Impact on sexual function of surgical treatment in rectal cancer.

INTRODUCTION: The development of new surgical techniques and medical devices, like therapeutical multimodal approaches has allowed for better outcomes on patients with rectal cancer (RCa). Owing to that, an increased awareness and investment towards better outcomes regarding patients' sexual and urinary function has been recently observed. AIM: Evaluate and characterize the sexual dysfunction of patients submitted to surgical treatment for RCa. MATERIALS AND METHODS: An observational retrospective study including all male patients who underwent a surgical treatment for RCa between January 2011 December 2014 (n=43) was performed, complemented with an inquiry questionnaire to every patient about its sexual habits and level of function before and after surgery. DISCUSSION: All patients were male, with an average of 64yo. (range 42-83yo.). The surgical procedure was a rectum anterior resection (RAR) in 22 patients (56%) and an abdominoperineal resection (APR) in 19(44%). Sixty three percent described their sexual life as important/very important. Sexual function worsening was observed in 76% (65% with complains on erectile function, and 27% on ejaculation). Fourteen patients (38%) didn't resume sexual activity after surgery. Increased age (p=0.007), surgery performed (APR) (p=0.03) and the presence of a stoma (p=0.03) were predictors of ED after surgery. A secondary analysis found that the type of surgery (APR) (p=0.04), lower third tumor's location (p=0.03) and presence of comorbidities (p=0.013) (namely, smokers and diabetic patients) were predictors of de novo ED after surgery. CONCLUSIONS: This study demonstrated the clear negative impact in sexual function of patients submitted to a surgical treatment for RCa. Since it is a valued feature for patients, it becomes essential to correctly evaluate/identify these cases in order to offer an adequate therapeutical option.

Inhaled Nitric Oxide in Acute Severe Pulmonary Hypertension and Severe Acute Respiratory Distress Syndrome Secondary to COVID-19 Pneumonia: A Case Report.

BACKGROUND Inhaled nitric oxide (iNO) is used as a treatment for pulmonary arterial hypertension (PAH). Severe hypoxia with hypoxic vasoconstriction caused by severe acute respiratory distress syndrome (ARDS) can induce pulmonary hypertension with hemodynamic implications, mainly secondary to right ventricle (RV) systolic function impairment. We report the case of the use of iNO in a critically ill patient with bilateral SARS-CoV-2 pneumonia and severe ARDS and hypoxemia leading to acute severe PAH, causing a ventilation/perfusion mismatch, RV pressure overload, and RV systolic dysfunction. CASE REPORT A 36-year-old woman was admitted to the Intensive Care Unit with a severe ARDS associated with SARS-CoV-2 pneumonia requiring invasive mechanical ventilation. Severe hypoxia and hypoxic vasoconstriction developed, leading to an acute increase in pulmonary vascular resistance, severe to moderate tricuspid regurgitation, RV pressure overload, RV systolic function impairment, and RV dilatation. Following 24 h of treatment with iNO at 15 ppm, significant oxygenation and hemodynamic improvement were noted, allowing vasopressors to be stopped. After 24 h of iNO treatment, echocardiography showed very mild tricuspid regurgitation, a non-dilated RV, no impairment of transverse free wall contractility, and no paradoxical septal motion. iNO was maintained for 7 days. The dose of iNO was progressively decreased with no adverse effects and maintaining an improvement of oxygenation and hemodynamic status, allowing respiratory weaning. CONCLUSIONS Sustained acute hypoxia in ARDS secondary to SARS-CoV-2 pneumonia can lead to PAH, causing a ventilation/perfusion mismatch and RV systolic impairment. iNO can be considered in patients with significant PAH causing hypoxemia and RV dysfunction.

Critical role of a K+ channel in Plasmodium berghei transmission revealed by targeted gene disruption.

