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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Synchronous colorectal liver metastasis: a network meta-analysis review comparing classical, combined, and liver-first surgical strategies.

BACKGROUND: In recent years, the management of synchronous colorectal liver metastasis has changed significantly. Alternative surgical strategies to the classical colorectal-first approach have been proposed. These include the liver-first and combined resections approaches. The objectives of this review were to compare the short- and long-term outcomes for all three approaches. METHODS: A systematic review of comparative studies was performed. Evaluated endpoints included surgical outcomes (5-year overall survival, 30-day mortality, and post-operative complications). Pair-wise and network meta-analysis (NMA) were performed to compare survival outcomes. RESULTS: Eighteen studies were included in this review, reporting on 3,605 patients. NMA and pair-wise meta-analysis of the 5-year overall survival did not show significant difference between the three surgical approaches: combined versus colorectal-first, mean odds ratio (OR) 1.02 (95% CI 0.8-1.28, P = 0.93); liver-first versus colorectal-first, mean OR 0.81 (95% CI 0.53-1.26, P = 0.37); liver-first versus combined, mean OR 0.80 (95% CI 0.52-1.24, P = 0.41). In addition NMA of the 30-day mortality among the three approaches also did not observe statistical difference. Analysis of variance showed that mean post-operative complications of all approaches were comparable (P = 0.51). CONCLUSION: There are considerable differences in the peri-operative management of synchronous CLM patients. This meta-analysis demonstrated no clear statistical surgical outcome or survival advantage towards any of the three approaches.

Variation in triggers and use of perioperative blood transfusion in major gastrointestinal surgery.

BACKGROUND: The decision to perform intraoperative blood transfusion is subject to a variety of clinical and laboratory factors. This study examined variation in haemoglobin (Hb) triggers and overall utilization of intraoperative blood transfusion, as well the impact of transfusion on perioperative outcomes. METHODS: The study included all patients who underwent pancreatic, hepatic or colorectal resection between 2010 and 2013 at Johns Hopkins Hospital, Baltimore, Maryland. Data on Hb levels that triggered an intraoperative or postoperative transfusion and overall perioperative blood utilization were obtained and analysed. RESULTS: Intraoperative transfusion was employed in 437 (15·6 per cent) of the 2806 patients identified. Older patients (odds ratio (OR) 1·68), patients with multiple co-morbidities (Charlson co-morbidity score 4 or above; OR 1·66) and those with a lower preoperative Hb level (OR 4·95) were at increased risk of intraoperative blood transfusion (all P < 0·001). The Hb level employed to trigger transfusion varied by sex, race and service (all P < 0·001). A total of 105 patients (24·0 per cent of patients transfused) had an intraoperative transfusion with a liberal Hb trigger (10 g/dl or more); the majority of these patients (78; 74·3 per cent) did not require any additional postoperative transfusion. Patients who received an intraoperative transfusion were at greater risk of perioperative complications (OR 1·55; P = 0·002), although patients transfused with a restrictive Hb trigger (less than 10 g/dl) showed no increased risk of perioperative morbidity compared with those transfused with a liberal Hb trigger (OR 1·22; P = 0·514). CONCLUSION: Use of perioperative blood transfusion varies among surgeons and type of operation. Nearly one in four patients received a blood transfusion with a liberal intraoperative transfusion Hb trigger of 10 g/dl or more. Intraoperative blood transfusion was associated with higher risk of perioperative morbidity.

Failure to rescue as a source of variation in hospital mortality after hepatic surgery.

BACKGROUND: The mechanisms that underlie the association between high surgical volume and improved outcomes remain uncertain. This study examined the impact of complications and failure to rescue patients from these complications on mortality following hepatic resection. METHODS: The Nationwide Inpatient Sample was used to identify patients who had liver surgery between 2000 and 2010. Hospital volume was stratified into tertiles (low, intermediate and high). Rates of major complications, failure to rescue and mortality following hepatic surgery were compared. RESULTS: Some 9874 patients were identified. The major complication rate was 19.6 per cent in low-volume, 19.3 per cent in intermediate-volume and 16.6 per cent in high-volume hospitals (P < 0.001). Most common major complications included respiratory insufficiency or failure (8.8 per cent), acute renal failure (4.2 per cent) and gastrointestinal bleeding (3.9 per cent), with each of these complications being less common in high-volume hospitals (P < 0.050). The incidence of major morbidity following hepatectomy remained the same over the past decade, but failure to rescue patients from these complications decreased (P = 0.011). The overall inpatient mortality rate following liver surgery was 3.2 per cent (3.8, 3.6 and 2.3 per cent for low-, intermediate- and high-volume hospitals respectively; P < 0.001). The rate of failure to rescue (death after a complication) was higher at low- and intermediate-volume hospitals (16.8 and 16.1 per cent respectively) compared with high-volume hospitals (11.8 per cent) (P = 0.032). After accounting for patient and hospital characteristics, patients treated at low-volume hospitals who had a complication were 40 per cent more likely to die than patients with a complication in a high-volume hospital (odds ratio 1.40, 95 per cent confidence interval 1.02 to 1.93). CONCLUSION: The risk of death following hepatic surgery is lower at high-volume hospitals. The reduction in mortality appears to be the result of both lower complication rates and a better ability in high-volume hospitals to rescue patients with major complications.

Surgical management of disappearing colorectal liver metastases.

BACKGROUND: Owing to expanded surgical indications for colorectal liver metastasis (CRLM) and improved systemic therapy, hepatic surgeons are increasingly faced with the problem of disappearing (no longer visible on imaging) liver metastasis (DLM). METHODS: A review of relevant studies was performed. Studies that reported on DLM associated with preoperative chemotherapy for CRLM were identified, and data were synthesized and tabulated. The PubMed database was searched for relevant articles published between January 2000 and December 2012. RESULTS: A complete response on imaging does not necessarily equate with a complete clinical or pathological response. Rather, residual macroscopic disease is found in about 25-45 per cent of patients at the time of operation. Even among patients with a complete pathological response, long-term remission occurs in only 20-50 per cent of those treated with systemic therapy. A durable response of DLM is more common following the use of hepatic artery infusion therapy. CONCLUSION: Liver resection should include all original sites of disease if possible.