Multimodal Treatment of Metastatic Rectal Cancer in a Young Patient: Case Report and Literature Review.

Metastatic colorectal cancer requires a multidisciplinary and individualized approach. Herein, we reported the case of a young woman diagnosed with metastatic rectal cancer who received an individualized multimodal treatment strategy that resulted in a remarkable survival. There were several particular aspects of this case, such as the early onset of the disease, the successful use of conversion therapy, the application of liquid biopsy to guide treatment, and the specific nature of the bone metastasis. To offer more insights for navigating such challenges in patients with metastatic colorectal cancer, we have conducted a literature review to find more data related to the particularities of this case. The incidence of early onset colorectal cancer is on the rise. Data suggests that it differs from older-onset colorectal cancer in terms of its pathological, epidemiological, anatomical, metabolic, and biological characteristics. Conversion therapy and surgical intervention provide an opportunity for cure and improve outcomes in metastatic colorectal cancer. It is important to approach each case individually, as every patient with limited liver disease should be considered as a candidate for secondary resection. Moreover, liquid biopsy has an important role in the individualized management of metastatic colorectal cancer patients, as it offers additional information for treatment decisions.

Parenchyma Sparing ALPPS Ultrasound Guided Partition Through Segment 4 to Maximize Resectability (with video).

Background: Associating liver partition and portal vein ligation (ALPPS) has evolved as a treatment strategy for patients with liver tumors who are not amenable for upfront hepatectomy because of an insufficient future liver remnant (FLR). Aim of this study was to test the applicability of ultrasound guided parenchyma sparing surgery to ALPPS concept, by non-anatomically shifting the plane of transection in favor of FLR, resulting in a new technical variant of ALPPS, entitled parenchyma sparing ALPPS (psALPPS). Materials and Methods: Patients who could not safely undergo right trisectionectomy ALPPS because of insufficient FLR were considered eligible for psALPPS, consisting in liver partition through segment 4 using ultrasound guidance. Results: Between April 2017 and April 2021, five patients with median age of 68 years (range: 66-78), four male and one female, underwent psALPPS for colorectal liver metastases (N=2), intrahepatic cholangiocarcinoma (N=2), and hepatocellular carcinoma (N=1). Standardized FLR (sFLR) for segments 2-3 before stage 1 surgery would have been a median of 11.6%. PsALPPS could double the sFLR at stage 1 resulting in an increase of ps-sFLR from a median of 22.7% (at stage 1) to 34.0% (at stage 2) after a median interstage interval of 15 days. All patients tolerated surgery well and no major complications were recorded. Conclusions: Applying the principles of parenchyma sparing surgery to ALPPS offers the advantage to maximize FLR and simultaneously reduce ischemic injury of segment 4 compared to conventional ALPPS. In this way, psALPPS may markedly increase resectability while reducing morbidity. Video: https://www.revistachirurgia.ro/pdfs/?EntryID=922974&art=2021-parenchyma-sparing-ALPPS-ultrasound-guided-partition.pdf

Parenchyma Sparing ALPPS - Ultrasound Guided Partition Through Segment 4 to Maximize Resectability (with video).

Background: Associating liver partition and portal vein ligation (ALPPS) has evolved as a treatment strategy for patients with liver tumors who are not amenable for upfront hepatectomy because of an insufficient future liver remnant (FLR). Aim of this study was to test the applicability of ultrasound guided parenchyma sparing surgery to ALPPS concept, by non-anatomically shifting the plane of transection in favor of FLR, resulting in a new technical variant of ALPPS, entitled parenchyma sparing ALPPS (psALPPS). Materials and Methods: Patients who could not safely undergo right trisectionectomy ALPPS because of insufficient FLR were considered eligible for psALPPS, consisting in liver partition through segment 4 using ultrasound guidance. Results: Between April 2017 and April 2021, five patients with median age of 68 years (range: 66-78), four male and one female, underwent psALPPS for colorectal liver metastases (N=2), intrahepatic cholangiocarcinoma (N=2), and hepatocellular carcinoma (N=1). Standardized FLR (sFLR) for segments 2-3 before stage 1 surgery would have been a median of 11.6%. PsALPPS could double the sFLR at stage 1 resulting in an increase of ps-sFLR from a median of 22.7% (at stage 1) to 34.0% (at stage 2) after a median interstage interval of 15 days. All patients tolerated surgery well and no major complications were recorded. Conclusions: Applying the principles of parenchyma sparing surgery to ALPPS offers the advantage to maximize FLR and simultaneously reduce ischemic injury of segment 4 compared to conventional ALPPS. In this way, psALPPS may markedly increase resectability while reducing morbidity. Video version: https://www.revistachirurgia.ro/pdfs/?EntryID=922974&art=2021-parenchyma-sparing-ALPPS-ultrasound-guided-partition.pdf

