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Background: Neoadjuvant chemotherapy is the standard of care for early stage breast cancer. Human epidermal growth factor receptor 2 (HER2) positive disease constitutes a large proportion of breast cancer patients, and HER2 overexpression is associated with poor prognosis. The induction of HER2+ targeted therapies, such as trastuzumab and pertuzumab, has resulted in improved outcomes in HER2+ breast cancers. Neoadjuvant chemotherapy in combination with HER2 targeted therapies aims at achieving pathological complete response (pCR) and an improved survival. Methods: We performed a retrospective review of HER2+ breast cancer patients who were treated at Medanta – The Medicity Hospital, Gurugram, Haryana, India, between 2011 and 2021. A total of 108 HER2+ breast cancer patients who received neoadjuvant chemotherapy with platinum, anthracycline or taxane-based regimens, along with trastuzumab alone or in combination with pertuzumab, were included. Results: Of 108 enrolled patients, 66 and 42 patients received single-blockade (trastuzumab) and dual-blockade (trastuzumab and pertuzumab) neoadjuvant anti-HER2 therapy, respectively. The majority of patients were aged < 60 years. The patient populations were comparable in terms of clinical stage, hormone receptor status, histopathology category (IDC being most common) and Ki67 status for single- and dual-blockade groups. All patients had IHC3+/FISH+ HER2 expression. No significant (p=0.896) difference was observed for breast conserving surgery between the groups. A higher pCR rate after surgery was reported in the dual-blockade group versus single-blockade group (50% vs. 39.2%; p=0.271). The median follow-up duration was 21.9 and 15.2 months in the single-blockade and dual-blockade groups, respectively. For dual- vs. single- blockade groups, the 1-year OS rates were 100% vs. 100%, and 3-year OS rates were 100% vs. 98.48%. For dual- vs. single- blockade groups, the 1-year DFS rates were 100% vs. 95.45%, and 3-year DFS rates were 92.85% vs. 80.3%. Conclusion: Neoadjuvant chemotherapy with dual HER2-blockade had higher pCR and survival rates compared with the single HER2-blockade strategy in HER2 positive breast cancer. Table. Patient characteristics BCS, breast conserving surgery; ER, estrogen receptor; PR, progesterone receptor; IDC, invasive ductal carcinoma; ILC, invasive lobular carcinoma. Citation Format: Ashok K. Vaid, Devender Sharma, Jyoti Wadhwa, Rajeev Agarwal, Kanchan Kaur, Shina Goyal, Dheeraj Gautam, Jyoti Arora, Sabhyata Gupta, Ashok Sen, Ruchika K. Goel, Shagun Mahajan. Real-World, Single-Center Experience on the Outcomes of Neoadjuvant Chemotherapy and Trastuzumab alone or in Combination with Pertuzumab in Human Epidermal Growth Factor Receptor 2 Breast Cancer Patients [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-07-62.

Recurrent or de novo nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are common after liver transplantation (LT) and may be associated with rapid progression to fibrosis; however, there is limited data in this regard after living donor liver transplantation (LDLT).This is a retrospective study at a high volume LDLT center of all liver biopsies performed in patients with post-transplant NAFLD diagnosed on ultrasound of the abdomen. Liver biopsy was indicated for raised transaminases and/or high liver stiffness on TE. The association between these prebiopsy parameters and inflammation and fibrosis on histology was analyzed. Data are shown as mean ± standard deviation or median (25-75 interquartile range).The study cohort consisted of 31 males and 3 females, aged 43 ± 10 years. The LT to liver biopsy interval was 44 (28-68) months. The prebiopsy AST and ALT were 71 (38-119) and 66 (50-156), respectively. The histology suggested no nonalcoholic steatohepatitis (NASH) in 7 (20%), borderline NASH in 15 (44%), and NASH in 12 (35%) patients. A total of 15 patients (44%) had stage 1 or stage 2 fibrosis. The proportion of patients having fibrosis was significantly higher in patients with NASH (83%) compared to patients with borderline NASH (33%) or no NASH (none had fibrosis,Over a third of the LDLT recipients with post-transplant NAFLD developed NASH, and nearly half, borderline NASH 3-5 years after transplant. Most with established NASH also had fibrosis on histology. Prevention of risk factors and early diagnosis is warranted in these patients.

