Mitochondrial Plasticity Promotes Resistance to Sorafenib and Vulnerability to STAT3 Inhibition in Human Hepatocellular Carcinoma

The multi-kinase inhibitor sorafenib is a primary treatment modality for advanced-stage hepatocellular carcinoma (HCC). However, the therapeutic benefits are short-lived due to innate and acquired resistance. Here, we examined how HCC cells respond to sorafenib and adapt to continuous and prolonged exposure to the drug. Sorafenib-adapted HCC cells show a profound reprogramming of mitochondria function and marked activation of genes required for mitochondrial protein translation and biogenesis. Mitochondrial ribosomal proteins and components of translation and import machinery are increased in sorafenib-resistant cells and sorafenib-refractory HCC patients show similar alterations. Sorafenib-adapted cells also exhibited increased serine 727 phosphorylated (pSer727) STAT3, the prevalent form in mitochondria, suggesting that STAT3 might be an actionable target to counteract resistance. Consistently, a small-molecule STAT3 inhibitor reduces pSer727, reverts mitochondrial alterations, and enhances the response to sorafenib in resistant cells. These results sustain the importance of mitochondria plasticity in response to sorafenib and identify a clinically actionable strategy for improving the treatment efficacy in HCC patients.

Spontaneous rupture of liver abscess with biliary communication presenting as a lumbar mass

Pyogenic liver abscess was first reported in the writings of Hippocrates, which was based on the type of fluid recovered from the abscess related to a high mortality rate ranging between 15% and 19% at that time. However in 1938, Ochsner and De Bakey described the recommended surgical treatment as the primary treatment modality. Surgery remained the therapy of choice until the mid-1980s, when percutaneous drainage was shown to be a safer alternative in many cases. Spontaneous rupture of liver abscess may occur free in the peritoneal cavity or in neighbouring organs, an event which is generally considered as a surgical emergency, while localized rupture can be managed with drainage, either percutaneous or surgical/minimal invasive techniques and addition of appropriate antibiotic treatment. In cases where there is uneventful rupture of abscess and localized to the neighbouring organs and tissues can be successfully treated by a combination of broad-spectrum antibiotics and percutaneous drainage and endoscopic management.

Endoscopic Management of Branchial Fistula: Diagnostic and Therapeutic.

Recurrent neck abscess is a typical feature of branchial anomaly. Open surgical excision has been the primary treatment modality for past decades however several alternative treatment modalities such as endoscopic electrocauterization has recently gained popularity and acceptance universally. This series aims to introduce endoscopic assessment as the first line diagnostic and therapeutic management for branchial fistula. 5 patients underwent examination under general anesthesia via direct laryngoscopy, endoscopic assessment and cauterization in our centre from 2016 to 2019. They were then followed up at our clinic to assess disease progression. Comparison between open neck surgery and endoscopic cauterization of internal sinus tract opening as the primary treatment has reported similar recurrence rate. Proposal of endoscopic assessment as the first line investigation and diagnostic tool with the aim of therapeutic cauterization at the same setting. MRI may be needed in scenarios such as failed endoscopic treatment or when open surgery is required.

COVID-19 and end stage renal disease treatment modalities in the United States

From the establishment of nearly universal health coverage for end stage renal disease in 1972 to 2021, the primary treatment modality has been in-center hemodialysis despite significant advances in home therapies such as peritoneal dialysis and home hemodialysis. There are many theories as to why peritoneal and home hemodialysis lack so far behind in prescriptions with profitability and or a patient’s compliance or support leading the logical explanations. But 2020 was a different year with the surge in COVID-19 cases.

