Microscopic Pathological Examination Research Articles

(004) ROUTINE PATHOLOGY EXAMINATION OF EXCISED SPECIMEN FROM PATIENTS WITH NEUROPROLIFERATIVE VESTIBULODYNIA

Abstract Introduction Neuroproliferative vestibulodynia (NPV) is suspected in individuals with vulvas with complaints of entrance dyspareunia, vestibular allodynia and hyperalgesia, after ruling out other causes. When conservative biopsychosocial treatments for suspected NPV are unsuccessful, vestibulectomy may be an appropriate option. Excised vestibular surgical specimens are routinely sent for pathologic assessment including hematoxylin and eosin (H&E) staining. Objective To review reports of gross and microscopic pathology examinations of excised vestibular specimens from a cohort of patients with NPV and compare immunohistochemical staining density among subgroups classified by severity of subepithelial inflammatory infiltrate. Methods Excised specimens from vestibulectomy surgeries were placed in 10% neutral buffered formalin prior to pathology examination. Routine pathology assessment included gross examination and cytological characterization of H&E-stained vestibular tissue for malignancy, viral nuclear changes (in addition to P16 staining as needed), and quality of the vestibular epithelium and subepithelial inflammatory infiltrate. Severity of this infiltrate was classified by the pathologist as mild, mild-moderate, moderate, or severe. Additional vestibular tissue sections were processed for immunohistochemical staining for CD117 and PGP9.5, protein markers consistent with mast cells and nerves, respectively. Separating the tissues into subgroups based on severity of subepithelial inflammatory infiltrate, they were compared to mast cell counts and immunopositive mean fractional area for CD117 and PGP9.5 using the Kruskal-Wallis test. Results Gross examinations of the 1:00-11:00 (n = 63) and 12:00 (n = 54) regions of vestibular tissue showed mean dimensions (length, width, thickness) to be 5.8 x 2.1 x 0.6 cm and 1.0 x 0.7 x 0.3 cm, respectively. Microscopic examinations revealed no malignant cells in any specimen, and viral nuclear findings were consistent with HPV in 3 specimens. Vestibular tissue was characterized as non-reactive squamous epithelium in 91% and 93% of specimens for the 1:00-11:00 and 12:00 regions, respectively. Mature lymphocytes were found in the subepithelial stromal infiltrate of 67% of specimens in both the 1:00-11:00 and 12:00 regions. Severity of subepithelial stromal infiltrate was reported as: mild in 67% and 65%; mild-moderate in 5% and 4%; moderate in 14% and 15%; and severe in 14% and 17% of cases for the 1:00-11:00 and 12:00 regions, respectively. Among the subgroups categorized by severity of inflammatory infiltrate, there were no significant differences for CD117-immunopositive cell counts or mean fractional area of CD117 and PGP9.5 in the 1:00-11:00 and 12:00 regions. Conclusions Routine pathology examination including H&E staining is standard for vestibulectomy specimens. There were no significant differences found among subgroups comparing severity of subepithelial inflammatory infiltrate with immunohistochemical data. Thus, information gleaned from routine pathology examination did not provide confirmation of the diagnosis of NPV. To better understand NPV, excised vestibular tissue should also be immunostained for CD117 and PGP9.5. Disclosure No.

(268) The Limited Role of Routine Pathology Examination in Neuroproliferative Vestibulodynia