Regulated K(+) transport across the plasma membrane is of vital importance for the survival of most cells. Two K(+) channels have been identified in the Plasmodium falciparum genome; however, their functional significance during parasite life cycle in the vertebrate host and during transmission through the mosquito vector remains unknown. We hypothesize that these two K(+) channels mediate the transport of K(+) in the parasites, and thus are important for parasite survival. To test this hypothesis, we identified the orthologue of one of the P. falciparum K(+) channels, PfKch1, in the rodent malaria parasite P. berghei (PbKch1) and examined the biological role by performing a targeted disruption of the gene encoding PbKch1. The deduced amino acid sequence of the six transmembrane domains of PfKch1 and PbKch1 share 82% identity, and in particular the pore regions are completely identical. The PbKch1-null parasites were viable despite a marked reduction in the uptake of the K(+) congener (86)Rb(+), and mice infected with PbKch1-null parasites survived slightly longer than mice infected with WT parasites. However, the most striking feature of the phenotype was the virtually complete inhibition of the development of PbKch1-null parasites in Anopheles stephensi mosquitoes. In conclusion, these studies demonstrate that PbKch1 contributes to the transport of K(+) in P. berghei parasites and supports the growth of the parasites, in particular the development of oocysts in the mosquito midgut. K(+) channels therefore may constitute a potential antimalarial drug target.

Composition and natural history of a snake community from the southern Cerrado, southeastern Brazil.

The natural history of a cerrado snake community in a protected area in southeastern Brazil (Santa Bárbara Ecological Station; SBES) is described. A visual guide and an identification key are also provided to assist researchers and local people in identifying snakes in that region. Sampling was performed through pitfall traps, time-constrained search, accidental encounters, and observations by local people for two years, which corresponded to 240 days of sampling. Among the 388 individuals found in the field, 33 snake species belonging to 21 genera of seven families were recorded. Most species were restricted or found at least once in non-forest vegetation types (campo sujo, campo cerrado, and cerrado sensu stricto) and a few were restricted to forest habitats (cerradão). Our results show that most species (1) occupy open areas; (2) present both diurnal and nocturnal activity; (3) are primarily terrestrial; (4) include lizards, mammals and/or anurans in the diet; (5) present seasonal reproductive activity; and (6) use mainly visually oriented defensive tactics. Despite its small size (3,154 ha), the SBES harbours preserved habitats and a rich and typical Cerrado snake fauna, including threatened species. Furthermore, most of the SBES snakes occur in non-forest environments (54%) and some species are sensitive to habitat disturbance.

Genetic Determinants for Prediction of Outcome of Patients with Papillary Thyroid Carcinoma.

Papillary thyroid carcinoma (PTC) usually presents an excellent prognosis, but some patients present with aggressive metastatic disease. BRAF, RAS, and TERT promoter (TERTp) genes are altered in PTC, and their impact on patient outcomes remains controversial. We aimed to determine the role of genetic alterations in PTC patient outcomes (recurrent/persistent disease, structural disease, and disease-specific mortality (DSM)). The series included 241 PTC patients submitted to surgery, between 2002-2015, in a single hospital. DNA was extracted from tissue samples of 287 lesions (primary tumors and metastases). Molecular alterations were detected by Sanger sequencing. Primary tumors presented 143 BRAF, 16 TERTp, and 13 RAS mutations. Isolated TERTpmut showed increased risk of structural disease (HR = 7.0, p < 0.001) and DSM (HR = 10.1, p = 0.001). Combined genotypes, BRAFwt/TERTpmut (HR = 6.8, p = 0.003), BRAFmut/TERTpmut (HR = 3.2, p = 0.056) and BRAFmut/TERTpwt (HR = 2.2, p = 0.023) showed increased risk of recurrent/persistent disease. Patients with tumors BRAFwt/TERTpmut (HR = 24.2, p < 0.001) and BRAFmut/TERTpmut (HR = 11.5, p = 0.002) showed increased risk of structural disease. DSM was significantly increased in patients with TERTpmut regardless of BRAF status (BRAFmut/TERTpmut, log-rank p < 0.001; BRAFwt/TERTpmut, log-rank p < 0.001). Our results indicate that molecular markers may have a role in predicting PTC patients' outcome. BRAFmut/TERTpwt tumors were prone to associate with local aggressiveness (recurrent/persistent disease), whereas TERTpmut tumors were predisposed to recurrent structural disease and DSM.

