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While minimally invasive liver resections (MILR) have demonstrated advantages in improved post-operative recovery, widespread adoption is hampered by inherent technical difficulties. Our study attempts to analyze the role of anthropometric measures in MILR-related outcomes.Between 2012 and 2020, 676 consecutive patients underwent MILR at the Singapore General Hospital of which 565 met study criteria and were included. Patients were stratified based on Body Mass Index (BMI) as well as Standardized Liver Volumes (SLV). Associations between BMI and SLV to selected peri-operative outcomes were analyzed using restricted cubic splines.A BMI of ≥ 29 was associated with increase in blood loss [Mean difference (MD) 69 mls, 95% CI 2 to 137] as well as operative conversions [Relative Risk (RR) 1.63, 95% CI 1.02 to 2.62] among patients undergoing MILR while a SLV of 1600 cc or higher was associated with an increase in blood loss (MD 30 mls, 95% CI 10 to 49). In addition, a BMI of ≤ 20 was associated with an increased risk of major complications (RR 2.25, 95% 1.16 to 4.35). The magnitude of differences observed in these findings increased with each unit change in BMI and SLV.Both BMI and SLV were useful anthropometric measures in predicting peri-operative outcomes in MILR and may be considered for incorporation in future difficulty scoring systems for MILR.

The majority of evidence with regards to minimally invasive liver resection (MILR) favors its application in minor hepatectomies. We conducted a propensity score-matched (PSM) analysis to determine its feasibility and safety in major hepatectomies (MIMH) for liver malignancies.Retrospective review of 130 patients who underwent MIMH and 490 patients who underwent open major hepatectomy (OMH) for malignant pathologies was performed. PSM in a 1:1 ratio identified two groups of patients with similar baseline clinicopathological characteristics. Perioperative outcomes were then compared. Major hepatectomies included traditional major (3 segments) and technical major hepatectomies (right anterior and right posterior sectionectomies).Both cohorts were well-matched for baseline characteristics after PSM. Of 130 MIMH cases, there were 12 conversions to open. Comparison of perioperative outcomes demonstrated a significant association of MIMH with longer operation time and more frequent application of Pringle's maneuver (PM), but decreased postoperative stay. These results were consistent on a subgroup analysis that only included patients undergoing traditional major hepatectomies. A second subgroup analysis restricted to cirrhotic patients demonstrated that while perioperative outcomes were equivalent, MIMH was similarly associated with a longer operative time. Subset analyses of resections performed after 2015 demonstrated that MIMH was additionally associated with a lower postoperative morbidity compared to OMH.Comparison of perioperative and short-term oncological outcomes between MIMH and OMH for malignancies demonstrated that MIMH is feasible and safe. It is associated with a shorter hospital stay at the expense of a longer operation time compared to OMH.

Minimally invasive distal pancreatectomy (MIDP) is being adopted increasingly worldwide. This study aimed to compare the short-term outcomes of patients who underwent MIDP versus open distal pancreatectomy (ODP). A retrospective review of all patients who underwent a DP in our institution between 2005 and 2019 was performed. Propensity score matching based on relevant baseline factors was used to match patients in the ODP and MIDP groups in a 1:1 manner. Outcomes reported include operative duration, blood loss, postoperative length of stay, morbidity, mortality, postoperative pancreatic fistula rates, reoperation and readmission. In total, 444 patients were included in this study. Of 122 MIDP patients, 112 (91.8%) could be matched. After matching, the median operating time for MIDP was significantly longer than ODP [260 min (200–346.3) vs 180 (135–232.5), p

