Can we optimize CEA as a response marker in rectal cancer?

BACKGROUND AND AIM: carcinoembryonic antigen (CEA) is a biomarker commonly used in colorectal cancer. However, its prognostic value is still controversial. Recent studies demonstrate that CEA produced locally by tumor cells has a higher prognostic value compared to serum CEA. This study aimed to determine whether there was an association between the CEA/tumor size ratio (CEA/ExT) and the pathological tumor response in patients with rectal adenocarcinoma (ADC), who underwent neoadjuvant chemoradiotherapy (N-CRT), followed by surgical tumor resection. METHODS: a retrospective study was performed of rectal ADC patients who underwent N-CRT followed by curative surgery between March/2012 and October/2017. CEA and tumor extension for pre-treatment CEA/ExT calculation and the pathological response in the surgical specimen after treatment were analyzed. RESULTS: eighty-nine patients were included, 60.7 % were male and the mean age was 63.8 ± 10.42. There was a good response to N-CRT in 41.6 % of the patients, tumor downstaging occurred in 83.1 % and a complete pathological response in 23.6 % of cases. The average CEA/ExT was 2.01 ng/ml/cm. In the univariate analysis, higher CEA/ExT values were related to a lower frequency of pathological response (p = 0.04) and to a lower frequency of tumor downstaging (p = 0.02). In the multivariate analysis, CEA/ExT was independently related to tumor downstaging (OR: 0.72; 95 % IC: 0.53-0.98, p-0.036). CONCLUSIONS: lower pre-treatment CEA/ExT values seem to be associated with tumor downstaging and this parameter may be a promising predictor of a more favorable response in patients with rectal ADC undergoing treatment with N-CRT.

Risk factors for severity and recurrence of colonic diverticular bleeding.

BACKGROUND: Colonic diverticular bleeding is the most common cause of lower gastrointestinal bleeding. Risk factors related to severity and repeated bleeding episodes are not completely clearly defined. OBJECTIVE: To characterize a Portuguese population hospitalized due to colonic diverticular bleeding and to identify the clinical predictors related to bleeding severity and rebleeding. METHODS: Retrospective analysis of all hospitalized patients diagnosed with colonic diverticular bleeding from January 2008 to December 2013 at our institution. The main outcomes evaluated were bleeding severity, defined as any transfusion support requirements and/or signs of hemodynamic shock, and 1-year recurrence rate. RESULTS: Seventy-four patients were included, with a mean age of 75.7 ± 9.5 years; the majority were male (62.2%). Thirty-six patients (48.6%) met the criteria for severe bleeding; four independent risk factors for severe diverticular bleeding were identified: low hemoglobin level at admission (≤ 11 g/dL; OR 18.8), older age (≥ 75 years; OR 4.7), bilateral diverticular location (OR 14.2) and chronic kidney disease (OR 5.6). The 1-year recurrence rate was 12.9%. We did not identify any independent risk factor for bleeding recurrence in this population. CONCLUSION: In this series, nearly half of the patients hospitalized with diverticular bleeding presented with severe bleeding. Patients with low hemoglobin levels, older age, bilateral diverticular location and chronic kidney disease had a significantly increased risk for severe diverticular bleeding. In addition, a small number of patients rebled within the first year after the index episode, although we could not identify independent risk factors associated with the recurrence of diverticular bleeding.

Comparison of the prognostic value of Chronic Liver Failure Consortium scores and traditional models for predicting mortality in patients with cirrhosis.

