In-House Validated Map of Lymph Node Stations in a Prospective Cohort of Colorectal Cancer: A Tool for a Better Preoperative Staging.

Preoperative staging of colorectal cancer (CRC) based on imaging techniques such as computed tomography (CT) or magnetic resonance imaging (MRI) is crucial for identification and then removal of the positive lymph nodes (LNs). The aim of this study was to evaluate the correlation between preoperatively seen morphologic criteria (number, size, shape, structure, borders, or enhancement patterns) and histopathological features of LNs using an in-house validated map of nodal stations. A total of 112 patients with CRC that underwent surgery were preoperatively evaluated by CT scans. The locoregional, intermediate, and central LNs were CT-mapped and then removed during open laparotomy and examined under microscope. The analysis of correlations was interpreted using the suspicious-to-positive ratio (SPR) parameter. The greatest correlation was found in tumors located in the sigmoid colon, descending colon and middle rectum; SPR value was 1.12, 1.18, and 1.26, respectively. SPR proved to be 0.59 for cases of the transverse colon. Regarding the enhancement type, the dotted pattern was mostly correlated with metastatic LNs (OR: 7.84; p < 0.0001), while the homogenous pattern proved a reliable indicator of nonmetastatic LNs (OR: 1.99; p < 0.05). A total of 1809 LNs were harvested, with a median value of 15 ± 1.34 LNs/case. Transdisciplinary approach of CRC focused on pre-, intra-, and postoperatively mapping of LNs might increase the accuracy of detecting metastasized nodes for tumors of the distal colon and middle rectum but not for those of the transverse colon. In addition to morphologic criteria, the enhancement pattern of LNs can be used as a predictor of nodal involvement improving the CT-based preoperative staging.

Pediatric COVID-19: Low Incidence, but Possible Fatality-A Case Report and a Review of the Literature.

BACKGROUND: Pediatric COVID-19 is a current health burden mostly due to the lack of knowledge in terms of symptoms, clinical course and management. COVID-19-associated coagulopathy is one of the most recently described complications among adults, along with acquired thrombophilia resulting in an increased risk for venous, arterial and microvascular thrombosis. CASE PRESENTATION: We report the case of a 4-year-old male child, admitted to our clinic for generalized seizures being intubated and mechanically ventilated before admission, with a personal history of ureterovesical junction obstruction, mild hydronephrosis, and an episode of generalized seizures. The laboratory tests revealed anemia, an increased number of monocytes, and a mildly increased C-reactive protein. A real-time polymerase chain reaction (RT-PCR) of the oropharyngeal swab was performed and it tested positive for SARS-CoV-2 in the child and both of his parents. The thoracic CT showed consolidation in the lower lobe of the left lung associated with an opacity in the right apex, suggesting possible atelectasis. We initiated antibiotic, antiviral, corticosteroids, as well as anticoagulants and antipyretics, continuing the chronic anticonvulsant therapy. The patient's condition deteriorated progressively, and, after 72 h of hospitalization, he developed desaturation and bradycardia. The laboratory parameters on the third day showed leucopenia, neutropenia, increased creatine kinase, a high ferritin level, hypoalbuminemia, a prolonged prothrombin time and an increased international normalized ration. The patient died on the fourth day of admission. CONCLUSION: In spite of its low incidence and frequent benign clinical course, COVID-19 complications such as coagulopathy might represent a leading cause of death, even in pediatric patients.

Synchronous Colorectal Cancer: Improving Accuracy of Detection and Analyzing Molecular Heterogeneity-The Main Keys for Optimal Approach.