Is Long-Term Survival in Metastases from Neuroendocrine Neoplasms Improved by Liver Resection?

Background and Objectives: Although many of the neuroendocrine neoplasms (NEN) have a typically prolonged natural history compared with other gastrointestinal tract cancers, at least 40% of patients develop liver metastases. This study aims to identify whether liver resection improves the overall survival of patients with liver metastases from NEN. Materials and Methods: We conducted a retrospective study at "Fundeni" Clinical Institute over a time period of 15 years; we thereby identified a series of 93 patients treated for NEN with liver metastases, which we further divided into 2 groups as follows: A (45 patients) had been subjected to liver resection complemented by systemic therapies, and B (48 patients) underwent systemic therapy alone. To reduce the patient selection bias we performed at first a propensity score matching. This was followed by a bootstrapping selection with Jackknife error correction, with the purpose of getting a statistically illustrative sample. Results: The overall survival of the matched virtual cohort under study was 41 months (95% CI 37-45). Group A virtual matched patients showed a higher survival rate (52 mo., 95% CI: 45-59) than B (31 mo., 95% CI: 27-35), (p < 0.001, Log-Rank test). Upon multivariate analysis, seven independent factors were identified to have an influence on survival: location (midgut) and primary tumor grading (G3), absence of concomitant LM, number (2-4), location (unilobar), grading (G3) of LM, and 25-50% hepatic involvement at the time of the metastatic disease diagnosis. Conclusions: Hepatic resection is nowadays the main treatment providing potential cure and prolonged survival, for patients with NEN when integrated in a multimodal strategy based on systemic therapy.

Resection of Giant Liver Metastasis of Gastrointestinal Stromal Tumor Using Intraoperative Ultrasound Guidance.

We present the case of a 37-year-old patient with a surgical history of a gastrointestinal stromal tumor with jejunal location, AFIP classification 6a, hospitalized in our center for synchronous liver metastases. The oncological assessment performed after 12 months from surgery for primary tumor, during which Imatinib was administered, reveals stable disease. CT scan showed a single very large centrally located liver metastasis, 14 cm in diameter, involving segments V and VIII IV, IV and VII, compressing the main portal bifurcation, right hepatic vein, umbilical (scizural) vein and left hepatic vein, invading the middle hepatic vein. We considered it feasible to apply the concept of R1 vascular resection, performing a limited, non-anatomical, ultrasound-guided central hepatectomy, allowing detachment of the tumor from the right hepatic vein and from the umbilical vein. Thus, we sacrificed only the ventral portal pedicles of segments V and VIII and partially preserved these segments to avoid the risk of post-resection liver failure.Currently, the patient is disease-free after 53 months, supporting the concept of ultrasound-guided R1 vascular resection, in the context of systemic therapy with tyrosine kinase inhibitors for metastases of stromal gastrointestinal tumors. (video article https://www.revistachirurgia.ro/pdfs/video/Liver-Resection-Metastases-Stromal-Tumors-2283.mp4).

En-Bloc Complete Segment 1 Resection and Left Hepatectomy for Klatskin Tumor.

