Systemic therapies in hepatocellular carcinoma: A revolution?

The evolution in systemic therapies in hepatocellular carcinoma (HCC) signifies a strategy of high-cost, high-gain innovation that originated with sorafenib, despite its limited impact on tumor response. This strategic approach paved the way for the emergence of a second wave of the short-lived competitive advantage, exemplified by the incorporation of atezolizumab plus bevacizumab and tremelimumab plus durvalumab. In the context of safety concerns within the liver cancer domain, the IMBRAVE150 and HIMALAYA trials boldly incorporated bevacizumab and tremelimumab, respectively, demonstrating the continuation of the high-risk, high-reward innovation paradigm. This review delves into the strengths, weaknesses, opportunities, and threats analysis of systemic therapies in the field of HCC.

Systematic review of the role of calprotectin in cirrhosis.

BACKGROUND: Calprotectin is a calcium-binding-S100-protein synthetized mainly in neutrophils which has been demonstrated to be an accurate biomarker of the presence of these cells. Gut barrier dysfunction in patients with advanced chronic liver disease (ACLD), in addition to the lack of noninvasive tools for diagnosis and prognosis of cirrhosis decompensations, has raised interest in this biomarker. AIMS: Our aim is to summarize the current evidence regarding the role of calprotectin in terms of its diagnostic and prognostic utility in ACLD. METHODS: We performed a systematic search (PROSPERO registration no. CRD42023389069) of original articles published without any restrictions on the publication date until January 2023 providing information about calprotectin for the prognosis or diagnosis of ACLD and its decompensations in adult patients. RESULTS: A total 227 articles were identified, and 26 observational studies finally met the inclusion criteria. In 14 studies, calprotectin was measured in ascitic fluid, all of which reported higher calprotectin values in spontaneous bacterial peritonitis, while cut-off points for its diagnosis were proposed in nine studies. Three studies reported higher faecal calprotectin levels in patients with hepatic encephalopathy and portal hypertension. Four studies evaluated faecal calprotectin and one plasma calprotectin as biomarkers for gut barrier integrity and bacterial translocation. CONCLUSIONS: Calprotectin is emerging as a promising biomarker in ACLD, particularly for the management of bacterial infections and alcohol-related liver disease. Further research with better study designs should help to determine the feasibility of calprotectin measurement in routine clinical practice.

Incidence, risk factors and clinical outcomes of multidrug-resistant microorganism infections among patients admitted for decompensated cirrhosis: A prospective study.

BACKGROUND: Bacterial infections remain one of the main complications in cirrhosis and worsen patients' prognosis and quality of life. An increase in multidrug resistant microorganism (MDRM) infections among patients with cirrhosis, together with infection-related mortality rates, have been reported in recent years. Therefore, adaptation of the initial empiric antibiotic approach to different factors, particularly the local epidemiology of MDRM infections, has been recommended. We aim to describe the main features, outcomes and risk factors of MDRM infections in patients with cirrhosis. METHODS: Prospective registry of all episodes of in-hospital infections occurring among cirrhotic patients admitted within a 2-year period at a single center. Clinical and microbiological data were collected at the time of infection diagnosis, and the in-hospital mortality rate of the infectious episode was registered. RESULTS: A total of 139 infectious episodes were included. The disease-causing microorganism was identified in 90 episodes (65%), of which 31 (22%) were caused by MDRM. The only two factors independently associated with MDRM infections were rectal colonization by MDRM and a nosocomial or healthcare-associated source. The infection-related mortality rate was 18.7%. MDRM infection and a past history of hepatic encephalopathy were independently associated with in-hospital mortality. CONCLUSIONS: Almost one fourth of bacterial infections occurring in admitted cirrhotic patients were due to MDRM. Rectal colonization was the most important risk factor for MDRM infections in decompensated cirrhosis. Screening for MDRM rectal colonization in patients admitted for decompensated cirrhosis should be assessed as a tool to improve local empiric antibiotic strategies.

Appropriateness of routine pre-endoscopic SARS-CoV-2 screening with RT-PCR in asymptomatic individuals and its impact on delayed diagnosis.

