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Locally advanced intestinal neoplasms including colon cancer may require radical en bloc pancreaticoduodenectomy and right hemicolectomy (PD-RC) to achieve curative, margin-negative resection, but the safety and benefit of this uncommon procedure has not been established. The Association of Coloproctology of Great Britain and Ireland IMPACT initiative has also highlighted a lack of awareness about current services available within the UK for patients with advanced colorectal cancer and concerns about low-volume centres managing complex cases. Thus, we aimed to review the feasibility, safety and long-term outcomes of this procedure at a single high-volume hepatopancreaticobiliary surgery unit in the UK.A retrospective cohort study was performed using a database of all consecutive patients with intestinal cancer who had been referred to our regional advanced multidisciplinary team and undergone PD-RC in a 7-year period (2013-2020). Clinico-pathological and outcome data were reviewed.Ten patients (mean age 54 ± 13, 8/10 men) were identified. Final histology revealed the primary tumour sites were colon (n = 7) and duodenum (n = 3). R0 resection was achieved in all cases. The major complication rate (Clavien-Dindo ≥ 3) was 10% (1/10) with no deaths within 90 days of surgery. The Kaplan-Meier estimated 5-year overall survival was 83.3% (95% CI 58.3%-100%). Univariate survival analysis identified perineural invasion and extra-colonic origin as predictors of poor survival (log-rank P 0.05).En bloc PD-RC for locally advanced intestinal cancer can be performed safely with a high proportion of margin-negative resections and resultant long-term survival in carefully selected patients.

A) CT and MRI of patient with prolonged partial response with MTL-CEBPA treatment B) IFN-gamma, NFkB and IL6 trend at days 1, 8 and 15 following treatment and C) AFP change at from baseline to 4, 8 and 16 weeks on treatment

Supplementary Legends

Showing complete radiological response of lung metastases

Dose escalation flow chart. DLT - dose limiting toxicity, MTD - maximum tolerated dose

Trial Protocol

Supplementary Table 1 CEBPA-51 PK parameters Supplementary Table 2 RECIST 1.1 response observed overall and per cohorts in HCC patients at cut-off (12 Sep 2018) presented as n (%)

Purpose:Transcription factor C/EBP-α (CCAAT/enhancer-binding protein alpha) acts as a master regulator of hepatic and myeloid functions and multiple oncogenic processes. MTL-CEBPA is a first-in-class small activating RNA oligonucleotide drug that upregulates C/EBP-α.Patients and Methods:We conducted a phase I, open-label, dose-escalation trial of MTL-CEBPA in adults with advanced hepatocellular carcinoma (HCC) with cirrhosis, or resulting from nonalcoholic steatohepatitis or with liver metastases. Patients received intravenous MTL-CEBPA once a week for 3 weeks followed by a rest period of 1 week per treatment cycle in the dose-escalation phase (3+3 design).Results:Thirty-eight participants have been treated across six dose levels (28–160 mg/m2) and three dosing schedules. Thirty-four patients were evaluable for safety endpoints at 28 days. MTL-CEBPA treatment–related adverse events were not associated with dose, and no maximum dose was reached across the three schedules evaluated. Grade 3 treatment-related adverse events occurred in nine (24%) patients. In 24 patients with HCC evaluable for efficacy, an objective tumor response was achieved in one patient [4%; partial response (PR) for over 2 years] and stable disease (SD) in 12 (50%). After discontinuation of MTL-CEBPA, seven patients were treated with tyrosine kinase inhibitors (TKIs); three patients had a complete response with one further PR and two with SD.Conclusions:MTL-CEBPA is the first saRNA in clinical trials and demonstrates an acceptable safety profile and potential synergistic efficacy with TKIs in HCC. These encouraging phase I data validate targeting of C/EBP-α and have prompted MTL-CEBPA + sorafenib combination studies in HCC.

