Complete and long-lasting response to immunotherapy: A case report of urothelial cancer

Introduction:Bladder cancer is the tenth most common cancer worldwide, with Europe having the highest incidence rates. Regarding the treatment of metastatic disease, first-line treatment for fit patients is cisplatin-containing combination chemotherapy. However, a significant percentage of patients are ineligible for platinum-based chemotherapy, or progress under these regimens. Recently, immune checkpoint blockade has become a treatment option for this group of patients. In this report, we present the case of a male patient diagnosed with metastatic bladder cancer who did not tolerate cisplatin-containing chemotherapy and achieved complete response after treatment with pembrolizumab.Patient concerns:A 58 years-old Caucasian man with a medical history of high-grade urothelial carcinoma pT3bN0R0 under a watchful waiting strategy for 6 months presented to the Medical Oncology appointment with two axillary and cervical adenopathies.Diagnosis:Cervicothoracoabdominal computed tomography confirmed the presence of two large necrotic lymphadenopathies in the cervical and axillary lymphatic chains, and bone scintigraphy revealed dorsal (D11) and lumbar (L5) metastatic lesions. Ultrasonography-guided biopsy of the axillary nodule revealed the presence of metastatic tissue of primary urothelial origin.Interventions:The patient was initiated on a palliative chemotherapy regimen of carboplatin area under the curve 5 plus gemcitabine (1000 mg/m²). During the first cycle of chemotherapy, acute kidney failure akin 2 developed due to nonobstructive toxic acute tubular necrosis with progressive deterioration of kidney function. Therefore, palliative chemotherapy with carboplatin plus gemcitabine was changed to 200 mg of pembrolizumab every 21 days.Outcomes:Overal survival of 57 months with an immune complete response according to the immune Response Evaluation Criteria in Solid Tumours criteria and an excellent quality of life.Conclusion:This case illustrates that second-line therapy with ICIs (pembrolizumab or atezolizumab) has favourable results in achieving an immune complete response after intolerance to cisplatin-based regimens. ICIs provide durable responses that improve overall survival and quality of life.     

Pro-Inflammatory Profile of Children Exposed to Maternal Chikungunya Virus Infection during the Intrauterine Period: A One-Year Follow-Up Study

Chikungunya virus (CHIKV) vertical transmission occurs due to maternal viremia in the prepartum. Clinical presentation in neonates can be varied; however, the consequences of intrauterine exposure on the immune response are unclear. Thus, we aimed to analyze inflammatory alterations in children exposed to maternal CHIKV infection. This is a cross-sectional study that included children exposed to maternal CHIKV infection (confirmed by RT-qPCR and/or IgM). Circulant immune mediators were analyzed by a multiplex assay. RESULTS: We included 33 children, with a mean age of 3 ± 2.9 months-old, and 19 (57.6%) were male. Only one child presented neurological alterations. CHIKV-exposed infants showed elevated levels of MIP-1α, MIP-1β, and CCL-2 (p < 0.05). Pro-inflammatory cytokines such as TNFα, IL-6, and IL-7 (p < 0.0001) were also increased. In addition, lower levels of PDGF-BB and GM-CSF were observed in the same group (p < 0.0001). Principal component (PC) analysis highlighted a distinction in the inflammatory profile between groups, where PC explained 56.6% of the alterations. Our findings suggest that maternal exposure to CHIKV can affect the circulating levels of pro-inflammatory cytokines during the infants’ first year of life. The long-term clinical consequences of these findings should be investigated.     

Chagasic meningoencephalitis: case report of a recently included AIDS-defining illness in Brazil

Recently, reactivation of Chagas disease (meningoencephalitis and/or myocarditis) was included in the list of AIDS-defining illnesses in Brazil. We report a case of a 52-year-old patient with no history of previous disease who presented acute meningoencephalitis. Direct examination of blood and cerebrospinal fluid (CSF) showed Trypanosoma cruzi. CSF culture confirmed the diagnosis. Serological assays for T. cruzi and human immunodeficiency virus (HIV) were positive. Despite treatment with benznidazol and supportive measures, the patient died 24 hours after hospital admission. In endemic areas, reactivation of Chagas disease should always be considered in the differential diagnosis of meningoencephalitis among HIV-infected patients, and its presence is indicative of AIDS.     