Background DNA methylation in blood may reflect adverse exposures accumulated over the lifetime and could therefore provide potential improvements in the prediction of cancer risk. A substantial body of research has shown associations between epigenetic aging and risk of disease, including cancer. Here we aimed to study epigenetic measures of aging and lifestyle-related factors in association with risk of breast cancer. Methods Using data from four prospective case–control studies nested in three cohorts of European ancestry participants, including a total of 1,655 breast cancer cases, we calculated three methylation-based measures of lifestyle factors (body mass index [BMI], tobacco smoking and alcohol consumption) and seven measures of epigenetic aging (Horvath-based, Hannum-based, PhenoAge and GrimAge). All measures were regression-adjusted for their respective risk factors and expressed per standard deviation (SD). Odds ratios (OR) and 95% confidence intervals (CI) were calculated using conditional or unconditional logistic regression and pooled using fixed-effects meta-analysis. Subgroup analyses were conducted by age at blood draw, time from blood sample to diagnosis, oestrogen receptor-positivity status and tumour stage. Results None of the measures of epigenetic aging were associated with risk of breast cancer in the pooled analysis: Horvath ‘age acceleration’ (AA): OR per SD = 1.02, 95%CI: 0.95–1.10; AA-Hannum: OR = 1.03, 95%CI:0.95–1.12; PhenoAge: OR = 1.01, 95%CI: 0.94–1.09 and GrimAge: OR = 1.03, 95%CI: 0.94–1.12, in models adjusting for white blood cell proportions, body mass index, smoking and alcohol consumption. The BMI-adjusted predictor of BMI was associated with breast cancer risk, OR per SD = 1.09, 95%CI: 1.01–1.17. The results for the alcohol and smoking methylation-based predictors were consistent with a null association. Risk did not appear to substantially vary by age at blood draw, time to diagnosis or tumour characteristics. Conclusion We found no evidence that methylation-based measures of aging, smoking or alcohol consumption were associated with risk of breast cancer. A methylation-based marker of BMI was associated with risk and may provide insights into the underlying associations between BMI and breast cancer.

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver with high rates of recurrence post-resection. Repeat hepatectomy (RH) and radiofrequency ablation (RFA) are the mainstays for managing recurrent HCC following initial curative resection. This retrospective study aims to determine the average treatment effect of RH and RFA in patients with recurrent HCC. From 2000 to 2016, a total of 219 consecutive patients with recurrent HCC who underwent either RH or RFA were included in the study. The analysis was performed using inverse probability of treatment weighting (IPTW), and propensity score-matched (PSM) methods. The minor and major post-operative morbidity after propensity score-matched analysis for the RH group was 30.0% and 6.0%, respectively, and 19.2% and 0.0% (p = 0.1006), respectively, for the RFA group. After propensity score matching, the median OS for RH and RFA was 85.5 (IQR, 33.5–not reached) and 53.3 months (IQR, 27.5–not reached) (p = 0.8474), respectively. There was no significant difference in 90-day mortality between both groups (p = 0.1287). RH showed improved long-term overall survival over RFA at the third [71.3% versus 65.7% (p = 0.0432)], fifth [59.9% versus 45.4% (p = 0.0271)] and tenth [35.4% versus 32.2% (p = 0.0132)] year follow-up, respectively. Median time to recurrence was 11.1 (IQR, 5.0–33.2) and 28.0 months (IQR, 9.1–not reached) (p = 0.0225) for the RFA and RH group, respectively. RH confers a late survival benefit compared with RFA for patients with recurrent HCC despite a higher morbidity rate.

The presence of previous abdominal surgery (PAS) has traditionally been considered to add difficulty to and increase risk of complications of laparoscopic procedures. This study aims to analyse the impact of non-liver-related PAS on the difficulty of minimally invasive liver resections (MILRs). After exclusion of patients with concomitant major surgical procedures as well as previous liver resections, 515 consecutive patients undergoing MILR in Singapore General Hospital from 2006 to 2019 were analysed, consisting of 161 MILR in patients with previous abdominal surgery (WPAS) and 354 MILR in patients without previous abdominal surgery (WOPAS). Propensity score-matched (PSM) comparison was performed between WPAS and WOPAS groups. In addition, subgroup analysis was made comparing previous upper or lower abdominal surgery and open versus minimally invasive approach of PAS. Outcomes measured include those associated with operative difficulty such as open conversion rates, operative time, blood loss, as well as morbidity and mortality rates. MILR outcomes in patients WPAS are not inferior to those WOPAS. Overall open conversion rate was 8.2%, higher in patients WOPAS compared to patients WPAS (11.9% versus 3.5%, p = 0.015). Operating time (p = 0.942), blood loss (p = 0.063), intraoperative blood transfusion (p = 0.750), length of hospital stay (p = 0.206), morbidity (p = 0.217) and 30- and 90-day mortality (p = 1 & p = 0.367) were comparable between the two groups and subgroup analysis. Outcomes of MILR in patients with previous non-liver-related abdominal surgery are not inferior to patients without previous abdominal surgery.