Longitudinal changes in WBC mRNA expression of CEBPA, adenosine, PD-1 & CXCR4 at screening, day2, 8 and 15 of a single patient treated in the 130mg/m2 cohort

qPCR of CEBPA mRNA levels at days 2, 8 and 15 following treatment

Study Design: Retrospective study.Purpose: This study was undertaken to compare the patterns of syringomyelia in patients with presumed idiopathic and congenital scoliosis.Overview of Literature: The incidence of neuraxial anomalies presenting as idiopathic scoliosis ranges from 2% to 14%; the common ones are idiopathic syringomyelia (IS) and Chiari malformation type 1 (CM1) with syringomyelia. Some authors have speculated that scoliosis is caused by the asymmetrical compression of anterior horn cells by a syrinx, which causes an imbalance of the trunk musculature. In congenital scoliosis, syringomyelia is the second commonest cord anomaly, and the deformity progression depends upon the underlying vertebral abnormality, the location of the abnormality, and the age of patient, and is independent of the intraspinal anomaly.Methods: We analyzed the radiological records of 44 consecutive patients with scoliosis and syringomyelia. Of these 44 patients, 13 had IS, 12 had CM1, and 19 had congenital scoliosis. The radiographs were evaluated to determine the curve magnitude, sagittal alignment, side of convexity, and type of vertebral anomaly, if any. T1- and T2-weighted magnetic resonance imaging of the whole spine was analyzed to determine the presence of craniovertebral anomalies, syrinx length, syrinx diameter, and syrinx-cord ratio (SCR).Results: The frequency of left convex curves was 26.1%, with no significant differences across the three groups. The mean length of the syrinx was 7.2±4.9 vertebral levels, and the mean SCR was 0.39±0.2. The mean syrinx length was significantly higher in patients with CM1 and IS, compared to patients with congenital scoliosis. The mean SCR was highest in patients with CM1. In congenital scoliosis, syringomyelia was seen most frequently in patients with a failure of formation, and 63.2% had concomitant cord anomalies.Conclusions: Syrinxes were smaller in size and length in patients with congenital scoliosis, and are distinct from those seen in IS and CM1.

This study analysed whether local anaesthetic wound catheter infiltration (LA-WCI) as an adjunct to intravenous patient-controlled analgesia (IV-PCA) provides superior outcomes compared to IV-PCA alone following liver resection.A systematic review and meta-analysis was conducted for randomised control trials (RCTs) comparing LA-WCI with IV-PCA(LA-WCI group) versus IV-PCA alone (IV-PCA group). PubMed and the Cochrane Library were searched for relevant articles.Six RCTs with a total of 440 patients were included. Opioid use in the initial 48 h was less in the LA-WCI group [MD -21.27 mg (-39.39,-3.15), p = 0.02]. Pain scores were lower in the LA-WCI group at rest at POD0 (post-operative day 0)6-8 h (p = 0.0009), POD1AM(p = 0.01), POD1PM(p = 0.02) and POD2 (p = 0.0006), and exertion at POD0 0-2 h (p = 0.05), POD1AM(p = 0.03), POD1PM(p = 0.03), POD2 (p = 0.03) and POD3 (p = 0.01). LA-WCI group had reduced length of hospital stay [MD -1.32 days (-2.23,-0.40),p = 0.005], time to ambulation [MD -5.94 h (-8.47,-3.42),p = 0.00001] and incidence of nausea and vomiting (PONV) [OR 0.17 (0.07,0.43),p = 0.0002]. No differences were observed in length of intensive care unit (ICU) stay or incidence of surgical site infections.LA-WCI as an adjunct to opiate IV-PCA post-hepatectomy reduces opioid use, pain scores at multiple time points at rest and exertion, length of hospital stay, time to ambulation and PONV. However, LA-WCI use does not alter length of ICU stay or incidence of wound infection.

