An unusual case of a gallbladder polyp.

A 63-year old female patient with a medical history of hypereosinophilic syndrome with neurological and pulmonary involvement presented for a routine follow-up. The patient was asymptomatic but a routine scheduled ultrasound showed a gallbladder polyp of 19mm. One month later this polyp had grown to 36 mm. On magnetic resonance imaging of the liver there was a suspicion of gallbladder cancer and for this reason cholecystectomy was performed. Pathology however showed eosinophilic infiltration. Serum analysis showed an increase in her eosinophil count. The diagnosis of hypereosinophilic syndrome with eosinophilic infiltration of the gallbladder was made. The dose of corticosteroids was augmented and she recovered completely post-operatively with no residual flares of other organ damage during follow up.

Primary sellar melanocytoma.

PURPOSE: We present an up-to-date review of all published cases of sellar melanocytoma, a benign melanocytic neoplasm arising from melanocytes present in the leptomeninges surrounding the pituitary. METHODS: Both the Medline and Embase databases were searched for case reports or case series of patients with a sellar mass consisting of melanocytes. RESULTS: All 14 identified patients developed symptoms due to compression of the surrounding structures. Symptoms included pituitary dysfunction and visual impairment. All patients received a transsphenoidal resection as first-line treatment. The diagnosis is made on pathological examination but deciding whether a sellar melanocytic tumor is best classified as a melanocytoma or a melanoma is not straightforward. DISCUSSION: Genetic analyses can help differentiate between central nervous system origin and metastasis of a cutaneous melanoma with the presence of a GNAQ and GNA11 mutations or a BRAF mutation, respectively. First choice treatment is complete resection, and in case of incomplete resection or recurrence additional radiotherapy is advised.

W' Recovery Kinetics after Exhaustion: A Two-Phase Exponential Process Influenced by Aerobic Fitness.

PURPOSE: The aims of this study were 1) to model the temporal profile of W' recovery after exhaustion, 2) to estimate the contribution of changing V˙O2 kinetics to this recovery, and 3) to examine associations with aerobic fitness and muscle fiber type (MFT) distribution. METHODS: Twenty-one men (age = 25 ± 2 yr, V˙O2peak = 54.4 ± 5.3 mL·min-1·kg-1) performed several constant load tests to determine critical power and W' followed by eight trials to quantify W' recovery. Each test consisted of two identical exhaustive work bouts (WB1 and WB2), separated by a variable recovery interval of 30, 60, 120, 180, 240, 300, 600, or 900 s. Gas exchange was measured and muscle biopsies were collected to determine MFT distribution. W' recovery was quantified as observed W' recovery (W'OBS), model-predicted W' recovery (W'BAL), and W' recovery corrected for changing V˙O2 kinetics (W'ADJ). W'OBS and W'ADJ were modeled using mono- and biexponential fitting. Root-mean-square error (RMSE) and Akaike information criterion (∆AICC) were used to evaluate the models' accuracy. RESULTS: The W'BAL model (τ = 524 ± 41 s) was associated with an RMSE of 18.6% in fitting W'OBS and underestimated W' recovery for all durations below 5 min (P < 0.002). Monoexponential modeling of W'OBS resulted in τ = 104 s with RMSE = 6.4%. Biexponential modeling of W'OBS resulted in τ1 = 11 s and τ2 = 256 s with RMSE = 1.7%. W'ADJ was 11% ± 1.5% lower than W'OBS (P < 0.001). ∆AICC scores favored the biexponential model for W'OBS, but not for W'ADJ. V˙O2peak (P = 0.009) but not MFT distribution (P = 0.303) was associated with W'OBS. CONCLUSION: We showed that W' recovery from exhaustion follows a two-phase exponential time course that is dependent on aerobic fitness. The appearance of a fast initial recovery phase was attributed to an enhanced aerobic energy provision resulting from changes in V˙O2 kinetics.

Weak MGMT gene promoter methylation confers a clinically significant survival benefit in patients with newly diagnosed glioblastoma: a retrospective cohort study.