The management of post-liver resection recurrence is often the life-limiting factor in HCC treatment. While much has been published on intrahepatic recurrence and lung metastasis, there is a relative lack of data on intraabdominal extrahepatic metastasis (EHM). We sought to evaluate the outcomes of patients post-resection of intraabdominal EHM and assess preoperative factors predictive of early recurrence post-metastasectomy. We performed a retrospective review of 25 consecutive patients who underwent metastasectomy for intraabdominal EHM from 2003 to 2016 at our institution. Of the 25 cases of EHM, 16 were in the peritoneum, 3 in the adrenal glands, 3 in the large bowel, 1 in the spleen, 1 in the pancreas and 1 in the omentum. Median overall survival was 27 months (IQR 15–89 months). Twenty-one patients (84%) developed recurrence post-metastasectomy of EHM of which 12 patients experienced early recurrence within 12 months. The median time to recurrence post-metastasectomy was 11(IQR 15.5) months. Multivariate analysis demonstrated both hepatitis B (11 (91.6%) versus 4 (44.4%), p = 0.00) status and high tumour grade (8 (66.6%) versus 3 (25%), p = 0.004) to be significant independent predictors of early recurrence. Patients who experienced early recurrence had a significantly shorter median overall survival (18 months (95% CI 12.9–23.0)) compared to those who did not (89 months (95% CI 24.8–153.1), p = 0.004). Patients with EHM who underwent metastasectomy had a median overall survival of 27 months. Hepatitis B positivity and high primary tumour grade were preoperative predictors of futile surgery. All 7 patients who had both hepatitis B and high tumour grade experienced early recurrence post-metastasectomy.

The impact of liver cirrhosis on the difficulty of minimal invasive liver resection (MILR) remains controversial and current difficulty scoring systems do not take in to account the presence of cirrhosis as a significant factor in determining the difficulty of MILR. We hypothesized that the difficulty of MILR is affected by the presence of cirrhosis. Hence, we performed a 1:1 matched-controlled study comparing the outcomes between patients undergoing MILR with and without cirrhosis including the Iwate system and Institut Mutualiste Montsouris (IMM) system in the matching process. Between 2006 and 2019, 598 consecutive patients underwent MILR of which 536 met the study inclusion criteria. There were 148 patients with cirrhosis and 388 non-cirrhotics. One-to-one coarsened exact matching identified approximately exact matches between 100 cirrhotic patients and 100 non-cirrhotic patients. Comparison between MILR patients with cirrhosis and non-cirrhosis in the entire cohort demonstrated that patients with cirrhosis were associated with a significantly increased open conversion rate, transfusion rate, need for Pringles maneuver, postoperative, stay, postoperative morbidity and postoperative 90-day mortality. After 1:1 coarsened exact matching, MILR with cirrhosis were significantly associated with an increased open conversion rate (15% vs 6%, p = 0.03), operation time (261 vs 238 min, p

Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) are the most common primary liver cancers. With the increasing incidence of ICC over the past two decades in Asia, it is essential to differentiate between HCC and ICC. However, ICC may mimic the radiological appearance of HCC on computed tomography scans (CT) and magnetic resonance imaging (MRI), leading to misdiagnosis of ICC. The objective of this study is to evaluate and describe the association of specific pre-operative imaging characteristics (arterial enhancement, portal venous washout) in patients with histologically proven resected ICC in our centre. Data on patients with histology-proven ICC and mixed hepatocellular-cholangiocarcinomas (HCC-CC) who had undergone surgical resection at Singapore General Hospital (SGH) were identified from a prospectively maintained database. Pre-operative cross-sectional imaging reports were analysed. Ninety-one patients underwent resection between 1 January 2000 and 31 December 2016. Among those with no risk factors for HCC, a significant percentage of patients with ICC (24.3%) show imaging characteristics of both arterial phase hyperenhancement and non-peripheral venous washout. Among patients with risk factors for HCC, between 20.0 and 33.3% of patients with pure ICC fulfilled the imaging criteria for HCC, and this proportion was generally even higher in the mixed HCC-CC group. A significant proportion of patients with pure ICC showed pre-operative imaging characteristics which fulfilled the diagnostic criteria for HCC. The differential of ICC should be borne in mind in populations where both malignancies are endemic.

