International Study Group Research Articles

Insights to advance our management of myocardial ischemia: From obstructive epicardial disease to functional coronary alterations

Study objectiveThe Coronary Vasomotor Disorders International Study Group (COVADIS) invited leading experts to address strategies to enhance our clinical understanding of INOCA with an emphasis on the management of coronary vasomotor disorders. DesignUnder-recognition of coronary vasomotor disorders, distinguishing different presentations of angina due to vasospasm and/or abnormal microvascular vasodilatation, developing invasive/non-invasive testing and treatment protocols, integrating diagnostic protocols into cardiologists' workflow and trials to inform guideline development were identified as key knowledge gaps and will be briefly addressed in this Viewpoint article. SettingVirtual international meeting. ParticipantsLeading international experts in ischemic heart disease with no obstructive coronary artery disease. InterventionsNone. Main outcome measuresNone. ResultsTopics discussed include: 1. Obstructive epicardial disease, functional vasospasm and microvascular disorders; 2. Under-recognition of coronary vasomotor disorders in clinical practice; 3. Complexity of coronary vasomotor disorders; 4. Understanding different presentations - vasospastic disease and microvascular angina; 5. Invasive/noninvasive testing and treatment protocols for vasospasm and microvascular angina assessment; 6. Treatment challenges; 7. Integrating diagnostic protocols into cardiologists' workflow; 8. The path forward to advance our approach to managing myocardial ischemia. ConclusionsObstructive epicardial disease, functional vasospasm and microvascular disorders often co-exist and contribute to myocardial ischemia. Under-recognition, the complexity of coronary vasomotor disorders, understanding different presentations, testing and treatment protocols, treatment challenges, and integrating diagnostic protocols into cardiologists' workflow all contribute to the path forward to advance our management of myocardial ischemia for improved patient outcomes.

Initial visit symptoms in probable Behçet's syndrome is predictive of ISG criteria fulfillment in Behçet's syndrome: data from New York and Amsterdam cohorts.

Behçet's syndrome (BS) is a systemic vasculitis with heterogeneous clinical presentation and a relapsing disease course. The International Study Group (ISG) criteria are most often used for classification. A significant proportion of patients is classified as probable BS because they do not fulfil the criteria at initial presentation. The aim of this study is to explore clinical BS symptoms present at initial patient visit predictive of ISG criteria diagnosis during follow-up. Patients classified as probable BS at initial visit were included. Follow-up ISG status (defined as meeting criteria ISG+ vs. not meeting criteria ISG-) was abstracted from last visit. Univariable logistic regression was used to screen initial visit clinical features and symptoms with follow-up ISG status. All variables that passed screening at p<0.10 were included in the final multivariable model, which was then used to create a probability risk score. 189 patients were included (169 from New York and 20 from Amsterdam). 71 (37.6%) patients were classified as ISG+ during follow-up. In the final model, presence of morning stiffness, genital ulcers, skin lesions, and eye disease were associated with increased odds of ISG+, adjusting for age, symptom duration and family history. This was used to create a probability risk score. Over a third of patients with suspected or probable BS developed new manifestations over time that led to classification as ISG+ BS. The presence of morning stiffness, genital ulcers, skin lesions and eye disease at initial visit were independently associated with significantly higher odds for developing ISG+ Behçet's during follow-up.

A trove for historians of Africa: reflections from the International Studies Group and research associates

Trove opens possibilities for collaborative, transnational and comparative research from scholars in the Global South, who often work with limited financial resources. Indeed, Trove has been indispensable for the South African-based historians in the International Studies Group, who would otherwise face difficulties accessing Australian primary sources. It also enables Australian perspectives to be incorporated into African histories, fostering the emergence of new historical insights. However, mass digitisation has the potential to create an unevenness in transnational history by privileging certain connections, particularly between British settler colonies. These reflections will offer crucial perspectives from a network of early career historians outside Australia.

S865 Prevalence and Association of Restless Leg Syndrome, Depression and Anxiety in Patients With Inflammatory Bowel Disease

