Anca-Associated but Not Vasculitis

Background/Aims A 72-year-old lady presented in primary care with complaints of generalised body aches, bilateral leg weakness and constitutional symptoms following a first dose of COVID-19 vaccine. Blood tests showed slightly raised inflammatory markers. She was initially diagnosed with polymyalgia rheumatica and was started on 40mg prednisolone with minimal improvement. Methods The examination in the rheumatology clinic was unremarkable. Investigations revealed raised white cell count, consistent with high dose steroid treatment, and elevated monocytes. There was mild improvement in inflammatory markers. The working diagnosis was of self-limiting viral illness. Further testing discovered strongly positive MPO ANCA (115 IU/ml), and the patient received three pulses of 500mg methylprednisolone for suspected vasculitis arranged by the medical team. There was no evidence of renal involvement. The diagnosis made at this point was autoimmune inflammatory disorder with unclear aetiology. At the subsequent clinic visit she reported mild shortness of breath, but no other symptoms suggestive of either vasculitis or connective tissue disease. Repeat ANCA showed significant reduction in MPO titre following pulse steroid treatment. CT of chest, abdomen and pelvis demonstrated a localised lobular/ nodular deformity of the liver. Viral hepatitis screen was negative. CA19-9 was raised at 100 U/ml. Liver biopsy was reported as poorly differentiated carcinoma without specific localising immunohistochemical features. Results The patient underwent hemi-hepatectomy for histologically confirmed pT2pNXM0R0 liver cholangiocarcinoma in a tertiary centre followed by adjuvant chemotherapy with capecitabine. With treatment, her MPO ANCA and CA19-9 levels declined. An interval CT scan of chest, abdomen and pelvis performed ten months after the surgery, showed no recurrence of malignancy. Given the fact that the patient's MPO ANCA fell following the treatment of cholangiocarcinoma, it is likely that positive MPO ANCA is associated with underlying malignancy rather than an active vasculitis. Conclusion This unusual case describes an evolution of the diagnostic process guided by non-specific symptoms and ANCA positivity, arriving at an unexpected diagnosis of malignancy. Although ANCA is a sensitive and specific marker of vasculitides, it can be positive in other conditions particularly hepatitis B, inflammatory bowel disease and autoimmune liver disorders. Malignancy can also be associated with ANCA in the absence of vasculitis. In one study, of 118 ANCA positive patients without ANCA-associated vasculitis, four were found to have malignancy. In a study of 1024 patients who had ANCA tested, 61 patients were found to have malignancy, predominantly haematological and lung cancers. However, after adjustment for sex, age and time of blood draw, no association was found between ANCA status and incidence of cancer. Interestingly, paraneoplastic vasculitis such as polyarteritis nodosa (PAN) has been described in the context of underlying cholangiocarcinoma, and is associated with ANCA rise. Moreover, patients with raised ANCA and PAN also have raised CA 19- 9.

Is It Cancer Hepatic Inflammatory Pseudotumor: An Important Hepatic Mass Differential

Introduction: Hepatic inflammatory pseudotumor (HIP), albeit rare, is an important pathology to be included in differentials for hepatic masses. The benign nature and treatment of this disease process should be considered especially in comparison to malignant hepatic processes. Case Description/Methods: A 66-year-old male with pre-existing history of compensated Hepatitis C cirrhosis status post direct-acting antivirals with sustained virologic response presented in shock after a syncopal episode. Initial work up revealed leukocytosis, thrombocytopenia, acute renal injury, elevated liver enzymes, and COVID-19 positive test. Patient underwent initial liver ultrasound revealing intrahepatic and extrahepatic biliary ductal dilation. Subsequent MRCP demonstrated diffuse thickening of intra and extra hepatic bile ducts suggestive of cholangitis and several hepatic masses concerning for abscesses versus possible metastatic cholangiocarcinoma. Patient improved symptomatically with antibiotics and supportive care. A liver biopsy was performed with pathology showing lymphoplasmacytic inflammation and fibroblastic infiltration suggestive of hepatic inflammatory pseudotumor. A repeat MRCP one week later showed interval decrease in size of liver lesions and repeat liver function tests also showed improvement. Patient was discharged on a course of ciprofloxacin and metronidazole. Patient had repeat MRCP 3 months after discharge, with further significant improvement in size of liver lesions. After multi-disciplinary discussion the plan was for further surveillance with imaging and labs in 2 months. Discussion(s): Inflammatory pseudotumors are benign and non-neoplastic lesions that can occur in any organ. They can appear as a malignant lesion when they arise in the liver and an accurate identification can allow for conservative management and prevent unnecessary invasive procedures. Hepatic inflammatory pseudotumors are often seen with concomitant infection or inflammatory processes. Liver biopsies distinguish these tumors from other malignant processes as they demonstrate a characteristic dense inflammatory infiltrate interspersed in stroma of interlacing bundles of myofibroblasts. This case highlights the importance of maintaining HIP on the differential diagnosis. (Figure Presented).