Abstract Introduction Neuroproliferative vestibulodynia (NPV) is suspected in women with entrance dyspareunia, vestibular allodynia, and hyperalgesia, after ruling out other causes. If conservative biopsychosocial treatments in patients with suspected NPV are unsuccessful, vestibulectomy may be an appropriate option. Excised vestibular surgical specimens are sent for routine pathology assessment, including hematoxylin and eosin (H&E) staining. Objective To review reports of gross and microscopic pathology examinations of excised vestibular specimens from a cohort of patients with NPV and compare immunohistochemical (IHC) staining density between subgroups classified by severity of subepithelial inflammatory infiltrate. Methods Excised specimens from NPV patients, the 1:00-11:00 region (n = 63) and 12:00 region (n = 54) of the vestibule, were placed in 10% formalin prior to pathology examination. Routine pathology assessment included gross examination and cytological characterization of H&E-stained vestibular tissue for malignancy, viral nuclear changes (in addition to P16 staining), and quality of the vestibular epithelium and subepithelial inflammatory infiltrate. Severity of this infiltrate was classified by the pathologist as mild, mild-moderate, moderate, or severe. Additional vestibular tissue sections were processed for IHC staining for CD117 and PGP9.5, protein markers consistent with mast cells and nerves, respectively. Mast cell counts and immunopositive mean fractional area for CD117 and PGP9.5, separated into subgroups based on severity of subepithelial inflammatory infiltrate, were compared using Kruskal-Wallis test. Results Gross examinations of the 1:00-11:00 and 12:00 regions of vestibular tissue showed mean dimensions (length, width, thickness) to be 5.8 x 2.1 x 0.6 cm and 1.0 x 0.7 x 0.3 cm, respectively. Microscopic examinations revealed no malignant cells in any specimen and viral nuclear findings were consistent with HPV in 3 specimens. Vestibular tissue was characterized as non-reactive squamous epithelium in 90.5% and 92.6% of specimens for the 1:00-11:00 and 12:00 regions, respectively. Mature lymphocytes were found in the subepithelial stromal infiltrate of 67% of specimens in both the 1:00-11:00 and 12:00 regions. Severity of subepithelial stromal infiltrate was reported as: mild in 67% and 65%; mild-moderate in 5% and 4%; moderate in 14% and 15%; and severe in 14% and 17% of cases for the 1:00-11:00 and 12:00 regions, respectively. Amongst the subgroups categorized by severity of inflammatory infiltrate, there were no significant differences for CD117-immunopositive cell counts or mean fractional area of CD117 and PGP9.5 in the 1:00-11:00 and 12:00 regions. Conclusions No significant differences were found between subgroups of severity of subepithelial inflammatory infiltrate and IHC data. While routine pathology examination including H&E staining is standard for vestibulectomy specimens, such standardized assessment did not provide any insight into the severe allodynia and hyperalgesia associated with NPV, and further, was not useful for confirmation of the diagnosis of NPV. To better understand NPV, excised vestibular tissue should also be stained for CD117 and PGP9.5. Disclosure No.

The MRI features of renal inflammatory pseudotumor: A case report and literature review.

Inflammatory pseudotumor is rare observed in renal immunoglobulin G4-related disease. A 65-year-old female presented with a mass in the right kidney which was found in physical examination. Based on the imaging findings and clinical manifestations, we preliminarily judged that the mass of the right kidney was renal cell carcinoma. The patient finally underwent total nephrectomy. The final result of microscopic pathological examination is renal inflammatory pseudotumor. There are some characteristics on magnetic resonance imaging of renal inflammatory pseudotumor, which can improve diagnosis rate by combining with medical history and clinical manifestations.

What Is Different about Teratoma-Associated Anti-LGI1 Encephalitis? A Long-Term Clinical and Neuroimaging Case Series

Introduction: Anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis is clinically heterogeneous, especially at presentation, and though it is sometimes found in association with tumor, this is by no means the rule. Methods: Clinical data for 10 patients with anti-LGI1 encephalitis were collected including one case with teratoma and nine cases without and compared for clinical characteristics. Microscopic pathological examination and immunohistochemical assay of the LGI1 antibody were performed on teratoma tissue obtained by laparoscopic oophorocystectomy. Results: In our teratoma-associated anti-LGI1 encephalitis case, teratoma pathology was characterized by mostly thyroid tissue and immunohistochemical assay confirmed positive nuclear staining of LGI1 in some tumor cells. The anti-LGl1 patient with teratoma was similar to the non-teratoma cases in many ways: age at onset (average 47.3 in non-teratoma cases); percent presenting with rapidly progressive dementia (67% of non-teratoma cases) and psychiatric symptoms (33%); hyponatremia (78%); normal cerebrospinal fluid results except for positive LGI1 antibody (78%); bilateral hippocampal hyperintensity on magnetic resonance imaging (44%); diffuse slow waves on electroencephalography (33%); good response to immunotherapy (67%); and mild residual cognitive deficit (22%). Her chronic anxiety and presentation with status epilepticus were the biggest differences compared with the non-teratoma cases. Conclusion: In our series, anti-LGI1 encephalitis included common clinical features in our series: rapidly progressive dementia, faciobrachial dystonic seizures, behavioral disorders, hyponatremia, hippocampal hyperintensity on magnetic resonance imaging, and residual cognitive deficit. We observed some differences (chronic anxiety and status epilepticus) in our case with teratoma, but a larger accumulation of cases is needed to improve our knowledge base.