video width="640" height="480" controls controlsList="nodownload" poster="https://www.revistachirurgia.ro/pdfs/video/Complete_segment_resection_hepatectomy_klatskin_tumor.jpg" style="margin-top: -20px;" source src="https://www.revistachirurgia.ro/pdfs/video/Complete_segment_resection_hepatectomy_klatskin_tumor.mp4" type="video/mp4" Your browser does not support the video tag. /video We present the case of a 37-year-old male patient with no significant history, hospitalized in our center for painless jaundice with sudden onset. CT contrast portal phase imaging revealed a tumor located at the main biliary confluence, in the proximity of the main portal bifurcation, with no venous or arterial vascular invasion, nor extrahepatic metastases. MRCP diagnosed a Bismuth- Corlette type Klatskin IIIb tumor. For complete assessment of biliary involvement and surgical planning, in addition to the Bismuth-Corlette classification, we took into consideration the presence of infiltration of the bile ducts for segment 1, documented at MRCP. Therefore, a left hepatectomy with en-bloc complete segment 1 resection, along with the main bile ducts and hilar lymphadenectomy, was considered best suited for achieving curative resection in this case. After an uneventful postoperative course, the patient was discharged in the 12th postoperative day. Currently, the patient is disease-free after 84 months. We consider that the long-term recurrence free survival was favored by the complete segment 1 resection. Therefore, for complete assessment of biliary involvement in Klatskin tumor, we recommend that in addition to Bismuth-Corlette classification, infiltration of the bile duct for segment 1 should always be evaluated. If present, the entire segment 1 should be removed for best oncological results.

Liver Resection for Metastases from Gastrointestinal Stromal Tumors: Does it Improve Long-Term Survival?

BACKGROUND AIMS: The emergence of tyrosine kinase inhibitors, radically altered the management of GISTs and sparked controversy regarding the role of hepatic resection for metastatic tumors. This study aims to identify whether there is improvement in the overall survival of patients with gastrointestinal liver metastases, undergoing hepatic resection in the context of multimodal treatment strategy, as to those approached only by systemic therapy. Methods: Using a retrospective database, we identified 57 patients treated at our center over a 12-year period: Group A (n=31) underwent hepatic resection alongside systemic therapies, and B (n=26) only systemic therapies. In order to obtain a more robust sample, needed for the survival analysis, we performed a propensity score matching and a bootstrapping selection with Jackknife correction for errors; thus, we created an extended sample of 1000 virtual patients. Results: The overall survival measured in all patients was 47 months (95%CI:34-60); significantly higher for group A (56 months, 95%CI:37-75) compared to group B (38 months, 95%CI:19-56), (p=0.007, Log Rank test). Multivariate analysis identified one risk factor: the presence synchronous liver metastases upon diagnosis of primary. Conclusions: Liver resection following TKI therapy is the current mainstay of treatment strategy for potential cure and prolonged survival, in appropriately selected patients evaluated in an multidisciplinary tumor board.

Definitive Surgery for Liver Trauma in a Tertiary HPB Center (with video).

Background: Surgery for severe liver trauma remains challenging even for HPB surgeons, mainly due the hemodynamical instability, involvement of major vascular and biliary elements, impaired background liver and frequent anatomical variants. In this setting, despite conservative policy, major liver resection is still required in selected cases. Also salvage liver transplantation may be needed. Our study aims to analyze the results after definitive surgery for hepatic injury (HI) in a tertiary HPB center. Methods: Sixty-six patients with HI were admitted and treated in our center between June 2000 and June 2021. The median age was 29 years (mean 35, range 10-76). The male/female ratio was 50/16. According to the American Association for the Surgery of Trauma (AAST) system, HIs were grade II in one patient (1.5%), grade III in 11 pts (16.7%), grade IV in 25 pts (37.9%), and grade V in 29 pts (43.9%); no patient had grade I or VI HI. Results: Fifty-two pts (78.8%) benefitted from surgery and 14 pts (21.2%) from non-operative treatment (NOT). Perihepatic packing was previously performed in 38 pts (73.1%). Surgery consisted in hepatic resections (HR) in 51 pts (77.3%) and liver transplantation in one patient (1.5%). The rate of major HR was 51.9% (27 HRs). The overall major morbidity and mortality rates were 33.3% (20 pts) and 13.6% (9 pts), respectively. For surgery, the major complication rate was 35.3% (18 pts), while for major and minor HR were 40.7% (11 pts) and 29.2% (7 pts), respectively; the mortality rate was 15.7% (8 pts). After NOT, the major morbidity and mortality rates were 14.3% (2 pts) and 7.1% (1 pt), respectively. Conclusions: Hepatic resections, especially major ones and/or involving vascular and biliary reconstructions, as well as non-operative treatment for severe hepatic injuries, are to be carried out in tertiary HPB centers, thus minimizing the morbidity and mortality rates, while having the liver transplantation as salvage option.