Introduction: Inflammatory bowel disease (IBD) is associated with many extraintestinal manifestations. Restless leg syndrome (RLS) is considered to be one of the neurological manifestations seen in IBD. There is limited data available regarding the RLS in the setting of IBD. We aimed to evaluate the prevalence of RLS, as well as concurrent anxiety and depression in patients with IBD. Methods: Patients having IBD were prospectively enrolled in the study from years 2017-2020 at outpatient clinics of our institution. Patients were screened for RLS, depression and anxiety. The severity of RLS was determined by using the international RLS study group rating scale. Beck depression and anxiety inventories were used to evaluate the severity of depression and anxiety. Patients with iron deficiency anemia and those are on anxiolytic and antidepressant medications were excluded. Laboratory and clinical data were obtained. All patients provided informed consent. Results: A total of 194 patients were included in the study (102 male, 92 female; mean age: 42.3 ±13.5). Of those, 76 (39.2%) had ulcerative colitis (UC) and 118 (60.8%) had Crohn’s disease (CD). IBD was present for a mean of 10.19 ±6.4 years at the time of the enrollment. In patients with CD, 46.3% had fistulizing CD, 41.6% had history of surgical operation and 33% had perianal involvement. Ninety-one (46.9%) patients with IBD were found to have RLS. Of those, 54 (45.8%) had CD and 37 (59.3%) had UC. Of 91 patients with RLS, 59 (64.8%) were female and 32 (35.2%) were male (p< 0.001). Hundred and eighty-seven patients were screened for depression, 58 (31%) patients had depression. Of those with depression, 37 (63.9%) were female and 21 (36.2%) were male (p=0.004). Hundred and fifty-six patients had anxiety, 92 (59%) were male and 64 (41%) were female (p< 0.001). The severity of anxiety was classified as mild, moderate and severe. In males, the severity was mild in 92.9%, moderate 7.1% and severe 0%, in females 71.9%, 24.7% and 3.4% of patients, respectively.Mean scores for RLS severity rating, Beck depression and anxiety inventory scores were shown in Table 1. Patients with CD with perianal involvement were more likely to have depression (46.9% vs 23.4%, p=0.034). Conclusion: RLS, depression and anxiety were found to be a common comorbid conditions in patients with IBD. Perianal involvement in CD should alert for the presence of depression. Screening for those conditions is important in implementing the treatment timely and to improve the quality of life.Table 1.: Clinical and laboratory characteristics of study patients (n=194).

Risk Factors of Postoperative Clinically Relevant Pancreatic Fistula following Distal Pancreatectomy with Stapler Closure.

To analyse clinicopathological variables to determine risk factors of postoperative pancreatic fistula in patients having distal pancreatectomy with stapler closure. Observational study. Adana City Training and Research Hospital, Adana, Turkey, from January 2015 to May 2020. Medical files of 38 cases having distal pancreatectomy with stapler closure of the pancreatic remnant for conditions emerging from the pancreas or other organs were analysed. Data about demographics, perioperative and pathological findings, postoperative outcomes were gathered. Univariate analysis was utilised for comparisons of categorical data. The possible risk factors found to be significant in the univariate analysis were included into the logistic regression analysis. Based on the description reported by the International Study Group of Pancreatic Surgery, 23.7% and 31.6% of the patients had biochemical leakage and clinically relevant postoperative pancreatic fistula (POPF) respectively. Univariate and multivariate analyses made to determine risk factors of POPF showed a relation between stapler closure alone (p = 0.018) and soft parenchymal texture (p = 0.002) and clinically relevant POPF. Multivariate analyses revealed that parenchymal texture was the sole independent predictor of clinically relevant POPF (OR, 0.016, p = 0.039). Soft pancreatic texture is independently predictive of clinically relevant POPF following distal pancreatectomy with stapler closure. However, reinforcement of the stapler line with extra sutures decreases the risk of clinically relevant POPF. Key Words: Distal pancreatectomy, Pancreatic fistula, Stapler closure, Suture reinforcement.

Cerebral venous thrombosis in Behcet's disease. A report on 24 cases

IntroductionCerebral venous thrombosis (CVT) is the most common manifestation of vasculo-Behçet's disease and may be superficial and/or deep localization. The aim of our study was to evaluate the clinical and radiological features of CVT associated with Behçet's disease in our population and to compare findings with previous studies. Materials and methodsWe report a retrospective study of 24 cases of CVT secondary to Behçet's disease, collected between 1999 and 2019 in the neurology department of the Mohamed V Military Hospital (Rabat), the Avicenne Military Hospital (Marrakech) and the Mohamed VI Hospital (Marrakech). The diagnosis of Behçet's disease was made in all cases according to the 2014 International Study Group Criteria for Behçet diseases. Patients received antithrombotic treatment, combined with corticosteroids, in six cases of superficial CVT and with immunosuppressants in cases of deep CVT. ResultsClinical manifestations were dominated by motor deficit in deep localizations and intracranial hypertension in superficial locations. The diencephalic-mesencephalic syndrome was found in 18 patients, whereas intracranial hypertension (71%) and headache (57%) were the most common presentations of superficial CVT. Unlike previous studies, magnetic resonance angiography and conventional angiography performed in our patients confirmed the predominance of deep venous thrombosis (18 cases), whereas superficial CVT was observed only in six cases. DiscussionIn our series, the benefit of conventional angiography was undeniable, by confirming the diagnosis of basal vein of Rosenthal thrombosis in 75% of our patients. Short-term outcome was favorable, but sequelae of CVT were noted in 20 patients (75%). The outcome of patients was commonly mRS 02, however 70% of patients presenting with deep CVT at the beginning had a poor outcome (mRS 03) and we did not record any case of venous thrombosis relapse.