A novel next‐generation FVIIIa mimetic, Mim8, has a favorable safety profile and displays potent pharmacodynamic effects: Results from safety studies in cynomolgus monkeys

BackgroundMim8 is a novel, next‐generation factor VIIIa mimetic in development for subcutaneous prophylactic treatment of patients with hemophilia A with and without inhibitors. In vitro and in vivo models indicate that Mim8 has a distinct hemostatic potential. ObjectivesTo test the nonclinical safety and pharmacodynamics of Mim8. MethodsThe Mim8 nonclinical safety program in cynomolgus monkeys consisted of three studies of 4–26 weeks in duration with Mim8 doses ranging from 0.3–60 mg/kg/week intravenously or subcutaneously. After sacrifice, macroscopic and microscopic pathological examinations were performed. ResultsMim8 was well tolerated with no noteworthy clinical observations. No signs of excessive coagulation or pathological macroscopic or microscopic findings were observed at doses 0.3–3 mg/kg/week subcutaneous. Thrombosis‐related findings were detected during histopathological examination in a small proportion of animals (16%) receiving doses ranging 6–20 mg/kg/week. Dose‐dependent increases in factor X (FX) and factor IX (FIX) concentrations were observed. Shortening of activated partial thromboplastin time (APTT) and increased thrombin generation under ex vivo hemophilia A‐like conditions were observed at all Mim8 dose levels. ConclusionsThrombosis‐related findings observed at doses above 6 mg/kg/week Mim8 may have been exaggerated pharmacological reactions to a procoagulant compound in normocoagulant animals. Increases in FX and FIX concentrations could be because of a half‐life prolongation due to binding to Mim8, but were limited at clinically relevant exposure levels. Subcutaneous administration of up to 3 mg/kg/week (several fold greater than expected clinical exposure) for 26 weeks resulted in relevant pharmacodynamic effects, observed in thrombin generation and APTT, with no signs of thrombi or excessive coagulation activation.

Diagnostic Investigation of 100 Cases of Abortion in Sheep in Uruguay: 2015-2021.

The aim of this work was to identify causes of abortion through laboratory investigations in sheep flocks in Uruguay. One hundred cases of abortion, comprising 58 fetuses, 36 fetuses with their placentas, and 6 placentas were investigated in 2015–2021. Cases were subjected to gross and microscopic pathologic examinations, and microbiological and serological testing for the identification of causes of abortion, including protozoal, bacterial, and viral pathogens. An etiologic diagnosis was determined in 46 (46%) cases, including 33 (33%) cases caused by infectious pathogens, as determined by the detection of a pathogen along with the identification of fetoplacental lesions attributable to the detected pathogen. Twenty-seven cases (27%) were caused by Toxoplasma gondii, 5 (5%) by Campylobacter fetus subspecies fetus, and 1 (1%) by an unidentified species of Campylobacter. Fourteen cases (14%) had inflammatory and/or necrotizing fetoplacental lesions compatible with an infectious etiology. Although the cause for these lesions was not clearly identified, T. gondii was detected in 4 of these cases, opportunistic bacteria (Bacillus licheniformis, Streptococcus sp.) were isolated in 2 cases, and bovine viral diarrhea virus 1 subtype i (BVDV-1i) was detected in another. Campylobacter jejuni was identified in 1 (1%) severely autolyzed, mummified fetus. BVDV-2b was identified incidentally in one fetus with an etiologic diagnosis of toxoplasmosis. Microscopic agglutination test revealed antibodies against ≥1 Leptospira serovars in 15/63 (23.8%) fetuses; however, Leptospira was not identified by a combination of qPCR, culture, fluorescent antibody testing nor immunohistochemistry. Neospora caninum, Chlamydia abortus, Chlamydia pecorum, Coxiella burnetii and border disease virus were not detected in any of the analyzed cases. Death was attributed to dystocia in 13 (13%) fetuses delivered by 8 sheep, mostly from one highly prolific flock. Congenital malformations including inferior prognathism, a focal hepatic cyst, and enterohepatic agenesis were identified in one fetus each, the latter being the only one considered incompatible with postnatal life. Toxoplasmosis, campylobacteriosis and dystocia were the main identified causes of fetal losses. Despite the relatively low overall success rate in establishing an etiologic diagnosis, a systematic laboratory workup in cases of abortion is of value to identify their causes and enables zoonotic pathogens surveillance.

What management for patients with R1 resection after total mesorectal excision for rectal cancer? A review of the literature.

Treatment for rectal cancer is very standardized. However, for total mesorectal excision (TME) with positive margins at microscopic pathological examination (classified R1 ), there is no consensus regarding management. The objective of this update was, through a review of the literature, to identify the most suitable management to improve overall survival and/or recurrence-free survival after R1 TME for rectal cancer. Published national quality guidelines and original studies were searched on Pubmed. Only studies and recommendations concerning the specific management of patients who had undergone R1 TME resection were selected. Five original non-randomized studies and seven published national quality guidelines were selected for review. For patients who have undergone R1 TME resection, the French and European published guidelines issued a Grade A recommendation in favor of post-operative radio-chemotherapy (RCT) for those in whom it had not already been performed pre-operatively. The French and European guidelines recommendation for adjuvant chemotherapy was based only on expert agreement. The original studies emphasized the survival benefit of adjuvant chemotherapy, as opposed to post-operative RCT, which did not seem to improve survival. Salvage surgery was not recommended in any of the studies. After R1 TME resection for rectal cancer, adjuvant chemotherapy seems to be indicated when feasible, whereas post-operative RCT and salvage surgery do not appear to improve patient survival.