Pancreatic neuroendocrine neoplasms (PNENs) are increasingly prevalent with modern imaging, and surgical excision remains mainstay of treatment. This study aims to perform a propensity-score-matched (PSM) comparison of perioperative and oncologic outcomes following minimally invasive pancreatectomy (MIP) versus open pancreatectomy (OP) for PNEN. A retrospective review was performed on patients who underwent curative-intent surgery for PNEN at Singapore General Hospital from 1997 to 2018. A 1:1 PSM was performed between MIP and OP, after which both groups were balanced for baseline variables. We studied 134 patients who underwent surgery (36 MIP and 98 OP) for PNEN. Propensity-score-matched comparison between 35 MIP and 35 OP patients revealed that the MIP group had a longer operating time (MD = 75.0, 95% CI 15.2 to 134.8, P = 0.015), lower intraoperative blood loss (MD = − 400.0, 95% CI − 630.5 to − 169.5, P = 0.001), shorter median postoperative stay (MD = − 1.0, 95% CI − 1.9 to − 0.1, P = 0.029) and shorter median time to diet (MD = − 1.0, 95% CI − 1.9 to − 0.1, P = 0.039). There were no differences between both groups for short-term adverse outcomes and oncologic clearance. Overall survival (HR = 0.84, 95% CI 0.28 to 2.51, P = 0.761) and disease-free survival (HR = 0.57, 95% CI 0.20 to 1.64, P = 0.296) were comparable. MIP is a safe and feasible approach for PNEN and is associated with a lower intraoperative blood loss, decreased postoperative stay and time to oral intake, at the expense of a longer operative time compared to OP.

Repeat liver resection (RLR) for recurrent HCC (rHCC) is a widely accepted treatment modality. However, early recurrence rate is high, frequently resulting in futile resection. We performed this study to evaluate preoperative factors, including the value of inflammatory indices, in predicting early (1 year) recurrence in patients who underwent RLR for rHCC. This may help clinicians better select patients for RLR, while excluding cases in which RLR for rHCC would likely be futile.This is a retrospective study of 80 patients where 90 operative cases of RLR and 84 cases of early recurrence (1 year) post-RLR were evaluated. Preoperative predictors of early recurrence and overall survival (OS) were assessed.There were 31 (34.4%) early recurrences with a 5-year OS of 38.9%. Elevated platelet-to-lymphocyte ratio (PLR)103.6 was a significant independent preoperative predictor of both early recurrence, relative risk (RR) 4.284 (P = 0.001) and OS, RR 2.139 (P = 0.027), while alphafetoprotein (AFP) ≥ 200 was a significant independent preoperative predictor of early recurrence only, RR 11.655 (P = 0.030). Patients were followed-up at a median of 14.3 months with 54.8% developing intrahepatic recurrences and 19.4% developing extrahepatic recurrences.Both, elevated PLR and AFP ≥ 200 were independent predictors of early (1 year) recurrence after RLR for rHCC, while only an elevated PLR was an independent preoperative prognosticators of overall survival. Indication for RLR should be carefully discussed in patients with relapsed HCC with an elevated PLR, due to the potential of early recurrence and poor overall survival.

OBJECTIVE(S): The technical complexity of laparoscopic liver resection (LLR) poses unique challenges distinct from open surgery. An objective scoring system was developed that preoperatively quantifies the difficulty of LRR to help guide surgeon decision-making regarding the feasibility and safety of minimally-invasive approaches. The aim of this multi-institutional study was to externally validate this scoring system. METHODS: Patients who underwent LLR at 2 institutions were reviewed. LLR difficulty score (LDS) was calculated based on patient, tumor, and anatomic characteristics by 2 independent, blinded hepatobiliary surgeons. Surrogates of case complexity (e.g. conversion rate, operative time) were used for validation of this index. RESULTS: From 2006-2016, 444 LLR were scored as low (n=94), intermediate (n=98), and high difficulty (n=152) with respective conversion rates of 5.3%, 15.7%, and 25%. Cases of higher LDS correlated with larger mean blood loss (203 ml vs. 331 ml vs. 635 ml). Mean operative and Pringle maneuver used were associated with increasing LDS (155 min vs. 202 min vs. 315 min and 14.4% vs. 29.7% vs. 45.1% respectively). These operative surrogates of difficulty correlated significantly with the LDS. (all p

