal and spatial development is documented and analyzed while electrical characterization using Lissajous plots provide key information on the power and capacitances of the funnel-DBD setup. It is reported that the funnel-DBD operates as a large surface and low power discharge. As with any air-DBD plasma, the modulation of the power density delivered across the air-DBD, processed with changing the pulse repetition rate, results in the control of the ozone concentration. Beyond the plasma electrode-DBD development and characterization, the main motivation of this work is the treatment of conductive samples with the perspective of large surface decontamination. Preliminary demonstrations of the bacterial and yeast inhibition are thus reported for in vitro cultivations through indirect treatment with the funnel-DBD delivering reactive nitrogen and oxygen species.
•Dermatofibroma is a common benign mesenchymal skin tumor.•Sweat duct cyst is an uncommon benign lesion containing squamous and glandular cells.•We report a rare case of a dermatofibroma surrounding ...a sweat duct cyst of the shin.
Dermatofibroma or fibrous histiocytoma is a very common benign mesenchymal skin tumor that usually involves lower limbs and shows slight predilection for young females. There are several histological subtypes with variable biological significance in terms of local recurrence risk. Herein, we present an interesting case of a middle-aged man presenting with a voluminous cystic skin tumor on the left shin which on histopathologic examination revealed a dermatofibroma associated with a large cyst lined with non-keratinizing squamous epithelium admixed with sweat gland-type glandular epithelial cells. There are two references describing similar cases in the literature.
Intramyocardial dissection or intramyocardial dissecting hematoma is uncommon complication either of myocardial infarction or severe thoracic injury. Intramyocardial dissecting hematoma is caused by ...intersecting bleeding between the layers of myocardial fibers. In contrast to cardiac rupture, the myocardial wall maintains its integrity. In this paper, we present a case of patient suffering with ischemic heart disease, reporting worsening chest pain and dyspnea 2 months after autovenous graft bypass surgery. The coronary angiography revealed severe stenosis of the autovenous graft, which was treated by stent implantation. Three hours after intervention, the patient showed signs of cardiogenic shock with clinical suspicion of heart tamponade because of ventricular wall rupture. The patient died despite the surgical drainage of the hematoma and blood transfusions. In the necropsy, the large intramyocardial dissecting hematoma in the very superficial layer of the left ventricular myocardium was found, accompanied with very small extent of necrotic myocardium in the neighborhood of the intramyocardial dissecting hematoma. The prevailing majority of the left ventricle thickness was vital. The lack of developed transmural infarction in our case leads us to hypothesis that the increased intravascular pressure during the reperfusion is the main contributor to the intramyocardial dissecting hematoma development, together with reduced biomechanical resistance of the capillaries affected by chronic ischemia.
•We report a case of a patient suffering with worsening chest pain and dyspnea 2 months after autovenous graft bypass surgery.•The revascularization intervention was complicated by signs of heart tamponade.•Despite the surgical drainage, the patient died and the autopsy revealed the intramyocardial dissecting hematoma.•Interestingly, the hematoma was situated in the very superficial layer of left ventricular wall lacking transmural infarction.•We propose the reperfusion damage of the vessels is the main mechanism of the intramyocardial dissecting hematoma.
Malignant melanoma is commonly known for its high probability of metastasizing to distant organs. Metastases to gastrointestinal tract are well documented, but resulting jaundice is only scarcely ...seen. We present a case of histologically verified metastasis of amelanotic melanoma to the head of pancreas infiltrating the common bile duct and consequently causing obstructive jaundice which constituted its first clinical manifestation. Multidisciplinary approach is essential in patients with malignant melanoma since early detection of the melanoma or its metastases may improve patients' clinical outcome, especially owing to the use of targeted biological treatment without any delay.
Localized insulin-derived amyloidosis (LIDA) is a rare local complication of subcutaneous insulin application occurring in patients with diabetes type 1 and 2. A 45-year-old woman with an 11-year ...history of insulin-dependent diabetes mellitus type 1 underwent a mini-abdominoplasty and excision of a long-standing palpable mass in left hypogastric subcutaneous tissue in the area of long-term insulin application. Histopathological examination revealed insulin amyloidosis as a substrate of the mass lesion. Several months after surgery, there was a transient improvement in previously poor diabetes compensation. In addition to local allergic reactions, abscess formation, scarring, lipoatrophy/dystrophy, and lipohypertrophy, LIDA broadens the differential diagnostic spectrum of local insulin injection complications. LIDA has been described as a cause of poor glycemia compensation, probably due to the conversion of soluble insulin into insoluble amyloid fibrils, which prevents insulin from circulating in the blood and regulating glucose blood concentration. Improvement in diabetes compensation has been described in several reports, including our case. LIDA is a rare local complication of subcutaneous insulin application; accurate diagnosis and treatment have clinical consequences. Immunohistochemical or immunofluorescence distinction from other amyloid types is highly recommended.
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