AIMS: Endoscopy units are considered to be at an increased risk of infection by SARS-CoV-2. Our aim is to assess the correlation between pre-endoscopic screening with reverse-transcription-polymerase-chain-reaction (RT-PCR) in asymptomatic individuals scheduled for elective endoscopy and the epidemiological data published by the local Health Administration. PATIENTS AND METHODS: Observational retrospective study collecting the results of our screening strategy spanning June/2020-June/2021, the effective potential growth (EPG), an index measuring the outbreak risk, and the 7 and 14-day cumulative incidence (CI). Indication, delay and the findings of the endoscopic examinations were registered for RT-PCR positive patients. RESULTS: A total of 5808 tests were performed, yielding 125 positive results (2.15%). All positive tests occurred in weeks of high/very high risk (EPG>100) with the highest monthly rate being 9.36%, recorded in January/2021. A significant correlation (rho=0.796; p<0.001) between weekly positive rates and EPG was observed, and a significantly lower weekly number of positive tests was recorded when EPG<100. Planning the screening strategy one week ahead according to EPG>100 would have avoided up to 826 tests with only one positive result to account for. One hundred and thirteen individuals tested positive and 89 endoscopies were delayed. The most common findings were colon polyps, colorectal cancer and gastric metaplasia. Oncological diagnosis was delayed 50±3 days. CONCLUSIONS: No positive RT-PCR test were registered out of high-risk periods. Epidemiological administrative data in the preceding two weeks showed a significant correlation with screening results and could be useful to plan pre-endoscopic screening and avoid unnecessary tests.

Orbital amyloid tumor associated with myasthenia gravis.

We present a case of a 53-year-old female with an 11 year history of myasthenia gravis (MG) with palpebral ptosis in the left eye which had become more marked over the previous year. Examination revealed a painless left orbital mass causing ptosis. The tumor was surgically removed and histopathology revealed deposits of a hyaline substance which when stained with Congo Red had an apple-green birefringence with polarized light, typical of amyloid. In the absence of amyloid deposits elsewhere in the body, amyloid tumor (AT) was diagnosed. No myelo- or lymphoproliferative syndromes, systemic involvement by amyloidosis or any autoimmune disease were found. The evolution and aesthetic results where satisfactory. Only two cases of orbital AT associated with MG have been described previously; however, in one of the cases, the symptoms of the AT had led to a false diagnosis of MG.

Impact of immunosuppressants on SARS-CoV-2 infection in elderly patients with inflammatory bowel disease.

BACKGROUND: Older age has been reported as a risk factor for severe SARS-CoV-2 disease (COVID-19). The impact of immunosuppressants (IMS) on COVID-19 is still under debate. AIM: To describe the incidence and severity of COVID-19 in elderly patients with inflammatory bowel disease (IBD) in relation to the use of IMS. METHODS: IBD patients over 65 years of age were selected and grouped in terms of IMS use. Confirmed COVID-19, adherence to IST, comorbidities and concomitant non-IBD-related treatments between 1st of March 2020 to 1st of March 2021 were recorded. RESULTS: Out of 418 patients included, 89 (21.3%) were on IMS. Thirty-two patients (7.7%) had COVID-19, 7 of whom were on IMS (7.6% not on IMS vs. 7.9% on IMS; P = 0.933) and 7 (22%) patients died. CONCLUSIONS: Incidence of COVID-19 among elderly IBD patients was similar to that reported in the background population, regardless of the use of IMS.

Impact of the ethmoid volume on endoscopic medial wall decompression outcomes in Graves' orbitopathy.

BACKGROUND: Endoscopic orbital decompression is a well-established technique for Graves orbitopathy treatment. AIMS: Measurement of the ethmoid volume and its correlation with proptosis reduction in patients undergoing endoscopic orbital decompression for Graves' orbitopathy. METHODS: We retrospectively reviewed clinical charts of 209 patients (319 orbits) operated by a surgeon at our institution between 1998 and 2019. RESULTS: Average age was 46.9 years. About 83.3% of the patients were female, 54.6% were smokers, 93.8% were euthyroid at the time of decompression, 3.8% were hypothyroid and 2.4% were hyperthyroid. About 77.5% of the patients underwent bilateral surgery, the remainder and unilateral. Subsequent stages included strabismus surgery in 22.5% patients, Müllerectomy 37.8%, with or without canthoplasty (14.8 vs. 23%). Mean proptosis reduction was 4.61 mm. Mean ethmoid volume was 5.57 mm3. Ethmoid volume had a moderate positive correlation with proptosis reduction (r s = 0.49, p < .001). Further investigation, statistically significant moderate correlation was found only in the small (SE) and big (BE) ethmoid groups. CONCLUSION: We advise evaluating ethmoid sinus pneumatization on computed tomography before decompression to estimate possible anatomical limitations. Additional wall decompression might be advocated in most severe cases.

Orbital cavernous haemangioma; profile and outcome of 76 patients managed surgically.