Background There is an ongoing debate on the feasibility, safety, and oncological efficacy of the associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) technique. The aim of this study was to compare ALPPS, two-staged hepatectomy (TSH), and portal vein embolization (PVE)/ligation (PVL) using updated traditional meta-analysis and network meta-analysis (NMA). Data sources Electronic databases were used in a systematic literature search. Updated traditional meta-analysis and NMA were performed and compared. Mortality and major morbidity were selected as primary outcomes. Results Nineteen studies including 1200 patients were selected from the pool of 436 studies. Of these patients, 315 (31%) and 702 (69%) underwent ALPPS and portal vein occlusion (PVO), respectively. Ninety-day mortality based on updated traditional meta-analysis, subgroup analysis of the randomized controlled trials (RCTs), and both Bayesian and frequentist NMA did not demonstrate significant differences between the ALPPS cohort and the PVE, PVL, and TSH cohorts. Moreover, analysis of RCTs did not demonstrate significant differences of major morbidity between the ALPPS and PVO cohorts. The ALPPS cohort demonstrated significantly more favorable outcomes in hypertrophy parameters, time to operation, definitive hepatectomy, and R0 margins rates compared with the PVO cohort. In contrast, 1-year disease-free survival was significantly higher in the PVO cohort compared to the ALPPS cohort. Conclusions This study is the first to use updated traditional meta-analysis and both Bayesian and frequentist NMA and demonstrated no significant differences in 90-day mortality between the ALPPS and other hepatic hypertrophy approaches. Furthermore, two high quality RCTs including 147 patients demonstrated no significant differences in major morbidity between the ALPPS and PVO cohorts.

Aims This study was undertaken to describe the pattern of vertebral, intraspinal and other organ anomalies in patients with congenital scoliosis and to determine the correlation between them. Methods Complete medical and radiological records of 227 consecutive patients with congenital scoliosis were analysed. The radiographs were examined for type of vertebral anomaly, location and severity of deformity. The median curve progression index (MCPI) was calculated in 198 patients. The magnetic resonance imaging (MRI) of the whole spine was analysed to detect the presence of cord abnormalities. The presence of other organ-system anomalies was also noted. The independent sample t test was used to compare severity of deformity between those with and without cord anomalies. The Chi-square test was used to compare frequency of cord abnormalities in different vertebral and organ-system anomalies. Results Hemivertebra with contralateral bar had the highest MCPI, while block vertebrae and wedge vertebrae had the lowest MCPI. Forty-eight patients had 83 cord anomalies. There was no statistically significant difference in severity of deformity, between those with and without cord anomalies. Failure of segmentation had the highest frequency of cord anomalies (p = 0.01). There was no significant difference in the frequency of cord anomalies between those with and without other organ defects. Conclusion Curve progression can be predicted by the underlying vertebral abnormalities. However, it cannot predict cord and other organ-system anomalies. Thus, all patients with congenital scoliosis must undergo MRI of the spine, electro- and echocardiography and ultrasonography of the abdomen to detect occult abnormalities and optimize the patient prior to deformity correction.

Hepatocellular carcinoma (HCC) is the most common primary liver tumor and has been considered a very immunogenic tumor. The treatment with radiofrequency ablation (RFA) has been established as the standard ablative therapy for early HCC, and is currently recognized as the main ablative tool for HCC tumors < 5 cm in size; however, progression and local recurrence remain the main disadvantages of this approach. To solve this clinical problem, recent efforts were concentrated on multimodal treatment, combining different strategies, including the combination of RFA and immunotherapy. This article reviewed the combination treatment of RFA with immunotherapy and found that this treatment strategy leads to an increased response of anti-tumor T cells, significantly reduces the risk of recurrence and improves survival rates compared to RFA alone. This review highlighted scientific evidence that supports the current recommendations for pre-clinical studies, and discuss the need for further research on this topic.

The pandemic of coronavirus disease 2019 (COVID-19) changed the surgical everyday practice overnight. Currently, the first articles reporting outcomes of liver transplant recipients infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are published. The aim of the present study was to summarise the existing evidence of impact of COVID-19 global pandemic on liver transplant recipients. Electronic databases were searched in accordance with Preferred Reporting Items in Systematic Reviews and Meta-Analyses (PRISMA). Five studies were selected from a pool of 12 studies with a total of 854 liver transplant recipients of whom 700 were children and the rest 154 were adults. The present evidence, based on case reports and series demonstrated lower mortality in liver transplant recipients compared to general population.