Clinicopathological Features as Prognostic Predictors of Poor Outcome in Papillary Thyroid Carcinoma.

Papillary thyroid cancer (PTC) has an indolent nature and usually excellent prognosis. Some PTC clinicopathological features may contribute to the development of aggressive metastatic disease. In this work, we want to evaluate PTC clinicopathological features that are presurgical prognostic predictors of patients' outcomes and find which indicators are more adequate for tailoring surgical procedures and follow-up. We studied a series of 241 PTC patients submitted to surgery. All patients' files and histological tumor samples were reviewed. The 8th edition AJCC/UICC (American Joint Committee on Cancer/Union for International Cancer) Controlstaging system and the 2015 American Thyroid Association risk stratification system were used. Total thyroidectomy was performed in 228 patients, lymphadenectomy in 28 patients. Gross extrathyroidal extension (ETE) was present in 10 patients and 31 tumor resection margins were incomplete. Cervical lymph node metastases (LNMs) were present in 34 patients and distant metastases at diagnosis in four patients. In multivariate analysis, male gender (OR = 15.4, p = 0.015), venous invasion (OR = 16.7, p = 0.022), and lateral compartment LNM (OR = 26.7, p = 0.004) were predictors of mortality; psammoma bodies (PBs) (OR = 4.5, p = 0.008), lymph vessel invasion (OR = 6.9, p < 0.001), and gross ETE (OR = 16.1, p = 0.001) were predictors of structural disease status; male gender (OR = 2.9, p = 0.011), lymph vessel invasion (OR = 2.8, p = 0.006), and incomplete resection margins (OR = 4.6, p < 0.001) were predictors of recurrent/persistent disease. Our study supports that the factors helping to tailor patient's surgery are male gender, presence of PBs, gross ETE, and lateral compartment LNM. Together with pathological factors, lymph vessel invasion, venous invasion, necrosis, and incomplete surgical resection, should be taken into consideration regarding treatment and follow-up of patients.

Murine model for assessment of Plasmodium falciparum transmission-blocking vaccine using transgenic Plasmodium berghei parasites expressing the target antigen Pfs25.

Currently, there is no animal model for Plasmodium falciparum challenge to evaluate malaria transmission-blocking vaccines based on the well-established Pfs25 target antigen. The biological activity of transmission-blocking antibodies is typically assessed using an assay known as the membrane feeding assay (MFA). It is an in vitro method that involves mixing antibodies with cultured P. falciparum gametocytes and feeding them to mosquitoes through an artificial membrane followed by assessment of infection in the mosquitoes. We genetically modified Plasmodium berghei to express Pfs25 and demonstrated that the transgenic parasites (TrPfs25Pb) are susceptible to anti-Pfs25 antibodies during mosquito-stage development. The asexual growth kinetics and mosquito infectivity of TrPfs25Pb were comparable to those of wild-type parasites, and TrPfs25Pb displayed Pfs25 on the surface of ookinetes. Immune sera from nonhuman primates immunized with a Pfs25-based vaccine when passively transferred to mice blocked transmission of TrPfs25Pb to Anopheles stephensi. Furthermore, mice immunized with Pfs25 DNA vaccine and challenged with TrPfs25Pb displayed reduced malaria transmission compared to mice immunized with wild-type plasmid. These studies describe development of an animal malaria model alternative to the in vitro MFA and show that the model can facilitate P. falciparum transmission-blocking vaccine evaluation based on the target antigen Pfs25. We believe that an animal model to test transmission-blocking vaccines would be superior to the MFA, since there may be additional immune factors that synergize the transmission-blocking activity of antibodies in vivo.

[Congenital absence of inferior vena cava associated to polispleenism. Case report]. / Agenésia da veia cava inferio associada a poliesplenismo. Casa clínico.