Prediction of pancreatic fistula after pancreatectomy by virtual touch tissue imaging and quantification (VTIQ) technology

ObjectivesThe aim of this study was to quantitatively evaluate the stiffness of pancreatic parenchyma and solid focal pancreatic lesions (FPLs) by virtual touch tissue imaging and quantification (VTIQ) technique and to investigate the potential usefulness of VTIQ method in the prediction of post-operative pancreatic fistula (POPF) after pancreatectomy. MethodsIn this prospective study, patients who scheduled to undergo pancreatectomy were initially enrolled and received VTIQ assessment within one week before surgery. VTIQ elastography (Siemens ACUSON Sequoia, 5C-1 transducer) was used to measure the shear wave velocity (SWV) value of FPLs and the body part pancreatic parenchyma. The palpation stiffness of pancreas was qualitatively evaluated during operation by surgeons. POPF was finally diagnosed and graded through a three-weeks post-operative follow-up according to international study group of pancreatic fistula (ISGPF). SWV values were compared between POPF positive and negative group. Receiver operating characteristic (ROC) analysis was used to evaluate the diagnostic efficacy of SWV value in predicting POPF. ResultsFrom December 2020 to June 2021, 44 patients were finally enrolled in this study, among which, 26 patients were identified to develop POPF after pancreatectomy. The SWV value of pancreatic parenchyma in POPF positive group was significantly lower than that in POPF negative group (P = 0.001). However, there was no significant difference in palpation stiffness between the two groups (P = 0.124). Besides, neither the SWV value of FPL nor the SWV ratio between FPL to surrounding pancreatic parenchyma differ significantly between POPF positive and negative group (P > 0.05). Taking SWV value of pancreatic parenchyma >1.10 m/s as a cut-off value for predicting POPF, area under the receiver operating characteristic curve (AUROC) was 0.864 with 72.2% sensitivity, 92.3% specificity, 86.7% positive predictive value (PPV) and 82.8% negative predictive value (NPV), respectively. ConclusionsVTIQ technique might be a potential non-invasive imaging method to predict POPF before pancreatectomy in future clinical practice.

Does intraoperative and postoperative analgesia cause bile leakage after hepatectomy?

To evaluate the effect of morphine or morphine equivalents on the risk of bile leakage (BL) after hepatectomy. The subjects of this retrospective study were 379 patients who underwent hepatectomy without biliary reconstruction and biliary decompression tube insertion at Gunma University between 2016 and 2020. Clinical BL was defined as International Study Group of Liver Surgery post-hepatectomy bile leakage Grade B or C. Intra- and post-operative analgesia comprised intravenous patient-controlled analgesia (IV-PCA) with fentanyl (n = 58), epidural analgesia with fentanyl (n = 157), epidural analgesia with morphine (n = 151), and epidural analgesia with ropivacaine or levobupivacaine (n = 13). Clinical BL was diagnosed in 14 of the 379 (3.7%) patients. The significant risk factors for clinical BL were hepatocellular carcinoma (HCC), elevated serum total bilirubin, high indocyanine green retention at 15min, elevated Mac-2-binding protein glycosylated isomer, prolonged duration of surgery, and a large volume of blood loss. There was no significant correlation of clinical BL with intra- and post-operative analgesia and total oral morphine equivalents. Intra- and post-operative IV-PCA and epidural analgesia were not related to clinical BL after hepatectomy. Based on our data, fentanyl and morphine can be administered safely as epidural or intravenous analgesic agents.

Pulmonary vasculitis in Hughes-Stovin syndrome (HSS): a reference atlas and computed tomography pulmonary angiography guide\u2014a report by the HSS International Study Group