Tumour heterogeneity is a common phenomenon in neuroendocrine neoplasms (NENs) and a significant cause of treatment failure and disease progression. Genetic and epigenetic instability, along with proliferation of cancer stem cells and alterations in the tumour microenvironment, manifest as intra-tumoural variability in tumour biology in primary tumours and metastases. This may change over time, especially under selective pressure during treatment. The gastroenteropancreatic (GEP) tract is the most common site for NENs, and their diagnosis and treatment depends on the specific characteristics of the disease, in particular proliferation activity, expression of somatostatin receptors and grading. Somatostatin receptor expression has a major role in the diagnosis and treatment of GEP-NENs, while Ki-67 is also a valuable prognostic marker. Intra- and inter-tumour heterogeneity in GEP-NENS, however, may lead to inaccurate assessment of the disease and affect the reliability of the available diagnostic, prognostic and predictive tests. In this review, we summarise the current available evidence of the impact of tumour heterogeneity on tumour diagnosis and treatment of GEP-NENs. Understanding and accurately measuring tumour heterogeneity could better inform clinical decision making in NENs.

Purpose: To evaluate the mechanisms of how therapeutic upregulation of the transcription factor, CCAAT/enhancer-binding protein alpha (C/EBPα), prevents tumor progression in patients with advanced hepatocellular carcinoma (HCC) and in different mouse tumor models. Experimental Design: We conducted a phase I trial in 36 patients with HCC (NCT02716012) who received sorafenib as part of their standard care, and were given therapeutic C/EBPα small activating RNA (saRNA; MTL-CEBPA) as either neoadjuvant or adjuvant treatment. In the preclinical setting, the effects of MTL-CEBPA were assessed in several mouse models, including BNL-1ME liver cancer, Lewis lung carcinoma (LLC), and colon adenocarcinoma (MC38). Results: MTL-CEBPA treatment caused radiologic regression of tumors in 26.7% of HCC patients with an underlying viral etiology with 3 complete responders. MTL-CEBPA treatment in those patients caused a marked decrease in peripheral blood monocytic myeloid-derived suppressor cell (M-MDSC) numbers and an overall reduction in the numbers of protumoral M2 tumor-associated macrophages (TAM). Gene and protein analysis of patient leukocytes following treatment showed CEBPA activation affected regulation of factors involved in immune-suppressive activity. To corroborate this observation, treatment of all the mouse tumor models with MTL-CEBPA led to a reversal in the suppressive activity of M-MDSCs and TAMs, but not polymorphonuclear MDSCs (PMN-MDSC). The antitumor effects of MTL-CEBPA in these tumor models showed dependency on T cells. This was accentuated when MTL-CEBPA was combined with checkpoint inhibitors or with PMN-MDSC–targeted immunotherapy. Conclusions: This report demonstrates that therapeutic upregulation of the transcription factor C/EBPα causes inactivation of immune-suppressive myeloid cells with potent antitumor responses across different tumor models and in cancer patients. MTL-CEBPA is currently being investigated in combination with pembrolizumab in a phase I/Ib multicenter clinical study (NCT04105335).

Introduction The surge in the number of trauma cases following relaxation of lockdowns in the backdrop of COVID-19 pandemic, has strained the existing infrastructure to cater to these patients and also prevent the spread of infection. Moreover, with the rise of newer strains, the period ahead has to be tread carefully to prevent resurgence of infections. There have been recommendations regarding the ideal setup to operate orthopaedic cases in this pandemic scenario. However, many of the hospitals in India with financial and logistic constraints are unable to implement these structural changes into their existing setup. We propose a model which can be used in an existing operation theatre which has a single entry and exit corridor, which is the layout in many hospitals. Methodology A protocol with the consultation of a panel of health care professionals was designed on the basis of WHO guidelines in a way so as to remain dynamic. Prior to its implementation, online classes were conducted and a dry run of the protocol was done with the whole team involved. The theatre layout is one with a single entry and exit and had predesignated rooms. The personnel were divided into 3 teams, each with a fixed set of people and preset workflow, to be followed during entry and exit. Five COVID positive cases have been operated since then using the protocol and has been used as a pilot study to further amend the protocol. Conclusion This model can be used as a guideline by hospitals having a limited infrastructure, to develop their own protocol to operate on COVID positive cases, in the present situation of increasing trauma cases post the relaxation of lockdown and also in any subsequent waves of infection with newer strains. Simulation and periodic stringent audits with the entire team would prove successful in rectifying errors and avoiding any possible contamination.

