Validation of a Nomogram to Predict Long Term Outcomes After Curative Surgery for Gastric Cancer in an Italian Cohort of Patients.

AIM OF THE STUDY: Nomograms have been proposed to assess prognosis following curative surgery for gastric cancer. The objective of the current study was to evaluate the performance of the Gastric Cancer Collaborative Group nomograms developed in 2014 by Kim et al., using a cohort of patients from a 10-year single institution experience in gastric cancer management. PATIENTS AND METHODS: We retrospectively reviewed patients who underwent curative-intent surgery for histologically confirmed gastric cancer at First Surgical Clinic of Padua University Hospital (Italy) from January 2010 to May 2020. Univariable and multivariable Cox proportional hazard models were employed to assess the effect of the variables of interest on mortality and recurrence. Multivariable analysis was performed by considering the variables included in the Gastric Cancer Collaborative Group nomograms in order to validate them. The performance of the nomograms was evaluated using Harrell's C-index and calibration plots. RESULTS: Overall, 168 patients were included, with a median follow-up of 20.1 months. On multivariable analysis, tumor location, lymph node ratio, and pathological T stage were associated with recurrence; age, tumor location, lymph node ratio, and pT stage were associated with OS (overall survival). The nomograms had good discriminatory capability to classify both OS (C-index: 0.75) and DFS (disease-free survival) (C-index 0.72). The corrected C-Index for DFS based on the AJCC staging system revealed better prediction (C-Index 0.75), while the corrected C-Index for OS had worse discrimination ability compared with the current nomogram (C-Index 0.72). CONCLUSIONS: The Gastric Cancer Collaborative Group nomograms demonstrated good performances in terms of prediction of both OS and DFS on external validation. The two nomograms are easy to apply, and variables included are widely available to most facilities.

Hepatocellular carcinoma tumour burden score to stratify prognosis after resection.

BACKGROUND: Although the Barcelona Clinic Liver Cancer (BCLC) staging system has been largely adopted in clinical practice, recent studies have emphasized the need for further refinement and subclassification of this system. METHODS: Patients who underwent hepatectomy with curative intent for BCLC-0, -A or -B hepatocellular carcinoma (HCC) between 2000 and 2017 were identified using a multi-institutional database. The tumour burden score (TBS) was calculated, and overall survival (OS) was examined in relation to TBS and BCLC stage. RESULTS: Among 1053 patients, 63 (6·0 per cent) had BCLC-0, 826 (78·4 per cent) BCLC-A and 164 (15·6 per cent) had BCLC-B HCC. OS worsened incrementally with higher TBS (5-year OS 77·9, 61 and 39 per cent for low, medium and high TBS respectively; P < 0·001). No differences in OS were noted among patients with similar TBS, irrespective of BCLC stage (61·6 versus 58·9 per cent for BCLC-A/medium TBS versus BCLC-B/medium TBS, P = 0·930; 45 versus 13 per cent for BCLC-A/high TBS versus BCLC-B/high TBS, P = 0·175). Patients with BCLC-B HCC and a medium TBS had better OS than those with BCLC-A disease and a high TBS (58·9 versus 45 per cent; P = 0·005). On multivariable analysis, TBS remained associated with OS among patients with BCLC-A (medium TBS: hazard ratio (HR) 2·07, 95 per cent c.i. 1·42 to 3·02, P < 0·001; high TBS: HR 4·05, 2·40 to 6·82, P < 0·001) and BCLC-B (high TBS: HR 3·85, 2·03 to 7·30; P < 0·001) HCC. TBS could also stratify prognosis among patients in an external validation cohort (5-year OS 79, 51·2 and 28 per cent for low, medium and high TBS respectively; P = 0·010). CONCLUSION: The prognosis of patients with HCC varied according to the BCLC stage but was largely dependent on the TBS.