Acute appendicitis: a case report of hyperinfection with Enterobius vermicularis.

Acute appendicitis is one of the most common causes of abdominal emergent surgical disease worldwide. Enterobius vermicularis, a human intestinal parasite, is reported to be associated with acute appendicitis. We report a case of an 8-year-old girl who was admitted to the emergency unit with complaints of severe abdominal pain and was diagnosed with acute appendicitis. Microscopic pathological examination showed lymphoid follicles with prominent germinal centers and mantle zones within the appendix wall. Cross-sections of multiple female and male Enterobius vermicularis worms and a few longitudinal sections of E.vermicularis were seen. vermicularis is one of the most common human parasitic infections, so the possibility of infection of the appendix with E. vermicularis should be considered in the differential diagnosis of agents of appendicitis. Keywords: Appendicitis, Parasite, Enterobius, Khoy. (Please cite as: Hooshyar H, Jannati Dastgerdi M, Kazemi E. Acute appendicitis: a case report of hyperinfection with Enterobius vermicularis. Gastroenterol Hepatol Bed Bench 2021;14(3):286-289).

Amoebiasis of the Penis: A Review and Update

Ulceration of the penis/foreskin which would tend to be painful, Swelling of the penis, Oedema of the penis, Discharge from ulcer or inflamed area of penis that could be purulent or may contain blood, Balanoposthitis, Exudation from a penile ulcer which could be mild, profuse, purulent or bloody, Sloughing off of part of the foreskin and other tissues with resulting hypospadias, indurated swelling of the penis which may initially involve one part of the penis but could quickly spread, A history of homosexual coital activity may be obtained, The spouse of a man who has Amoebiasis of the penis could also have Amoebiasis of vulva, cervix or endometrium, The prepuce may not be retractable, There may be ulceration or swelling of the glans penis that may be irregular. Clinical examination findings in cases of Amoebiasis of the penis could reveal some of the ensuing: The general and systematic examinations may be normal. Examination of the penis may show: Tight non-retractile foreskin, Ulceration of foreskin, Swelling of the foreskin, Swelling of the glans penis, Ulceration and swelling of glans penis., Swelling and inflammation of the shaft of the penis, Ulceration on the shaft of the penis, Development of an iatrogenic hypospadias which was not there before, The inguinal lymph nodes may not be palpable but sometimes they may be enlarged on one side or on both sides, The penile swelling may involve part of the penis but at times on rare occasions the entire penis may be swollen, the penile swelling could on rare occasions extend to the supra-pubic area, On rare occasions the swelling of the penis could extend to include the scrotum but this is extremely rare. Amoebiasis of the penis does mimic various common conditions that affect the penis including: squamous cell carcinoma of the penis, chancroid, primary syphilitic ulcer of the penis, granuloma inguinale, balanoposthitis, and many other lesions affecting the penis. A high-index of suspicion is required to diagnose Amoebiasis of the penis. Clinicians need to be aware that male homosexuals who practice penetrative penis-anal coital activity have a higher risk of developing amoebiasis of the penis especially in Amoebiasis endemic countries. If an individual is suspected to have balanoposthitis or non-specific infection of the penis and is treated with antibiotics but the lesion does not respond to treatment, amoebiasis of the penis should be suspected. Secretions and discharges from the penile ulcer as well as biopsies of the penile lesion should be submitted for pathology examination which would demonstrate trophozoites, entamoebae as well as inflammatory cells. Even if carcinoma of the penis is initially suspected biopsy of the penile lesion would show features of Amoebiasis in the absence of any features of malignancy but in the very rare situation of a combination of Amoebiasis of the penis and carcinoma of the penis microscopic pathology examination of a biopsy specimen of the penile lesion would show features of Amoebiasis and carcinoma of the penis. .Amoebiasis of the penis does quickly and effectively respond to anti-amoebic medicaments.