Additional file 2.

4093 Background: Early-stage hepatocellular carcinoma (HCC) can be treated with liver resection (LR), but up to 70% of patients experience relapse within two years after surgery. Despite their established use in advanced disease, immune checkpoint inhibitors (ICPI) are still under investigation in the peri-operatory setting. Methods: PRIME‐HCC is a phase Ib study investigating safety and bioactivity of the nivolumab (3 mg/kg, day 1 and day 22) plus ipilimumab (1mg/kg, day 1 only) combination (Nivo+Ipi) prior to LR in early-stage HCC. The primary safety analysis assessed treatment-related adverse events (trAE) and delays to surgery. Secondary endpoint included objective response rate (ORR) by RECIST v1.1 and pathologic response rate on resection specimens. Results: At data censoring on the 27th of January 2022, 17 patients were enrolled, of whom 82% (n = 14) were male, with a median age of 64 years (range 47-76). Performance status was 0 in 88% of patients (n = 15) according to the Eastern Cooperative Oncology Group scale. Liver cirrhosis was found in 65% (n = 11) of the patients, mostly secondary to viral hepatitis (41%, n = 7). All patients were Child-Pugh A, with 53% (n = 9) classified as albumin-bilirubin (ALBI) grade 2, and the rest grade 1. Median tumour diameter was 3.4 cm (interquartile range [IQR] 2.4-4.0), and the median number of liver nodules was 1 (range 1-3). Any-grade trAEs were reported by 73% of the patients receiving at least one dose of treatment (n = 11, tot n = 15). Four patients (27%) reported grade 2 trAEs including hypothyroidism (n = 2), diarrhoea (n = 1), and fatigue (n = 1), and one (7%) grade 3 ALT/AST elevation. After a median follow-up of 6.3 months (IQR 1.9-23.0), no deaths had occurred. One patient had experienced relapse 20.8 months after treatment commencement, and he achieved partial response to subsequent treatment with atezolizumab plus bevacizumab. Median time to LR from screening was 2.5 months (IQR 2.3-3.2). Only one patient had a surgery delay due to liver function worsening (ICPI-unrelated) and experienced disease progression 12.4 months post-screening. One patient was found to have cholangiocarcinoma (CCA) on LR specimen and was excluded from efficacy analyses. Of the 13 patients with an available radiological assessment, ORR was 23%, with two partial responses and one complete response. Disease control rate was 92%, with one patient with mixed HCC/CCA histology showing primary progression. Of the nine pathologically evaluable patients, seven (78%) achieved a pathological response, including two (22%) complete responses. Conclusions: Nivo+Ipi can be safely administered in the neoadjuvant setting for HCC and does not delay LR. The combination demonstrates promising evidence of anti-tumour efficacy in terms of radiological and pathological response. Clinical trial information: NCT03682276.

Background After liver resection (LR), patients with hepatocellular cancer (HCC) are at high risk of recurrence. There are no approved anti-cancer therapies known to affect such risk, highlighting the acute need for novel systemic therapies to control the probability of disease relapse. Immunotherapy is expanding as a novel treatment option for HCC. Emerging data from cohort 4 of the CA209–040 study, which investigated the safety and preliminary efficacy of nivolumab/ipilimumab co-administration in advanced HCC, suggest that the combination can be delivered safely with an acceptable proportion of reversible grade 3–4 toxicities (27.1%) and a low discontinuation rate (2%) in patients with HCC. Here, we describe the design and rationale of PRIME-HCC, a two-part, multi-centre, phase Ib study to assess safety and bioactivity of the nivolumab/ipilimumab combination prior to LR in early-stage HCC. Methods The study involves an initial safety run-in phase (Part 1) to allow for preliminary safety characterisation within the first 6 patients enrolled and a subsequent expansion (Part 2). Ipilimumab will be administered once only on Day 1. Nivolumab will be administered on Day 1 and Day 22 (± 3 days) for a total of two 21-day cycles (i.e. 6 weeks of treatment). The primary objective of the study is to determine the safety and tolerability of the nivolumab/ipilimumab combination prior to LR. The secondary objective is to preliminarily characterize the efficacy of the combination prior to LR, including objective response rate (ORR) and pathologic response rates. Additional exploratory objectives include preliminary evidence of long-term disease control and to identify predictive correlates of response to the nivolumab/ipilimumab combination in HCC. Discussion The results of this study will help define the positioning of neoadjuvant nivolumab/ipilimumab combination in the perioperative management of HCC, with potential to improve survival outcomes in this patient population. Trial registration EudraCT Number: 2018–000987-27 Clinical trial registry & ID: ClinicalTrials.gov: NCT03682276.