ANTECEDENTES: Aunque el sistema de estadificación del Barcelona Clinic Liver Cancer (BCLC) ha sido adoptado en gran medida en la práctica clínica, estudios recientes han enfatizado la necesidad de un mayor refinamiento y subclasificación del sistema BCLC. MÉTODOS: Los pacientes con carcinoma hepatocelular (hepatocellular cancer, HCC) BCLC-0, A y B que se sometieron a una hepatectomía con intención curativa entre 2000 y 2017 fueron identificados utilizando una base de datos multi-institucional. Se calculó la puntuación de carga tumoral (tumour burden score, TBS) y se examinó la supervivencia global (overall survival, OS) en relación con la TBS y los estadios BCLC. RESULTADOS: En la serie de 1.053 pacientes, 63 (6%) tenían HCC BCLC-0, 826 (78,4%) HCC BCLC-A y 164 (15,6%) HCC BCLC-B. La OS disminuyó de forma incremental en función de la mayor TBS (OS a 5 años; TBS baja: 77,9% versus TBS media: 61% versus TBS alta: 39%, P < 0,001). No se observaron diferencias en la OS entre pacientes con una puntuación TBS similar, independientemente del estadio BCLC (BCLC-A/TBS media: 61,6% versus BCLC-B/TBS media: 58,9%, P = 0,93; BCLC-A/TBS alta: 45,1% versus BCLC-B/TBS alta: 12,8%, P = 0,175). Los pacientes con BCLC-B/TBS media tuvieron una mejor OS que los pacientes con BCLC-A/TBS alta (58,9% versus 45,1%, P = 0,005). En el análisis multivariable, la TBS se mantuvo asociada a la OS en el caso de BCLC-A (TBS media: cociente de riesgos instantáneos, hazard ratio, HR = 2,07, i.c. del 95%: 1,42-3,02, P < 0,001; TBS alta: HR = 4,05, i.c. del 95%: 2,40-6,82, P < 0,001) y BCLC-B pacientes (TBS alta: HR = 3,85, i.c. del 95%: 2,03-7,30, P < 0,001). La TBS también pudo estratificar el pronóstico entre pacientes en una cohorte de validación externa (OS a 5 años; TBS baja: 78,7% versus TBS media: 51,2% versus TBS alta: 27,6%, P = 0,01). CONCLUSIÓN: El pronóstico de los pacientes con HCC varió según el estadio BCLC, pero dependió en gran medida de la TBS.

Impact of postoperative infective complications on long-term survival after liver resection for hepatocellular carcinoma.

BACKGROUND: Postoperative complications have a great impact on the postoperative course and oncological outcomes following major cancer surgery. Among them, infective complications play an important role. The aim of this study was to evaluate whether postoperative infective complications influence long-term survival after liver resection for hepatocellular carcinoma (HCC). METHODS: Patients who underwent resection with curative intent for HCC between July 2003 and June 2016 were identified from a multicentre database (8 institutions) and analysed retrospectively. Independent risk factors for postoperative infective complications were identified. After excluding patients who died 90 days or less after surgery, overall survival (OS) and recurrence-free survival (RFS) were compared between patients with and without postoperative infective complications within 30 days after resection. RESULTS: Among 2442 patients identified, 332 (13·6 per cent) had postoperative infective complications. Age over 60 years, diabetes mellitus, obesity, cirrhosis, intraoperative blood transfusion, duration of surgery exceeding 180 min and major hepatectomy were identified as independent risk factors for postoperative infective complications. Univariable analysis revealed that median OS and RFS were poorer among patients with postoperative infective complications than among patients without (54·3 versus 86·8 months, and 22·6 versus 43·2 months, respectively; both P < 0·001). After adjustment for other prognostic factors, multivariable Cox regression analyses identified postoperative infective complications as independently associated with decreased OS (hazard ratio (HR) 1·20, 95 per cent c.i. 1·02 to 1·41; P = 0·027) and RFS (HR 1·19, 1·03 to 1·37; P = 0·021). CONCLUSION: Postoperative infective complications decreased long-term OS and RFS in patients treated with liver resection for HCC.

Long-term follow-up of hepatic adenoma and adenomatosis: analysis of size change on imaging with histopathological correlation.