Interruption of the inferior vena cava with azygos continuation is an uncommon vascular anomaly that results from aberrant development during embryogenesis. We report a case of this anomaly in a young boy of 19 years old sent for our observation for presenting an hipotransparency in the chest x-ray, which study revealed a prominence of the azygos cross. Further evaluation by CT-scans disclosed the diagnosis of congenital absence of the inferior vena cava, associated to multiple spleens (polispleenism).

Hemosuccus pancreaticus: a rare complication of chronic pancreatitis.

Hemosuccus pancreaticus is a very rare cause of gastrointestinal bleeding and it should be considered in every patient with history of chronic pancreatitis who presents with acute or intermittent gastrointestinal haemorrhage. A 54-year-old man with a history of chronic alcoholic pancreatitis was admitted to hospital for an acute exacerbation. During hospital stay, he presented with haematemesis and haemodynamic instability. Upper gastrointestinal endoscopy revealed a blood clot on Vater papilla. CT investigation showed a 4 cm cephalopancreatic pseudocyst and angiography identified a large pseudoaneurysm of the right gastroepiploic artery, bleeding into the pseudocyst-hemosuccus pancreaticus. Microcoil transcatheter embolisation was performed with success.

Conventional clinical and pathological features fail to accurately predict recurrence in patients with gastric cancer staged N0.

INTRODUCTION: Despite the medical-surgical advances, even after R0 gastric resections, some patients without apparent metastatic disease develop cancer recurrence and eventually die. AIMS: We aimed to define recurrence in patients with node-negative gastric adenocarcinoma and to determine whether any clinicopathological features are predictive for recurrence. MATERIALS AND METHODS: This was a retrospective cohort study on patients with gastric adenocarcinoma, consecutively diagnosed at our institution, staged as N0M0 between January 2000 and December 2008. RESULTS: We recruited 129 patients; 53% were men and 56% were older than 60 years. A total of 22% of the patients developed recurrence, with a mortality rate of 93%. Overall, 71% of the patients, N0, with recurrence presented lymphatic permeation. In univariate analysis, on comparing recurrent patients with those with no recurrence, age, size, T status, lymphatic, and venous permeation were factors that were associated significantly with recurrence, but in multivariate analysis, only age (odds ratio:19.5; 95% confidence interval: 2.3-168; P=0.008) and venous permeation (odds ratio: 6.34; 95% confidence interval: 1.8-22.8; P=0.005) were associated with recurrence. On the basis of only these two factors, the proportion of missed recurrent patients by age and venous permeation was 13 and 39%, respectively. CONCLUSION: A total of 22% of patients, N0, developed recurrence of their disease. Age and venous permeation were independent risk factors for recurrence, but on the basis of these factors, up to 40% of patients may be missed for recurrence. New methods to predict recurrence are needed.

Plasmodium falciparum MAEBL is a unique member of the ebl family.

Malaria is one of the deadliest human diseases and efforts to control it have been difficult due to the protozoan parasites' complex biology. Malaria merozoite invasion of erythrocytes is an essential part of blood-stage infections. The invasion process is mediated by numerous parasite molecules, such as EBA-175, a member of the ebl family of erythrocyte binding proteins. We have identified maebl, an ebl paralogue, in Plasmodium falciparum and found it highly conserved with its orthologues in P. yoelii and P. berghei, but distinct from other Plasmodium ebl. Importantly, the putative MAEBL ligand domains are highly conserved and are similar to AMA-1, but not the consensus DBL ligand domains present in all other ebl. In mature merozoites, MAEBL localized with rhoptry proteins (RhopH2, RAP-1), including surface localization with RhopH2, but not microneme proteins (EBA-175, BAEBL). MAEBL appears as proteolytically processed fragments in P. falciparum parasites. The amino cysteine-rich ligand domains were present primarily in culture supernatants, while the carboxyl cysteine-rich domain adjacent to the transmembrane domain was preferentially isolated from Triton X-100 extracted fractions. These data indicate that the primary structure of maebl is highly conserved among Plasmodium species, while its characteristics demonstrate a function unique among the ebl proteins.

Molecular complexity of sexual development and gene regulation in Plasmodium falciparum.