INTRODUCTION: Quantitative methylation specific PCR (qMSP) is a frequently used technique to assess MGMT gene promoter methylation in glioblastoma patients. The optimal technical cut-off value to distinguish methylated from unmethylated samples is nevertheless still undetermined. In literature, a "grey zone" of diagnostic uncertainty has been described. METHODS: We performed a retrospective analysis of newly diagnosed glioblastoma patients treated according to the Stupp protocol. Epidemiological data were gathered from the individual patient files. MGMT gene promoter methylation status was determined on stored tumour samples using qMSP. A strong, weak or absent promoter methylation was determined based on Cq values (quantification value) of the MGMT and ACTB primers as well as a positive control sample. RESULTS: In total, 181 patient files were reviewed and included for statistical analysis. MGMT promoter hypermethylation was detected in 38.7% of glioblastoma patients. The median overall survival of unmethylated and strongly methylated patients was 10.1 months and 19.7 months respectively. Furthermore, 11% of the total patient cohort had a weak MGMT gene promoter methylation. The median OS in this subgroup was 15.4 months, significantly better compared to the unmethylated cohort (P < 0.001). Multivariate Cox regression analysis showed weak MGMT promoter methylation as an independent prognostic parameter for overall survival. CONCLUSION: Glioblastoma patients with weak promoter methylation show a statistically significant longer overall survival when compared to clearly unmethylated patients. Patients with grey zone qMSP test results should receive additional molecular analysis in future to further direct individual therapy strategies.

Androgen receptor expression in preputial dartos tissue correlates with physiological androgen exposure in congenital malformations of the penis and in controls.

INTRODUCTION: The androgen receptor (AR) plays an important role in the development of male genitalia, and impaired androgen signalling has been hypothesised to underlie congenital penile malformations (CPM) such as hypospadias. Previous studies exploring the role of AR expression in the development of CPM have yielded conflicting results. OBJECTIVES: To assess AR expression in human foreskin of boys/men born with hypospadias, buried penis versus controls. STUDY DESIGN: Foreskin samples of 428 boys and men undergoing primary penile surgery (198 controls, 197 hypospadias, and 33 buried penis) were collected between October 2013 and July 2018. AR staining was performed in all samples and semi-quantitatively scored by two researchers independently, using a modified quick score (mQuicks) that assesses the proportion and intensity of AR staining in smooth muscle fibres. RESULTS: The interobserver variability of the mQuicks had a high level of agreement for the total score, as well as for the subscores. Two phases of high AR expression were observed in all groups, the first following the postnatal gonadotropin surge (i.e., mini-puberty) and the second in (pre-) puberty. No differences in AR expression were found in hypospadias or buried penis cases as compared to controls matched for age at time of surgery. DISCUSSION: This study describes the physiological evolution in AR expression in the human foreskin of boys with CPM and explains the cause of the previously reported, conflicting results. Despite the very large cohort, the limitations of this study are the low number of cases younger than six months at the time of surgery and the lack of Tanner stages to correlate with the mQuicks in adolescents. CONCLUSIONS: The mQuicks is a straightforward and informative tool to semi-quantitatively assess AR expression in the dartos tissue. In this study, AR expression in human foreskin shows a bimodal distribution in boys with CMP and controls, following physiological androgen exposure. No statistically significant difference in AR expression could be found between both groups. Whether other local mechanisms are affected by these physiological changes is currently unclear. However, strict age-matching should be considered when exploring the mechanisms underlying disturbed penile and urethral development in CMP.

Routine histopathological examination after female-to-male gender-confirming mastectomy.

BACKGROUND: The number of transmen seeking gender-confirming surgery has risen steadily throughout the last decade. Pathologists are increasingly confronted with transmale mastectomy specimens. It is not clear whether routine histopathological examination is useful. This study explored the possible benefit of routine investigation through detailed description of lesions encountered in mastectomy specimens after female-to-male gender-confirming surgery. METHODS: Breast tissue from a cohort of transmen was reviewed. The presence of benign and malignant breast lesions was recorded. The number of terminal duct-lobule units (TDLUs) per ten low-power fields (LPFs) was quantified. Information on hormone therapy and morphometry was retrieved for selected patients. RESULTS: The cohort included 344 subjects with a mean age of 25·8 (range 16-61) years at the time of surgery; the age at surgery decreased significantly over time. Older individuals presented with a significantly higher number of breast lesions. The number of TDLUs per LPF was lower in heavier breasts, but did not correlate with age. Breast lesions, either benign or malignant, were present in 166 individuals (48·3 per cent). Invasive breast cancer was found in two (0·6 per cent); one tumour was an unexpected finding. The number of breast lesions encountered on histopathological examination increased significantly when more tissue blocks were taken. CONCLUSION: The discovery of an unexpected breast cancer in a 31-year-old transman emphasizes the importance of thorough routine histopathological examination of mastectomy specimens. The number of tissue blocks taken should be based on age and breast weight.