AIM: To analyse the change in size on follow-up of hepatic adenomas (HAs) and adenomatosis, and to investigate the relationship of imaging features with size change. MATERIALS AND METHODS: The study included 44 patients (142 lesions) who underwent magnetic resonance imaging (MRI) or computed tomography (CT) for diagnosis and follow-up of HA. The imaging features and percentage change in maximum tumour dimension were observed over a follow-up duration of up to 139 months. RESULTS: With an average follow-up of 43 months, 37% lesions decreased in size, 58% were stable, 4% increased; one lesion regressed completely. Adenomas were stratified into size groups (<3, 3-5, and ≥5 cm). Size change among the three groups was similar (p>0.05). Percent size change was different for lesions followed for ≤12 months (-7.2%) compared with lesions followed for 13-60 months (-20.5%), and those followed for ≥60 months (-23.5%; p<0.05); there was no difference between lesions followed for 13-60 months and ≥60 months (p=0.523). Baseline size and percent size change was similar between the hepatocyte nuclear factor 1α-inactivated HA (HA-H) and inflammatory HA (HA-I) subtype (p>0.05). CONCLUSION: Most adenomas were either stable or regressed on follow-up. Size change was independent of baseline size. After an initial size decrease within 5 years, no further size reduction was noted on extended follow-up. The percent size change in the HA-H and HA-I subtype was similar.

Genetic And Morphological Evaluation (GAME) score for patients with colorectal liver metastases.

BACKGROUND: This study sought to develop a clinical risk score for resectable colorectal liver metastasis (CRLM) by combining clinicopathological and clinically available biological indicators, including KRAS. METHODS: A cohort of patients who underwent resection for CRLM at the Johns Hopkins Hospital (JHH) was analysed to identify independent predictors of overall survival (OS) that can be assessed before operation; these factors were combined into the Genetic And Morphological Evaluation (GAME) score. The score was compared with the current standard (Fong score) and validated in an external cohort of patients from the Memorial Sloan Kettering Cancer Center (MSKCC). RESULTS: Six preoperative predictors of worse OS were identified on multivariable Cox regression analysis in the JHH cohort (502 patients). The GAME score was calculated by allocating points to each patient according to the presence of these predictive factors: KRAS-mutated tumours (1 point); carcinoembryonic antigen level 20 ng/ml or more (1 point), primary tumour lymph node metastasis (1 point); Tumour Burden Score between 3 and 8 (1 point) or 9 and over (2 points); and extrahepatic disease (2 points). The high-risk group in the JHH cohort (GAME score at least 4 points) had a 5-year OS rate of 11 per cent, compared with 73·4 per cent for those in the low-risk group (score 0-1 point). Importantly, in cohorts from both the JHH and MSKCC (747 patients), the discriminatory capacity of the GAME score was superior to that of the Fong score, as demonstrated by the C-index and the Akaike information criterion. CONCLUSION: The GAME score is a preoperative prognostic tool that can be used to inform treatment selection.

Trends in use of lymphadenectomy in surgery with curative intent for intrahepatic cholangiocarcinoma.

BACKGROUND: The role of routine lymph node dissection (LND) in the surgical treatment of intrahepatic cholangiocarcinoma (ICC) remains controversial. The objective of this study was to investigate the trends of LND use in the surgical treatment of ICC. METHODS: Patients undergoing curative intent resection for ICC in 2000-2015 were identified from an international multi-institutional database. Use of lymphadenectomy was evaluated over time and by geographical region (West versus East); LND use and final nodal status were analysed relative to AJCC T categories. RESULTS: Among the 1084 patients identified, half (535, 49·4 per cent) underwent concomitant hepatic resection and LND. Between 2000 and 2015, the proportion of patients undergoing LND for ICC nearly doubled: 44·4 per cent in 2000 versus 81·5 per cent in 2015 (P < 0·001). Use of LND increased over time among both Eastern and Western centres. The odds of LND was associated with the time period of surgery and the extent of the tumour/T status (referent T1a: OR 2·43 for T2, P = 0·001; OR 2·13 for T3, P = 0·016). Among the 535 patients who had LND, lymph node metastasis (LNM) was noted in 209 (39·1 per cent). Specifically, the incidence of LNM was 24 per cent in T1a disease, 22 per cent in T1b, 42·9 per cent in T2, 48 per cent in T3 and 66 per cent in T4 (P < 0·001). AJCC T3 and T4 categories, harvesting of six or more lymph nodes, and presence of satellite lesions were independently associated with LNM. CONCLUSION: The rate of LNM was high across all T categories, with one in five patients with T1 disease having nodal metastasis. The trend in increased use of LND suggests a growing adoption of AJCC recommendations in the treatment of ICC.