Background: Pancreaticoduodenectomy is associated with high rates of morbidity. This combined with the psychological burden of cancer, may impact on a patient’s quality of life (QoL), which can be measured by using patient-reported outcomes (PRO). Objective: To perform a systematic review to evaluate the measurement of PRO after pancreaticoduodenectomy for cancer. Methods: 7 different databases were searched using 2 groups of search terms, one relating to pancreaticoduodenectomy, and one to PRO. Three authors screened the search results independently in a systematic manner based on predefined inclusion and exclusion criteria. Results: 27 studies, with 2173 eligible patients were included in the final analysis. Most of the included studies used validated instruments. The European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire was most popular and used in 12 studies. The methodology of all included studies was also scrutinised. 12 studies were deemed to have high quality methodology according to pre-defined criteria. Conclusion: The instruments and methods used to measure PRO are variable. The quality of PRO within the available literature has improved over time, as has the number of studies measuring PRO. PRO should be measured with uniformity in future trials so that patients can be provided with more comprehensive information regarding post-operative recovery and QoL during the shared decision-making process preoperatively.

Purpose: Transcription factor C/EBP-α (CCAAT/enhancer-binding protein alpha) acts as a master regulator of hepatic and myeloid functions and multiple oncogenic processes. MTL-CEBPA is a first-in-class small activating RNA oligonucleotide drug that upregulates C/EBP-α. Patients and Methods: We conducted a phase I, open-label, dose-escalation trial of MTL-CEBPA in adults with advanced hepatocellular carcinoma (HCC) with cirrhosis, or resulting from nonalcoholic steatohepatitis or with liver metastases. Patients received intravenous MTL-CEBPA once a week for 3 weeks followed by a rest period of 1 week per treatment cycle in the dose-escalation phase (3+3 design). Results: Thirty-eight participants have been treated across six dose levels (28–160 mg/m2) and three dosing schedules. Thirty-four patients were evaluable for safety endpoints at 28 days. MTL-CEBPA treatment–related adverse events were not associated with dose, and no maximum dose was reached across the three schedules evaluated. Grade 3 treatment-related adverse events occurred in nine (24%) patients. In 24 patients with HCC evaluable for efficacy, an objective tumor response was achieved in one patient [4%; partial response (PR) for over 2 years] and stable disease (SD) in 12 (50%). After discontinuation of MTL-CEBPA, seven patients were treated with tyrosine kinase inhibitors (TKIs); three patients had a complete response with one further PR and two with SD. Conclusions: MTL-CEBPA is the first saRNA in clinical trials and demonstrates an acceptable safety profile and potential synergistic efficacy with TKIs in HCC. These encouraging phase I data validate targeting of C/EBP-α and have prompted MTL-CEBPA + sorafenib combination studies in HCC.

The conventional posterior approach is mostly advocated for excision of sacral tumours below S2. We describe an operative technique of single-stage en bloc resection of sacral tumours, extending up to S1, through an extended posterior approach. Nine patients, who had undergone resection of sacral tumours, by the described technique formed the basis of this study. Four patients had chordomas, whereas schwannoma, neurilemmoma, giant-cell tumour, malignant paraganglioma and recurrent Ewing’s sarcoma were seen in one patient each. They were followed up at regular intervals with a mean follow-up of 45.4 months. Perioperative complications, their functional and oncological outcomes at final follow-up were analysed. None of the patients had any perioperative complications like uncontrolled haemorrhage, injury to the rectum, deep vein thrombosis or pulmonary embolism. One patient had a superficial wound infection which subsided with regular dressing, and another patient developed a wound breakdown that required an additional flap procedure. At final follow-up, six patients were able to walk without any assistive devices, six patients had normal bladder function, and five patients had normal bowel function. Five patients did not have any recurrence at final follow-up, whereas two were alive with the disease and two had died. The reported technique allows en bloc resection of sacral tumours up to S1, through a posterior-only approach. It is less invasive with minimal morbidity. The functional and oncological outcomes are similar to those reported by other investigators. These slides can be retrieved from electronic supplementary material.