Background: Orbital cavernous haemangioma (OCH) is one of the most common primary orbital tumours in adults. They can encroach on intraorbital or adjacent structures and be considered 'anatomically' malignant. Aims: To report a series of patients that were all managed surgically, with possible specificities and propose predictors of treatment outcome. Methods: We realised a hospital-based retrospective case review including data from 76 patient files. Results: The mean age was 37.8 years. Unilateral proptosis was observed in all patients. Visual loss was found in 32 patients (42.1%). Findings on eye examination included lagophthalmos (76.3%), blepharoptosis (21.1%), complications of corneal exposure (19.6%), strabismus (13.2%) and fundoscopic abnormalities (60.5%). Abnormal fundoscopy was significantly associated with decreased visual acuity (VA) (p < .001). Small tumours were predominant (65.8%) and size was associated with VA (correlation coefficient r = -0.5, p < .001). Surgery was mainly by lateral orbitotomy (94.7%), with early post-operative complications in 18 patients (23.7%). Multivariable analysis showed that tumour size, preoperative VA and abnormal fundoscopy were significantly associated with postoperative VA. Conclusion: Clinical and radiological profiles are consistent. Tumour size, preoperative VA, and abnormal fundoscopy seem to be important factors that could influence outcome expectations. Surgical management is still predominantly by open approaches. Severe complications remain rare.

Silent sinus syndrome: combined sinus surgery and orbital reconstruction - report of 15 cases.

BACKGROUND: Silent sinus syndrome (SSS) is defined as spontaneous, painless enophthalmos, hypoglobus with orbital floor resorption and maxillary sinus collapse on the ipsilateral side. Different methods of orbital floor reconstruction have been proposed. AIMS/OBJECTIVES: The purpose was to analyse the results of combined endoscopic sinus surgery (ESS) and reconstruction using orbital floor implant of 15 patients with SSS and to present recent histological findings. MATERIALS AND METHODS: Retrospective case review of 15 patients with SSS treated in clinic between 2007 and 2017. RESULTS: Eleven women and four men presented with unilateral, spontaneous enophthalmos. Averaged duration of enophthalmos was 10.7 months. On affected side, mean enophthalmos was 2.6 mm and hypoglobus 2.7 mm. Computed tomography imaging (CT) imaging showed maxillary sinus opacification on the affected side in every case, and the orbital floor was displaced downwards in all cases. In total, 13 patients underwent simultaneous ESS and rebuilding of orbital floor with a titanium implant. Statistical analysis confirmed significant differences for pre- and postoperative measure of enophthalmos and hypoglobus. CONCLUSION AND SIGNIFICANCE: Implementation of titanium implants is the reliable method of reconstruction that allows good aesthetic result, shorter time of procedure with an excellent long-term outcome and satisfactory patient's tolerance.

Lacrimal gland pleomorphic adenoma: a review of 52 cases, 15-year experience.

BACKGROUND: Lacrimal gland (LG) tumours are rare neoplasms. Pleomorphic adenoma (PA) is the most common histologic variant, representing ∼20% of all LG tumours. PA tends to recur leading to great morbidity. AIMS: We carried out this study to share our experience and provide recent data on the clinical aspects, radiologic findings, management and outcome after treatment. METHODS: We realised a hospital-based retrospective case review including data collected from 52 patients, managed over 15 years. RESULTS: The mean age was 39.8 ± 2 years. Unilateral painless proptosis was the most constant sign (51.9%). CT-scan showed predominantly isodense lesions (96.2%), with regular borders (94.2%), measuring on average 2 cm. MRI showed isointense lesions on T1-weighted images in 96.2% of cases. No pre-operative biopsy was done. Surgical management was mainly external lateral orbitotomy (94.2%). There was no recurrence, considering a mean follow-up period of 12.6 years. Size of tumour at the time of diagnosis increased with age (r = +0.36, p = .01). CONCLUSIONS: Clinical and radiologic characteristics are consistent with literature. Older patients seem to present larger tumours. We believe that biopsy is not necessary if appropriate imaging is done. Complete, intact resection is generally sufficient to minimise the risk of recurrence.

Treatment of recurrent retinal detachment secondary to optic nerve coloboma with injection of autologous platelet concentrate.

A 14-year-old girl presented with a recurrent retinal detachment secondary to optic nerve coloboma in her left eye with a small retinal hole in the bed of the coloboma, confirmed by optical coherence tomography. The patient was treated by injection of 0.05 mL of autologous platelet concentrate into the coloboma along with vitrectomy and gas exchange. After 8 months, the retina was attached and optical coherence tomography revealed closure of the retinal hole. Considering our experience, autologous platelet injection may be considered a treatment option for recurrent retinal detachment secondary to optic nerve coloboma.