Management of Hepato- biliary-pancreatic Surgery during the COVID-19 Pandemic

Purpose: We examined the effect of COVID-19 on diseases treated with hepato- biliary- pancreatic surgery from the experience of nosocomial infection at our hospital. Method(s): We examined the treatment of 106 patients admitted by the Division of Hepato- Biliary- Pancreatic Surgery to The Jikei University Hospital for elective surgery from January through May 2020. Result(s): Of the 106 operations, 90 (85%) were performed as scheduled and did not include COVID-19-positive patients. Operations for 16 patients (15%) were postponed, but 5 (31%) of these operations were urgent or quasiurgent and were performed during the study period. Of 95 patients who underwent surgery, 50 (53%) had a malignant tumor, 3 (3%) had a borderline malignant tumor, and 42 (44%) had a benign lesion, of which 41 were gallstones or gallbladder polyps and 1 was an intraductal papillary mucinous neoplasm that caused pancreatitis. Surgery for the latter tumor was postponed while conservative treatment improved conditions, but pancreatitis recurred 2 weeks after discharge, leading to a quasiurgent surgery. Conclusion(s): Owing to COVID-19, 15% of the scheduled elective hepato- biliary- pancreatic operations were postponed. Even lesions considered benign or not requiring emergency surgery should be treated promptly. Thus, the timing of treatment should be determined so that the risks of exacerbation and COVID-19 can be balanced.Copyright © 2022 Jikei University School of Medicine. All rights reserved.

Volumetric modulated arc radiotherapy with concomitant chemotherapy for the anal squamous carcinoma: A Welsh experience

Category: Outcomes of treatment (including chemotherapy, chemo-RT and RT) Purpose: To describe the five-year treatment outcomes of patients with anal squamous carcinoma treated with concurrent chemoradiotherapy (CRT) specified with volumetric modulated arc radiotherapy (VMAT) at a Welsh tertiary referral centre. Methods and materials: A total of 80 anal cancer patients received radical CRT between 2016 and 2021. CRT consisted of 50.4 Gy/28 fractions (1.8 Gy daily) to the gross tumour volumes (GTV), and the elective nodes were prescribed 40 Gy/28 fractions (1.42 Gy/daily) for patients having a cT1/2N0M0. Patients with cT3-T4/N0-N1a-cM0 were prescribed 53.2 Gy/28 fractions (1.9 Gy daily) to the GTV;gross nodal volumes were prescribed 50.4 Gy/28 fractions (1.8 Gy daily) if sized <=3 cm or 53.2 Gy/28 fractions (1.9 Gy daily) if >3 cm;elective nodal areas were given 40 Gy/28 fractions (1.42 Gy daily). Mitomycin and capecitabine were administered concurrently. The primary outcome was colostomy-free survival (CFS). Secondary outcomes were cancer-specific survival (CSS), disease-free survival (DFS), overall survival (OS) and adverse effects. Result(s): Median follow-up was 31.3 months (3-61). The five-year CFS was 94.3% (95% CI: 50.0%-96.5%). The five-year CSS, DFS and OS were 92% (95% CI: 60.5-95%), 86.7% (95% CI: 58-89%) and 67.9% (95% CI: 56.6-75.1%) respectively. A total of four (5%) local recurrences and one (1.3%) regional recurrence was observed. A total of seven patients (8.7%) had distant metastasis (liver was a frequent site;57.1%);three patients (3.7%) died of COVID pneumonia. Late toxicities were as: vaginal stenosis (6.3%), sexual dysfunction (1.25%) and urine incontinence (1.25%). Second malignancies were as: lung (2.5%), gastric (1.3%), pancreatic cancer (1.3%) and cholangiocarcinoma (1.3%). Conclusion(s): Our experience supports the use of VMAT on a routine basis for the CRT of anal squamous cell carcinoma. Copyright © 2022