During the coronavirus disease 2019 (COVID-19) pandemic, increasing cases of COVID-19 associated mucormycosis (CAM) have been reported. This may be attributed directly to the COVID-19 infection or the associated unrecognised uncontrolled hyperglycaemia compounded by the use of COVID-19 treatment strategies such as steroids and IL-6 inhibitors. As mucormycosis is one of the most rapidly progressing fungal infection, an early diagnosis and early appropriate management are of prime importance in reducing mortality. Rhino-orbital-cerebral and pulmonary mucormycosis have been the most common presentations of CAM. Osteomyelitis in mucormycosis is very rare, although a few cases of maxillary bone involvement have been reported with CAM. We report a very rare and challenging case of extensive frontal bone osteomyelitis in a patient with CAM with frontal sinusitis and without orbital or maxillary bone involvement.

BACKGROUND: Recidivism in patients who underwent liver transplantation for alcohol-related liver disease (ALD) is shown to be associated with poor survival in some studies. METHODS: Living donor liver transplantation (LDLT) recipients for ALD with at least 2 years of follow-up and history of significant alcohol relapse were included. The recipients underwent LDLT from June 2010 to December 2016, and data were analyzed until June 2019. The cohort had a median follow-up of 54 (33–78 IQR) months. Recidivism (significant alcohol intake) was defined as >21 units per week. RESULTS: A total of 27 of 463 (5.8%) LDLT recipients (all men), aged 43.5 ± 9.6 years, had significant alcohol intake. A liver biopsy was performed on demand in 14 patients (in the presence of raised levels of liver enzymes or jaundice). The histological diagnoses in these patients were as follows: alcoholic hepatitis in 7 (50%), alcoholic hepatitis and acute cellular rejection or chronic rejection in 4 (28.5%), cirrhosis in 2 (14.2%), and acute cellular rejection and cirrhosis in 1 (7.1%) patient. Four of 5 patients with a biopsy diagnosis of acute or chronic rejection were noncompliant with immunosuppression. Six of these patients died. The mortality after 1 year of transplant was significantly more in patients with recidivism. CONCLUSION: Recidivism was associated with significant morbidity and mortality after liver transplantation.

Background and aims Liver transplantation (LT) recipients such as all organ transplant recipients, have a risk of developing de novo malignancies owing to prolonged immunosuppression. However, there is limited data on this after living donor liver transplantation (LDLT), wherein immunosuppression levels are less than in deceased donor transplantation. We aim to describe experience of de novo malignancies from a predominantly LDLT center. Materials and methods A total of 2100 adults (age >18 years) who underwent LT between January 2006 and December 2017 were retrospectively analyzed from a prospectively collected database. The data were analyzed up to June 2019. Data are shown as number, percentage, mean ± standard deviation, and median (interquartile range). Results Of 2100 patients who underwent LDLT, 21 (1%) patients developed de novo malignancy after transplantation. The de novo malignancy cohort comprised 20 males and 1 female, aged 50 ± 8.8 years. The distribution of de novo malignancies was as follows: 7 oropharyngeal (carcinoma of buccal and oral mucosa), 4 lung, 2 squamous cell carcinoma of skin, 2 lymphoma, 1 each of brain, colonic, gastric; ovary, pancreatic, and prostate. These malignancies were diagnosed at a median follow-up of 42 months (32–73) after LT. Over a median follow-up of 38 months (10–56) after the diagnosis of de novo malignancy, 6 patients (28.5%) died. Patients with de novo malignancy had a higher follow-up after LDLT, 94.3 ± 32.9 versus 62.5 ± 41.8 months, P = 0.000. Patients with alcohol as etiology for LT had higher trend of de novo malignancies (33.3% versus 26.4%), P = 0.46. Conclusion The incidence of de novo malignancy was 1% at a median follow-up of 42 (32–73) months. De novo malignancies following LDLT, although uncommon, are associated with significant mortality. A careful screening protocol should be followed after transplantation for early detection of de novo malignancies.

Background Mulibrey-Nanism (Muscle-liver-brain-eye Nanism = dwarfism; MUL) is a rare genetic syndrome. The underlying TRIM37 mutation predisposes these children to develop tumors frequently. In the largest published series of MUL, 8% patients were reported to develop Wilms tumor (WT). The published literature lacks data regarding the best treatment protocol and outcome of this cohort of children with WT and MUL. We report here a 2-year-old boy with WT and MUL and present a review of literature on WT in MUL. Case Our patient had associated cardiac problems of atrial septal defect, atrial flutter and an episode of sudden cardiac arrest. We managed him successfully with chemotherapy, surgery and multi-speciality care. He is alive and in remission at follow-up of 6 months. Conclusion A total of 14 cases (including present case) of WT have been reported in MUL and treatment details were available for six cases. They were managed primarily with surgery, chemotherapy with/without radiotherapy, and all achieved remission. The outcome data is available only for two cases, one has been followed up till 15 years post treatment for WT and other is our patient.