Study Design: Cross-sectional study. Purpose: To evaluate the association between zygapophyseal joint angle (ZJA), facet tropism (FT), and lumbar intervertebral disc prolapse (IVDP). Overview of Literature: Several studies have shown that FT increases the risk of IVDP and have postulated that a more sagittally oriented zygapophyseal joint provides less mechanical resistance to axial torque, thereby exerting excessive rotational strain on the intervertebral disc, resulting in an annular tear. In contrast, other studies have found no definitive association between FT and IVDP. Therefore, conclusive evidence regarding the role of FT in the pathogenesis of disc prolapse is currently lacking. Methods: Magnetic resonance imaging scans of 426 patients with single-level lumbar IVDP were analyzed. Right and left ZJAs of the lumbar segments were measured on axial sections. The frequency and severity of FT were determined by calculating the absolute difference between the right and left ZJAs. Patients without IVDP at L4–L5 and L5–S1 served as controls for those with IVDP at L4–L5 and L5–S1, respectively. Chi-square test and t -test were used to compare the severity and frequency of FT between patients with and without IVDP. The receiver operating characteristic analysis was performed to determine the critical FT values that were predictive of IVDP. Results: Patients with IVDP exhibited a higher frequency (L4–L5: 47% vs. 15.08%; L5–S1: 39.62% vs. 22.69%; p =0.001) and severity (L4–L5: 7.85°±3.5° vs. 4.05°±2.62°; L5–S1: 7.30°±3.07° vs. 4.82°±3.29°; p

Background Survival advantage following trans-arterial chemoembolization (TACE) is variable in patients with hepatocellular carcinoma (HCC). We combined pre-TACE radiologic features to derive a novel prognostic signature in HCC. Methods A multi-institutional dataset of 98 patients was generated from two retrospective cohorts from United Kingdom (65%) and Italy (36%). The prognostic impact of a number baseline imaging parameters was assessed and factors significant on univariate analysis were combined to create a novel radiologic signature on multivariable analyses predictive of overall survival (OS) following TACE. Results Median OS was 15.4 months. Tumour size > 7 cm (p 7 cm, ITN and AEN identified patients with poor prognosis (p

Tumor associated macrophages (TAM) and myeloid-derived suppressor cells (MDSC) are widely implicated in the suppression of immune responses in cancer and are associated with negative clinical outcomes. We report that in mouse tumor models, therapeutic up-regulation of the transcriptional factor C/EBPα with small activating RNA (MTL-CEBPA) blocks the suppressive activity of monocytic (M) MDSC and TAM without affecting polymorphonuclear (PMN) MDSC. MTL-CEBPA treatment demonstrated antitumor activity that was dependent on T cells. Combination of MTL-CEBPA and anti-PD1 antibody or with PMN-MDSC targeted therapy resulted in marked antitumor effect. A phase I trial was conducted in 36 patients with advanced hepatocellular carcinoma (HCC). Marked decrease in M-MDSC and the expression of genes and proteins involved in immune suppressive activity of these cells were observed. Combined treatment with MTL-CEBPA and sorafenib resulted in a 27% objective radiological response and three complete responses in patients with virally associated HCC. Tissue biopsies from these patients demonstrated decrease in M2 polarized macrophages within the tumors. Thus, therapeutic up-regulation of C/EBPα inhibited suppressive myeloid cells that resulted in potent antitumor effect in mice and with encouraging clinical response in cancer patients. We are currently recruiting to a multi-centre study of MTL-CEBPA in combination with a PD-1 inhibitor (pembrolizumab) in adult patients with advanced solid tumors (TIMEPOINT - ClinicalTrials.gov Identifier: NCT04105335). Citation Format: Ayumi Hashimoto, Debashis Sarker, Vikash Reebye, Sheba Jarvis, Mikael H. Sodergren, Andrew Kossenkov, Nina Raulf, Jenni Vasara, Pinelopi Andrikakou, Tim Meyer, Kai-Wen Huang, Ruth Plummer, Cheng Ean Chee, Duncan Spalding, Madhava Pai, David J. Pinato, Rohini Sharma, Bristi Basu, Daniel Palmer, Yuk-Ting Ma, Robert Habib, Anna Martirosyan, Naouel Elasri, Adeline Reynaud, John Rossi, Mark Cobbold, Nagy Habib, Dmitry Gabrilovich. Up-regulation of C/EBPα inhibits suppressive activity of myeloid cells and potentiates antitumor response in mice and cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1730.

