Chemotherapy and repeat resection abrogate the prognostic value of neutrophil lymphocyte ratio in colorectal liver metastases.

BACKGROUND: Evolution in surgical and oncological management of CRLM has called into question the utility of clinical risk scores. We sought to establish if neutrophil lymphocyte ratio (NLR) has a prognostic role in this patient cohort. METHODS: From 2005 to 2015,379 hepatectomies were performed for CRLM, 322 underwent index hepatectomy, 57 s hepatectomies were performed. Clinicopathological data were obtained from a prospectively maintained database. Variables associated with longterm survival following index and second hepatectomy were identified by Cox regression analyses and reviewed along with 30-day post-operative morbidity and mortality. RESULTS: Following index hepatectomy 1-,3-and 5-year survival was 90.7%, 68.1% and 48.6%. Major resection, positive margins and >5 tumours were negatively associated with survival. Those with elevated NLR(>5) had a median survival of 55 months, compared to 70 months with lower NLR(p = 0.027). Following neoadjuvant chemotherapy, no association between NLR and survival was demonstrated (p = 0.93). Furthermore, NLR >5 had no impact on prognosis following repeat hepatectomy. Tumour diameter >5 cm (p = 0.04) was the sole predictor of poorer survival (p = 0.049). CONCLUSION: Despite elevated NLR correlating with shorter survival following index hepatectomy, this effect is negated by neoadjuvant chemotherapy and second hepatectomy for recurrent disease. This data would not support the use of NLR in the preoperative decision algorithm for patients with CRLM.

Depleted polymorphonuclear leukocytes in human metastatic liver reflect an altered immune microenvironment associated with recurrent metastasis.

BACKGROUND: Hepatic immunity, normally protective against neoplasia, is subverted in colorectal liver metastasis (CRLM). Here, we compare the inflammatory microenvironment of CRLM-bearing liver tissue to donor liver. METHODS: Twenty-five patients undergoing resection for CRLM were recruited, 13 of whom developed intrahepatic recurrence within 18 months. Biopsies were obtained from tumour and normal liver tissue adjacent to and distal from, the tumour. Donor liver biopsies were obtained during transplantation. Biopsies were cultured and conditioned media (CM) screened for 102 inflammatory mediators. Twelve of these were validated by Luminex assay. Transwell assays measured cancer cell chemotaxis. Polymorphonuclear leukocytes (PMN) and lymphocytes were quantified in H&E sections. RESULTS: Fewer periportal tissue-resident PMN were present in metastatic liver compared to donor liver. Patients with the fewest PMN in liver tissue distal to their tumour had a shorter time to intrahepatic recurrence (P < 0.001). IL-6, CXCL1, CXCL5, G-CSF, GM-CSF, VEGF, LIF, and CCL3 were higher in liver-bearing CRLM compared to donor tissue. Consequently, cancer cells migrated equally towards CM of all regions of metastatic liver but not towards donor liver CM. CONCLUSIONS: The local inflammatory environment may affect both immune cell infiltration and cancer cell migration contributing to recurrence following resection for CRLM.

Extratumoral PD-1 blockade does not perpetuate obesity-associated inflammation in esophageal adenocarcinoma.

Checkpoint inhibitors, such as anti-PD-1 (Programmed death-1), are transforming cancer treatment for inoperable or advanced disease. As the incidence of obesity-associated malignancies, including esophageal adenocarcinoma (EAC) continues to increase and treatment with checkpoint inhibitors are being FDA approved for a broader range of cancers, it is important to assess how anti-PD-1 treatment might exacerbate pre-existing inflammatory processes at other sites. Outside the EAC tumor, the omentum and liver were found to be enriched with substantial populations of PD-1 expressing T cells. Treatment of omental and hepatic T cells with anti-PD-1 (clone EH12.2H7) did not enhance inflammatory cytokine expression or proliferation, but transiently increased CD107a expression by CD8+ T cells. Importantly, PD-1-expressing T cells are significantly lower in EAC tumor post neoadjuvant chemoradiotherapy, suggesting that combination with specific conventional treatments may severely impair the efficacy of anti-PD-1 immunotherapy. This study provides evidence that systemically administered anti-PD-1 treatment is unlikely to exacerbate pre-existing T cell-mediated inflammation outside the tumor in obesity-associated cancers, such as EAC. Furthermore, our data suggests that studies are required to identify the negative impact of concomitant therapies on PD-1 expression in order to boost overall response rates.

Laparoscopic Spigelian Hernia Repair: A Series of 40 Patients.