BACKGROUND: Generally diagnosis of non-alcoholic fatty disease is made on imaging, however, mild steatosis is difficult to diagnose on imaging. Liver biopsy is the procedure of choice but is not carried out as it is an invasive procedure. We describe our experience of 157 liver biopsies in living liver donors with normal body mass index (BMI) 150 mg/dl as compared with 12.5% in the normal histology group, p = 0.009. Other metabolic risk factors were not statistically different. CONCLUSION: One third of lean donors had NAFL. Among all metabolic risk factors, only higher TGs levels showed a significant association with NAFL.

While antibody mediated hyper-acute vasculitic rejection is rare in liver transplant recipients, acute and chronic rejection have clinical significance. The liver allograft behaves differently to other solid organ transplants as acute rejection generally does not impair graft survival and chronic rejection (CR) is uncommon. The incidence of acute and chronic rejection has declined in current era due to improved immunosuppressive regimens. Acute rejection generally improves with steroid boluses and steroid resistant rejection is uncommon. CR may improve with escalation of immunosuppression or may result in irreversible loss of graft function leading to retransplantation or death. The current review discusses diagnosis and management of acute and chronic liver allograft rejection.

Mucormycosis is a rare but emerging fungal infection complicating solid organ transplantation. It is associated with a high mortality rate. We describe an unusual case of hepatic mucormycosis in a living donor liver transplant recipient presenting as delayed graft dysfunction, which was successfully treated with combination of liposomal amphotericin B and oral posaconazole therapy, without surgical resection. The patient had clinical improvement with normalization of liver function tests.

Post-transplant relapse is a major factor influencing the long-term outcome in alcoholic liver disease (ALD) patients. The aim of this study was to evaluate the relapse rates following living donor liver transplantation (LDLT) in patients with ALD in the Indian context with strong family support. Of 458 patients who underwent LDLT for ALD, 408 were included in the study. Post-transplant relapse was determined by information provided by the patient and/or family by means of outpatient and e-mail questionnaire, supported by clinical/biochemical parameters/liver histopathology. All except one were males, with a mean age of 46.9 ± 8.5 years. The overall rate of relapse was 9.5 % at 34.7 months (interquartile range (IQR) 15–57.6), lower than that reported in the literature from the West. The relapse rate was higher in patients with a shorter duration of pre-transplant abstinence (17.4 % and 15.4 % for recipients with pre-transplant abstinence of

Treatment of recurrent hepatitis C after liver transplantation is associated with poor sustained virological response (SVR) in genotype 1, and data on genotype 3 is limited to small numbers. We report one of the largest series of genotype 3 patients treated for recurrent hepatitis C following living donor liver transplantation (LDLT). From January 2002 to November 2013, of 1349 transplants, 359 patients had hepatitis C. Patients with histological recurrence were treated with pegylated interferon in escalating dose regimen for 48 weeks and weight-based ribavirin. Virological response was defined as rapid virological response (RVR—4 weeks), early virological response (EVR—12 weeks), end of treatment response (ETR—48 weeks), and SVR (24 weeks after end of treatment). SVR and no-SVR groups were compared for age, sex, body mass index (BMI), diabetes, total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides, ferritin, genotype, and hepatitis C virus (HCV) RNA levels before initiation of treatment. The study included 67 patients who had at least 18 months of follow up after treatment initiation (45 males), aged 51 ± 6.3 years. Treatment was started after 16 months (median); baseline median RNA was 2.7 × 106 IU/mL. There was no significant difference between the SVR and no-SVR groups regarding age, sex ratio, follow up period, total cholesterol, triglycerides, HDL, BMI, prevalence of diabetes, HCV RNA, and ferritin levels. Genotype 3, RVR, EVR, ETR, and higher LDL levels were significantly associated with SVR. Genotype 3 had a significantly higher SVR rate of 71 % as compared to an SVR rate of only 14 % in genotype 1, p = 0.0003. Absence of RVR and EVR predicted treatment failure with a specificity of 88 % and 92 %, respectively. Genotype 3 and higher LDL levels predict SVR in patients treated for hepatitis C recurrence following LDLT, whereas absence of RVR and EVR strongly predict treatment failure.