The malaria parasite, Plasmodium falciparum, has a complex life cycle which alternates between the vertebrate host and the invertebrate vector. Various morphological changes as well as stage-specific transcripts and gene expression profiles that accompany parasite's asexual and sexual life cycle suggest that gene regulation is crucial for the parasite's continual adaptations to survive the changing environments as well as for pathogenesis. Development of sexual stages is crucial for malaria transmission and relatively little is known about the role of specific gene products during asexual to sexual differentiation and further development. Therefore, in order to have a full understanding of the biology of the malaria parasite, gene regulation on a genome-wide global level must be understood, an area remaining to be elucidated in P. falciparum. Parasite features, such as A-T bias, difficulties in cloning, labor-intensive culture and purification of specific stages of the parasite, all contribute to the difficulties to investigate many aspects of parasite biology. However, despite these challenges, limited studies have revealed a number of parallelisms with eukaryotic transcription. For example, the parasite's genes are organised in a similar fashion, contain promoter elements and upstream activation sequences, as shown by structural searches and functional assays, and some of the basal machinery and general transcription factors have been found in Plasmodium. The completion of the full genome sequence of P. falciparum and other species of Plasmodium has resulted in the search for specific transcription factors through genome mining. Although genome mining may identify some of the factors, search for these factors solely by primary sequence homology would result in a non-comprehensive list for transcription factors present in the genome. Here, we present further discussion on putative transcription factors like activities detected in the asexual and sexual stages of P. falciparum.

Analysis of clinicopathologic characteristics and prognosis of gastric cancer in young and older patients.

BACKGROUND: The worldwide incidence of gastric cancer is gradually declining, however it remains the fourth highest in cancer incidence and the second leading cause of cancer death. Gastric cancer in young people is a disturbing problem and the routine screening does not include people less than 35 years. The clinicopathological features of gastric carcinoma are said to differ between young and elderly patients and it is thought that the prognosis of this disease is worse for younger patients. It is also suggested that the diagnosis is usually made later or have a more aggressive behaviour. Although, others report that tumor staging and prognosis for young patients is similar to older patients and depends on whether the patients undergo a curative resection. All these data need more investigation and studies. Although Portugal has a high incidence of gastric cancer, no studies have yet been performed comparing the clinicopathologic features and prognosis of young and elderly patients with gastric cancer. AIMS: This study intend to assess whether the clinicopathological features and prognosis of gastric cancer in young patients (YGC) is similar to older ones (OGC). METHODS: Between 2000 and 2005, 406 patients with histological diagnosis of primary gastric cancer, treated in the Departments of Surgery and Oncology at the Centro Hospitalar of Vila Nova de Gaia / Espinho, were regularly followed at least for five years after surgery. These were reviewed retrospectively. Several variables were analyzed in young patients and compared with the elder ones. We used the chi-square and Fisher to evaluate the statistical association between categorical variables and t-test for numeric variables. Survival was estimated by the Kaplan-Meier method and used the log-rank test to assess differences in survival among different subgroups of patients. The criteria for statistical significance was p < 0.05. Data analysis was performed using the SPSS 18. RESULTS AND CONCLUSIONS: With regard to resectability, 78 % of the tumors were resected in the group of younger patients, the surgery more frequently achieved was total gastrectomy with anastomosis in Y of Roux. In the elder group, about 62 % of the tumors were resected and BII gastrectomy was the most frequent surgery. The diffuse adenocarcinoma was the most frequent histological type in younger patients, whereas in older patients was intestinal adenocarcinoma. With regard to the stage in the first group there was a predominance of stages: IA and IV (26.1 %) in the second: IV (25.8 %). The survival for stage III e IV was significantly worst in YGC compared with OGC.

Ruptured jejunal artery aneurysm.