Primary Laryngeal Amyloidosis and CO2 Laser as the Treatment Modality

Introduction Amyloidosis is brought about by intracellular and/or extracellular accumulation of insoluble abnormal amyloid fibrils that alters the normal function of the tissues. Localized laryngeal amyloidosis is a rare disease which lacks long-term follow-up studies. It is prone to recurrence; hence meticulous excision is required. We are doing this study to analyse clinical features of primary laryngeal amyloidosis, the subsites commonly found in, and the effectiveness of CO2 laser as treatment modality. Materials and Methods It is a retrospective study of 13 patients diagnosed as Primary Laryngeal Amyloidosis in between 2005 to 2018, where clinical features, histologic and immuno-histochemical patterns of the patients were evaluated. Systemic amyloidosis was ruled out by the non-appearance of Bence-Jones proteins in urine and serum electrophoresis examination. Systemic workups were pursued during the follow-up. The patients were followed up 3 monthly for the first year, then 6 monthly after that, for 3 years. The last patient who underwent the surgery was in the 2018 and had just finished his 2nd follow up, while the rest have been followed up for 3 years. Results Hoarseness was the most common complaint in all the patients. The subsites most common for amyloid deposition were seen in the true vocal cords followed by supraglottis, anterior commissure, ventricle and the subglottis. Microscopically, the amyloid was deposited within the submucosa surrounded by lymphoplamocytic infiltration. All cases were treated with microlaryngoscopic CO2 Laser excision. With the exception of one patient, the rest had no recurrence. Conclusion Primary Laryngeal Amyloidosis is an uncommon benign disease that has a predisposition for recurrence. With use of CO2 laser as the primary treatment modality, the percentage of recurrence has drastically reduced. Systemic involvement should be ruled out. A frequent follow-up of the patients is desirable for early detection of recurrences. Laser is a novel treatment of laryngeal amyloidosis.

Urethral Prolapse in Prepubertal Girls in Port Harcourt, Nigeria: A Multicentre Study

Background: Urethral mucosa prolapse is a rare condition mainly seen in prepubertal girl with racial predilection for black girls. Methodology: This was a multicenter 7-year retrospective analysis of 27 cases of urethral mucosa prolapse treated at the university of Port Harcourt teaching hospital and private health facilities in Port Harcourt from 2011-2018. Relevant information extracted from the case files include age, clinical presentation, examination findings, treatment modality and post-operative complications. Data was entered and analyse using SPSS version 25 and results were presented in simple percentages and frequency tables Results: The institutional prevalence of urethral prolapse was 0.14%. The commonest presenting complaint was blood stains on the underwear in 23 (85.2%) patients while all patients presented with the characteristic ‘doughnut sign’ of a circumscribed fleshy mass surrounding the urethral meatus. All patients had intact hymen. Surgery was the primary treatment modality in 24 (88.9%) cases while conservative medical management was carried out in three (11.1%) patients. The success rate for surgical management was 100% and 33.3% for medical treatment. The commonest post-operative complication was dysuria reported in 7 (25.9%) cases and acute urinary retention was reported in one (3.75) patient. Conclusion: Urethral mucosa prolapse is a rare but important condition in prepubertal girls presenting with vaginal bleeding due to the suspicion of sexual abuse. Surgical treatment offers better outcome amongst the studied population.

Endovascular versus surgical treatment of cranial dural arteriovenous fistulas: a single-center 8-year experience

Background Cranial dural arteriovenous fistulas (dAVFs) are rare lesions managed mainly with endovascular treatment (EVT) and/or surgery. We hypothesize that there may be subtypes of dAVFs responding better to a specific treatment modality in terms of successful obliteration and cessation of symptoms and/or risks. Methods All dAVFs treated during 2011–2018 at our hospital were analyzed retrospectively. Presenting symptoms, radiological variables, treatment modality, complications, and residual symptoms were related to dAVF type using the original Djindjian classification. Results We treated 112 dAVFs in 107 patients (71, 66% males). They presented with hemorrhage (n = 23; 21%), non-hemorrhagic symptoms (n = 75; 70%), or were discovered incidentally (n = 9; 8%). There were 25 (22%) type I, 29 (26%) type II, 26 (23%) type III, and 32 (29%) type IV fistulas. EVT was the primary treatment modality in 72/112 (64%) dAVFs whereas 40/112 (36%) underwent primary surgery with angiographic obliteration rates of 60% and 90%, respectively. Using a secondary treatment modality in 23 dAVFs, we obtained a final obliteration rate of 93%, including all type III/IV and 26/27 (96%) type II dAVFs. Except for headache, residual symptoms were rare and minor. Permanent neurological complications consisted of five cranial nerve deficits. Conclusions We recommend EVT as first treatment modality in types I, II, and in non-hemorrhagic type III/IV dAVFs. We recommend surgery as first treatment choice in acute hemorrhagic dAVFs and as secondary choice in type III/IV dAVFs not successfully occluded by EVT. Combining the two modalities provides obliteration in 9/10 dAVF cases at a low procedural risk.