BACKGROUND AND AIM: Recently, the European Association for the Study of the Liver - Chronic Liver Failure (CLIF) Consortium defined two new prognostic scores, according to the presence or absence of acute-on-chronic liver failure (ACLF): the CLIF Consortium ACLF score (CLIF-C ACLFs) and the CLIF-C Acute Decompensation score (CLIF-C ADs). We sought to compare their accuracy in predicting 30- and 90-day mortality with some of the existing models: Child-Turcotte-Pugh (CTP), Model for End-Stage Liver Disease (MELD), MELD-Na, integrated MELD (iMELD), MELD to serum sodium ratio index (MESO), Refit MELD and Refit MELD-Na. METHODS: Retrospective cohort study that evaluated all admissions due to decompensated cirrhosis in 2 centers between 2011 and 2014. At admission each score was assessed, and the discrimination ability was compared by measuring the area under the ROC curve (AUROC). RESULTS: A total of 779 hospitalizations were evaluated. Two hundred and twenty-two patients met criteria for ACLF (25.9%). The 30- and 90-day mortality were respectively 17.7 and 37.3%. CLIF-C ACLFs presented an AUROC for predicting 30- and 90-day mortality of 0.684 (95% CI: 0.599-0.770) and 0.666 (95% CI: 0.588-0.744) respectively. No statistically significant differences were found when compared to traditional models. For patients without ACLF, CLIF-C ADs had an AUROC for predicting 30- and 90-day mortality of 0.689 (95% CI: 0.614-0.763) and 0.672 (95% CI: 0.624-0.720) respectively. When compared to other scores, it was only statistically superior to MELD for predicting 30-day mortality (p=0.0296). CONCLUSIONS: The new CLIF-C scores were not statistically superior to the traditional models, with the exception of CLIF-C ADs for predicting 30-day mortality.

Rectal Perforation by a Balloon Spacer: A Rare Cause of Rectal Perforation Addressed Endoscopically.

Prostate cancer is the second most frequent cancer in men worldwide. Dose escalation is currently the standard of care for the treatment of prostate cancer with radiation therapy. However, the rectum tends to be the dose-limiting structure when treating prostate cancer, given its proximity. The injection of biodegradable spacers between the prostate and the rectum may optimize radiotherapy treatment delivery for patients with localized disease. Nevertheless, although the overall complication rate of spacers is marginal, the benefits of spacer technologies need to be evaluated against the complication risks such as rectum perforation/necrosis. We report a case of a 59-year-old man with a diagnosis of prostate adenocarcinoma for whom hormonal treatment followed by intensity modulated radiation therapy (IMRT) was proposed. A biodegradable and expandable balloon (BioProtect®) was injected into the perirectal space without detectable immediate complications. One month later, the patient presented with a 3-day persistent rectal bleeding. The investigation confirmed a rectal perforation by the balloon spacer system.

O cancro da próstata é atualmente, em todo o mundo, o segundo cancro mais frequente no homem. As recomendações atuais indicam o uso doses de radiação progressivamente maiores ao longo do processo de radioterapia no tratamento do cancro da próstata. Contudo, a proximidade anatómica do reto é um fator limitante na dose de radiação usada ao longo do tratamento. A colocação de espaçadores biodegradáveis entre a próstata e o reto pode otimizar o tratamento de radioterapia em doentes com doença localizada. No entanto, embora a taxa de complicações dos espaçadores seja reduzida, o benefício desta técnica precisa de ser contrabalançada com o risco de complicações, como perfuração/necrose do reto. Apresentamos o caso de um paciente do sexo masculino de 59 anos com diagnóstico de adenocarcinoma da próstata para o qual foi proposto tratamento hormonal seguido de radioterapia com intensidade modulada (IMRT). Um balão biodegradável e expansível (Bio-Protect®) foi injetado no espaço peri-retal sem complicações imediatas detetáveis. Após um mês, o paciente apresentou hematoquézias persistentes durante três dias. A investigação confirmou tratar-se de uma perfuração retal pelo balloon spacer.

Expression of DUSP4 transcript variants as a potential biomarker for colorectal cancer.