A Novel Next-Generation FVIII Mimetic, Mim8, Has a Favourable Safety Profile. Results from a 26-Week Safety Study in Cynomolgus Monkeys

Introduction Mim8 is in clinical development as a novel, next generation FVIII mimetic for subcutaneous prophylactic treatment for people with Hemophilia A (HA) with and without inhibitors. Mim8 is a fully human bispecific antibody bridging FIXa and FX. Mim8 showed approximately 15-fold higher potency compared to a sequence identical analogue (SIA) of the FVIII mimetic emicizumab (Hemlibra®) in thrombin generation assays (TGAs) and in vivo in mouse bleeding models (Kjellev et al., 2019; Ley et al. 2020). Mim8 binds to cynomolgus monkey and human FIX and FX with comparable affinities, and the pharmacological activity of Mim8 in cynomolgus monkeys was demonstrated both in vitro in TGA and in vivo in a cynomolgus bleeding model (Ley et al., 2020). The present study examined the safety and ex vivo pharmacodynamic effects of Mim8 in cynomolgus monkeys after weekly dosing for 26 weeks. Material and Methods Sexually mature cynomolgus monkeys were dosed subcutaneously (SC) with Mim8 at dose-levels of 0, 0.3, 1 or 3 mg/kg/week (4 males and 4 females at each dose-level) for 26 weeks. These dose-levels were chosen based on a previous 13-week safety study showing histopathological changes consistent with exaggerated pharmacology in a few animals dosed ≥6 mg/kg/week. During the study, the animals were monitored clinically and blood was sampled for measurement of standard clinical pathology, Mim8 exposure, anti-drug antibodies (ADA). The pharmacodynamic activity was assessed by ex vivo TGA in plasma under antibody-induced HA-like conditions and measurement of activated partial thromboplastin time (aPTT). After 26 weeks of exposure, the animals were euthanised, followed by macroscopic and microscopic pathological examination on all major organ systems. Results Weekly dosing with Mim8 at dose-levels up to 3 mg/kg/week for 26 weeks was well tolerated and the macroscopic and microscopic pathological examinations revealed no thrombi or other signs of excessive coagulation activation. In accordance, no significant changes in platelet counts, fibrinogen concentration or prothrombin time were observed. A pharmacodynamic effect was observed in dosed animals as a dose-dependent increase in ex vivo thrombin generation (TG; Figure 1) and shortening of aPTT. The steady state exposure increased with increasing dose level in a dose-proportional manner, reaching concentrations at least 10-fold above the expected clinical concentrations. However, as expected when dosing a human antibody to monkeys, ADAs developed in approximately half of the animals at all dose levels, leading to lack of exposure and reversal of the aPTT and TG towards the predose levels. Conclusion In conclusion, administration of up to 3 mg/kg/week Mim8 to cynomolgus monkeys for 26 weeks showed relevant pharmacodynamic effect and was well tolerated with no observation of thrombi or other signs of excessive coagulation activation, providing a favourable safety ratio to expected clinical exposure levels. Mim8 is currently being evaluated in a clinical Phase 1/2 trial. References Kjellev SL et al. (2019) Mim8 - a next-generation FVIII mimetic bi-Specific antibody - potently restores the hemostatic capacity in hemophilia a settings in vitro and in vivo. Blood, 134 (Supplement 1): 96. Ley CD et al. (2020) Improved effect of Mim8, a next-generation FVIII mimetic, translates from human in vitro to humanized mouse and cynomolgus models. European Association for Haemophilia and Allied Disorders (EAHAD 2020). Haemophilia, 26 (S2), P028. Disclosures Kjalke: Novo Nordisk A/S: Current Employment, Current equity holder in publicly-traded company.

Causes of abortion in dairy cows in Uruguay

ABSTRACT: A case series study was conducted to determine the frequency of causes of abortion in dairy cattle in Uruguay. The sample size of 102 cases was composed of 53 fetuses, 35 fetuses with placentas, and 14 placentas without an associated fetus. All cases underwent gross and microscopic pathologic examinations as well as microbiological and serological testing. The etiology was determined in 54 (53%) of cases, 51 of which were caused by infectious agents. Within the observed 102 cases, 30 (29%) were caused by Neospora caninum, six (6%) by Coxiella burnetii and two (2%) by Campylobacter fetus subsp. venerealis. Bovine Parainfluenza-3 virus and Salmonella enterica serovar Newport caused one abortion each. Opportunistic bacteria (Escherichia coli, Streptococcus sp., Staphylococcus sp., Mannheimia sp., Trueperella pyogenes, and Providencia stuartii) were associated with 11 abortions. In two cases the fetal death was attributed to dystocia, and in one case the fetus had a congenital mesothelioma. Bovine viral diarrhea virus (BVDV) infection was identified in three fetuses; two of which were co-infected with and had typical lesions of N. caninum. No lesions were observed in the other fetus infected by BVDV. Leptospira interrogans was identified in one fetus without lesions. Despite the relatively low overall success rate in establishing an etiological diagnosis in cases of abortion in cattle, a systemic workup of bovine abortion is necessary to establish prevention and control strategies. This also facilitates monitoring and surveillance of reproductive diseases in dairy cattle, some of which represent a risk to public health.