SARS-CoV-2-correlated ASGR1 is a novel potential marker for the treatment and identification of multiple human cancers

Objectives: Cancer patients are reported to be more susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the COVID-19 (the Corona Virus Disease 2019) patients with cancer suffer from certain serious complications. ASGR1 has been recently identified as a novel receptor of SARS-CoV-2 in human cells;however, there are limited studies on ASGR1 in various human cancers. Method(s): This study utilized a comprehensive analysis of COVID-19-related ASGR1 in multiple human cancers based on 18,589 multi-center samples. Using Wilcoxon rank-sum analysis, a difference in ASGR1 expression between cancer and control tissues was detected. Cox regression analysis, Kaplan-Meier curves, and receiver operating characteristic curves were utilized to determine the correlation between ASGR1 expression and the clinical parameters of cancer patients. The immune relevance and potential mechanisms of ASGR1 in various cancers were also investigated. Result(s): Abnormal ASGR1 mRNA expression was observed in 16 of 20 different cancers (e.g., it was upregulated in colon adenocarcinoma but downregulated in cholangiocarcinoma;P < 0.05). ASGR1 was related to prognosis, e.g., overall survival, in 14 cancers (P < 0.05), such as adrenocortical carcinoma. The gene was also found to be a potential marker that can be utilized to distinguish eleven cancers from controls with moderate to high accuracy (e.g., the area under the curve for cholangiocarcinoma = 1.000). ASGR1 expression was related to DNA methyltransferases, mismatch repair genes, immune checkpoints, levels of tumor mutational burden, microsatellite instability, neoantigen count, and immune infiltration levels in certain cancers (P < 0.05). The gene plays a role in multiple cancers by affecting four signaling pathways, such as cytokine-cytokine receptor interaction. Cancer patients with high ASGR1 expression are sensitive to 25 drugs, including ulixertinib. Conclusion(s): SARS-CoV-2-correlated ASGR1 is a novel marker that can be used for treating and identifying multiple human cancers. Copyright © 2022 E-Century Publishing Corporation. All rights reserved.

Quality of death in cancer patients managed by gastroenterologists

Background: Care in hospitals is generally focused on prolonging life and may not adequately address the needs of dying patients. The incidence of oncologic diseases is rising, and efforts should be made to guarantee a better quality of death and dying. Aim: to evaluate the end-of-life care in patients with cancer under gastroenterologist care. Methods: Cross-sectional study including all in-patients with cancer who deceased in a Gastroenterology department in Portugal between 2012-2021. Demographic characteristics, clinical attitudes, therapeutic interventions and symptom control up to 6 months prior to the patient’s death were assessed. Results: We included 120 patients, 73% male, mean age 71±12.5 years. The most common cancers were hepatocellular carcinoma (35%), gastric cancer (16%), pancreatic cancer (15%) and cholangiocarcinoma (14%). One third of the patients had ECOG of 0-1 at admission and 77% (n=92) had advanced disease (stage IV or Barcelona Clinic Liver Cancer C/D). The median number of emergency consultations and hospitalizations in the 6 months before death was 2 (IQR 1-4). In their last month of life, the median time of hospitalization was 21.5 (IQR 12-25) days. It was documented the presence of an available caregiver in 56%(n=68) and spiritual support in only 2% (n=2) of the cases. One quarter of the patients experienced not adequately controlled pain and 72% received opioids. Palliative care consultation occurred in 60% (n=72) with a median time between that and death of 12 (IQR 3-18) days. Invasive procedures (diagnostic and therapeutic endoscopy, ERCP and EUS) were performed in half of the patients, achieving technical and clinical success in 62% (n=38) and 32% (n=19) of the cases, respectively. The mean time between those interventions and death was 12±10 days. The prognosis was discussed with the patient and family in 35% and 68% of the cases, respectively. At least 73% of the patients had visits at the end of life, which was negatively affected by the COVID-19 pandemic (p=0.022). Conclusions: In our cohort, we found a high hospitalization length of stay in the last month of life and high percentage of invasive treatments until shortly before dying. Thus, it is urgent to define and implement metrics of quality of death to prevent futile/potentially inappropriate treatment. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.