BACKGROUND: In patients with synchronous colorectal cancer (SCRC), understanding the underlying molecular behavior of such cases is mandatory for designing individualized therapy. The aim of this paper is to highlight the importance of transdisciplinary evaluation of the pre- and post-operative assessment of patients with SCRCs, from imaging to molecular investigations. METHODS: Six patients with SCRCs presented with two carcinomas each. In addition to the microsatellite status (MSS), the epithelial mesenchymal transition was checked in each tumor using the biomarkers ß-catenin and E-cadherin, same as KRAS and BRAF mutations. RESULTS: In two of the patients, the second tumor was missed at endoscopy, but diagnosed by a subsequent computed-tomography-scan (CT-scan). From the six patients, a total of 11 adenocarcinomas (ADKs) and one squamous cell carcinoma (SCC) were analyzed. All the examined carcinomas were BRAF-wildtype microsatellite stable tumors with an epithelial histological subtype. In two of the six cases, KRAS gene status showed discordance between the two synchronous tumors, with mutations in the index tumors and wildtype status in the companion ones. CONCLUSIONS: Preoperative CT-scans can be useful for detection of synchronous tumors which may be missed by colonoscopy. Where synchronous tumors are identified, therapy should be based on the molecular profile of the indexed tumors.

The Association Between Mycoplasma pneumoniae and Chlamydia pneumoniae, a Life-Threatening Condition in Small Children-A Case Report and a Review of the Literature.

Mycoplasma pneumoniae (MP) and Chlamydia pneumoniae (CP) are two atypical pathogens that may result in mild, moderate or severe acute respiratory infections. We report the case of a 2 years and 9-month-old male child admitted with prolonged fever, dry cough, and shortness of breath for which he underwent symptomatic treatment. The laboratory tests showed leukocytosis with neutrophilia, anemia, and elevated inflammatory biomarkers and the thoracic radiography revealed pleural effusion raising the suspicion of inferior right pneumonia. Although we the initial evolution was favorable being treated with 3rd class cephalosporin and Oxacillin, on the 8th day of admission the fever and the acute phase reactants levels increased as well as the quantity of the pleural effusion, requiring surgical drainage. We ruled out lung tuberculosis, but we identified positive IgM for both MP and CP. Based on these findings we changed the antibiotic therapy on Levofloxacin for 10 days with favorable evolution. MP and CP are two atypical pathogen that are difficult to be diagnosed due to their slow-growing pattern. Despite their self-limiting feature, the association between them might carry a vital risk in small children, especially in the lack of a proper and timely diagnosis.

Primary rhabdomyosarcoma: An extremely rare and aggressive variant of male breast cancer.

BACKGROUND: Rhabdomyosarcoma (RMS) of the breast, a mesenchymal neoplasm with skeletal muscle differentiation, is an extremely rare tumour in males, with less than 30 cases published in English-language literature. We report on the first case of a male breast RMS, with an unusual ectomesenchymal/neuroectodermal component. CASE SUMMARY: A 55-year-old, previously healthy male, underwent a radical left mastectomy for an ulcerated tumour mass, occupying the breast and left anterior thoracic wall. The biopsy specimen indicated the presence of a tumour with neural origins, namely a peripheral neuroectodermal tumour (PNET). The surgical specimens identified two components. The rhabdomyosarcomatous component (over 70%) was represented by large pleomorphic cells with positivity for desmin, sarcomeric actin and myogenin. The PNET-like ectomesenchymal component, which was admixed with the RMS cells, and was also revealed during the preoperative biopsy, consisted of small cells which expressed neurofilament, neuron specific enolase and CD99. The microscopic examination, along with the immunohistochemical profile, allowed the diagnosis of an RMS, with unusual ectomesenchymal differentiation. The patient refused the postoperative oncologic therapy and died three months after surgery. CONCLUSION: In patients with RMS of the breast, the PNET-like ectomesenchymal component increases the diagnosis difficulty, especially in biopsy specimens. This differentiation can be immunohistochemically proven and might highlight the possible development of high-grade sarcoma of the breast from remnants of the embryological ectodermal layer.

Hypercalcemia, an Important Puzzle Piece in Uncommon Onset Pediatric Sarcoidosis-A Case Report and a Review of the Literature.