IntroductionHughes-Stovin syndrome (HSS) is a systemic vasculitis characterized by widespread venous/arterial thrombosis and pulmonary artery aneurysms (PAAs), which is associated with serious morbidity and mortality. All fatalities reported in HSS resulted from unpredictable fatal suffocating hemoptysis. Therefore, it is necessary to recognize pulmonary complications at an early stage of the disease.ObjectivesThe aims of this study are to develop a reference atlas of images depicting the characteristic features of HSS by computed tomography pulmonary angiography (CTPA). To make a guide for physicians by developing a classification of PAAs according to the severity and risk of complications associated with each distinct lesion type.MethodsThe Members of the HSS International Study Group (HSSISG) collected 42 cases, with high-quality CTPA images in one radiology station and made reconstructions from the source images. These detailed CTPA studies were reviewed for final image selection and approved by HSSISG board members. We classified these findings according to the clinical course of the patients.ResultsThis atlas describes the CTPA images that best define the wide spectrum of pulmonary vasculitis observed in HSS. Pulmonary aneurysms were classified into six radiographic patterns: from true stable PAA with adherent in-situ thrombosis to unstable leaking PAA, BAA and/or PAP with loss of aneurysmal wall definition (most prone to rupture), also CTPA images demonstrating right ventricular strain and intracardiac thrombosis.ConclusionThe HSSISG reference atlas is a guide for physicians regarding the CTPA radiological findings, essential for early diagnosis and management of HSS-related pulmonary vasculitis.Key Points• The Hughes-Stovin syndrome (HSS) is a systemic vasculitis characterized by extensive vascular thrombosis and pulmonary artery aneurysms (PAAs) that can lead to significant morbidity and mortality.• All fatalities reported in HSS were related to unpredictable massive hemoptysis; therefore, it is critical to recognize pulmonary complications at an early stage of the disease.• The HSS International Study Group reference atlas classifies pulmonary vasculitis in HSS at 6 different stages of the disease process and defines the different radiological patterns of pulmonary vasculitis notably pulmonary artery aneurysms, as detected by computed tomography pulmonary angiography (CTPA).• The main aim of the classification is to make a guide for physicians about this rare syndrome. Such a scheme has never been reached before since the first description of the syndrome by Hughes and Stovin since 1959. This classification will form the basis for future recommendations regarding diagnosis and treatment of this syndrome.

THE ROLE OF PRIVATE LAW IN PROMOTING SOCIAL JUSTICE

The first contribution published in this edition is an abridged version of the inaugural lecture delivered by Professor Eltjo JH Schrage on 24 August 2009 in Port Elizabeth. The Faculty of Law is honoured that such an internationally esteemed jurist accepted the appointment as first Honorary Professor of the Faculty of Law in 2009. Prof Eltjo JH Schrage was born in Groningen. He studied law at the University of Groningen, where he obtained his doctorandus, a degree which is analogous to our master’s degree. In 1975 he defended his doctoral thesis entitled Libertas est facultas naturalis. Menselijke vrijheid in een tekst van de Romeinse jurist Florentinus (Human liberty in a text of the Roman jurist Florentinus). His academic career commenced in 1969 at the Free University, Amsterdam. In 1980 he was appointed as professor at the Free University in Roman Law and Legal History. In 1998 he became the director of the Paul Scholten Institute at the University of Amsterdam. Some of his other academic appointments include the following:• Chairperson: International Study Group on the Comparative Legal History of the Law of Restitution;• Chairperson: International Study Group on the Comparative Legal History of the Law of Torts;• Visiting Professor: University of Cape Town;• Visiting Fellow: Magdalen College, Oxford University as well as visiting professor at Oxford;• Visiting Professor: University of the North (now Limpopo) in Polokwane; and• Visiting Fellow: Trinity College, Cambridge University as well as visiting professor, Cambridge. Prof Schrage has published extensively in International journals in Dutch, English, German French, and Italian. He has edited, written and contributed to more than 30 books, and written more than 100 articles. He has been the supervisor of numerous doctoral students, including Prof Marita Carnelley of the University of KwaZulu-Natal and erstwhile member of the Faculty of Law, Nelson Mandela Metropolitan University and Prof André Mukheibir, Head of Department, Private Law of the Nelson Mandela Metropolitan University. He was also the promoter of the honorary doctorate awarded by the University of Amsterdam to the former chief justice of South Africa, Arthur Chaskalson in 2002. Prof Schrage has also acted as judge in the Amsterdam court since 1981. Prof Schrage is married to Anneke Buitenbos-Schrage and the couple have four children and one grandchild.

Laparoscopic Compared with Open D2 Gastrectomy on Perioperative and Long-Term, Stage-Stratified Oncological Outcomes for Gastric Cancer: A Propensity Score-Matched Analysis of the IMIGASTRIC Database.