Identifying a consensus sample type to test for Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium, Trichomonas vaginalis and human papillomavirus.

OBJECTIVES: Sexually transmitted infections (STIs) are a global cause of acute illness. Early detection plays a crucial role in interrupting transmission and preventing complications. However, the accessibility of STI testing is curbed by the lack of an overall preferred sample type. By means of a prospective study in female sex workers (FSW), we compared the sensitivity of samples from different anatomical sites in detecting Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis, Mycoplasma genitalium and human papillomavirus. Besides, we documented the prevalence of each STI in this high-risk population. METHODS: We selected 303 FSW and tested them for each STI by nucleic acid amplification testing on two vaginal and cervical swabs from different manufacturers, cervical smear and first-void urine. The sensitivity of each sample type was compared for each infectious agent in order to identify a consensus sample type. RESULTS: Vaginal swabs were superior to all other sample types, with an overall sensitivity of 86%. The sensitivity was the lowest for first-void urine, detecting only 63% of positive cases. The prevalence was 3.3% (10/299) for Neisseria gonorrhoeae; 9.0% (27/299) for Chlamydia trachomatis; 7.4% (22/298) for Trichomonas vaginalis; 10.8% (32/296) for Mycoplasma genitalium and 55.6% (158/284) for human papillomavirus. CONCLUSIONS: When testing for STIs, vaginal swabs are the sample of choice and first-void urine should be avoided. Designating (self-sampled) vaginal swabs as a consensus sample type enables harmonization of STI testing and extension of testing to large numbers of unscreened females.

Desmoid tumour of the breast: case report and review of the literature.

Fibromatosis or desmoid tumour of the breast is an extremely rare, locally aggressive tumour with a tendency to relapse. Nevertheless these tumours do not have metastatic potential. Early recognition and wide local excision of the tumour is the treatment of choice. We present a case of a desmoid tumour of the breast in a 67-year-old woman and provide a review of the literature.

Azathioprine induced serious portal hypertension: a case series of three IBD patients and review of the literature.

We report 3 male IBD patients (2 Crohn's Disease, 1 Ulcerative Colitis) developing thrombocytopenia and splenomegaly on azathioprine treatment. All patients were diagnosed with significant portal hypertension due to histological proven nodular regenerative hyperplasia (NRH) of the liver. In two of three patients, liver function tests remained completely normal. In addition we provide a short literature review of azathioprine induced NRH covering etiology, imaging, pathology, prognosis and treatment.

Isolated synchronous meningioma of the external ear canal and the temporal lobe.

BACKGROUND: Extracranial meningiomas are common tumours but may occur in unexpected locations. Awareness can avoid misdiagnosis and inappropriate management of these tumours. We report the case of a 54-year-old Caucasian male with en plaque meningioma of the external ear canal and an intracranial temporal lobe meningioma. INTERVENTION: The patient underwent extended canal wall down atticomastoidectomy with preservation of the ossicular chain and tympanic membrane and en bloc resection of the bony posterior canal wall, tumour, and overlying skin. RESULTS: Radical removal of a grade I meningothelial meningioma was achieved. The tegmen tympani and dura were not breached. No connection with the temporal lobe meningioma was demonstrated. The patient recovered completely and experienced a marked improvement in hearing. No clinical signs of recurrent or residual tumour have occurred. CONCLUSION: Careful clinical examination and extensive radiological workup is required to avoid missing the unusual diagnosis of concurrent meningioma of the temporal bone and temporal lobe, and miss the chance to treat this disease adequately.

Membranous glomerulopathy in a patient with selective IgA deficiency: is there a link?

We report a 42-year-old woman, who presented with proteinuria (3.85 g/day) and malleolar oedema. She had a medical history of Graves' disease, recurrent upper respiratory tract infections, episodes of Raynaud phenomenon and dysphagia. Biochemistry showed a selective IgA deficiency (SIgAD). Percutaneous renal needle biopsy showed diffuse global thickening of the glomerular basement membranes on light microscopy and granular deposits of IgG and C3 along the glomerular basement membranes on immunofluorescence. The pathological diagnosis was membranous glomerulopathy stage II. A treatment with dietary salt restriction and an angiotensin-converting enzyme inhibitor was initiated, resulting in a reduction of proteinuria. Despite the fact that selective IgA deficiency is associated with various autoimmune disorders, the association with glomerular disease is rather rare and the pathogenesis is not fully understood.