Sarcoidosis (SD) is a systemic granulomatous condition that is especially encountered in young adults and rarely in children, affecting predominantly the lungs and lymph nodes. We report the case of a 14-year-old teenage boy admitted to our clinic for nausea, vomiting, and weight loss. Clinical examination at the time of admission revealed malaise, pallor, and abdominal tenderness in the epigastric area at palpation. Laboratory tests revealed an elevated level of hemoglobin, mild thrombocytosis, increased erythrocyte sedimentation rate, and a mild increase in creatinine and urea levels along with hypercalcemia. An abdominal ultrasound revealed a right ectopic kidney, whereas the upper digestive endoscopy showed intense hyperemia and edema of the gastric mucosa. Thoracic computed tomography scan revealed giant hilar and mediastinal lymphadenopathy, along with multiple micronodules within the lung parenchyma and ground-glass aspect. The level of angiotensin-converting enzyme was high, parathormone was normal, and vitamin D level was low. Pathological examination of the bronchial, mediastinal, and lung biopsies established the diagnosis of SD. We administered oral corticosteroids for 2 months with outstandingly favorable outcome and no signs of recurrence 6 months after the cessation of the therapy.

Immunohistochemical-based molecular subtyping of colorectal carcinoma using maspin and markers of epithelial-mesenchymal transition.

The aim of the present study was to classify colorectal carcinoma (CRC) into molecular subtypes, based on immunohistochemical (IHC) assessments. A total of 112 CRC samples were molecularly classified based on the expression levels of epithelial-mesenchymal transition (EMT)-associated IHC markers. A total of three molecular subtypes were defined: Epithelial, membrane positivity for E-cadherin and ß-catenin, negative for vimentin; mesenchymal, E-cadherin-negative, nuclear ß-catenin- and vimentin-positive; and hybrid cases, epithelial tumor core and mesenchymal tumor buds. Most of the cases were diagnosed as moderately differentiated adenocarcinoma (n=89; 79.46%). The majority of cases (n=100; 89.28%) exhibited a mismatch repair proficient status (microsatellite stable CRCs). A predominance of epithelial-type (n=51; 45.54%) and hybrid CRCs (n=47; 41.96%) was observed, whereas a few cases (n=14; 12.50%) were classified as mesenchymal-type CRCs. This molecular classification was associated with pathological stage (P<0.01), pT stage (P=0.04), pN stage (P<0.01), the grade of tumor budding (P=0.04), and maspin expression in both the tumor core (P=0.04) and the invasion front (P<0.01). The mesenchymal-type cases predominantly exhibited lymph node metastases, high-grade budding and a tendency towards maspin nuclear predominance. All epithelial-type cases with maspin-only expression (n=18) were non-metastatic. Patients with CRC of the epithelial subtype and those with a lymph node ratio (LNR) ≤0.15 presented the best overall survival, followed by those with hybrid and mesenchymal subtypes. Nuclear maspin positivity was more frequent in cases with a high-budding degree compared with those with a low-budding degree (P=0.03). The EMT-associated molecular classification of CRCs may be used to identify the most aggressive CRCs, which show a mesenchymal phenotype, high-budding degree, maspin nuclear positivity and lymph node metastases. The pN stage, LNR and budding degree of patients, which can be evaluated with maspin expression, remain the most important prognostic factors.

Acute ischemic stroke in a 7-month-old infant, risk factors, and diagnosis peculiarities: A case report.

INTRODUCTION: Ischemic stroke is an extremely rare disorder in children. The timely diagnosis is essential for the outcome of these children, but unfortunately, delays in diagnosis occur frequently. PATIENT CONCERNS: We report the case of a 7-month-old infant admitted in our clinic for limited movements of the superior and inferior right limbs whose onset was 27 hours before with repeated clonic movements of the right hand associated with the same manifestations in the right oral commissure lasting approximately 10 seconds. DIAGNOSIS: The laboratory tests revealed high D-dimers, and positive IgG anti-cardiolipin and anti-beta2 glycoproteins I antibodies, whereas the genetic profile for thrombophilia revealed heterozygote mutation in MTHFR C677T and A1298C genes. Brain imaging established the diagnosis of left frontal ischemic stroke, frontal ischemic stroke, hypoplasia of internal carotid artery, and agenesia of segment M1 of median cerebral artery and segment A1 of left anterior cerebral artery. INTERVENTION: We administered low-molecular-weight heparin, antiplatelet therapy along with vasodilators and depletive treatment, wide-spectrum antibiotics, and anticonvulsant therapy. OUTCOME: The neurological deficit was greatly improved, especially in the inferior limb after 6 month from the incident of stroke, and all laboratory parameters were within normal limits including the antibodies mentioned above. CONCLUSION: Cerebral vascular malformation, excessive weight, and altered lipid profiles contributed to the development of acute ischemic stroke in our patient.