Simple SummaryGastric resection with D2 lymphadenectomy is considered the gold standard for the treatment of both advanced and early gastric cancer with lymph node metastasis. The performance of D2 lymphadenectomy is technically challenging and represents a key factor in improving patients’ survival. For these reasons, the execution of gastrectomy with D2 lymphadenectomy using the traditional open surgical technique still represents the most widespread approach and, based on current international guidelines, the indication for laparoscopic surgery is limited to early gastric cancer that does not require a D2 lymphadenectomy. The present study aimed to investigate the use of laparoscopic versus open surgical approaches in performing gastrectomy with D2 lymphadenectomy for cancer in terms of intraoperative and postoperative outcomes and long-term survival. The study was conducted using the data collected in the International study group on Minimally Invasive surgery for Gastric Cancer (IMIGASTRIC) international database.Background: The laparoscopic approach in gastric cancer surgery is being increasingly adopted worldwide. However, studies focusing specifically on laparoscopic gastrectomy with D2 lymphadenectomy are still lacking in the literature. This retrospective study aimed to compare the short-term and long-term outcomes of laparoscopic versus open gastrectomy with D2 lymphadenectomy for gastric cancer. Methods: The protocol-based, international IMIGASTRIC (International study group on Minimally Invasive surgery for Gastric Cancer) registry was queried to retrieve data on patients undergoing laparoscopic or open gastrectomy with D2 lymphadenectomy for gastric cancer with curative intent from January 2000 to December 2014. Eleven predefined, demographical, clinical, and pathological variables were used to conduct a 1:1 propensity score matching (PSM) analysis to investigate intraoperative and recovery outcomes, complications, pathological findings, and survival data between the two groups. Predictive factors of long-term survival were also assessed. Results: A total of 3033 patients from 14 participating institutions were selected from the IMIGASTRIC database. After 1:1 PSM, a total of 1248 patients, 624 in the laparoscopic group and 624 in the open group, were matched and included in the final analysis. The total operative time (median 180 versus 240 min, p < 0.0001) and the length of the postoperative hospital stay (median 10 versus 14.8 days, p < 0.0001) were longer in the open group than in the laparoscopic group. The conversion to open rate was 1.9%. The proportion of patients with in-hospital complications was higher in the open group (21.3% versus 15.1%, p = 0.004). The median number of harvested lymph nodes was higher in the laparoscopic approach (median 32 versus 28, p < 0.0001), and the proportion of positive resection margins was higher (p = 0.021) in the open group (5.9%) than in the laparoscopic group (3.2%). There was no significant difference between the groups in five-year overall survival rates (77.4% laparoscopic versus 75.2% open, p = 0.229). Conclusion: The adoption of the laparoscopic approach for gastric resection with D2 lymphadenectomy shortened the length of hospital stay and reduced postoperative complications with respect to the open approach. The five-year overall survival rate after laparoscopy was comparable to that for patients who underwent open D2 resection. The types of surgical approaches are not independent predictive factors for five-year overall survival.

In-Hospital Morbidities for Neonates with Congenital Diaphragmatic Hernia: The Impact of Defect Size and Laterality

To determine in-hospital morbidities for neonates with right-sided congenital diaphragmatic hernia (R-CDH) compared with those with left-sided defects (L-CDH) and to examine the differential effect of laterality and defect size on morbidities. This retrospective, multicenter, cohort study from the international Congenital Diaphragmatic Hernia Study Group registry collected data from neonates with CDH surviving until hospital discharge from 90 neonatal intensive care units between January 1, 2007, and July 31, 2020. Major pulmonary, cardiac, neurologic, and gastrointestinal morbidities were compared between neonates with L-CDH and R-CDH, adjusted for prenatal and postnatal factors using logistic regression. Of 4123 survivors with CDH, those with R-CDH (n=598 [15%]) compared with those with L-CDH (n=3525 [85%]) had an increased odds of pulmonary (1.7; 95% CI, 1.4-2.2, P<.0001), cardiac (1.4; 95% CI, 1.1-1.8; P=.01), gastrointestinal (1.3; 95% CI, 1.1-1.6; P=.01), and multiple (1.6; 95% CI, 1.2-2.0; P<.001) in-hospital morbidities, with a greater likelihood of morbidity with increasing defect size. There was no difference in neurologic morbidities between the groups. Neonates with R-CDH and a larger defect size are at an increased risk for in-hospital morbidities. Counseling and clinical strategies should incorporate knowledge of these risks, and approach to neonatal R-CDH should be distinct from current practices targeted to L-CDH.

Prognostic factors for relapse and poor outcome in neuro-Behçet's syndrome: results from a clinical long-term follow-up of a single centre.