Retrohepatic Gallbladder Masquerading as Hydatid Cyst in a Patient with Right Liver Agenesis.

Agenesis of the right liver is a rare congenital anomaly which can be associated with an ectopic gallbladder. Hereby, it is presented the case of a 39-year-old man investigated for right upper quadrant abdominal pain and diagnosed at computed tomography with a cystic liver mass initially considered as hydatid cyst. At laparotomy, it was discovered agenesis of the right liver and the presumed hydatid cyst was a retrohepatic gallbladder with lithiasis. Cholecystectomy was performed with an uneventful outcome. Reassessment of the computed tomography images by an experienced radiologist confirmed the intraoperative diagnosis. Although agenesis of the right liver with retrohepatic gallbladder is an exceptional appearance, surgeons should be aware of this anomaly because it can raise challenging issues of diagnosis and surgical planning during cholecystectomy.

The Role of Histopathology and Immunohistochemistry in the Diagnosis of Neuroendocrine Biliary Duct Tumor.

Neuroendocrine tumors of the biliary tract are rare entities developed form Kulchitsky cells which undergo a process of malignant transformation. However, the differential diagnostic between neuroendocrine tumors of the biliary tract and hilar cholangiocarcinoma is very difficult to be established during the preoperative workup; therefore, most patients are submitted to surgery with radical intent and the final diagnostic remains to be confirmed through histopathological and immunohistochemistry studies of the specimen of resection. We present the case of a 60 year old patient who was submitted to en bloc extended right hepatectomy (including segment IV and caudate lobe) with extra hepatic biliary tree resection and left hepatic duct preservation, left cholangiojejunostomy (Roux-En-Y technique), celiac and common hepatic arteries lymphadenectomy and segmental portal vein resection with end-to-end anastomosis for a tumor of the biliary carrefour extended to the right biliary duct and invading the portal vein. The histopathological and immunohistochemistry studies confirmed the presence of a grade 1 neuroendocrine tumor, the staining being positive for Chromogranin A, Neuron-Specific Enolase (NSE) and Ki-67 (1% nuclear positive). At 24 months follow-up the patient is free of recurrent disease.

Parietal Endometriosis: A Challenge for the General Surgeon.

Background: Parietal endometriosis (PE) is a rare pathology, which usually develops in fertile women, after surgical or gynecological procedures. Its quasi-pathognomonic symptomatology consists in catamenial pain with or without palpable mass. The diagnosis can be challenging because it may be confused with stitch granuloma, hematoma, hernia or even cancer. Patients and methods: Between January 2007 and December 2017, 10 female patients with PE were referred for diagnosis and surgery to our clinic. Results: The mean age of the patients was 35.8 years. The primary symptom was pain (9/10 patients) and a palpable mass was present in all patients. Five cases were correctly preoperatively diagnosed as PE and five were misdiagnosed as tumors (4 patients) and stitch granuloma (1 patient). Eight patients had a history of gynecological procedure (cesarean section, episiotomy) and two had no previous surgical interventions. The size of the mass varied from 1 cm to 14 cm. Resection of PE required parietal reconstruction with mesh in five patients but for the rest of the patients no mesh was needed. Conclusions: Our study confirms PE as a rare surgical entity and indicates the necessity of thorough history and physical examination, as well as imaging exams, for making the correct diagnosis in order to choose the appropriate surgical procedure.

Liver Resections in a High-Volume Center: Form Standard Procedures to Extreme Surgery and Ultrasound-guided Resections.