Several studies published mainly from pioneers and early adopters have documented the evolution of minimally invasive hepatectomy (MIH). However, questions remain if these reported experiences are applicable and reproducible today. This study examines the changing trends, safety, and outcomes associated with the adoption of MIH based on a contemporary single-institution experience. This is a retrospective review of 400 consecutive patients who underwent MIH between 2006 and 2017 of which 360 cases (90%) were performed since 2012. To determine the evolution of MIH, the study population was stratified into four equal groups of 100 patients. Analyses were also performed of predictive factors and outcomes of open conversion. Four hundred patients underwent MIH of which 379 (94.8%) were totally laparoscopic/robotic. Eighty-eight (22.0%) patients underwent major hepatectomy and 160 (40.0%) had resection of tumors located in the posterosuperior segments. There were 38 (9.5%) open conversions. Comparison across the four groups demonstrated that patients were older, had higher ASA score, and had increased frequency of previous abdominal surgery and repeat liver resections. There was also an increase in the proportion of patients who underwent totally laparoscopic/robotic surgery, major liver resection, resection of ≥ 3 segments, and multiple resections. Comparison of outcomes demonstrated that there was a significant decrease in open conversion rate, longer operation time, and increased use of Pringles maneuver. The presence of cirrhosis and institution experience (1st 100 cases) were independent predictors of open conversion. Patients who required open conversion had significantly increased operation time, blood loss, blood transfusion rate, morbidity, and mortality. The case volume of MIH performed increased rapidly at our institution over time. Although the indications of MIH expanded to include higher risk patients and more complex hepatectomies, there was a decrease in open conversion rate and no change in other perioperative outcomes.

Most studies analyzing the learning experience of laparoscopic liver resection (LLR) focused on the experience of one or two expert pioneering surgeons. This study aims to critically analyze the impact of individual surgeon experience on the outcomes of LLR based on the contemporary collective experiences of multiple surgeons at single institution.Retrospective review of 324 consecutive LLR from 2006 to 2016. The cases were performed by 10 surgeons over various time periods. Four surgeons had individual experience with20 cases, four surgeons with 20-30 cases, and two surgeons with90 cases. The cohort was divided into two groups: comparing a surgeon's experience between the first 20, 30, 40, and 50 cases with patients treated thereafter. Similarly, we performed subset analyses for anterolateral lesions, posterosuperior lesions, and major hepatectomies.As individual surgeons gained increasing experience, this was significantly associated with older patients being operated, decreased hand-assistance, larger tumor size, increased liver resections, increased major resections, and increased resections of tumors located at the posterosuperior segments. This resulted in significantly longer operation time and increased use of Pringle maneuver but no difference in other outcomes. Analysis of LLR for tumors in the posterosuperior segments demonstrated that there was a significant decrease in conversion rates after a surgeon had experience with 20 LLR. For major hepatectomies, there was a significant decrease in morbidity, mortality, and length of stay after acquiring experience with 20 LLR.LLR can be safely adopted today especially for lesions in the anterolateral segments. LLR for lesions in the difficult posterosuperior segments and major hepatectomies especially in cirrhosis should only be attempted by surgeons who have acquired a minimum experience with 20 LLR.