To describe the clinical characteristics of neuro-Behçet's syndrome (NBS) and to define the factors associated with relapses and poor outcome. Among 2118 patients with Behçet's syndrome who fulfilled the international study group criteria, 208 (9.8%) patients had NBS. Retrospective data of 125 NBS patients (55.5% male; mean age 37.2 ± 11.8years) were analysed. We divided patients into two subgroups, either parenchymal (p-NBS) or non-parenchymal (np-NBS), according to international consensus recommendations for NBS. We assessed the predictor factors associated with relapse and poor outcome-which was defined as a modified Rankin score (mRS) ≥ 3 at last follow-up and/or death-using Cox and logistic regression analyses, respectively. In total, 79 (63.2%) patients presented with p-NBS and 46 (36.8%) presented with np-NBS. Ocular involvement was more common in p-NBS than np-NBS (55.7% vs. 37.0%, p = 0.04), whereas vascular involvement excluding cerebral vein thrombosis was more frequent in patients with np-NBS (19.0% vs. 52.2%, p < 0.001). Forty-two patients (33.6%) experienced at least one relapse. Factors associated with relapse were BS diagnosis at a younger age and cranial nerve dysfunction (HR 0.96 95% CI 0.93-0.99 and 2.36 95% CI 1.23-4.52, respectively). After a median of 68 (Q1-Q3: 25-125)months, 23 patients (18.4%) had a poor outcome. Indicators of a poor outcome were higher initial mRS and the progressive p-NBS type (OR 8.28 95% CI 1.04-66.20 and 33.57 95% CI 5.99-188.21, respectively). Our findings indicate that clinical characteristics and prognosis differ between NBS subgroups, of which patients with p-NBS have worse outcomes.

Management of postoperative complications after laparoscopic left hemicolectomy: an approach in modern times after incorporation of indocyanine green and full mobilization of the splenic flexure.

The aim of this study was to report our experience in the management of complications after laparoscopic left hemicolectomy (LLH) after the incorporation in our clinical practice of intraoperative indocyanine green (ICG) fluorescence angiography (FA). In our last period after incorporation of ICG-FA, 277 unselected consecutive patients underwent laparoscopic colorectal surgery with this technology. Ninety-seven (35%) right hemicolectomy, 19 segmental resection of the splenic flexure (6.9%), 54 anterior resection of the rectum (19.5%) and 107 LLH (38.6%) were performed. Complications were graded according to Clavien-Dindo classification, and anastomotic leakages (AL) were graded according to Clavien-Dindo classification and to International Study Group of Rectal Cancer (ISGRC) classification. Eight surgical and one medical complications (8.4%) were observed. Two AL occurred (1.9%). One drained spontaneously by drainage placed intraoperatively (Clavien-Dindo I, ISGRC A) and one treated by laparoscopic peritoneal lavage, leakage suture and ileostomy (Clavien-Dindo III-b, ISGRC C). Other complications were: wound infection (Clavien-Dindo II) (2); postoperative anemia caused by rectorrhagia (Clavien-Dindo II) (2); pelvic abscess between bladder and uterus (Clavien-Dindo III-a) (1); hemoperitoneum secondary to inferior mesenteric artery bleeding treated with peritoneal lavage and hemostasis (Clavien-Dindo III-b) (1); atrial fibrillation (Clavien-Dindo II) (1). All complications have been resolved. The complication rate after LLH after the incorporation of ICG-FA is low, since the number of AL have dramatically decreased in comparison to our previous experience. The management of these patients proved to be safe and effective due to in all cases the complication has been resolved. Further studies are required to standardize the management of these patients.

TCL-445: Case of T-Cell Prolymphocytic Leukemia Successfully Treated with Fludarabine, Mitoxantrone, and Cyclophosphamide

Context T-cell prolymphocytic leukemia (T-PLL) is an extremely rare mature T-cell neoplasm associated with an aggressive clinical course, poor response to conventional chemotherapy, and a dismal prognosis. Current therapeutic strategies conventionally employ the anti-CD52 antibody alemtuzumab as the most active agent. Alemtuzumab, originally marketed for use in cancer (Mabcampath®), is currently licensed and formulated for the treatment of relapsing multiple sclerosis (Lemtrada®), causing a lack of drug availability, with potentially grave consequences for T-PLL patients’ prognosis. Design We present the case of a 68-year-old male patient diagnosed with T-PLL in December 2020, who underwent four cycles of fludarabine 25 mg/m2, mitoxantrone 8 mg/m2, and cyclophosphamide 200 mg/m2, and achieved complete remission (CR), according to the criteria established by the T-PLL International Study Group. Results A 68-year-old Caucasian male presented to our center with fatigue and weakness for several months and a history of persistent, progressive lymphocytosis for the past 18 months. A computed tomography scan revealed bilateral cervical, axillary, and intra-abdominal lymph nodes, measuring approximately 3 cm each; an enlarged spleen of 180 mm in length; and mild hepatomegaly, measuring 177 mm on the midclavicular line. Laboratory studies revealed leukocytosis (282 × 109/L) and an absolute lymphocyte count of 255 × 109/L, with no anemia or thrombocytopenia. The metabolic profile was normal, except for an elevated lactate dehydrogenase of 974 U/L. The bone marrow aspirate showed 86%–88% polymorphic lymphoid cells, while the flow cytometry analysis indicated T cells positive for CD2 and surface and cytoplasmic CD3, CD5, and CD7, 70% of which were CD4+CD8+, and 30% CD4+. The core biopsy revealed a markedly hypercellular marrow (80%), with a lymphoid infiltrate made up of small/medium-sized cells, some with cerebriform nuclei, some with prominent nucleoli, with weakly positive immunohistochemistry staining for CD52. Conclusions The patient presented in this case study was treated with conventional chemotherapy alone and achieved CR of T-PLL, maintaining the treatment response to date (3 months after completion of the therapy). Despite this, alemtuzumab remains a crucial element in the arsenal of treatment for T-PLL, and its lack of availability poses a serious challenge for clinicians.