Endovenous laser ablation: the role of intraluminal blood.

OBJECTIVE: In this histological study, the role of the intraluminal blood during endovenous laser ablation was assessed. METHODS: In 12 goats, 24 lateral saphenous veins were treated with a 1500-nm diode laser. Four goats were treated in an anti-Trendelenburg position (group 1). The next four goats were treated in a Trendelenburg position (group 2) and the remaining four goats in the Trendelenburg position with additional injection of tumescent liquid (group 3). Postoperatively, the veins were removed after 1 week and sent for histological examination. We measured the number of perforations. Vein wall necrosis and the perivenous tissue destruction were quantified using a graded scale. RESULTS: The 'calculated total vein wall destruction' was significantly higher in the third group (81.83%), as compared with groups one (61.25%) (p < 0.001) and two (65.92%) (p < 0.001). All three groups showed a significant difference in the perivenous tissue destruction scale (p < 0.001) with the lowest score occurring in the third group. Vein wall perforations were significantly more frequent in groups one and two as compared with the third group (T-test respectively p < 0.001, p = 0.02). CONCLUSION: A higher intraluminal blood volume results in reduced total vein wall destruction. Injection of tumescent liquid prevents the perivenous tissue destruction and minimises the number of perforations.

Relapsing infiltrates after pneumocystis pneumonia in stem cell transplant patients: think about BOOP!

Bronchiolitis Obliterans Organizing Pneumonia (BOOP) can complicate allogeneic haematopoietic stem cell transplantation. It is associated with prior graft-versus-host disease (GVHD) and the case fatality is 21%. In 22%, diagnosis is preceded by tapering the corticosteroids given as a treatment for GVHD. We report a fatal case of BOOP after tapering the corticosteroids that the patient received for a Pneumocystis jirovecii pneumonia after stem cell transplantation.

Intraluminal fibre-tip centring can improve endovenous laser ablation: a histological study.

OBJECTIVE: In this histological study, the lateral saphenous vein of the goat was treated using a laser fibre to which a tulip-shaped, self-expandable catheter had been fixed to achieve endovenous laser ablation (EVLA). The catheter centres the laser fibre in the vein preventing direct contact with the vein wall. This study aims to establish whether prevention of direct contact between the fibre tip and the vein wall prevents ulceration and perforation of the vein wall and perivenous tissue destruction. MATERIALS AND METHODS: Ten lateral saphenous veins were treated, using the tulip catheter, in goats under general anaesthesia. Ten more veins were treated with a normal bare fibre. We used a 980 nm diode laser to provide the energy. Postoperatively the veins were removed immediately, at 10 days and after 3 weeks for histological examination. Destruction of the vessel wall was measured and perivenous tissue destruction was quantified using a graded scale. RESULTS: Ulceration and perforation were prevented when using the tulip catheter. It also achieved more even vein wall necrosis. Tulip-catheter-treated veins show a transmural vein wall necrosis in, on average, 80% of the total circumference compared to 64% in bare-fibre treated veins. Less perivenous tissue destruction was seen with the new catheter (perivenous tissue destruction scale: tulip catheter: 1.7 vs. bare fibre: 3.8). Three weeks after treatment, we found regression of the perivenous tissue destruction as the healing process continued. CONCLUSIONS: EVLA using the tulip catheter avoids ulceration and perforation of the vein associated with treatment using a bare fibre. It also results in more even circumferential vein wall necrosis and less perivenous tissue destruction.

Acral myxoinflammatory fibroblastic sarcoma in a renal transplant patient: a case report.

Herein, we have reported a case of a 62-year-old patient who presented at 10 months after renal transplantation with a nodular mass on the dorsum of his foot. Local excision was performed and an acral myxoinflammatory fibroblastic sarcoma was diagnosed. This is a rare, low-grade sarcoma with a high rate of local recurrence, sometimes leading to amputation. Metastasis to the lungs and liver has been reported, but is rare. Since our patient received triple immunosuppressive therapy, our major concern was a much more aggressive behavior. However, more than 2 years after excision of the tumor, the patient is still free of disease.

Endovenous laser treatment: a morphological study in an animal model.