Histopathological and immunophenotypic features of ipilimumab-associated colitis compared to ulcerative colitis.

BACKGROUND: Use of the immune checkpoint inhibitor ipilimumab is sometimes complicated by ipilimumab-associated colitis (Ipi-AC), an immune-mediated colitis that mimics inflammatory bowel disease. OBJECTIVE: We sought to characterize the histopathologic and immunophenotypic features of Ipi-AC and to directly compare these features to ulcerative colitis (UC). METHODS: This is a retrospective cohort study of 22 patients with Ipi-AC, 12 patients with treatment-naïve UC and five controls with diarrhoea but normal endoscopic findings. Immunohistopathologic features were described, and quantitative immunohistochemistry (IHC) was performed for CD4, CD8, CD20, CD138 and FOXP3. RESULTS: Endoscopic findings in both the Ipi-AC and UC groups included ulcerated, oedematous and erythematous mucosa. Involvement of the GI tract was more diffuse in Ipi-AC. As compared to UC, a smaller proportion of Ipi-AC biopsies had basal plasmacytosis (14% for Ipi-AC vs. 92% for UC, P < 0.0001) and crypt distortion (23% for Ipi-AC vs. 75% for UC, P = 0.003), whereas Ipi-AC biopsies had more apoptotic bodies in the left colon (17.6 ± 15.3 for Ipi-AC vs. 8.2 ± 4.2 for UC, P = 0.011). Cryptitis, ulcerations and crypt abscesses were common in both groups. Biopsy specimens from Ipi-AC had a lower density of CD20-positive lymphocytes than UC (275.8 ± 253.3 cells mm-2 for Ipi-AC vs. 1173.3 ± 1158.2 cells mm-2 for UC, P = 0.022) but had a similar density of CD4, CD8, CD138 and FOXP3-positive cells. CONCLUSIONS: Ipi-AC is a distinct pathologic entity with notable clinical and histopathological differences compared to UC. These findings provide insights into the pathophysiology of immune-related adverse events (iAEs) from ipilimumab therapy.

Early versus late recurrence of intrahepatic cholangiocarcinoma after resection with curative intent.

BACKGROUND: The objective of this study was to investigate the characteristics, treatment and prognosis of early versus late recurrence of intrahepatic cholangiocarcinoma (ICC) after hepatic resection. METHODS: Patients who underwent resection with curative intent for ICC were identified from a multi-institutional database. Data on clinicopathological characteristics, initial operative details, timing and sites of recurrence, recurrence management and long-term outcomes were analysed. RESULTS: A total of 933 patients were included. With a median follow-up of 22 months, 685 patients (73·4 per cent) experienced recurrence of ICC; 406 of these (59·3 per cent) developed only intrahepatic disease recurrence. The optimal cutoff value to differentiate early (540 patients, 78·8 per cent) versus late (145, 21·2 per cent) recurrence was defined as 24 months. Patients with early recurrence had extrahepatic disease more often (44·1 per cent versus 28·3 per cent in those with late recurrence; P < 0·001), whereas late recurrence was more often only intrahepatic (71·7 per cent versus 55·9 per cent for early recurrence; P < 0·001). From time of recurrence, overall survival was worse among patients who had early versus late recurrence (median 10 versus 18 months respectively; P = 0·029). In multivariable analysis, tumour characteristics including tumour size, number of lesions and satellite lesions were associated with an increased risk of early intrahepatic recurrence. In contrast, only the presence of liver cirrhosis was independently associated with an increased likelihood of late intrahepatic recurrence (hazard ratio 1·99, 95 per cent c.i. 1·11 to 3·56; P = 0·019). CONCLUSION: Early and late recurrence after curative resection for ICC are associated with different risk factors and prognosis. Data on the timing of recurrence may inform decisions about the degree of postoperative surveillance, as well as help counsel patients with regard to their risk of recurrence.