Aim: To provide novel data on the expression of DUSP4 transcripts in colorectal cancer (CRC) tissues and to explore their potential as biomarkers. Materials & methods:DUSP4 transcripts expression was determined by quantitative real-time PCR in tissues from 28 CRC patients. Their association with clinicopathological factors and survival analysis was performed. Data from 380 CRC patients available at The Cancer Genome Atlas project were also analyzed. Results: All transcripts were overexpressed in CRC tissues. Variant X1 was the most upregulated and associated with KRAS mutations and poorly differentiated tumor. Overexpression of DUSP4 transcripts could distinguish all tumor stages from normal tissues. Similar results were found in The Cancer Genome Atlas cohort. Conclusion:DUSP4 transcripts have the potential to serve as diagnostic biomarkers for CRC, particularly variant X1.

Data on the evaluation of FGF2 gene expression in Colorectal Cancer.

The data presented in this article is related with the research paper entitled "Evaluation of MGP gene expression in colorectal cancer", available on Gene journal [1]. From all the transcription factors known to regulate MGP, FGF2 is the most described in colon adenocarcinoma and colon tumor cell lines, where it was shown to: i) contribute for the invasiveness potential; and ii) promote proliferation and survival of colorectal cancer cells. These in vitro studies pose the hypothesis that FGF2 associated signaling pathways could be promoting the regulation of others genes, such as MGP, that may lead to tumor progression which ultimately could result in poor prognosis in colon adenocarcinoma.

Evaluation of MGP gene expression in colorectal cancer.

PURPOSE: Matrix Gla protein (MGP) is a vitamin K-dependent, γ-carboxylated protein that was initially found to be a physiological inhibitor of ectopic calcifications affecting mainly cartilage and the vascular system. Mutations in the MGP gene were found to be responsible for a human pathology, the Keutel syndrome, characterized by abnormal calcifications in cartilage, lungs, brain and vascular system. MGP was recently implicated in tumorigenic processes such as angiogenesis and shown to be abnormally regulated in several tumors, including cervical, ovarian, urogenital and breast. This fact has triggered our interest in analyzing the expression of MGP and of its regulator, the transcription factor runt related transcription factor 2 (RUNX2), in colorectal cancer (CRC). METHODS: MGP and RUNX2 expression were analyzed in cancer and non-tumor biopsies samples from 33 CRC patients and 9 healthy controls by RT-qPCR. Consequently, statistical analyses were performed to evaluate the clinical-pathological significance of MGP and RUNX2 in CRC. MGP protein was also detected by immunohistochemical analysis. RESULTS: Showed an overall overexpression of MGP in the tumor mucosa of patients at mRNA level when compared to adjacent normal mucosa and healthy control tissues. In addition, analysis of the expression of RUNX2 mRNA demonstrated an overexpression in CRC tissue samples and a positive correlation with MGP expression (Pearson correlation coefficient 0.636; p ≤ 0.01) in tumor mucosa. However correlations between MGP gene expression and clinical-pathological characteristics, such as gender, age and pathology classification did not provide relevant information that may shed light towards the differences of MGP expression observed between normal and malignant tissue. CONCLUSIONS: We were able to associate the high levels of MGP mRNA expression with a worse prognosis and survival rate lower than five years. These results contributed to improve our understanding of the molecular mechanism underlying MGP deregulation in cancer.

Pain and Swelling after Percutaneous Endoscopic Gastrostomy Removal: An Unexpected Evolution.

Gastrostomy site metastization is considered an uncommon complication of percutaneous endoscopic gastrostomy (PEG) placement in patients with head and neck tumours, but it is important to consider this possibility when evaluating gastrostomy-related symptoms. The authors present the case of a 40-year-old male with excessive alcohol consumption and active smoking, diagnosed with a stage IV oropharyngeal squamous cell carcinoma. The patient developed a paraneoplastic demyelinating motor polyneuropathy that, associated with tumour mass effect, caused dysphagia with need for nasogastric tube feeding. Treatment with radiotherapy and then chemoradiotherapy was administered and a PEG was placed with the pull method. Cancer remission and resolution of polyneuropathy was achieved, so PEG was removed. Two weeks later, the patient presented with pain and swelling at the gastrostomy site suggesting a local abscess, with improvement after drainage and antibiotic therapy. After 1 month, there was a tumour mass at the gastrostomy site and an oropharyngeal cancer metastasis was diagnosed. The patient underwent surgical excision of abdominal wall metastasis and abdominal disease was controlled. Nevertheless, there was subsequent oropharyngeal neoplasia recurrence and the patient died 6 months later. This case raises the discussion about gastrostomy placement methods that could avoid gastrostomy site metastization, the possible differential diagnosis, and diagnostic workout. Surgical resection may allow metastatic disease control, but by primary disease evolution greatly affects prognosis.