Background: Liver resection (LR) is the treatment of choice for most benign and malignant focal liver lesions, as well as in selected patients with liver trauma. Few other therapies can compete with LR in selected cases, such as liver transplantation in hepatocellular carcinoma (HCC) and ablative therapies in small HCCs or liver metastases. The present paper analyses a single center experience in LR, reviewing the indications of LR, the operative techniques and their short-term results. MATERIAL AND METHOD: Between January 2000 and December 2016, in "œDan Setlacec" Center of General Surgery and Liver Transplantation were performed 3165 LRs in 3016 patients, for pathologic conditions of the liver. In the present series, liver resections for living-donor liver transplantation were excluded. The median age of the patients was 56 years (mean 58 years; range 1-88), with male/female ratio 1524/1492 and adult/pediatric patient ratio 2973/43. Results: Malignant lesions were the main indication for LR (2372 LRs; 74.9%). Among these, colorectal liver metastases were the most frequent indication (952 LRs; 30.1%), followed by hepatocellular carcinoma (575 patients, 18.2%). The highest number of resected tumors per patient was 21, and the median diameter of the largest tumor was 40 mm (mean 51 mm; range 3-250). Major resections rate was 18.6% (588 LRs) and anatomical LRs were performed in 789 patients (24.9%). The median operative time was 180 minutes (mean 204 minutes; range 45-920). The median blood loss was 500 ml (mean 850 ml; range 500-9500), with a transfusion rate of 41.6% (1316 LRs). The morbidity rate was 40.1% (1270 LRs) and the rate of major complications (Dindo-Clavien IIIa or more) was 13.2% (418 LRs). Mortality rate was 4.2% (127 pts). CONCLUSION: LRs should be performed in specialized high-volume centers to achieve the best results (low morbidity and mortality rates).

Curative Intent Treatment of Hepatocellular Carcinoma - 844 Cases Treated in a General Surgery and Liver Transplantation Center.

Background: The objective of this study is to assess the outcome of the patients treated for hepatocellular carcinoma (HCC) in a General Surgery and Liver Transplantation Center. Methods: This retrospective study includes 844 patients diagnosed with HCC and surgically treated with curative intent methods. Curative intent treatment is mainly based on surgery, consisting of liver resection (LR), liver transplantation (LT). Tumor ablation could become the choice of treatment in HCC cases not manageable for surgery (LT or LR). 518 patients underwent LR, 162 patients benefited from LT and in 164 patients radiofrequency ablation (RFA) was performed. 615 patients (73%) presented liver cirrhosis. Results: Mordidity rates of patient treated for HCC was 30% and mortality was 4,3% for the entire study population. Five year overall survival rate was 39 % with statistically significant differences between transplanted, resected, or ablated patients (p 0.05) with better results in case of LT followed by LR and RFA. Conclusions: In HCC patients without liver cirrhosis, liver resection is the treatment of choice. For early HCC occurred on cirrhosis, LT offers the best outcome in terms of overall and disease free survival. RFA colud be a curative method for HCC patients not amenable for LT of LR.

The Romanian National Program for Liver Transplantation - 852 Procedures in 815 Patients over 17 Years (2000-2017): A Continuous Evolution to Success.

Background: Liver transplantation (LT) has become an established treatment for end-stage liver disease, with more than 20.000 procedures yearly worldwide. The aim of this study was to analyze the results of Romanian National Program of LT. Methods: Between April 2000 and April 2017, 817 pts received 852 LTs in Romania. Male/female ratio was 487/330, while adult/pediatric ratio was 753/64, with a mean age of 46 years (median 50 yrs; range 7 months - 68 yrs). Main LT indications were HBV cirrhosis (230 pts; 28.2%), HCC (173 pts; 21.2%), and HCV cirrhosis (137 pts; 16.8%). Waiting time and indications for LT, patient and donor demographics, graft features, surgical procedures, and short and long-term outcomes were analyzed. Results: DDLT was performed in 682 pts (83.9%): whole LT in 662 pts (81%), split LT in 16 pts (2.3%), reduced LT in 2 pts (0.2%), and domino LT in 1 pts (0.1%). LDLT was performed in 135 pts (16.5%): right hemiliver in 93 pts (11.4%), left lateral section in 28 pts (3.4%), left hemiliver in 8 pts (1%), left hemiliver with segment 1 in 4 pts (0.5%), and dual graft LDLT in 2 pts (0.2%). Overall major morbidity rate was 31.4% (268 pts), while perioperative mortality was 7.9% (65 pts). Retransplantation rate was 4.3% (35 pts): 27 whole LTs, 3 reduced LTs, 3 split LTs, and 2 LDLT. Long-term overall 1-, 3-, and 5-year estimated survival rates for patients were 87.9%, 81.5%, and 79.1%, respectively. One-, 3-, and 5-year overall mortality on waiting list also decreased significantly over time from 31.4%, 54.1% and 63.5%, to 4.4%, 13.9% and 23.6%, respectively. Conclusions: The Romanian National program for liver transplantation addresses all causes of acute and chronic liver failure or liver tumors in adults and children, using all surgical techniques, with good long-term outcome. The program constantly evolved over time, leading to decreased mortality rate on the waiting list.