Functional hepatic imaging as a biomarker of primary and secondary tumor response to loco-regional therapies.

Objective criteria to measure tumor response are a key tenet for assessment of treatment efficacy when evaluating a therapeutic modality. Several response criteria have been proposed including the Response Evaluation Criteria in Solid Tumors (RECIST), modified RECIST (mRECIST), RECIST 1-1, and European Association for the Study of the Liver (EASL) guidelines. Response following loco-regional therapies (LRT) can be particularly difficult to assess as post-treatment changes may not always relate to changes in lesion size. As imaging modalities and solid tumor therapies continue to advance, there has been growing recognition that measurement of actual tumoricidal activity may not always be related to tumor size, and accurate assessment of treatment response may vary by therapeutic modality. As such, the objective change in the physical size characteristics of a tumor may not accurately reflect biological response to treatment. Functional imaging encompasses methods that are capable of detecting or measuring changes in tissue metabolism, blood flow, or composition. Conventional imaging modalities such as magnetic resonance imaging (MRI) and computed topography (CT) now include techniques such as diffusion-weighted imaging (DWI), apparent diffusion coefficient (ADC) maps, dynamic contrast enhancement (DCE-MRI), and perfusion CT (pCT). Use of functional cross-sectional imaging is particularly relevant to assess primary and secondary hepatic malignancies treated with LRT, such as trans-arterial chemoembolization (TACE), radiofrequency ablation (RFA), yttrium-90 (Y-90), and hepatic arterial infusion (HAI) chemotherapy. We herein review the imaging techniques, as well as the methodologies for measuring tumor response and survival, among patients treated with LRT for primary and secondary hepatic malignancies.

Aspartate ß-hydroxylase disrupts mitochondrial DNA stability and function in hepatocellular carcinoma.

The mechanism of aberrant mitochondrial genome and function in hepatocellular carcinoma (HCC) remains largely unknown. Our previous study demonstrated an increased expression of aspartate ß-hydroxylase (ASPH) in HCC tissues, which was associated with tumor invasiveness and a worse prognosis. Currently, we unexpectedly observed the presence of ASPH in purified mitochondrial protein fraction. In addition, immunostaining of both exogenously and endogenously expressed ASPH showed a colocalization with mitochondrial biomarkers. This study aimed to investigate whether the mitochondrial ASPH is involved in mitochondrial malfunction in HCC. Our results showed that ASPH overexpression in HCC tissues was correlated with decreased copy numbers of displacement loop (D-loop) and NADH dehydrogenase subunit 1 (ND-1) and enhanced D-loop mutation, suggesting the disrupted mitochondrial DNA (mtDNA) stability. The reduced mtDNA copy numbers were associated with aggressive clinicopathological features of HCC. The loss of mtDNA integrity induced by enforced expression of ASPH was accompanied with mitochondrial dysfunction, which was characterized by the aberrant mitochondrial membrane potential, decreased ATP generation and enhanced reactive oxygen species. In contrast, knocking down ASPH by siRNA in HCC cell lines showed the opposite impact on mtDNA integrity and function. Mass spectrometry and co-immunoprecipitation further identified that ASPH interacted with histone H2A member X (H2AX). ASPH overexpression diminished the interaction between H2AX and mitochondrial transcription factor A (mtTFA), an important DNA-binding protein for mtDNA replication, which then reduced the binding of mtTFA to D-loop region. Collectively, our results demonstrate that ASPH overexpression disrupts the mtDNA integrity through H2AX-mtTFA signal, thereby affecting mitochondrial functions in HCC.

Prognostic impact of margin status in liver resections for colorectal metastases after bevacizumab.