A metastização do local de gastrostomia é considerada uma complicação incomum da colocação de gastrostomia endoscópica percutânea (PEG) em pacientes com tumores da cabeça e pescoço, no entanto é importante considerar essa possibilidade ao avaliar sintomas relacionados com a gastrostomia. Os autores apresentam o caso de um homem de 40 anos com consumo excessivo de álcool e tabagismo ativo, diagnosticado com carcinoma espinocelular orofaríngeo no estádio IV. O paciente desenvolveu uma polineuropatia motora desmielinizante paraneoplásica que, associada ao efeito de massa tumoral, causou disfagia com necessidade de alimentação por sonda nasogástrica. Foi administrado tratamento com radioterapia, seguido de quimioradioterapia e foi colocada PEG com o método de pull. Foi obtida remissão tumoral e resolução da polineuropatia, sendo removida a PEG. Duas semanas depois, o paciente apresentou dor e edema no local da gastrostomia, sugerindo um abscesso local, com melhoria após drenagem e antibioterapia. Um mês depois o local da gastrostomia apresentava uma massa tumoral e foi diagnosticada uma metástase do cancro orofaríngeo. O paciente foi submetido a excisão cirúrgica da metástase da parede abdominal, com controlo da doença abdominal. Contudo, houve recorrência neoplásica orofaríngea subsequente e o paciente faleceu 6 meses depois. Este caso levanta a discussão sobre os métodos de realização de gastrostomia que poderiam evitar a metastização do local de gastrostomia, possíveis diagnósticos diferenciais e marcha diagnóstica. A ressecção cirúrgica pode permitir o controle da doença metastática, no entanto o prognóstico é muito afetado pela evolução da doença primária.

Peritoneal tuberculosis as a cause of ascites in a patient with cirrhosis.

A 59-year-old Portuguese Caucasian man with a history of heavy alcohol intake and no significant medical history presented with ascites, weight loss and general malaise. The ascitic fluid analysis showed 921 cells/mm3 with mononuclear predominance (93.6%), elevated total proteins and a slightly elevated serum-ascites albumin gradient. The abdominal ultrasound confirmed the presence of chronic liver disease with ascites, and additionally on CT there was evidence of peritoneal thickening. On repeat paracentesis, the ascitic fluid analysis showed elevated adenosine deaminase but it was negative for the presence of mycobacteria by Ziehl-Neelsen stain, Löwenstein-Jensen culture and PCR amplification. Due to the persistent suspicion of tuberculosis, a laparoscopy was performed showing multiple small white tubercles scattered over the peritoneum. Peritoneal biopsies showed the presence of necrotising granulomas and cultures were positive for Mycobacterium tuberculosis complex. After a 6-month course of tuberculostatics, the ascites resolved completely. The patient remained asymptomatic.

Eosinophilic oesophagitis and coeliac disease: is there an association?

A 25-year-old man was seen in outpatient clinic for progressive solid food dysphagia. He was already medicated with a proton pump inhibitor with no improvement. His blood tests showed a slight microcytic anaemia and peripheral eosinophilia. The oesophago-gastro-duodenoscopy showed longitudinal furrows in the distal two-thirds of the oesophagus and a concentric distal stenosis. The biopsies taken showed eosinophilic infiltrates consistent with eosinophilic oesophagitis. There was no improvement with topical fluticasone, so the patient was started on a systemic corticosteroid with resolution of dysphagia and of the oesophageal stenosis. He was kept on topical steroids for symptomatic control. On repeat endoscopy, the duodenal mucosa showed multiple papules that were biopsied. Histology showed features consistent with coeliacdisease. The patient was asymptomatic but there was evidence of iron deficiency anaemia, and so a gluten-free diet was started. Despite only a partial adherence to the diet, the iron deficiency anaemia resolved.