Endovascular Stenting for Idiopathic Stenosis of the Superior Mesenteric Vein: A Case Report.

Idiopathic superior mesenteric vein (SMV) stenosis, where no clear causative factor is identifiable, remains a clinical rarity. We present a detailed case report of a patient with idiopathic stenosis of the SMV who underwent successful endovascular stenting. This report outlines the patient's clinical presentation, diagnostic imaging findings, procedural approach by the interventional radiology team, and subsequent management. Endovascular stenting is a viable therapeutic option for patients with idiopathic SMV stenosis. This case demonstrates that with appropriate interventional and post-procedural management, long-term stent patency and thrombosis prevention can be achieved. The success of this case encourages further investigation into endovascular treatments for venous stenoses.

Pancreatic Adenocarcinoma: Imaging Modalities and the Role of Artificial Intelligence in Analyzing CT and MRI Images.

Pancreatic ductal adenocarcinoma (PDAC) stands out as the predominant malignant neoplasm affecting the pancreas, characterized by a poor prognosis, in most cases patients being diagnosed in a nonresectable stage. Image-based artificial intelligence (AI) models implemented in tumor detection, segmentation, and classification could improve diagnosis with better treatment options and increased survival. This review included papers published in the last five years and describes the current trends in AI algorithms used in PDAC. We analyzed the applications of AI in the detection of PDAC, segmentation of the lesion, and classification algorithms used in differential diagnosis, prognosis, and histopathological and genomic prediction. The results show a lack of multi-institutional collaboration and stresses the need for bigger datasets in order for AI models to be implemented in a clinically relevant manner.

Liver Transplant in Patients with Hepatocarcinoma: Imaging Guidelines and Future Perspectives Using Artificial Intelligence.

Hepatocellular carcinoma is the most common primary malignant hepatic tumor and occurs most often in the setting of chronic liver disease. Liver transplantation is a curative treatment option and is an ideal solution because it solves the chronic underlying liver disorder while removing the malignant lesion. However, due to organ shortages, this treatment can only be applied to carefully selected patients according to clinical guidelines. Artificial intelligence is an emerging technology with multiple applications in medicine with a predilection for domains that work with medical imaging, like radiology. With the help of these technologies, laborious tasks can be automated, and new lesion imaging criteria can be developed based on pixel-level analysis. Our objectives are to review the developing AI applications that could be implemented to better stratify liver transplant candidates. The papers analysed applied AI for liver segmentation, evaluation of steatosis, sarcopenia assessment, lesion detection, segmentation, and characterization. A liver transplant is an optimal treatment for patients with hepatocellular carcinoma in the setting of chronic liver disease. Furthermore, AI could provide solutions for improving the management of liver transplant candidates to improve survival.

Case report: High-risk acute promyelocytic leukemia and COVID-19-related myocarditis one patient, two cytokine storms.

Acute promyelocytic leukemia (APL) is a unique, highly curable subtype of acute myeloid leukemia, owing to the therapeutic advances of the last decades which led to high complete remission rates and excellent long-term survival. Nevertheless, it remains associated with high early mortality rates. Early death is the major cause of treatment failure in APL and is mainly attributed to coagulopathy, differentiation syndrome, and less commonly, infectious events. Timely recognition of each complication plays a crucial role in the management of patients diagnosed with APL. Coronavirus Infectious Disease 2019 (COVID-19) has shown great heterogeneity in patient presentation. Clinical manifestations range from asymptomatic disease to severe forms, mainly characterized by a hyperinflammatory syndrome leading to acute respiratory distress and multiorgan failure. Patients with acute leukemia and concomitant COVID-19-related hyperinflammatory syndrome have particularly poor outcomes. We hereby report the case of a 28-year-old male patient who was diagnosed with high-risk APL, with severe associated coagulopathy at presentation. He was treated with chemotherapy according to the AIDA regimen. The first week of induction therapy was complicated by a differentiation syndrome manifesting as fever not attributable to infection and respiratory distress with pulmonary infiltrates, resolved after ATRA discontinuation and corticotherapy. On the fourth week of treatment, he tested positive for acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with minor pulmonary involvement. Clinical manifestations over the following days included tachycardia and hypotension, associated with elevated inflammatory markers and cardiac biomarkers (troponin I x58 upper NV). Cardiovascular magnetic resonance imaging was consistent with myocarditis. COVID-19-associated myocarditis was successfully treated with methylprednisolone, intravenous immunoglobulins and Anakinra. Differentiation syndrome and COVID-19-associated myocarditis are two life-threatening complications that adversely impact survival. However, early recognition and prompt treatment initiation can improve clinical outcomes, as was the case of our patient.