Direct Bilirubin in Drainage Fluid 3 days after Hepatectomy Is Useful for Detecting Severe Bile Leakage

Introduction: The International Study Group of Liver Surgery (ISGLS) definition of bile leakage is an elevated total bilirubin concentration in the drainage fluid after post-operative day (POD) 3, which has been widely accepted. However, there were no reports about direct bilirubin in drainage fluid to predict bile leakage. Methods: Data from 257 patients who underwent hepatectomy were retrospectively reviewed. The optimal cut-off value was investigated using receiver-operating characteristic curves. The predictive power of drainage fluid total bilirubin (dTB) and drainage fluid direct bilirubin (dDB) to predict bile leakage, which was defined using ISGLS grade B or grade C, were compared. Results: ISGLS grade B bile leakage occurred in 16 patients (6.2%). Area under the curve (AUC) of dDB was always higher than that of dTB on each POD. The AUC of dDB was >0.75 on PODs 2, 3, and 5, and then it increased with the increasing POD. The dDB on POD 5 showed the highest accuracy (0.91) and positive predictive value (PPV) (0.67), which was followed by dTB/serum total bilirubin (sTB) on POD 3 (accuracy, 0.91; PPV, 0.33). Because the PPV of dDB increased as the POD increased, dDB was better than dTB for predicting clinically significant bile leakage. dDB on POD 3 showed the highest negative predictive value (0.97). The positive likelihood of dDB increased and the negative likelihood of dDB decreased on the basis of the POD. Among patients with dTB/sTB ≤3 on POD 3, 19.1% of these patients had bile leakage when dDB was >0.44 on POD 3. Conclusions: Measurement of both dDB and dTB, which are easy to perform, can be used to effectively predict clinically significant bile leakage.

Extracellular Histones H3 as a Prognostic Blood Marker for Delayed Liver Function Recovery After Donor Hepatectomy

Early prediction of liver dysfunction after liver resection remains a challenge. We hypothesized that extracellular histone concentrations are a promising new biomarker for the detection of liver injury after donor hepatectomy. This prospective study considered 93 living donors who underwent hepatectomy. Blood samples of donors were collected on postoperative day 1, and histone levels in the plasma samples of the patients were measured with total histone H3 sandwich ELISA kits. Among 86 right lobe donors, 23 (26.7%) were deemed to have a delayed liver function recovery according to the International Study Group of Liver Surgery's definition of posthepatectomy liver failure, whereas 63 (73.3%) were considered to have an adequate liver function recovery. The area under the receiver operating characteristic (ROC) curve for circulating histones in predicting persistent liver dysfunction was 0.618 ± 0.06 (95% confidence interval [CI], 0.501-0.735; P=.091). The cutoff point value obtained from the analysis of ROC curves was 0.895, with a sensitivity of 95.7% and a specificity of 32.9%, respectively, for examining a delayed liver function recovery (P=.015). The Fisher analysis significantly verified these results empirical influence function % 7.90 (95% CI, 3.91-11.90; P=.006). The univariate analysis determined that postoperative histones were identified as an independent risk factor of delayed liver function recovery (odds ratio, 10.8; 95% CI, 1.4-84.9; P = .024). The circulating histone negatively correlates with liver dysfunctions after donor hepatectomy and had the best value in predicting liver dysfunction within 24 hours after liver resection.

Wearable devices for seizure detection: Practical experiences and recommendations from the Wearables for Epilepsy And Research (WEAR) International Study Group.

The Wearables for Epilepsy And Research (WEAR) International Study Group identified a set of methodology standards to guide research on wearable devices for seizure detection. We formed an international consortium of experts from clinical research, engineering, computer science, and data analytics at the beginning of 2020. The study protocols and practical experience acquired during the development of wearable research studies were discussed and analyzed during bi-weekly virtual meetings to highlight commonalities, strengths, and weaknesses, and to formulate recommendations. Seven major essential components of the experimental design were identified, and recommendations were formulated about: (1) description of study aims, (2) policies and agreements, (3) study population, (4) data collection and technical infrastructure, (5) devices, (6) reporting results, and (7) data sharing. Introducing a framework of methodology standards promotes optimal, accurate, and consistent data collection. It also guarantees that studies are generalizable and comparable, and that results can be replicated, validated, and shared.