Acute Pulmonary Embolism in a Teenage Female - A Case Report.

Thrombophilia represents a tendency towards excessive blood clotting and the subsequent development of venous thromboembolism (VTE). VTE is a rare condition in children that comprises both deep venous thrombosis (DVT) and pulmonary embolism (PE). This paper reports the case of a 16-year-old girl, admitted to the Pediatrics Clinic No. 1, Tîrgu Mureș, Romania, for dyspnea, chest pain and loss of consciousness. Her personal history showed that she had had two orthopedic surgical interventions in infancy, two pregnancies, one spontaneous miscarriage and a recent caesarian section at 20 weeks of gestation for premature detachment of a normally positioned placenta associated with a deceased fetus. Laboratory tests showed increased levels of D-dimers. Angio-Computed Tomography (Angio-CT) showed multiple filling defects in both pulmonary arteries, establishing the diagnosis of PE. The laboratory tests were undertaken to assist in the diagnoses of a possible thrombophilia underlined a low level of antithrombin III. Antiphospholipid syndrome was ruled out and genetic tests revealed no specific mutation. Anticoagulant therapy was initiated with unfractionated heparin and afterwards subcutaneously low molecular heparin was prescribed for three months. Later it has been changed to oral therapy with acenocoumarol. The patient was discharged in good general status with the recommendation of life-long anticoagulation therapy. Thrombophilia is a significant risk factor for PE, and it must be ruled out in all cases of repeated miscarriage.

Clinical and Serological Biomarkers of Treatment's Response in Multiple Sclerosis Patients Treated Continuously with Interferonß-1b for More than a Decade.

INTRODUCTION: We evaluated the peripheral immune panel of Multiple Sclerosis (MS) patients treated for more than 10 years with interferon-beta1b (IFNß-1b) and aimed to identify possible biomarkers of treatment response. MATERIAL AND METHODS: Serum samples from 70 MS patients treated with IFNß-1b more than a decade were analysed for 15 cytokines, that were correlated with the disability score, annual relapse ratio (ARR): the total number of relapses-ARR_0, relapse on treatment-ARR_1 and demographic data. Two groups were defined based on the levels of disability, calculated using the Expanded Disability Status Scale (EDSS): G1 - recurrent-remissive and G2 - secondary-progressive. Furthermore, we split the patients based on gender (G1_f, G1_m, G2_f, G2_m). RESULTS: The ARR was reduced after treatment was instituted. We found positive correlations between IL_25 and EDSS in G1_f and G2_f, tumor necrosis factor α (TNFα) and ARR_1 and ARR_0 in G1, and IL_17F with ARR_1. Negative correlations were for IL_25 and ARR_0 and ARR_1. SCD40L intensely positively correlated with IL_31 in G1 and G2. CONCLUSION: After more than a decade of treatment, IFNß-1b offers good results by reducing relapses and slowing disability progression. Several biomarkers can be used to assess the patient's response. High levels of IL_17 and TNFα will indicate a more active form of the disease. IL-25 may exert a positive influence in male MS patients and should be considered for future studies, together with the co-modulation between sCD40L and IL_31. Our method allowed us to screen the peripheral immune panel and can be used for assessing the peripheral levels of the above-mentioned cytokines.

A Rare Case of Double-System With Ectopic Ureteral Openings Into Vagina.

The presence of an ectopic ureter may be indicated by continuous wetting, despite a normal voiding pattern, especially in girls. In most cases, an ectopic ureter is associated with a duplex collecting system and complete ureteral duplication. A 5-year-old girl presented with urinary incontinence regardless of the successful toilet training and a suspicion of left duplex kidney on a previous ultrasound. Contrast-enhanced computed tomography revealed a double left kidney with double ureters, both inserting together into the vagina. The surgical treatment consisted in the "en block" reimplantation of the ectopic ureters into the bladder, with complete resolution of the symptoms. The reported case does not represent just a typical presentation of a single ectopic ureter, as the duplex kidney system had ectopic both ipsilateral ureters (with insertion into the vagina). This case reminds us that congenital abnormalities of the genito-urinary tract should be considered in case of urinary incontinence and recurrent urinary tract infections.