Evaluation of hepatic resection for hepatocellular carcinoma on cirrhotic livers

BACKGROUND: The hepatocellular carcinoma is a disorder that affects patients suffering from cirrhosis. Liver resection, orthotopic liver transplantation and percutaneous ablation are some forms of therapy currently used to provide a cure for this disease. AIM: To assess the results achieved through liver resection for the treatment of the hepatocellular carcinoma in patients with cirrhosis being under treatment in a general hospital. METHODS: Clinical observation, laboratory test results, endoscopic and histopathologic analysis were taken into consideration in the case of 22 patients who underwent liver resection between 1996 and 2005. To verify the survival rates, identify the prognostic factors and determine the risk of recurrence, special attention was given to the serologic levels of bilirubins and alpha-fetoprotein, and to the level of the hepatocellular dysfunction (classified according to the Child-Pugh-Turcotte and the Model for End-Stage Liver Disease parameters). The size and number of tumours, microvascular invasion and the presence of satellite lesions were also taken into consideration. The level of statistic significance employed was of 95%. RESULTS: In the cases studied, patients had an average age of 62.09 years, being 17 of them male. In 10 cases the liver cirrhosis was associated to the hepatitis C chronic infection; in 4 cases there was a combination of chronic ingestion of ethanol and the hepatitis C virus; in 3 cases there was an association with the hepatitis B virus chronic infection. Two cases were related to the chronic ingestion of ethanol alone and in one case the use of medications was reported. It was not possible to establish the etiology in two of the cases studied. Eighteen patients had a single tumour, 11 of them smaller than 5 cm. The survival rate varied between 10 days and 120 months, being of 33.5 months on average. At the end of the 1st, 3rd and 5th year, the survival rates were 61.90%, 16.67% and 11.11%, respectively. Three patients died within the first 3 months after the liver resection. Thirteen patients died after the first 3 months, 12 of the cases associated to tumour recurrence and tumour progression. There was one death in the immediate post-operative period of a second operation carried out to remove a recurrent tumour. When it comes to the survival rate and the identification of prognostic factors, a relationship between patients survival and microvascular invasion was observed. No statically significant relationship was established between the survival rate and the serologic levels of bilirubins and alpha-fetoprotein or the level of hepatocellular dysfunction, size or number of tumours. However, a more significant incidence of tumour recurrence was observed in patients with microvascular invasion in the histopathologic study. CONCLUSION: In spite of the reduced number of cases studied, the surgical treatment of the hepatocellular carcinoma produced bad results. A careful selection of cases where surgery could be an option may be a decisive factor to improve such results. A careful selection of cases might be a decisive factor in order to improve such results.     

Swallowing in Patients with Parkinson’s Disease: A Surface Electromyography Study

Our goal was to study deglutition of Parkinson??s disease (PD) patients and normal controls (NC) using surface electromyography (sEMG). The study included 15 patients with idiopathic PD and 15 age-matched normal controls. Surface electromyography was collected over the suprahyoid muscle group. Conditions were the following: swallow at once 10 and 20?ml of water and 5 and 10?ml of yogurt of firm consistency, and freely drink 100?ml of water. During swallowing, durations of sEMG were significantly longer in PD patients than in normal controls but no significant differences of amplitudes were found. Eighty percent of the PD patients and 20?% of the NC needed more than one swallow to consume 20?ml of water, while 70?% of the PD patients and none of the NC needed more than one swallow to consume 5?ml of yogurt. PD patients took significantly more time and needed significantly more swallows to drink 100?ml of water than normal controls. We conclude that sEMG might be a simple and useful tool to study and monitor deglutition in PD patients.     

Blinded, Externally Controlled Multicenter Evaluation of Light Microscopy and PCR for Detection of Microsporidia in Stool Specimens

The quality parameters for the detection of microsporidia in identical sets of 50 stool samples were determined for six laboratories where technicians used light microscopy and for six laboratories where technicians used PCR. The average overall sensitivities were 67% (89% for patient samples only) for the PCR laboratories and 54% (80% for patient samples only) for the light microscopy laboratories. Specificities were 98 and 95%, respectively. Differences in results were most apparent between the individual laboratories rather than between the two major methods used.     

Cell-surface sialoglycoconjugate structures in wild-type and mutant Crithidia fasciculata

The cell-surface expression of sialoglycoconjugate structures in wild-type Crithidia fasciculata and its TFR^R1 drug-resistant mutant was analyzed with the aid of an influenza C virus strain, lectin, enzymatic treatment, and flow cytofluorimetry analysis probed with fluorescein isothiocyanate-labeled (FITC) lectins. 9-O-Acetyl-N-acetyl neuraminic acid (Neu5,9Ac₂) structures mediate influenza C virus cell-binding. The SAα2,3Gal and SAα2,6Gal sequences are specifically recognized by Maackia amurensis (MAA) and Sambucus nigra (SNA) lectins, respectively. On the basis of these param- eters the TFR^R1 mutant strain of C. fasciculata was found to contain exposed sialoglycoconjugates bearing Neu5,9Ac₂ surface structures. After the removal of sialic acid residues by neuraminidase activity the marked increases in PNA (peanut agglutinin)-mediated agglutinating activity showed that those acidic units on C. fasciculata cells were glycosidically linked to d-galactose. The bond involves SAα2,6Gal and SAα2,3Gal linkages as suggested by the use of FITC-SNA and FITC-MAA lectins, respectively. Both SAα2,3Gal and SAα2,6Gal sequences were preferentially expressed by the TFR^R1 mutant. The SAα2,6 linkage markedly predominated. In the TFR^R1 mutant, but not in wild-type cells, two distinct populations of cells were distinguished by reactivity with FITC-SNA, one of which was enriched with surface SAα2,6Gal sequences. These diverse findings suggest that sialoglycoconjugate structures present on the flagellate surface may be associated with mutation and the cell growth cycle in C. fasciculata. Received: 17 September 1998 / Accepted: 22 October 1998