OBJECTIVES: The destruction induced during endovenous laser treatment (ELT) of the saphenous vein and the perivenous tissue in an animal model (goats) was analysed. Differences in vein wall destruction produced by two laser types, the 980 and 1500 nm diode lasers, were evaluated histologically. METHODS: In 14 goats, 28 lateral saphenous veins were treated with ELT. In 14 veins we used the 980 nm diode laser and in the remnant a 1500 nm laser. Postoperatively the veins were removed at different stages and sent for histological examination. RESULTS: Immediately removed veins after ELT show an uneven destruction of the vein wall. Veins harvested one week postoperatively show inflammatory tissue at their periphery. Two and three weeks postoperatively, organization is very extensive. In some cases, recanalization begins in a semi-lunar manner at the contralateral side of the laser hit. Veins treated with a 980 nm laser show deeper ulceration with more perivenous tissue destruction compared with veins treated with a 1500 nm diode laser. CONCLUSIONS: The ELT of veins produces an unevenly distributed damage. The cell necrosis is far more extensive than expected. Uneven vein wall destruction can lead to recanalization. Using a 1500 nm laser correlates with less penetrating ulcerations and more circumferential damage.

Chordoid glioma of the third ventricle.

BACKGROUND: Chordoid glioma is a rare tumour (World Health Organisation grade II) originating from the third ventricle with both glial and chordoid features. It was first described by Brat in 1998. Since there is no detailed information available on the outcome after surgery and adjuvant treatment, we reviewed the literature. METHODS: A literature search through PUBMED revealed 50 cases of chordoid glioma. Most reports were found in pathology journals. Information on the postoperative course was sometimes very limited. We reviewed the available literature and studied in detail the presenting symptoms, mortality and postoperative complications in relation to the extent of resective surgery, as well as the importance of adjuvant treatment. CONCLUSIONS: Mortality in the immediate postoperative period is 32% and is higher after gross total resection as compared to subtotal resection. Non-fatal postoperative complications are hypothalamic disorders and mental alterations. Gross total resection is the treatment of choice since no recurrence has been reported after macroscopically complete resection, but this is often difficult because of the location and adherence to the hypothalamus. The role of postoperative radiotherapy is uncertain. There is some indication that radiosurgery with or without conventional irradiation is superior to conventional radiation alone. Planned subtotal resection followed by stereotactic radiosurgery can be a safe and effective alternative in a patient in whom gross total resection is considered to be too risky. There is no report on the use of chemotherapy in the treatment of chordoid gliomas. More information about the optimal treatment strategy is needed, and more reports are also needed.

Aggressive cutaneous squamous cell carcinoma associated with prolonged voriconazole therapy in a renal transplant patient.

A 69-year-old man, with a history of end-stage renal disease due to polyarteritis nodosa, followed by invasive pulmonary aspergillosis secondary to cyclophosphamide and corticosteroids, received a renal transplant 2 years ago under prophylactic treatment with voriconazole. Because of the severity of the aspergillosis, it was decided to continue voriconazole for a prolonged period. Eighteen months after transplantation, the patient developed a severe facial phototoxic reaction. A few months later, he developed multiple actinic keratoses and a large, rapidly expanding, poorly differentiated squamous cell carcinoma (SCC) with perineural invasion and metastatic lymph nodes, necessitating radical surgery and radiotherapy. Voriconazole therapy has been suggested to be involved in the development of multi-focal invasive SCC when complicated by a phototoxic reaction. Therefore, an alternative antifungal prophylaxis regimen (for instance with posaconazole) should be considered when evaluating patients for solid organ transplantation who are at high risk for the development of cutaneous malignancies.

Neonatal neuronal overexpression of glycogen synthase kinase-3 beta reduces brain size in transgenic mice.

Glycogen synthase kinase-3beta (GSK-3beta) is important in neurogenesis. Here we demonstrate that the kinase influenced post-natal maturation and differentiation of neurons in vivo in transgenic mice that overexpress a constitutively active GSK-3beta[S9A]. Magnetic resonance imaging revealed a reduced volume of the entire brain, concordant with a nearly 20% reduction in wet brain weight. The reduced volume was most prominent for the cerebral cortex, without however, disturbing the normal cortical layering. The resulting compacted architecture was further demonstrated by an increased neuronal density, by reduced size of neuronal cell bodies and of the somatodendritic compartment of pyramidal neurons in the cortex. No evidence for apoptosis was obtained. The marked overall reduction in the level of the microtubule-associated protein 2 in brain and in spinal cord, did not affect the ultrastructure of the microtubular cytoskeleton in the proximal apical dendrites. The overall reduction in size of the entire CNS induced by constitutive active GSK-3beta caused only very subtle changes in the psychomotoric ability of adult and ageing GSK-3beta transgenic mice.