Complete progressive ophthalmoplegia and numb chin syndrome, the first clinical manifestations of a lethal abdominal Burkitt lymphoma.

A 57-year-old patient was admitted to the Neurology Clinic for hypoesthesia, intense pain in the right chin and double vision. During the hospitalization, the patient developed progressive complete bilateral ophthalmoplegia and numbness of both sides of the chin. Brain CT and MRI scans with gadolinium were normal. Standard laboratory tests on admission were normal. The cerebral spinal fluid examination and the infectious and autoimmune workup were also normal. A thoracic-abdominal and pelvic CT scan revealed two hypodense lesions in the liver, irregular thickening of the gastric and ileal wall, and multiple abdominal adenopathies. Meanwhile, the patient developed marked fatigue, fever, sweats, nausea, vomiting and abdominal pain. An exploratory laparotomy was performed that showed multiple tumours of the small intestinal wall, stomach wall, multiple liver masses in both lobes and appendicular tumour. Histopathological findings of the liver biopsy and appendicular walls revealed Burkitt lymphoma. The patient died two days after surgery by cardiopulmonary arrest. This case underscores the importance of keeping BL in the differential diagnosis of patients with rapidly progressive ophthalmoplegia and numb chin syndrome, with normal brain MRI and CSF examinations.

Natalizumab Changes the Peripheral Profile of the Th17 Panel in MS Patients: New Mechanisms of Action.

INTRODUCTION: Natalizumab (NAT) is an effective treatment for relapsing remitting multiple sclerosis (RRMS), as it makes the blood-brain-barrier impenetrable by binding to the α4integrin subunit. The objectives of our study were to find new peripheral mechanisms of action of NAT and new biomarkers of treatment response. MATERIAL AND METHODS: We prospectively assessed the serum levels of 15 cytokines from the Th17 Cytokine Panel using Bio-plex Pro Human in a group of 29 RRMS patients treated with NAT and 29 healthy subjects (HS) at inclusion and after 8 months of NAT treatment. For each patient, demographic data, number of relapses and Expanded Disability Status Scale (EDSS) were collected and compared with the initial and final values of each cytokine. Moreover, the Th17/Treg shift was assessed using the interleukine (IL)-17F/IL-10 ratio and the cytokine signature (the sum of all the cytokines). Advanced statistical analysis was used. RESULTS: RRMS patients had significantly lower serum levels of IL-23, IL-17F, IL-1ß and IL-31 compared to HS. Serum sCD40L, IL-17F, IL-31 and cytokine signature levels significantly decreased after 8 months of NAT treatment. Positively correlations were found between the relapse number and IL- 17F, IL-1ß, IL-31 serum levels and between EDSS and tumor necrotic factor-α, IL-1ß and IL-17/IL-10 serum levels. IL-10 serum levels correlated negatively with the EDSS score. CONCLUSION: In evaluating the mode of action of NAT, it is important to determine the value of each cytokine, the Th17/Treg shift and the cytokine signature. NAT significantly decreased peripheral serum levels of some pro-inflammatory cytokines as a novel mechanism of action. IL-17F, sCD40L and IL-31 were the best biomarkers to assess the effectiveness of NAT.

Lethal Subarachnoid and Intracerebral Haemorrhage Associated with Temporal Arteritis. A Case Report.

Giant cell arteritis is a systemic inflammatory vasculitis, typically involving the superficial temporal arteries, but with possible ischemic and hemorrhagic cerebrovascular complications. The case is reported of a patient with a clinical picture of giant cell arteritis, who had multiple occupational exposures to various infectious agents. His initial favourable progress was followed by an atypical outcome. Despite immunosuppressive treatment, he developed fatal subarachnoid and intracerebral haemorrhages, possibly due to rupture of a microaneurysm of the posterior cerebral artery.

Giant tubular adenoma with malignancy clinical characteristics in a female teenager: Case report and a review of the literature.