Abortion outbreak caused by Campylobacter fetus subspecies venerealis and Neospora caninum in a bovine dairy herd

In November 2015, an abortion outbreak occurred in a commercial dairy herd of 650 Holstein cows in Florida department, Uruguay. Forty-five cows aborted within three weeks. Five fetuses were subjected to gross and microscopic pathologic examination, and microbiological testing. One fetus had fibrinous epicarditis and peritonitis, and neutrophilic bronchopneumonia. Campylobacter fetus subsp. venerealis was detected by direct immunofluorescence, isolated and identified by PCR and sequencing of the 16S rDNA in the abomasal fluid and/or lung. Histologic examination of two other fetuses revealed non-suppurative necrotizing encephalitis, lymphohistiocytic myositis and myocarditis, and lymphocytic interstitial nephritis. In these fetuses, N. caninum antigen was detected intralesionally by immunohistochemistry, and N. caninum DNA was amplified by PCR on formalin-fixed paraffin-embedded brain. Antibodies against N. caninum were detected by indirect immunofluorescence in 10 of 27 cows, with titers ranging from 1/200 to 1/3200. The results indicate that two abortigenic microorganisms may coexist and cause contemporaneous abortion in a herd. We highlight the importance of performing multiple diagnostic tests in various aborted dams and fetuses from the same herd for the etiologic confirmation of bovine abortion syndrome.

Right-sided Bochdalek hernia containing retroperitoneal fat in the elderly: report of a case

BackgroundMost cases of Bochdalek hernias are diagnosed during the neonatal period and arise on the left side. We report a rare case of a right-sided Bochdalek hernia in an elderly patient.Case presentationA 72-year-old man presented with chest tightness and nausea. He had no history of thoracic and abdominal trauma. Preoperative CT scan showed a well-circumscribed mass in the right thoracic cavity of 28-cm diameter compressing the right lower lobe. The mass was mostly fat component and seemed to connect with retroperitoneal fat. We made some diagnoses: lipoma, liposarcoma, and diaphragmatic hernia. Surgical resection was performed by thoracotomy so as to resect the mass and repair the defect of the diaphragm. The mass seemed to be retroperitoneal fat which escaped from the hernia orifice. The neck of the mass was separated by a vessel-sealing device immediately above the hernia orifice. The defect of the diaphragm was repaired by direct suturing after completion of resection. Microscopic pathologic examination showed that the mass was maturated fat tissue. Four months postoperatively, there was no evidence of recurrence of the hernia.ConclusionsThe diagnosis of an adult Bochdalek hernia is often difficult, so it is important to consider the examination carefully and to determine the better surgical procedure.

Villous adenoma coexistent with focal well-differentiated adenocarcinoma of female urethral orifice: A case report and review of literature

BACKGROUNDVillous adenomas of the urinary tract are uncommon. They are morphologically similar to and difficult to differentiate from their counterpart in the colon. The histogenesis and malignant potential are uncertain.CASE SUMMARYA 63-year-old woman was admitted to our hospital with a mass in the urethral orifice. Gross and microscopic pathological examination was suggestive of urethral villous adenoma with focal well-differentiated adenocarcinoma. The whole urethra and part of the bladder were excised. No further treatment was offered. Carcinoembryonic antigen, cytokeratin 7, cytokeratin 20, epithelial membrane antigen, and p53 protein were positive, and the ratio of Ki-67 was 60%. After follow-up at 11 mo, the patient was cured and had no recurrence.CONCLUSIONImmunohistochemistry is important for differential diagnosis of villous adenoma of the urinary system. Complete surgical resection of the urinary tract is curative.

Administration of recombinant FVIIa (rFVIIa) to concizumab‐dosed monkeys is safe, and concizumab does not affect the potency of rFVIIa in hemophilic rabbits

