Undifferentiated colonic neoplasm with SMARCA4 germline gene mutation and loss of SMARCA4 protein expression: a case report and literature review

Background Nonsense mutation or inactivation of SMARCA4 (BRG1) is associated with a monomorphic undifferentiated histological appearance in tumors at different sites. The association between SMARCA4 alteration and undifferentiated colonic carcinoma needs to be further elucidated. Methods A 61-year-old male patient presented to the hospital with intermittent epigastric pain in the right upper abdomen and abdominal distension. The enhanced computed tomography detected a mass in the hepatic flexure of the colon and multiple liver metastases. Results The right hemicolectomy contained a 4.5-cm undifferentiated malignancy with cells arranged in sheets, abundant necrosis, and areas showing rhabdoid morphology. The immunohistochemistry result showed that these tumor cells were focally positive for cytokeratin (CK), CK8, and CK18; however, diffusely positive for vimentin, P53, Fli-1, and SALL-4. Notably, tumor cells showed a heterogeneous loss of SMARCA4 expression pattern and intact SMARCB1 expression. Next-generation sequencing showed a germline SMARCA4 c.3277C>T(p.R1093*)mutation, somatic APC mutation, and no abnormal SMARCB1 gene. The tumor exhibited microsatellite stability, negative PD-L1 expression, and few infiltrating CD8 + T cells. The patient died a month later after surgery. Conclusions We presented a rare case of undifferentiated colonic neoplasm with loss of SMARCA4 protein expression and germline SMARCA4 mutation. Moreover, the role of SMARCA4 alterations in tumor diagnosis and treatment was also summarized.

Colon Carcinogenesis: The Interplay Between Diet and Gut Microbiota

Colorectal cancer (CRC) incidence increases yearly, and is three to four times higher in developed countries compared to developing countries. The well-known risk factors have been attributed to low physical activity, overweight, obesity, dietary consumption including excessive consumption of red processed meats, alcohol, and low dietary fiber content. There is growing evidence of the interplay between diet and gut microbiota in CRC carcinogenesis. Although there appears to be a direct causal role for gut microbes in the development of CRC in some animal models, the link between diet, gut microbes, and colonic carcinogenesis has been established largely as an association rather than as a cause-and-effect relationship. This is especially true for human studies. As essential dietary factors influence CRC risk, the role of proteins, carbohydrates, fat, and their end products are considered as part of the interplay between diet and gut microbiota. The underlying molecular mechanisms of colon carcinogenesis mediated by gut microbiota are also discussed. Human biological responses such as inflammation, oxidative stress, deoxyribonucleic acid (DNA) damage can all influence dysbiosis and consequently CRC carcinogenesis. Dysbiosis could add to CRC risk by shifting the effect of dietary components toward promoting a colonic neoplasm together with interacting with gut microbiota. It follows that dietary intervention and gut microbiota modulation may play a vital role in reducing CRC risk.

P867 Mitral stenosis: from mild to severe in less than a year

We report the case of an 82-year-old woman, with personal history of hypertension, diabetes mellitus, dyslipemia and permanent atrial fibrillation. In 2013 aortic valve substitution surgery was performed with a mechanic prosthetic valve. In her last echocardiogram in May 2018 a mild double mitral lesion was detected, with a normal aortic valve functioning. In March of 2019 she was admitted in hospital with symptoms of heart failure and 38ºC fever. A transthoracic echocardiogram was performed, which revealed a vegetation in the native mitral valve that caused a severe mitral stenosis (area 0.64 cm2). In blood cultures Streptococcus gallolyticycus was isolated. In this situation, a tranesophagical echocardiogram was performed, which confirmed the diagnosis of an infective endocarditis in the native mitral valve. It also showed spontaneous echocontrast as well as a thrombus in the left atrial appendage, despite anticoagulant medication. Given these findings, antibiotic therapy was initiated and surgery programmed. Substitution of the native mitral valve for a biological prosthesis was made. In the transthoracic echocardiographic control the prosthesis was normal functioning. A colonoscopy was performed taking into account the strong association between Streptococcus gallolyticus and colonic lesions, which showed no abnormal findings. At the discharge the patient had no signs or symptoms suggestive of heart failure or infection. Streptococcus gallolytycus is included in the D group of Streptococci. Among hospitalized patients, this group accounts for approximately 5% of streptococcal bloodstream isolates. For humans, the gastrointestinal tract is the most frequent entry point, other potential sources include the hepatobiliary tree and the urinary tract. Clinical manifestations include bacteremia and endocarditis, which is usually highly destructive and frequently bivalvular. Bone infection, meningitis or peritonitis can also be present. Due to the frequent association between this microorganism and colonic neoplasm, colonoscopy is necessary to dismiss pathological findings. Typically D Streptococci can be treated with penicillins, ceftriaxone, carbapenems, vancomycin, daptomycin, and linezolid. The preferred regimen for streptococcal prosthetic valve endocarditis includes a beta-lactam combined with an aminoglycoside, to achieve synergistic effect. Abstract P867 Figure. Mitral stenosis

241 “From SIAD to Happy”: a Case of Effective Use of Tolvaptan for Hyponatremia in an Older Person

Background Hyponatremia commonly affects the older person, leading to morbidity and mortality. Tolvaptan use is rare in this cohort, but may have benefit in select cases of syndrome of inappropriate antidiuresis (SIAD). Methods An 84-year-old gentleman presented with a history of increasing confusion, fatigue and lethargy attributed to symptomatic hyponatremia. He had background of a recent prolonged admission with small bowel obstruction, treated conservatively. That hospital course was complicated by hypovolaemic hyponatremia, sepsis and clostridium difficile colitis. On this admission, he had no clinical symptoms or signs of infection and his septic screen was negative. He had a Rockwood clinical frailty scale score of 7. His biochemical abnormality was a persistent hyponatremia of 129 mmol/L. Clinically, he was euvolaemic. Further biochemical work up revealed serum osmolality of 263 mmol/kg, serum urea of 6.3 umol/L, urine sodium 108 mmol/L and urine osmolality 541 mmol/kg. Thyroid function, cortisol, and HbA1c were normal. CT brain and chest x ray were unremarkable. A diagnosis of SIAD was made. Fluid restriction was ineffective and Tolvaptan (a selective non-peptide arginine vasopressin receptor antagonist) was commenced on consultation with Endocrinology. Results With initiation of Tolvaptan there was significant clinical improvement. Sodium normalised to 134 mmol/L. He became alert, less confused and more engaged with the multidisciplinary team. He was discharged home well, and on follow up four months later, his clinical frailty scale score was 4 with significant improvement in his mobility on continued Tolvaptan therapy. An underlying colonic neoplasm is the clinically suspected driver of his SIAD but he is declining further investigation at present. Conclusion This case reflects the positive benefits of careful selected use of Tolvaptan in the older population with refractory SIAD, resulting in improved functional status and quality of life.