While Autoimmune Hepatitis (AIH) may recur in patients after liver transplant, an AIH like presentation (positive auto antibodies, raised immunoglobulin G, raised transaminases and histology showing plasma cell rich infiltrate) may also occur in liver transplant recipients who had transplant for some other disease, called De novo Autoimmune Hepatitis (DAIH). A timely diagnosis and treatment can prevent further graft dysfunction. We report 4 cases of DAIH after living donor liver transplantation.

INTRODUCTION: Results of Sofosbuvir based regimens for hepatitis C (HCV) recurrence after liver transplantation are available from well-designed clinical trials. Most of the data is from deceased donor liver transplant (DDLT) setting, and data on “real world” experience for HCV recurrence after living donor liver transplantation (LDLT) is limited. MATERIAL AND METHODS: Consecutive 78 patients who completed Sofosbuvir based HCV treatment after liver transplantation were included. Following Sofosbuvir based regimens were used; Sofosbuvir + Ribavirin (n = 58), Sofosbuvir + Ledipasvir ± Ribavirin (n = 5), Sofosbuvir + Daclatasvir ± Ribavirin (n = 15). Treatment was given for 12 weeks (triple therapy) or 24 weeks (dual therapy). RESULTS: A total of 74/78 (94.8%) patients achieved end of treatment response (ETR) while 4 did not achieve ETR. A total of 68/76 (89.4%) patients achieved sustained virological response at 12 weeks (SVR12). while 2 are waiting for 12 weeks follow up after ETR. Twelve patients had history of failed previous treatment with Peginterferon and Ribavirin after LDLT, all these patients achieved ETR and 11/12 had SVR12. There was no statistical difference in response rates between genotype 1 or 3. Eighteen patients (16 on Ribavirin) had hemoglobin

Introduction Although liver transplantation is a definitive cure for Wilson's disease (WD), there is limited data about results of living donor liver transplantation (LDLT) in adults. Material and methods 18 adults underwent LDLT for WD. The presentations before LDLT were decompensated cirrhosis (n = 16), acute on chronic liver failure (n = 1) and acute liver failure (n = 1). The donors were parents (n = 2), siblings (n = 3), cousin (n = 1), daughter (n = 1), nephew (n = 1), spouse or relatives of spouse (n = 9) and from swap transplantation (n = 1). All genetically related donors were negative for screening of WD. Results The study cohort comprised of 15 males and 3 females, aged 32 ± 10 years. Severity of liver disease (excluding acute liver failure patient) was as follows; Child's score 10 ± 2, model for end-stage liver disease (MELD) score 18 ± 6. The graft to recipient weight ratio was 1 ± 0.2. The ICU and hospital stay were 5.5 ± 0.9 and 15 ± 5 days. Two patients died in first month after liver transplantation, rest of patients are doing well at median 15 (8–38 months). Two patients had acute cellular rejection that responded to steroids, one had hepatic artery thrombosis and 2 had biliary strictures. Three patients had neurological symptoms; 2 of these patients had partial recovery while one had complete recovery. There was no significant difference between LDLT from genetically related or unrelated donors. Conclusion LDLT for WD in adults is associated with good outcomes.

A 25-year-old female, with systemic lupus erythematosus and antiphospholipid antibody syndrome, presented with exertional dyspnoea. Echocardiography showed a large (2.0 cm × 1.1 cm), echogenic, heterogeneous mass in the left ventricular outflow tract, under the aortic valve, attached to the ventricular aspect of the anterior mitral leaflet. Tiny flagellar, frond-like structures were seen attached to the surface of the mass. There was mitral regurgitation. These echocardiographic features were suggestive of a papillary fibroelastoma, but the histopathology of the excised mass revealed it to be a thrombus, which was consistent with a diagnosis of non-bacterial thrombotic endocarditis (NBTE). This case represents a rare histopathologically confirmed NBTE presenting as an unusually large mass in the left ventricular outflow tract.