Essentials Hemophilia patients on concizumab prophylaxis may need rFVIIa to treat breakthrough bleeds. Effect and safety of concizumab+rFVIIa were tested invitro and invivo. Concizumab+rFVIIa had no additive effects on bleeding in hemophilic rabbits. High steady-state levels of concizumab did not affect the safety of rFVIIa in cynomolgus monkeys. SUMMARY: Background Concizumab is a monoclonal antibody (mAb) against tissue factor pathway inhibitor (TFPI), currently in clinical development as a subcutaneous prophylactic therapy for hemophiliaA/B with and without inhibitors. In patients with inhibitors, the treatment choice for breakthrough bleeding will comprise bypassing agents, e.g. activated recombinant FVIIa (rFVIIa) or activated prothrombin complex concentrates. Objectives To explore the effect and safety of concizumab and rFVIIa when they are simultaneously present. Methods Human blood made hemophilic with a FVIII antibody was spiked with increasing concentrations of concizumab, rFVIIa, or concizumab and rFVIIa in combination, and this was followed by thrombin generation test or thromboelastography. Blood loss in hemophilic rabbits was measured when concizumab, rFVIIa or concizumab+rFVIIa was administered either before or during cuticle bleeding. In a safety study, cynomolgus monkeys were exposed to high steady-state concizumab concentrations and given three doses of rFVIIa, and then subjected to full necropsy and histopathological examination. Results In human blood, concizumab+rFVIIa had more pronounced procoagulant effects under hemophilic conditions than the sum of individual responses. In contrast, concizumab+rFVIIa had no additional effects on blood loss in hemophilic rabbits as compared with rFVIIa or concizumab alone. In cynomolgus monkeys, the macroscopic and microscopic pathological examinations revealed no thrombi or other signs of excessive coagulation activation. Both rFVIIa and concizumab caused increases in thrombin-antithrombin and D-dimer concentrations; this effect tended to be additive with concomitant administration. Conclusions Concizumab did not affect the potency or safety of rFVIIa invivo. These results support a clinical evaluation of rFVIIa at standard dose (90μgkg-1 ) to treat breakthrough bleeds in concizumab clinical trials.

Occurrence and Levels of Aflatoxins in Fish Feeds and Their Potential Effects on Fish in Nyeri, Kenya

Aflatoxins are fungal metabolites that contaminate foods and feeds, causing adverse health effects in humans and animals. This study determined the occurrence of aflatoxins in fish feeds and their potential effects on fish. Eighty-one fish feeds were sampled from 70 farms and 8 feed manufacturing plants in Nyeri, Kenya for aflatoxin analysis using competitive enzyme-linked immunosorbent assay. Fish were sampled from 12 farms for gross and microscopic pathological examination. Eighty-four percent of feeds sampled tested positive for aflatoxins, ranging from 1.8 to 39.7 µg/kg with a mean of 7.0 ± 8.3 µg/kg and the median of 3.6 µg/kg. Fifteen feeds (18.5%) had aflatoxins above the maximum allowable level in Kenya of 10 µg/kg. Homemade and tilapia feeds had significantly higher aflatoxin levels than commercial and trout feeds. Feeds containing maize bran and fish meal had significantly higher aflatoxin levels than those without these ingredients. Five trout farms (41.7%) had fish with swollen abdomens, and enlarged livers with white or yellow nodules, which microscopically had large dark basophilic hepatic cells with hyperchromatic nuclei in irregular cords. In conclusion, aflatoxin contamination of fish feeds is prevalent in Nyeri, and may be the cause of adverse health effects in fish in this region.

A Rare Case of Metastatic Colon Cancer Involving the Right Atrium Presenting as Superior Vena Cava Syndrome

Colorectal cancer is one of the most common forms of malignancies and is well documented to metastasize to liver, lungs and peritoneum. Only a handful of well-documented cases of colorectal cancer metastasis to the right atrium have been documented. As such, we report a rare case of colon adenocarcinoma that metastasized to the right atrium and resulted in superior vena cava (SVC) syndrome. The patient is a 50-year-old male with history of hyperlipidemia, anxiety and metastatic colon cancer involving lungs and liver previously treated with chemotherapy and recently with immunotherapy who was transferred to our hospital for management of occluded SVC with the mass extending into the left atrium. The patient initially presented at another hospital for facial and upper extremity swelling and shortness of breath. A CT of the chest noted occluded SVC with a right atrial mass. This was further confirmed on transesophageal echocardiography which noted a large mass occupying most of the right atrial cavity measuring 6.8cm x 4.6cm and was noted to prolapse across the tricuspid valve in to the right ventricle. He was started on Eliquis and was transferred to our hospital for further management. He underwent an angiovac thrombectomy with Interventional Radiology (IR). During the procedure, findings of right atrial mass extending into the SVC were noted with subsequent partial debulking of the mass. Post procedure, the patient reported moderated improvement of his symptoms of dyspnea and swelling. Microscopic pathologic examination of the excised mass exhibited histomorphological features of metastatic colorectal cancer as cells demonstrated strong and diffuse nuclear reactivity for CDX2 stain. CT surgery evaluated patient for further surgical evaluation of right atrial mass, however he was deemed a poor surgical candidate. As such, IR placed a stent in the SVC to further alleviate SVC occlusion. Prior to discharge, Oncology also evaluated patient and recommend continued palliative radiation as outpatient. Conclusion: Although rare, any patient with a history of colorectal adenocarcinoma who presents with cardiopulmonary symptoms and suspicious cardiac mass should undergo evaluation for possible cardiac metastasis. It is recommended that a multidisciplinary approach involving cardiologists, oncologists, IR, and cardiothoracic surgeons is essential for determining the optimal therapeutic regimen for such patients.1483_A Figure 1. CT of the chest exhibiting the Right atrial mass1483_B Figure 2. Right atrial mass and thrombus extending into superior vena cava1483_C Figure 3. Microscopic pathologic examination of the excised mass exhibited histomorphological features of metastatic colorectal cancer as cells demonstrated strong and diffuse nuclear reactivity for CDX2 stain