Olmesartan-Induced Enteropathy: An Unusual Cause of Villous Atrophy.

We report a case of a 63-year-old-man presenting with chronic diarrhea and weight loss while on olmesartan treatment for hypertension. Investigation showed multiple nutritional deficiencies associated with diffuse intestinal villous atrophy. Serologies for celiac disease were negative and other causes of villous atrophy were excluded. Olmesartan as a precipitant agent was suspected and withdrawn. Clinical improvement occurred in days with no need for other therapeutic measures. Follow-up at three months showed clinical remission and almost complete recovery of intestinal atrophy. Olmesartan is an angiotensin receptor blocker commonly prescribed for the management of hypertension. Spruelike enteropathy associated with this drug is a recently described entity with few cases reported. It presents with chronic diarrhea and intestinal villous atrophy and should be included in its differential diagnosis. This case intends to alert clinicians for the possibility of this event in a patient on treatment with this drug.

Apresentamos o caso de um homem de 63 anos com diarreia crónica e perda ponderal. Apresentava hipertensão arterial tratada com olmesartan. A investigação complementar mostrou múltiplos défices nutricionais associados a atrofia vilositária intestinal difusa. As serologias de doença celíaca foram negativas e outras causas de atrofia vilositária foram excluídas. Suspeitou-se do olmesartan como agente precipitante, sendo este suspenso. Observou-se melhoria clínica em dias, sem necessidade de outras medidas terapêuticas. No seguimento, aos 3 meses, constatou-se remissão clínica e recuperação quase completa da atrofia intestinal.O olmesartan é um bloqueador dos recetores da angiotensina, geralmente prescrito no tratamento da hipertensão. A enteropatia "spruelike" associada a este fármaco é uma entidade recentemente descrita, com poucos casos reportados. Manifesta-se por diarreia crónica associada a atrofia vilositária intestinal, devendo ser incluída no seu diagnóstico diferencial. Com este caso pretende-se alertar os clínicos para a possibilidade deste evento em doentes sob tratamento com este fármaco.

Rare complication of percutaneous endoscopic gastrostomy: Ostomy metastasis of esophageal carcinoma.

The authors present the case of a 55-year-old male with a stage III (T4N1M0) squamous-cell esophageal carcinoma, who underwent percutaneous endoscopic gastrostomy (PEG). The pull method of tube placement was used. Five months after the procedure, the patient was referred to the hospital with a hard palpable tumour at the ostomy site. The histologic exam revealed an abdominal wall metastasis of the esophageal cancer. The authors present this case because of the rarity of metastasis in ostomy after placement of PEG in patients with tumours located in the head and neck. In this particular context and judging by the rarity of situation, the clinical impact of this phenomenon is limited. Nevertheless, metastasis in ostomy site could be prevented by the push method, laparoscopy or laparotomy.

Contribution of endosonography in an uncommon case of pancreatic cysts.

Here we present the case of a 35-year-old female patient with long standing dyspepsia and imaging studies showing the presence of multiple cysts in the head and tail of the pancreas. The patient underwent endosonography that confirmed the presence of multiple simple cysts throughout the entirety of the pancreas without dilation of the pancreatic duct. The majority of the cysts were less than one centimeter in size, and the largest cyst showed a honeycomb appearance. Cytology of aspirates from the two largest cysts was compatible with benign pancreatic cysts. Endosonography also revealed cysts within the left kidney and spleen. Genetic testing confirmed Von Hippel-Lindau disease. We highlight this case because it is unusual for Von Hippel-Lindau disease, a rare clinical entity, to present solely with cysts in the absence of more common manifestations, such as hemangioblastomas in the central nervous system and malignancy.