Melanocytomas are present in leptomeninges and arise from neural crest during early embryonic development. They are a rare entity and usually occur in the thoracic spine and infratentorial region. We report a 32-year-old female with meningeal melanocytoma of D9-10. Magnetic resonance imaging revealed an intramedullary spinal tumor at D9-D10. Intraoperatively, the tumor was greyish-black in color with moderate vascularity, and was adherent to the cord. The clinical differential diagnoses included cavernoma and melanocytoma. On microscopic examination, the lesion showed sheets of cells with marked pigment deposition, which was obscuring the cellular morphology. The pigment was confirmed to be melanin by Masson's Fontana stain. Immunohistochemistry was performed, which showed positivity for HMB-45, S-100, Vimentin and Melan-A. The cells were negative for cytokeratin, epithelial membrane antigen, Glial fibrillary acidic protein and neuron-specific enolase. Mib-1 labeling index was less than 1%. In view of the lack of nuclear atypia, mitoses, necrosis and low Mib-1-labeling index along with immunohistochemistry profile, the diagnosis of Melanocytoma was made. Melanocytomas are rare pigmented tumors of the spinal cord and posterior cranial fossa. They are benign in nature, but can also be locally aggressive. Melanocytic lesions of the nervous system are to be differentiated from metastatic melanomas and also tumors showing melanin pigment deposition like schwanomma, paraganglioma, medulloblastoma and various gliomas.

Background Liver steatosis is the leading cause of donor rejection in living donor liver transplantation. Rapid weight loss is difficult to achieve in a short period of time, moreover it has been thought to worsen liver histology. Methods Donors who had significant steatosis based on liver biopsy were recommended 1200 Kcal/day and a minimum of 60 min/day moderate cardio training. Two patients were advised statins for dyslipidemia. None of the donors had metabolic syndrome. A second ultrasound guided liver biopsy was done at 28 ± 10 days. Donors with nonalcoholic steatohepatitis/fibrosis or >30% steatosis were not included. Results From July 2010 to January 2015, 16 donors were advised aggressive life style modification after initial biopsy; 15 (10 males, age 27.5 ± 6.5 years, baseline body mass index 28.4 ± 2.1 Kg/M 2 ) successfully reduced weight and 14 underwent donation after favorable second biopsy. Mean weight loss was 7 ± 4.3 kg (8.4 ± 4.6%). Second liver biopsy was done at 28 ± 10 days, there was decrease in steatosis in all but one including normalization of liver biopsy in 7 donors. Three donors had mild inflammation on first biopsy and they had improvement in second biopsy. All the donors and their recipients had an uneventful post-operative course. Conclusion Steatosis can be reversed in a short duration by aggressive life style modifications in highly motivated liver donors.

Purpose.To evaluate histological changes and neural elements in 100 posterior cruciate ligaments (PCLs) in patients with osteoarthritis.Methods.100 PCLs were obtained from a consecutive series of 46 women and 16 men aged 49 to 91 (mean, 67) years who underwent primary PCL-retaining total knee replacement for osteoarthritis. Histology was examined using conventional light microscopy. The PCLs were graded histologically in terms of parallel orientation of collagen fibres, mucoid degeneration, inflammation, and haemosiderin deposition. Histological changes were graded as normal, mild degeneration, moderate degeneration, and severe degeneration. The neural elements were assessed using immunohistochemical staining for S100 protein and neurofilaments. The histopathologist was blinded to the age, gender, and clinical and radiological grades of osteoarthritis.Results.One specimen was excluded from analysis owing to inadequate tissue. In the remaining 99 specimens, histology was normal in 72, mildly degenerative in 4, moderately degenerative in 4, and severely degenerative in 15. 76 specimens were positive for S100 protein or neurofilament or both by immunohistochemical staining, indicating the presence of neural elements.Conclusion.Most knees with osteoarthritis present with viable PCLs. Retaining the PCL in total knee replacement is a good option for better kinematics, stability, and proprioception.

Drug induced liver injury (DILI) is a cause of significant morbidity; timely diagnosis is important and requires a high index of suspicion. Terbinafine induced liver injury is rare. We report a case of Terbinafine induced hepatitis-cholestatic injury. The patient had a prolonged recovery phase lasting 3 months after discontinuation of drug.

Histoplasmosis normally do not affect immunocompetent individuals. Prolonged exposure may cause chronic disseminated histoplasmosis. Elderly male patient presented with fever, hematuria and pain in right hypochondrium. He had pallor, fever and mild hepatosplenomegaly. Investigations revealed anemia and thrombocytopenia. Giemsa stained bone marrow aspirate showed yeast-like cells, suggestive of Histoplasma capsulatum. PAS stained bone marrow aspirate and biopsy confirmed the diagnosis.