BACKGROUND: Adenomas of the colon are usually benign tumors which carry a tendency for malignancy. These tumors can be villous, tubular, tubulovillous, or sessile serrated. Those with adenomatous structure can develop malignant characteristics in 1.5% to 9.4% of cases. METHODS: We present a case report of a 16-year-old female adolescent with an adenoma of the descending colon. History revealed prolonged diarrheic syndrome for the past 6 months, repeated headache, and a weight loss of ∼5 kg in the past month. One week before the admission, the patient presented an episode of inferior digestive hemorrhage. RESULTS: On admission laboratory tests revealed iron deficiency anemia, and a mildly increased erythrocyte sedimentation rate. The abdominal ultrasound revealed an inhomogeneous mass of the descending colon and 2 hyperechoic lesions in the liver. The colonoscopy showed a tumor of the descending colon, a tubular adenoma according to the pathological examination. Additionally, we noted an atypical presentation of the tumor and the signs of mild dysplasia identified at the pathological examination. CONCLUSION: Weight loss, bowel transit alterations, loss of appetite, and inferior hemorrhage in an adolescent can be symptoms of a benign or malignant tumor of the colon.

A coin-like peripheral small cell lung carcinoma associated with acute paraneoplastic axonal Guillain-Barre-like syndrome.

A 65-year-old previously healthy male heavy smoker was hospitalized with a 2-week history of progressive muscle weakness in the lower and upper extremities. After 10 days of hospitalization, urinary sphincter incompetence and fecal incontinence were added and tetraparesis was established. The computer-tomography scan examination revealed a massive right hydrothorax and multifocal solid acinar structures with peripheral localization in the left lung, which suggested pulmonary cancer. Bone marrow metastases were also suspected. Based on the examination results, the final diagnosis was acute paraneoplastic axonal Guillain-Barre-like syndrome. The patient died 3 weeks after hospitalization. At autopsy, bronchopneumonia and a right hydrothorax were confirmed. Several 4 to 5-mm-sized round peripherally located white nodules were identified in the left lung, without any central tumor mass. Under microscope, a coin-shaped peripheral/subpleural small cell carcinoma was diagnosed, with generalized bone metastases. A huge thrombus in the abdominal aorta and acute pancreatitis was also seen at autopsy. This case highlights the difficulty of diagnosis of lung carcinomas and the necessity of a complex differential diagnosis of severe progressive ascending neuropathies. This is the 6th reported case of small cell lung cancer-associated acute Guillain-Barre-like syndrome and the first report about an association with a coin-like peripheral pattern.

Cerebral lesions of multiple sclerosis: is gadolinium always irreplaceable in assessing lesion activity?

PURPOSE: We aimed to identify imaging characteristics on conventional magnetic resonance imaging that could predict multiple sclerosis (MS) brain lesion activity without contrast media administration. MATERIALS AND METHODS: Magnetic resonance data sets of forty-two patients with relapsing-remitting MS who presented symptoms or signs suggestive of new disease activity were retrospectively reviewed. We classified the MS lesions into three types according to different patterns present on T2-weighted images and evaluated their relationship with the contrast uptake. Evolving aspects of each type of lesion were observed in 18 patients during a follow-up period ranging from nine to 36 months. RESULTS: On T2-weighted images, only the pattern consisting of a thin border of decreased intensity compared with the lesion's center and perifocal edema (Type II) reached diagnostic accuracy in terms of its relationship with gadolinium enhancement (P = 0.006). The sensitivity was 0.461, and the specificity was 0.698. In contrast, enhancement was not significantly related to the pattern consisting of a lesion center that was homogeneously brighter than its periphery (Type I) or less-hyperintense T2 focal lesions with either homogeneous or inhomogeneous center (Type III) (P > 0.05 for both). CONCLUSION: The assessment of MS lesion activity should include a careful evaluation of T2-weighted images in addition to contrast enhancement assessment. The presence of an accompanying peripheral thin rim of hypointensity on T2-weighted images related best with contrast enhancement and subsequent lesion activity and may represent an additional pattern for disease activity assessment when gadolinium examination is contraindicated or influenced by prior therapy.