Spigelian hernias are a rare abdominal wall hernia. The aim of this study was to assess the efficacy and outcomes of patients who underwent a laparoscopic spigelian hernia repair. A retrospective study was performed reviewing all patients who had a laparoscopic spigelian hernia repair. We assessed the success of the procedure including conversion rates, postoperative morbidities, and recurrence rates. Forty patents had a laparoscopic repair. Two thirds (n=25) had an intraperitoneal repair. There was no conversion to open repair. Four patients had postoperative morbidities. At 6-month follow-up all patients were pain free, with 1 recurrence. There is considerable evidence supporting the opinion that laparoscopic repair offers excellent outcomes. This report is the largest series to date, and we advocate that this approach should become the standard of care.

Techniques and outcomes of combined inferior vena cava and visceral resection for benign and malignant disease.

BACKGROUND: Involvement of the inferior vena cava (IVC) by neoplasm has traditionally been considered a contra-indication to curative surgery because of high surgical risks and poor long-term prognosis. Advances in surgical and anaesthetic techniques however have made this feasible. The aim of this study is to evaluate the outcome of combined IVC and visceral resection in a single institution. METHODS: A retrospective review of a prospectively maintained database was performed. Pre-operative clinicopathological data, operative details and post-operative outcomes including overall and disease-free survival were analysed. Clinicopathological data of patients over a seven-year period undergoing combined IVC and visceral resection was reviewed, including overall and disease-free survival. RESULTS: Between 2006 and 2012, 14 patients underwent IVC resection was accompanied by major hepatectomy (8), nephrectomy (6) and multivisceral resection (3). Post resection, the IVC was reconstructed primarily (3); with PTFE tube graft (9) or using a Gore-tex patch graft (2). All patients underwent a R0 resection. There were two postoperative deaths within 30 days. 6 patients had postoperative complications. There was 1 early and one late (after 6 months) IVC thrombosis. With a median follow up of 20 months (range 5-84 months), two patients died of tumour recurrence and ten are alive with (n = 5) or without (n = 5) disease. CONCLUSION: Combined IVC and visceral resection can be safely performed in selected patients. Surgery provides the possibility of negative margins, acceptable perioperative morbidity/mortality and prolonged survival. These factors combined with lack of alternative treatments justify this approach. However, specialist teams should perform the surgery preferably in centres with expertise in liver transplantation.

Incidence and risk factors of delirium in patients post pancreaticoduodenectomy.

BACKGROUND: Post-operative delirium is an important and common complication of major abdominal surgery characterized by acute confusion with fluctuating consciousness. The aim of this study was to establish the incidence of post-operative delirium in patients undergoing a pancreaticoduodenectomy and to determine the risk factors for its development. METHODS: From a prospectively maintained database, a retrospective cohort analysis was performed of 50 consecutive patients who underwent a pancreaticoduodenectomy at the National Surgical Centre for Pancreatic Cancer in St. Vincent's University Hospital, Dublin and whose entire post-operative stay was in this institution, between July 2011 and December 2012. Two independent medical practitioners assessed all data and delirium was diagnosed according to criteria of the Diagnostic and Statistical Manual Disorder (DSM), fourth edition. Univariate and multivariate analyses were performed. RESULTS: Seven patients (14%) developed post-operative delirium. The median onset was on the second post-operative day. Older age was predictive of an increased risk of delirium post-operatively. Those who developed delirium had a significantly increased length of stay (LOS) as well as a significantly increased risk of developing at least a grade 3 complication (Clavien-Dindo classification). CONCLUSION: This study demonstrates that post-operative delirium is associated with a more complicated recovery after a pancreaticoduodenectomy and that older age is independently predictive of its development. Focused screening may allow targeted preventative strategies to be used in the peri-operative period to reduce complications and costs associated with delirium.

Initial impact of a systematic multidisciplinary approach on the management of patients with gastroenteropancreatic neuroendocrine tumor.