811 Management of Patients with HPV-associated Oropharyngeal Cancer: A Units' Experience

Aim The low positive predictive value (PPV) of initial post-therapy PET-CT in patients with Human papillomavirus (HPV-) associated oropharyngeal squamous cell carcinoma (OPSCC) presents a challenge for teams managing residual disease after initial treatment. We aimed to investigate current management, post treatment surveillance protocols and outcomes of these patients within our unit. Method A retrospective review was performed of p16 positive OPSCC patients treated in 2018. Their primary treatment modality (radiotherapy (RT) or chemoradiotherapy (CRT), neck dissection), post-therapy PET-CT results, management decisions and final clinical outcomes were recorded. Results 38 patients with p16 positive OPSCC were included in the study. 36 (94.7%) received primary CRT or RT, and 2 (5.3%) had primary neck dissections with adjuvant RT. 21 patients were found to have residual disease on the 3-month post-treatment PET-CT. Of these, 9 underwent further PET-CT surveillance, all showing no residual disease. 8 patients received ultrasound +/- fine needle aspiration, from which 1 showed incurable residual and distant metastasis. 2 underwent clinical surveillance, showing no residual disease. 1 had immediate salvage surgery, with further recurrence. 1 patient with persistent disease and lung metastasis received palliative immunotherapy. Conclusions 31 patients were disease free at the end point of this study. This study explores the need for further investigation into features of residual disease in post treatment PET-CT that would indicate initial treatment failure and possible further early intervention. A surveillance strategy following initial post treatment PET-CT needs to be developed to aid in making this decision as early as possible in the post treatment phase.

SURG-13. Multiplicity does not affect outcomes in patients with surgically treated brain metastases

Background Having multiple brain lesions has been considered a negative prognostic factor in patients with brain metastases. The role of surgery in the management of these patients remains a matter of debate. Methods We retrospectively reviewed our patients who underwent surgical resection of brain metastases from January 2018 to December 2019, and examined outcomes including overall survival (OS), progression free survival (PFS) and rates of local failure. Results We identified 130 patients who underwent surgical resection as the primary treatment modality of brain metastases. At the time of surgery, 117 patients harbored 1–3 lesions, 13 had more than 3 lesions. Overall survival at two years for our entire cohort was 46%. The difference in OS between patients with > 3 metastases (21%) and 1–3 metastases (49%) was not statistically significant (HR=1.34, 95% CI: 0.67–2.68, p=0.41). Similarly, 27% of patients had PFS at two years, with 25% in the multiple metastases group and 28% in the comparison group (HR=1.19, 95% CI: 0.63–2.23, p=0.59). Additionally, 32% of patients overall experienced local failure at two years and there was no significant difference between patients with >3 metastases (15%) and those with fewer (33%) (HR=0.68, 95% CI: 0.21–2.19, p=0.52). A multivariate regression model examining multiple preoperative features revealed large tumor volume to be the only independent predictor of limited OS (p = 0.017) and PFS (p = 0.023), and local failure (p = 0.031). Conclusions In carefully selected patients, surgical resection is a reasonable management option for patients with multiple brain metastases.

Management of post-traumatic ischaemic ileal stricture using intraoperative indocyanine green fluorescence-guided resection

Blunt abdominal trauma can affect mesenteric circulation which may lead to bowel strictures. Indocyanine green (ICG) angiography can be used to assess mesenteric blood flow and bowel perfusion as a guide to resect length intraoperatively. But this concept has not been applied to ischaemic bowel strictures. We present a case of ischaemic ileal stricture induced by blunt abdominal trauma which was managed by resection and anastomosis. Intraoperative near-infrared (NIR) ICG angiography was used as a guide to resect the bowel length. This case emphasises that ischaemic bowel strictures should be suspected in patients presenting with intestinal obstruction following trauma. Resection and anastomosis of the affected segment remains the primary treatment modality with excellent outcomes. NIR ICG angiography is a real-time objective and useful resource for assessing bowel perfusion and could be used to determine the length of the segment to be resected in patients with ischaemic bowel stricture.