BACKGROUND: Margin status with resection of colorectal liver metastasis (CRLM) was an important prognostic factor in the years before the introduction of biological chemotherapy. This study examined outcomes following CRLM resection in patients who received neoadjuvant chemotherapy with or without the monoclonal antiangiogenic antibody bevacizumab. METHODS: Patients who underwent surgery for CRLM at the Johns Hopkins Hospital between 2000 and 2015 were identified from an institutional database. Data regarding surgical margin status, preoperative bevacizumab administration and overall survival (OS) were assessed using multivariable analyses. RESULTS: Of 630 patients who underwent CRLM resection, 417 (66·2 per cent) received neoadjuvant chemotherapy with (214, 34·0 per cent) or without (203, 32·2 per cent) bevacizumab. The remaining 213 (33·8 per cent) did not receive neoadjuvant chemotherapy. Univariable analysis found that positive margins were associated with worse 5-year OS than R0 resection (36·2 versus 54·9 per cent; P = 0·005). After dichotomizing by the receipt of preoperative bevacizumab versus chemotherapy alone, the prognostic value of pathological margin persisted among patients who did not receive preoperative bevacizumab (5-year OS 53·0 versus 37 per cent after R0 versus R1 resection; P = 0·010). OS was not significantly associated with margin status in bevacizumab-treated patients (5-year OS 46·8 versus 33 per cent after R0 versus R1 resection; P = 0·081), in whom 5-year survival was slightly worse (presumably reflecting more advanced disease) than among patients treated with cytotoxic agents alone. Pathological margin status was not significantly associated with 5-year OS in patients with a complete or near-complete response to chemotherapy and bevacizumab (43 versus 30 per cent after R0 versus R1 resection; P = 0·917), but this may be due to a type II error. CONCLUSION: The impact of margin status varied according to the receipt of bevacizumab. Bevacizumab may have a role to play in improving outcomes among patients with more advanced disease.

Nomogram to predict perioperative blood transfusion for hepatopancreaticobiliary and colorectal surgery.

BACKGROUND: Predictive tools assessing risk of transfusion have not been evaluated extensively among patients undergoing complex gastrointestinal surgery. In this study preoperative variables associated with blood transfusion were incorporated into a nomogram to predict transfusion following hepatopancreaticobiliary (HPB) or colorectal surgery. METHODS: A nomogram to predict receipt of perioperative transfusion was developed using a cohort of patients who underwent HPB or colorectal surgery between January 2009 and December 2014. The discriminatory ability of the nomogram was tested using the area under the receiver operating characteristic (ROC) curve and internal validation performed via bootstrap resampling. RESULTS: Among 4961 patients undergoing either a HPB (56·3 per cent) or colorectal (43·7 per cent) resection, a total of 1549 received at least 1 unit of packed red blood cells, giving a perioperative transfusion rate of 31·2 per cent. On multivariable analysis, age 65 years and over (odds ratio (OR) 1·52), race (versus white: black, OR 1·58; Asian, OR 1·86), preoperative haemoglobin 8·0 g/dl or less (versus over 12·0 g/dl: OR 26·79), preoperative international normalized ratio more than 1·2 (OR 2·44), Charlson co-morbidity index score over 3 (OR 1·86) and procedure type (versus colonic surgery: major hepatectomy, OR 1·71; other pancreatectomy, OR 2·12; rectal surgery, OR 1·39; duodenopancreatectomy, OR 2·65) were associated with a significantly higher risk of transfusion and were included in the nomogram. A nomogram was constructed to predict transfusion using these seven variables. Discrimination and calibration of the nomogram revealed good predictive abilities (area under ROC curve 0·756). CONCLUSION: The nomogram predicted blood transfusion in major HPB and colorectal surgery.

Impact of early postoperative platelet count on volumetric liver gain and perioperative outcomes after major liver resection.