Outcome of pancreatic anastomoses during pancreatoduodenectomy in two national audits

BackgroundEvidence on the optimal pancreatic anastomosis during pancreatoduodenectomy is inconclusive. Large multicenter and nationwide registries may provide additional insights. The study compared the practice and outcome of different pancreatic anastomoses during pancreatoduodenectomy, focusing on the rate of postoperative pancreatic fistula, in two large audits of pancreatic surgery. MethodsPosthoc analysis of patients after pancreatoduodenectomy in the Dutch Pancreatic Cancer Audit and the German DGAV StuDoQ|Pancreas registries (January 2014 to December 2017). Postoperative pancreatic fistula (International Study Group of Pancreatic Surgery B/C), postpancreatectomy hemorrhage (International Study Group of Pancreatic Surgery B/C) and Clavien-Dindo ≥3 complications rates were compared for the three most common anastomoses: duct-to-mucosa pancreatojejunostomy, non-duct-to-mucosa pancreatojejunostomy, and non-duct-to-mucosa pancreatogastrostomy. Multivariable adjustment for potential confounders was performed. ResultsOverall, 6,149 patients were included. The most common anastomosis was duct-to-mucosa pancreatojejunostomy (duct-to-mucosa pancreatojejunostomy 59.8%, non-duct-to-mucosa pancreatojejunostomy 21.1%, non-duct-to-mucosa pancreatogastrostomy 12.4%). The overall postoperative pancreatic fistula rate was 14%: duct-to-mucosa pancreatojejunostomy 12.9%, non-duct-to-mucosa pancreatojejunostomy 14.4% (P = .162), non-duct-to-mucosa pancreatogastrostomy 18.3% (P < .001). The rate of postpancreatectomy hemorrhage was the lowest after duct-to-mucosa pancreatojejunostomy: duct-to-mucosa pancreatojejunostomy 6.9%, non-duct-to-mucosa pancreatojejunostomy 10% (P < .001), non-duct-to-mucosa pancreatogastrostomy 17.9% (P < .001). The rate of Clavien-Dindo ≥3 complications was the lowest after duct-to-mucosa pancreatojejunostomy: duct-to-mucosa pancreatojejunostomy 28%, non-duct-to-mucosa pancreatojejunostomy 32.7% (P = .002), non-duct-to-mucosa pancreatogastrostomy 43.1% (P < .001). In the multivariable analysis, the risk of postoperative pancreatic fistula did not differ significantly between the three anastomoses. The risk of hemorrhage (odds ratio 2.4, 95% confidence interval 1.6–3.5, P < .001) and Clavien-Dindo ≥3 (odds ratio 1.6, 95% confidence interval 1.2–2.1, P = .001) remained significantly higher only for non-duct-to-mucosa pancreatogastrostomy. ConclusionData from two national audits showed no difference in the risk-adjusted postoperative pancreatic fistula rate among the three most used pancreatic anastomoses during pancreatoduodenectomy. Pancreatogastrostomy was inferior to pancreatojejunostomy regarding bleeding and overall major complications.

Postoperative pancreatic fistulas after pancreaticoduodenectomy for malignancy: A Northeast Indian tertiary cancer center study.

Background and AimPostoperative pancreatic fistula (POPF) is an important cause of major morbidity and mortality after pancreaticoduodenectomy. We intend to estimate the incidence and study the risk factors and outcomes of patients who developed this dreaded complication.MethodsThis is a retrospective observational study. We included all patients who underwent pancreaticoduodenectomy at a specialized surgical unit of a single tertiary care cancer center in Northeast India. The period of study was from 23 April 2012 to 27 December 2019. The 2016 update on the definition of POPF by the International Study Group for Pancreatic Fistula was used to define the complication. Chi‐square test and Fischer's exact test were applied to categorical variables. t‐test was used to quantify mean difference among continuous variables. P value <0.05 was considered statistically significant at 95% confidence interval.ResultsA total of 59 patients underwent pancreaticoduodenectomy during the study period with almost equal distribution among males and females (29 and 30 patients respectively). The mean age of the patients was 54.0 years (range 20–72). Grade A, B, and C pancreatic fistulas were seen in five (8.5%), three (5.1%), and two (3.4%) patients, respectively. Preoperative hyperbilirubinemia, pancreatic duct size ≤3 mm, hypoalbuminemia, preoperative biliary decompression, and prolonged duration of surgery were identified as risk factors for POPF. POPF also resulted in increased 90‐day mortality (20%).ConclusionPOPF remains a potentially life‐threatening complication of pancreaticoduodenectomies. The knowledge and management of modifiable risk factors for this condition may help in mitigating this problem.