Tuberous sclerosis with negative genetic testing and multiple cerebral cavernomas: A new association (Case report).

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder with multisystemic involvement usually resulting from mutations in the tuberous sclerosis 1 (TSC1) or TSC2 genes. However, 10 to 25% of patients do not exhibit these mutations. Cerebral cavernous malformations (CCMs) are capillary-venous malformations that can be asymptomatic or cause variable neurological manifestations, including seizures. Familial CCMs are recognized. In both conditions, specific dermatological lesions are associated. We present the case of a 31-year-old female with TSC diagnosed at the age of 18 years who presented with negative genetic testing. She was admitted to our department in 2019 for a sudden increased frequency of focal seizures. Patient examination revealed multiple facial and intraoral angiofibroma, diplopia, right hemihypoesthesia, brisk deep tendon reflexes, and distal leg paresthesia. VideoEEG indicated a frontal paramedian epileptogenic focus. Cerebral magnetic resonance imaging (MRI) and angioMRI identified multiple fronto-parietal cortical tubers, as well as multiple CCMs, with evidence of bleeding in one. Under antiepileptic drug (AED) and mTOR inhibitor treatment, the seizure frequency significantly improved in a short period of time. This is the first reported case of tuberous sclerosis with negative genetic testing associated with multiple cerebral cavernoma. Such complex patients require multidisciplinary management and detailed genetic testing for increasing knowledge on neuro-cutaneous disorders.

Anticoagulation Therapy for Portal Vein Thrombosis in Patients with Cirrhosis in a Tertiary Center Experience.

BACKGROUND AND AIMS: The evidence regarding the use of anticoagulant (AC) agents in portal vein thrombosis (PVT) is increasing and, most patients undergo chronic treatment with low molecular weight heparin (LMWH) or vitamin K antagonists (VKA). Nevertheless, there are no clear data about who should receive antithrombotic therapy, when to initiate it, how long and what dose should be used for this set of patients. The aim of the study was to assess the outcome of patients with cirrhosis and portal vein thrombosis who received AC therapy, in terms of thrombus regression, bleeding events and survival rates. METHODS: This observational and retrospective study included 107 cirrhotic patients diagnosed with PVT in a single tertiary center between 2010-2019. 54 received low molecular weight heparin or vitamin K antagonist (AC treatment group) and 53 were untreated. All patients were periodically follow-up to assess the evolution of PVT (regression, progression, stable thrombus) and potential occurrence of bleeding events. RESULTS: The regression of portal vein thrombosis was significantly higher in the AC treatment group (OR=2.430; 95% CI=1.11-6.167; p=0.026), more than 50% of on-treatment patients experiencing regression of the thrombus. However, bleeding events were significantly more frequent in the AC treatment group (18.5% vs. 7.5%) and the risk of bleeding was associated with thrombocytes less than 50x103/mm3 (OR=8.266; 95%CI: 2.310-39.211; p=0.002). Survival was better in the AC treatment group (68.4% vs 48.7% at 5 years and 92.7% vs 77.8% at 1 year, p=0.038) and was lower in patients that experienced bleeding events (37.22% survival at 5 years, mean time survival 44 months, p=0.008). CONCLUSIONS: In our cohort of cirrhotic patients with PVT more than 50% of patients receiving AC therapy presented regression of the thrombus; most of them obtained partial recanalization. The bleeding complication rate was higher than expected, reaching 18%. The overall mortality was lower in the treated group.