THE CLINICAL IMPACT OF COVID-19 DELAYS ON PLASTIC BILIARY STENT REMOVAL IN NOVA SCOTIA

Background: The COVID-2019 pandemic continues to restrict access to endoscopy, resulting in delays or cancellation of non-urgent endoscopic procedures. A delay in the removal or exchange of plastic biliary stents may lead to stent occlusion with consensus recommendation of stent removal or exchange at three-month intervals [1-4]. We postulated that delayed plastic biliary stent removal (DPBSR) would increase complication rates. Aims: We aim to report our single-centre experience with complications arising from DPBSR. Methods: This was a retrospective, single-center, observational cohort study. All subjects who had ERCP-guided plastic biliary stent placement in Halifax, Nova Scotia between Dec 2019 and June 2020 were included in the study. DPBSR was defined as stent removal >=90 days from insertion. Four endpoints were assigned to patients: 1. Stent removed endoscopically, 2. Died with stent in-situ (measured from stent placement to documented date of death/last clinical encounter before death), 3. Pending removal (subjects clinically well, no liver enzyme elevation, not expired, endpoint 1 Nov 2020), and 4. Complication requiring urgent reintervention. Kaplan-Meier survival analysis was used to represent duration of stent patency (Fig.1). Results: 102 (47.2%) had plastic biliary stents placed between 2/12/2019 and 29/6/2020. 49 (48%) were female, and the median age was 68 (R 16-91). Median follow-up was 167.5 days, 60 (58.8%) subjects had stent removal, 12 (11.8%) died before replacement, 21 (20.6%) were awaiting stent removal with no complications (median 230d, R 30-332), 9 (8.8%) had complications requiring urgent ERCP. Based on death reports, no deaths were related to stent-related complications. 72(70.6%) of patients had stents in-situ for >= 90 days. In this population, median time to removal was 211.5d (R 91-441d). 3 (4.2%) subjects had stent-related complications requiring urgent ERCP, mean time to complication was 218.3d (R 94-441). Stent removal >=90 days was not associated with complications such as occlusion, cholangitis, and migration (p=1.0). Days of stent in-situ was not associated with occlusion, cholangitis, and migration (p=0.57). Sex (p=0.275), cholecystectomy (p=1.0), cholangiocarcinoma (p=1.0), cholangitis (p=0.68) or pancreatitis (p=1.0) six weeks prior to ERCP, benign vs. malignant etiology (p=1.0) were not significantly associated with stent-related complications. Conclusions: Plastic biliary stent longevity may have been previously underestimated. The findings of this study agree with CAG framework recommendations [5] that stent removal be prioritized as elective (P3). Limitations include small sample size that could affect Kaplan-Meier survival analysis. Despite prolonged indwelling stent time as a result of COVID-19, we did not observe an increased incidence of stent occlusion or other complications.

HYBRID ENDOSCOPIC ULTRASOUND IN THE COVID-19 ERA FOR THE TISSUE DIAGNOSIS OF SOLID LESIONS: AN INITIAL EXPERIENCE FROM A TERTIARY CARE CENTRE IN PAKISTAN

AIM: Endoscopic Ultrasound (EUS) is well-established mode of intervention for tissue acquisition in solid organs with rapid on-site evaluation (ROSE). In the Covid-19 era implementation of infection control mechanisms has led modified hybrid technique to get high diagnostic yield for tissue sampling. Combination of Covid-19 SOPs and tissue acquisition method outline this hybrid technique to get high diagnostic Yield.We share our initial experience of EUS cases performed with this approach without ROSE. METHODS: All 84 cases who underwent EUS guided biopsy from June 2020 till December 2021 were included. The Procedure was done in a negative pressure room with all SOPs as per institutional guidelines for patient and staff safety with a minimum number of persons during procedure. RESULTS: Among these cases, 55 were male, mean age 56 years (range 22-90), Mean duration of procedure 25 min mean (10-90 min). 63 came for organ targeted for malignant pathology include pancreas 35, liver 02, lymph nodes 17, subepithelial lesions 06, mediastinal lesions 08, common-bile duct/gall bladder 04. 17 cases had a multi-targeted biopsy for the additional staging of disease. The number of 'passes' with the needle was average 02 with single pass 17, two pass 39, three passes 11, multitarget single pass in 17. Needle size (Franseen design) used for procedures was 22G in 78 cases and 25G in 6. Common tissue diagnoses include pancreatic adenocarcinoma 26, neuroendocrine tumours 04, tuberculosis 05, gastrointestinal stromal tumours 02, leiomyoma 03, lymphoma 03, metastatic renal cell carcinoma 04, squamous cell carcinoma 04, cholangiocarcinoma/ gall bladder adenocarcinoma 07, Sarcoma 02 and solid pseudopapillary epithelial neoplasm of pancreas (SPEN) 01. There were no immediate or early complications in all cases. CONCLUSIONS: Hybrid EUS in Covid 19 Era has emerged as a useful/cost-effective and safe approach to get tissue yield without the need for ROSE.