Controversy related to endoscopic or surgical management of pain in patients with chronic pancreatitis remains. Despite improvement in endoscopic treatments, surgery remains the best option for pain management in these patients.

// David J. Pinato 1 , Tadaaki Arizumi 2 , Jeong Won Jang 3 , Elias Allara 4, 5 , Puvan I. Suppiah 1 , Carlo Smirne 4 , Paul Tait 6 , Madhava Pai 7 , Glenda Grossi 4 , Young Woon Kim 3 , Mario Pirisi 4, 8 , Masatoshi Kudo 2 , Rohini Sharma 1 1 Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital, London, UK 2 Department of Gastroenterology and Hepatology, Kinki University School of Medicine, Osaka-Sayama, Osaka, Japan 3 Department of Internal Medicine, The Catholic University of Korea Incheon St. Mary’s Hospital, Seoul, Republic of Korea 4 Department of Translational Medicine, Universita degli Studi del Piemonte Orientale “A. Avogadro”, Novara, Italy 5 School of Public Health, Universita degli Studi di Torino, Torino, Italy 6 Department of Radiology, Imperial College NHS Trust, Hammersmith Hospital, London, UK 7 Department of Surgery, Imperial College NHS Trust, Hammersmith Hospital, London, UK 8 Interdisciplinary Research Center of Autoimmune Diseases, Universita degli Studi del Piemonte Orientale “A. Avogadro”, Novara, Italy Correspondence to: David James Pinato, email: david.pinato@imperial.ac.uk Keywords: prognosis, hepatocellular carcinoma, TACE, ART score, HAP score Received: February 22, 2016 Accepted: April 26, 2016 Published: May 26, 2016 ABSTRACT Background: The prognosis of patients with hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE) is variable, despite a myriad of prognostic markers. We compared and integrated the established prognostic models, HAP and ART scores, for their accuracy of overall survival (OS) prediction. Results: In both training and validation sets, HAP and ART scores emerged as independent predictors of OS ( p

To evaluate the short and long term outcomes of duodenum preserving pancreatic head resection (DPPHR) procedures in the treatment of painful chronic pancreatitis.A systematic literature search was performed to identify all comparative studies evaluating long and short term postoperative outcomes (pain relief, morbidity and mortality, pancreatic exocrine and endocrine function).Five published studies fulfilled the inclusion criteria including 1 randomized controlled trial comparing the Beger and Frey procedure. In total, 323 patients underwent surgical procedures for chronic pancreatitis, including Beger (n = 138) and Frey (n = 99), minimal Frey (n = 32), modified Frey (n = 25) and Berne's modification (n = 29). Two studies comparing the Beger and Frey procedure were entered into a meta-analysis and showed no difference in post-operative pain (RD = -0.06; CI -0.21 to 0.09), mortality (RD = 0.01; CI -0.03 to 0.05), morbidity (RD = 0.12; CI -0.00 to 0.24), exocrine insufficiency (RD = 0.04; CI -0.10 to 0.18) and endocrine insufficiency (RD = -0.14 CI -0.28 to 0.01).All procedures are equally effective for the management of pain for chronic pancreatitis. The choice of procedure should be determined by other factors including the presence of secondary complications of pancreatitis and intra-operative findings. Registration number CRD42015019275. Centre for Reviews and Dissemination, University of York, 2009.