BACKGROUND: Although perioperative platelet count has been associated with postoperative morbidity and mortality, its impact on liver regeneration has not been examined directly. This study sought to determine the impact of platelet count on liver regeneration after major liver resection using cross-sectional imaging volumetric assessment. METHODS: Patients who underwent major liver resection between 2004 and 2015 and had available data on immediate postoperative platelet count, as well as preoperative and postoperative CT images, were identified retrospectively. Resected liver volume was subtracted from total liver volume (TLV) to define postoperative remnant liver volume (RLVp ). The liver regeneration index was defined as the relative increase in liver volume within 2 months ((RLV2m - RLVp )/RLVp , where RLV2m is the remnant liver volume around 2 months after surgery). The association between platelet count, liver regeneration and outcomes was assessed. RESULTS: A total of 99 patients met the inclusion criteria. Overall, 25 patients (25 per cent) had a low platelet count (less than 150 × 10(9) /l), whereas 74 had a normal-high platelet count (at least 150 × 10(9) /l). Despite having comparable clinicopathological characteristics and RLVp /TLV at surgery (P = 0·903), the relative increase in liver volume within 2 months was considerably lower in the low-platelet group (3·9 versus 16·5 per cent; P = 0·043). Patients with a low platelet count had an increased risk of postoperative complications (72 versus 38 per cent; P = 0·003), longer hospital stay (8 versus 6 days; P = 0·004) and worse median overall survival (24·5 versus 67·3 months; P = 0·005) than those with a normal or high platelet count. CONCLUSION: After major liver resection, a low postoperative platelet count was associated with inhibited liver regeneration, as well as worse short- and long-term outcomes. Immediate postoperative platelet count may be an early indicator to identify patients at increased risk of worse outcomes.

Patient outcomes and provider perceptions following implementation of a standardized perioperative care pathway for open liver resection.

BACKGROUND: Enhanced recovery after surgery (ERAS) pathways have been associated with improved perioperative outcomes following several surgical procedures. Less is known, however, regarding their use following hepatic surgery. METHODS: An evidence-based, standardized perioperative care pathway was developed and implemented prospectively among patients undergoing open liver surgery between 1 January 2014 and 31 July 2015. Perioperative outcomes, including length of hospital stay, postoperative complications and healthcare costs, were compared between groups of patients who had surgery before and after introduction of the ERAS pathway. Provider perceptions regarding the perioperative pathway were assessed using an online questionnaire. RESULTS: There were no differences in patient or disease characteristics between pre-ERAS (42 patients) and post-ERAS (75) groups. Although mean pain scores were comparable between the two groups, patients treated within the ERAS pathway had a marked reduction in opioid use on the first 3 days after surgery compared with those treated before introduction of the pathway (all P < 0·001). Duration of hospital stay was shorter in the post-ERAS group (median 5 (i.q.r. 4-7) days versus 6 (5-7) days in the pre-ERAS group; P = 0·037) and there was a lower incidence of postoperative complications (1 versus 10 per cent; P = 0·036). Implementation of the ERAS pathway was associated with a 40·7 per cent decrease in laboratory costs (-US $333; -€306, exchange rate 4 January 2016) and a 21·5 per cent reduction in medical supply costs (-US $394; -€362) per patient. Although 91·0 per cent of providers endorsed the ERAS pathway, 33·8 per cent identified provider aversion to a standardized protocol as the greatest hurdle to implementation. CONCLUSION: The introduction of a multimodal ERAS programme following open liver surgery was associated with a reduction in opioid use, shorter hospital stay and decreased hospital costs. ERAS was endorsed by an overwhelming majority of providers.

Clinical and morphometric parameters of frailty for prediction of mortality following hepatopancreaticobiliary surgery in the elderly.

BACKGROUND: Although frailty is a known determinant of poor postoperative outcomes, it can be difficult to identify in patients before surgery. The authors sought to develop a preoperative frailty risk model to predict mortality among patients aged 65 years or more. METHODS: Clinical and morphometric data including total psoas area (TPA), total psoas volume (TPV) and psoas density (Hounsfield unit average calculation, HUAC) were collected for patients undergoing hepatopancreaticobiliary (HPB) surgery between 2012 and 2014. Multivariable Cox proportional hazards regression was used to identify preoperative risk factors associated with 1-year mortality. RESULTS: The median age of the 518 patients included in the study was 72 (i.q.r. 68-76) years; 55·6 per cent of patients were men, and half of the cohort had multiple co-morbidities (Charlson co-morbidity index (CCI) of 4 or more, 55·6 per cent). TPA cut-offs to define sarcopenia were 552·7 mm(2) /m(2) in women and 702·9 mm(2) /m(2) in men; cut-offs for TPV were 18·2 cm(3) /m(2) in women and 26·2 cm(3) /m(2) in men, whereas HUAC cut-offs were 31·1 HU in women and 33·3 HU in men. The overall 1-year mortality rate was 14·1 per cent. In multivariable analysis, risk factors associated with 1-year mortality included CCI of 4 or above (hazard ratio (HR) 2·91, 95 per cent c.i. 1·47 to 5·77; P = 0·002), malignant disease (HR 3·94, 1·17 to 13·30; P = 0·027) and sarcopenia by HUAC (HR 1·85, 1·10 to 3·10; P = 0·021). A weighted 25-point composite score was developed to stratify patients at risk of 1-year postoperative mortality. The 1-year mortality rate was noted to be 2·5 per cent among patients scoring 0-10 (low risk), 17·3 per cent among patients scoring 11-20 (intermediate risk) and 29·2 per cent among those scoring between 21 and 25 (high risk) (P < 0·001). CONCLUSION: Clinical and morphometric measures of frailty accurately predict the risk of 1-year mortality following HPB surgery in elderly patients, and can be used to risk-stratify patients appropriately.