MULTI-TARGET ENDOSCOPIC ULTRASOUND EUS-M GUIDED BIOPSY IS SUPERIOR TO PET SCAN FOR STAGING MALIGNANCIES

AIM: EUS modality to get tissue diagnosis and with multi-target approach can help stage disease more accurately with histopathological results. METHODS: Total of 15 cases underwent EUS-M from June 2020 till Dec 2021. Informed consent was obtained, with Covid screen test with PCR was performed before procedure. Procedures were done with all SOPs as per institutional guidelines. 22G FNB needle with Franseen design with capillary suction method used to obtain visible core samples for histopathology without ROSE. All cases have confirmed histopathological diagnosis with same pathology from other site of Biopsy. Order of Biopsy was Nodes→Liver metatatic lesion→Primary Tumor. In cases of nodes mediastinal→portahepatis/ pancreatic→Para-aortic RESULTS: Among total 15 cases, Age 55 Mean (22-74) with 08 Males. Duration of procedure 41 min Mean (20-85). Cases with multiple lymphadenopathy from different anatomical regions were 05 while other sites include Liver for metastasis and Primary tumor from pancreas/CBD in 10 cases. Multiple site single pass was performed in 14 cases. Final diagnosis of Disease was pancreatic adenocarcinoma 05, NETs 01, Lymphoma 03, GB Adenocarcinoma/Cholangiocarcinoma 05 and metastatic RCC 01. All procedures were done under Conscious sedation as day care procedure. There were no immediate or early complication in all cases. CONCLUSIONS: EUS-M is safe and accurate modality to stage malignancy with superiority over PET Scan to obtain histological diagnosis.

Good Outcome of Living Donor Liver Transplant in Primary Sclerosing Cholangitis- An Experience From North India

Primary sclerosing cholangitis (PSC) is a cholestatic disorder wherein liver transplant is the definitive treatment for advance stages. However, recurrence of PSC after liver transplant is of concern which can leads to graft failure and may require retransplant. There is limited data on outcomes of living donor liver transplant (LDLT) in PSC. Also, in LDLT as donors are related there is possibility of disease recurrence. So, we conducted this retrospective study to analyse the outcomes of LDLT in PSC at a tertiary liver transplant centre in north India. Methods: We conducted a retrospective analysis of 3213 transplant recipients who underwent LDLT from January 2006 to May 2021. Of these 26 (0.80%) patients has PSC as indication for liver transplantation (PSC=24, PSC/AIH overlaP=2). Data analysis was done to look for baseline demographics, clinical details, transplant outcomes, PSC recurrence and survival. Results: Mean age of study group was 42(±13.8) years and 19 (73.1%) were males. All patients had decompensated cirrhosis at time of transplant. Mean CTP score and MELD score were 9.5(±1.8) and 18.9(±7.1) respectively. 16 patients received modified right lobe graft, 7 extended right lobe graft and 5 patients received left lateral graft. Average graft weight and GRWR were 633.5(IQR 473.5-633.5) grams and 1.23(SD±0.42) respectively. Most common biliary anastomosis was hepaticojejunostomy, done in 19(73.1%) while duct to duct anastomosis was performed in 7(26.9%) patients. Median follow- up was 96(36-123) months. One patient had ulcerative colitis and none had cholangiocarcinoma. Two (7.7%) patients had bile leak during early post-transplant period. Three (11.1%) patients developed graft rejection and managed successfully with steroid pulses. Three patients died during early post-transplant period while 7 deaths occurred during long term follow-up including one death due to COVID-19. Five (19.2%) patients had recurrence of PSC of which 2 patients lost their grafts including one after retransplantation. The overall 1 year and 5-year survival rates were 88.5% and 75% respectively. Conclusion: LDLT can be performed in PSC with good long-term outcomes with a risk of PSC recurrence in about 1/5th patients.