Cervical image classification based on image segmentation preprocessing and a CapsNet network model

AbstractCervical cancer is one of the most common gynecological malignancies, and when detected and treated at an early stage, the cure rate is almost 100%. Colposcopy can be used to diagnose cervical lesions by direct observation of the surface of the cervix using microscopic biopsy and pathological examination, which can improve the diagnosis rate and ensure that patients receive fast and effective treatment. Digital colposcopy and automatic image analysis can reduce the work burden on doctors, improve work efficiency, and help healthcare institutions to make better treatment decisions in underdeveloped areas. The present study used a deep‐learning model to classify the images of cervical lesions. Clinicians could determine patient treatment based on the type of cervix, which greatly improved the diagnostic efficiency and accuracy. The present study was divided into two parts. First, convolutional neural networks were used to segment the lesions in the cervical images; and second, a neural network model similar to CapsNet was used to identify and classify the cervical images. Finally, the training set accuracy of our model was 99%, the test set accuracy was 80.1%, it obtained better results than other classification methods, and it realized rapid classification and prediction of mass image data.

Secretory carcinoma of the breast: clinical histopathologic and biological behaviors

Objective: To investigate the clinicopathological and immunohistochemistrical features of secretory carcinoma of the breast (SCB), as well as its diagnosis and prognosis. Methods: Five cases of SCB were collected and specimens were fully drawn. Microscopic pathology examinations and immunohistochemistry(SP method)were performed. Results: Five cases were all female patients aged from 31 to 54 years old (with an average age of 38 years), and all patients initially presented with the painless breast lump, often near the areola. Macroscopically, all the tumors were relatively circumscribed, with a mean diameter of 2.1 cm(1.2-3.0 cm). Histologically, the tumors revealed different patterns (microcystic, solid, ductal, and so forth) and appeared large amounts of intracellular and extracellular eosinophilic PAS- and AB-PAS- positive secretory materials, as well as the granular eosinophilic cytoplasm. Immunohistochemistrically, the tumor cells were strongly positive for epithelial membrane antigen (EMA) and S-100. Three cases had negative expression for estrogen receptor (ER) and progesterone (PR), and two cases had weakly focal expression. Human epidermal growth factor receptor 2 (HER2) and P53 were negative, while only one case had weakly focal expression. The tumors were positive for CK7, CK5/6, CD10, but they were negative for CEA, smooth muscle actin (SMA) and P63 . The proliferation index of Ki-67 was 5%-8%. There was no patient with metastasis of the tumor in axillary lymph node. Except 1 case lost follow-up, and the rest had no recurrence or distant metastasis. Conclusions: SCB is very rare, with low malignancy, and has better prognosis, but it is usually classified as triple-negative breast cancer because of the immune phenotype. The correct diagnosis of this lesion depends on clinical characteristics, morphology and immunohistochemistry.

Safety evaluation of subchronic feeding of nisI transformed Lactobacillus plantarum in Sprague‐Dawley rats

AbstractThe nisI gene was inserted into Lp (Lactobacillus plantarum) genome and obtained Lp590 (L. plantarum 590). The nisI gene can help Lp590 tolerate higher concentration of nisin. Although Lp was generally recognized as safe, the safety of the nisI transformed Lp is unknown. In this study, six groups of Sprague‐Dawley (three groups/sex) rats were orally administered with Lp, Lp590 or physiological saline for 90 days. Nutritional status and growth performance were evaluated followed by analysis of blood biochemistry, hematology and organ variables. Compared with control, we did not find any treatment‐related adverse or toxic effects on the examination of clinical signs, body weight, organ weight, serum biochemistry, hematology, gross, and microscopic anatomic pathological examination. These results demonstrated that the Lp590 is as safe as Lp in our subchronic feeding trial.Practical applicationsThe purpose of this study is to evaluate the safety of transformed Lactobacillus plantarum. In this current 90‐day feeding study, body weight, feed consumption and toxicological response variables (hematological parameters, serum chemistry, absolute, and relative organ weight) were measured, and gross as well as microscopic pathology were examined. No adverse effects were observed on animals. The results indicated that Lp590 is as safe as Lp. The result can add the safety evidence of transformed microorganism.