A validated, risk assessment tool for predicting readmission after open ventral hernia repair.

BACKGROUND/PURPOSE: To present a validated model that reliably predicts unplanned readmission after open ventral hernia repair (open-VHR). STUDY DESIGN: A total of 17,789 open-VHR patients were identified using the 2011-2012 ACS-NSQIP databases. This cohort was subdivided into 70 and 30% random testing and validation samples, respectively. Thirty-day unplanned readmission was defined as unexpected readmission for a postoperative occurrence related to the open-VHR procedure. Independent predictors of 30-day unplanned readmission were identified using multivariable logistic regression on the testing sample (n = 12,452 patients). Subsequently, the predictors were weighted according to ß-coefficients to generate an integer-based Clinical Risk Score (CRS) predictive of readmission, which was validated using receiver operating characteristics (ROC) analysis of the validation sample (n = 5337 patients). RESULTS: The rate of 30-day unplanned readmission was 4.7%. Independent risk factors included inpatient status at time of open-VHR, operation time, enterolysis, underweight, diabetes, preoperative anemia, length of stay, chronic obstructive pulmonary disease, history of bleeding disorders, hernia with gangrene, and panniculectomy (all P < 0.05). ROC analysis of the validation cohort rendered an area under the curve of 0.71, which demonstrates the accuracy of this prediction model. Predicted incidence within each 5 risk strata was statistically similar to the observed incidence in the validation sample (P = 0.18), further highlighting the accuracy of this model. CONCLUSION: We present a validated risk stratification tool for unplanned readmissions following open-VHR. Future studies should determine if implementation of our CRS optimizes safety and reduces readmission rates in open-VHR patients.

Neutrophil-lymphocyte and platelet-lymphocyte ratio in patients after resection for hepato-pancreatico-biliary malignancies.

BACKGROUND AND OBJECTIVES: We sought to determine whether Neutrophil-lymphocyte ratio (NLR) or platelet-lymphocyte ratio (PLR) were associated with outcomes of patients undergoing surgery for a hepatopancreatico-biliary (HPB) malignancy. METHOD: Between 2000 and 2013, 452 patients who underwent an HPB procedure for a malignant indication were identified. Clinicopathological characteristics, NLR, and PLR, as well as short- and long-term outcomes were analyzed. High NLR and PLR were classified using a cut-off value of 5 and 190, respectively, based on ROC curve analysis. RESULTS: Patients with low versus high NLR and PLR had similar baseline characteristics with regard to performance status and tumor stage (all P > 0.05). Elevated PLR (HR = 1.40) tends to be association with shorter recurrence-free survival (RFS) (P = 0.05), whereas NLR was not a predictor of shorter RFS. Differently, both elevated NLR (HR = 1.94) and PLR (HR = 1.79) were associated with worse overall survival (OS) (both P < 0.05). Patients with NLR ≥5 and those with PLR ≥190 had a significantly shorter OS compared to patients with NLR <5 and PLR <190, respectively (log-rank test, both P < 0.05). Moreover, patients who had both NLR and PLR elevated had worse OS compared to patients with either one or none inflammatory markers elevated (log-rank P = 0.02). CONCLUSION: Elevated NLR and PLR were predictors of worse long-term outcome among patients with HPB malignancy undergoing resection.