Visceral artery aneurysms (VAAs), unlike aortic aneurysms, are very rare, but are also a potentially lethal vascular disease. Jejunal artery aneurysms only account for less than 3% of VAAs, but have a 30% risk of rupture, with 20% death rate, presenting with only few and vague symptoms. We report the case of a 76-year-old man presenting at the emergency department (ED) with a crampy epigastric pain and vomiting. An ultrasound performed diagnosed free abdominal fluid and immediate CT scan diagnosed jejunal artery aneurysm spontaneously rupturing, followed by hypovolaemic shock. Emergent surgery was undertaken, and aneurysmectomy, followed by partial enterectomy with primary anastomosis were performed, because of segmentary jejunal ischaemia. The patient's recovery was unremarkable. High level of suspicion, rapid diagnosis capability and prompt surgical or endovascular intervention, as well as an effective teamwork in the ED are critical to avoid the devastating consequences of ruptured VAAs.

Impact on sexual function of surgical treatment in rectal cancer

ABSTRACT Introduction The development of new surgical techniques and medical devices, like therapeutical multimodal approaches has allowed for better outcomes on patients with rectal cancer (RCa). Owing to that, an increased awareness and investment towards better outcomes regarding patients' sexual and urinary function has been recently observed. Aim Evaluate and characterize the sexual dysfunction of patients submitted to surgical treatment for RCa. Materials and Methods An observational retrospective study including all male patients who underwent a surgical treatment for RCa between January 2011 December 2014 (n=43) was performed, complemented with an inquiry questionnaire to every patient about its sexual habits and level of function before and after surgery. Discussion All patients were male, with an average of 64yo. (range 42-83yo.). The surgical procedure was a rectum anterior resection (RAR) in 22 patients (56%) and an abdominoperineal resection (APR) in 19(44%). Sixty three percent described their sexual life as important/very important. Sexual function worsening was observed in 76% (65% with complains on erectile function, and 27% on ejaculation). Fourteen patients (38%) didn't resume sexual activity after surgery. Increased age (p=0.007), surgery performed (APR) (p=0.03) and the presence of a stoma (p=0.03) were predictors of ED after surgery. A secondary analysis found that the type of surgery (APR) (p=0.04), lower third tumor's location (p=0.03) and presence of comorbidities (p=0.013) (namely, smokers and diabetic patients) were predictors of de novo ED after surgery. Conclusions This study demonstrated the clear negative impact in sexual function of patients submitted to a surgical treatment for RCa. Since it is a valued feature for patients, it becomes essential to correctly evaluate/identify these cases in order to offer an adequate therapeutical option.

Breast angiosarcoma secondary to phyllodes tumour.

Angiosarcomas are rare malignant tumours that arise from endothelial cells lining vascular channels, representing 0.04% of malignant neoplasms of the breast. Breast angiosarcomas (BAs) were first described by Schmidt in 1887, and may be primary or secondary to the pre-existing conditions. Primary BAs are more common in young women and present as a palpable mass. Secondary BAs arise in older patients, frequently 5-6 years after radiotherapy, and present as a rash.The authors describe the case of an 83-year-old woman with no history of thoracic radiotherapy or surgery. She had been observed for a breast nodule where biopsy revealed phyllodes tumour. The patient refused surgery and returned 2 years later because of an impressive increase in tumour volume and skin ulceration. She underwent mastectomy with local skin flaps. Histopathological result revealed high-grade angiosarcoma of 15×12 cm. There was follow-up without evidence of recurrence, after radiotherapy.

Neuroendocrine breast cancer.

Neuroendocrine breast cancer is thought to account for about 1% of all breast cancers. This rare type of breast malignancy is more common in older women and presents as a low-grade, slow-growing cancer. The most definitive markers that indicate neuroendocrine carcinoma are the presence of chromogranin, synaptophysin or neuron-specific enolase, in at least 50% of malignant tumour cells. The authors present a case report of an 83-year-old woman, admitted to their institution with right breast lump. Physical examination, mammography and ultrasonography showed a 2.4 cm nodule, probably a benign lesion (BI-RADS 3). A fine needle aspiration biopsy was performed and revealed proliferative epithelial papillary lesion. She was submitted to excisional biopsy and histology showed endocrine breast cancer well differentiated (G1). Immunohistochemically, tumour cells were positive for synaptophysin. These breast cancers are characterised for their excellent prognosis and conservative treatment is almost always enough to obtain patient cure.