According to the international guidelines, a multidisciplinary approach is currently advised for the optimal care of patients with a gastroenteropancreatic neuroendocrine tumor (GEP NET). In our institution (tertiary care center), a systematic multidisciplinary approach was established in May 2007. In this study, we have aimed to assess the initial impact of establishing a systematic multidisciplinary approach to the management of GEP NET patients. We have collected and compared the biochemical, imaging, and pathological data and the therapeutic strategies in GEP NET patients diagnosed, treated, or followed-up from January 1993 to April 2007 versus GEP NET patients attending our institution after the multidisciplinary approach starting, from May 2007 to October 2008. Data of 91 patients before and 42 patients after the establishment of the multidisciplinary approach (total: 133 consecutive GEP NET patients) have been finally collected and analyzed. Before the establishment of the multidisciplinary approach, a lack of consistency in the biochemical, imaging, and pathological findings before treatment initiation as well as during follow-up of GEP NET patients was identified. These inconsistencies have been reduced by the systematic multidisciplinary approach. In addition, the therapeutic management of GEP NET patients has been altered by the multidisciplinary approach and became more consistent with recommended guidelines. We think that a systematic multidisciplinary approach significantly impacts on GEP NET patient care and should be established in all centers dealing with these tumors.

Quality of life after iatrogenic bile duct injury: a case control study.

OBJECTIVE: To compare quality of life (QOL) of patients following iatrogenic bile duct injuries (BDI) to matched controls. SUMMARY BACKGROUND DATA: BDI complicate approximately 0.3% of all cholecystectomy procedures. The literature regarding impact on quality of life is conflicted as assessment using clinical determinants alone is insufficient. METHODS: The medical outcomes study short form 36 (SF-36), a sensitive tool for quantification of life quality outcome, was used. The study group of iatrogenic BDI was compared with an age- and sex-matched group who underwent uncomplicated cholecystectomy. Telephone questionnaire using the SF-36 quality of life tool was administered to both groups at a median postoperative time of 12 years 8 months (range, 2 months -20 years). RESULTS: Seventy-eight patients were referred with BDI but due to mortality (n = 10) and unavailability (n = 6) 62 participated. The age- and sex-matched control cohort had undergone uncomplicated cholecystectomy (n = 62). Comparison between groups revealed that 7 of 8 variables examined were statistically similar to those of the control group (physical functioning, role physical, bodily pain, general health perceptions, vitality and social functioning, and mental health index). Mean role emotional scores were slightly worse in the BDI group (46 vs. 50) but the significance was borderline (P = 0.045). Subgroup analysis by method of intervention for BDI did not demonstrate significant differences. CONCLUSION: Quality of life of surviving patients following BDI compares favorably to that after uncomplicated laparoscopic cholecystectomy.

Lower expression of Nrf2 mRNA in older donor livers: a possible contributor to increased ischemia-reperfusion injury?

BACKGROUND: The cellular mechanisms involved in mediating cytoprotection against ischemia-reperfusion (IR) injury are not well understood. In animal models, NF-E2-related factor-2 (Nrf2) protects against IR injury by transcriptional activation of phase II antioxidants. Here, we investigate how the expression of Nrf2 mRNA in human donor livers in the setting of liver transplantation (LT) correlates with the histological damage associated with IR injury and whether or not this influences the outcome of LT. METHODS: Pairs of biopsies were acquired from 14 donor livers; the first biopsy of each pair was taken at the start of the retrieval operation, prior to the IR phase of LT and the second at the end of transplantation. RNA was extracted from snap frozen tissue and cDNA was prepared. Nrf2 mRNA expression was determined using real-time polymerase chain reaction (PCR). The modified Suzuki scoring system was used for histological grading of IR injury and relevant donor, recipient, and after LT clinical data were compiled. RESULTS: Nrf2 expression was observed in all biopsies, both before and after IR. Some donor organs had greater expression of Nrf2 mRNA before IR injury, and these organs had lower Suzuki scores and better liver functions (ALT) after LT. Donors of livers with greater Nrf2 levels were significantly younger (40.5 yrs, range 28-53 yrs) than those with low Nrf2 levels (55.5 yrs, range 48-61 yrs), P<0.05. CONCLUSION: Livers from older donors have lower levels of Nrf2 perhaps exposing these organs to more IR-related damage.

Amiodarone hepatotoxicity complicating obstructive jaundice due to ampullary cancer.

BACKGROUND: The presence of dual pathology can cause diagnostic dilemmas. We present a case of adenocarcinoma of the ampulla of Vater with concurrent amiodarone hepatotoxicity. METHODS: Painless jaundice associated with a palpable gallbladder was investigated clinically, radiologically, endoscopically and via liver biopsy. RESULTS: Liver biopsy showed amiodarone hepatotoxicity. Endoscopic biopsy identified an ampullary adenoma. However, the endoscopic ultrasound and intra-operative findings suggested a malignancy, which was confirmed postoperatively. CONCLUSIONS: While the classic findings of Courvoisier's Law are borne out in this case, the etiology of jaundice is twofold. Although dual pathology is uncommon it should always be considered.