Background Hepatocellular carcinoma is the second most deadly cancer with late presentation and limited treatment options, highlighting an urgent need to better understand HCC to facilitate the identification of early-stage biomarkers and uncover therapeutic targets for the development of novel therapies for HCC. Methods Deep transcriptome sequencing of tumor and paired non-tumor liver tissues was performed to comprehensively evaluate the profiles of both the host and HBV transcripts in HCC patients. Differential gene expression patterns and the dys-regulated genes associated with clinical outcomes were analyzed. Somatic mutations were identified from the sequencing data and the deleterious mutations were predicted. Lastly, human-HBV chimeric transcripts were identified, and their distribution, potential function and expression association were analyzed. Results Expression profiling identified the significantly upregulated TP73 as a nodal molecule modulating expression of apoptotic genes. Approximately 2.5% of dysregulated genes significantly correlated with HCC clinical characteristics. Of the 110 identified genes, those involved in post-translational modification, cell division and/or transcriptional regulation were upregulated, while those involved in redox reactions were downregulated in tumors of patients with poor prognosis. Mutation signature analysis identified that somatic mutations in HCC tumors were mainly non-synonymous, frequently affecting genes in the micro-environment and cancer pathways. Recurrent mutations occur mainly in ribosomal genes. The most frequently mutated genes were generally associated with a poorer clinical prognosis. Lastly, transcriptome sequencing suggest that HBV replication in the tumors of HCC patients is rare. HBV-human fusion transcripts are a common observation, with favored HBV and host insertion sites being the HBx C-terminus and gene introns (in tumors) and introns/intergenic-regions (in non-tumors), respectively. HBV-fused genes in tumors were mainly involved in RNA binding while those in non-tumors tissues varied widely. These observations suggest that while HBV may integrate randomly during chronic infection, selective expression of functional chimeric transcripts may occur during tumorigenesis. Conclusions Transcriptome sequencing of HCC patients reveals key cancer molecules and clinically relevant pathways deregulated/mutated in HCC patients and suggests that while HBV may integrate randomly during chronic infection, selective expression of functional chimeric transcripts likely occur during the process of tumorigenesis.

Laparoscopic wedge resection (LWR) for small gastric gastrointestinal stromal tumors (GIST) is now widely accepted, but its application for large GISTs remains controversial. This study aims to evaluate the feasibility and safety of LWR for suspected large (≥5 cm) gastric GISTs.Retrospective review of 82 consecutive patients who underwent attempted LWR for suspected gastric GIST. LWR for large (≥5 cm) (n = 23) tumors was compared with LWR for small (5 cm) tumors (n = 59). The 23 patients with LWR for large tumors were also compared to 36 consecutive patients who underwent open wedge resection (OWR) for large tumors.Comparison between patients who underwent LWR for large versus small tumors demonstrated that resection of large tumors was associated with a longer operating time. There was no difference in other perioperative outcomes, and oncological outcomes such as frequency of close margins (≤1 mm) and recurrence-free survival. Comparison between patients who underwent LWR versus OWR for large tumors showed that LWR was associated with decreased median time to fluid or solid diet, shorter postoperative stay but longer operating times. There was no difference in oncological outcomes.LWR for suspected large gastric GIST is feasible and safe. It is associated with similar short-term outcomes with LWR for small tumors and favorable short-term outcomes over OWR for large tumors without compromising on oncological outcomes.

To validate the Memorial Sloan Kettering Cancer Center (MSKCC) prognostic nomogram in a single-institution cohort of patients with gastrointestinal stromal tumors (GISTs), and to compare its predictive accuracy against other established risk classification systems, including the National Institutes of Health (NIH), Armed Forces Institute of Pathology (AFIP), and Joensuu criteria. We retrospectively reviewed 289 patients who underwent surgical resection for primary localized GISTs without adjuvant imatinib therapy and compared the actuarial recurrence-free survival (RFS) with the predicted RFS. Tumors >5 cm in size, with high mitotic index, and which had ruptured were significantly associated with recurrent disease. The 2-year RFS was 77.2 % [95 % confidence interval (CI) 71.6–81.8], and the 5-year RFS was 67.9 % (95 % CI 61.7–73.4). The concordance probability of the nomogram of 2-year RFS was 0.71 (SE 0.02), and 5-year RFS was 0.71 (SE 0.19). The 2-year and 5-year MSKCC nomogram probability calculations and the AFIP criteria gave a better estimation of RFS compared to the NIH (p

Circulating tumour DNA (ctDNA) has the potential to be a specific biomarker for the monitoring of tumours in patients with colorectal cancer (CRC). Here, our aim was to develop a personalised surveillance strategy to monitor the clinical course of CRC after surgery. We developed patient-specific ctDNA assays based on multiplexed detection of somatic mutations identified from patient primary tumours, and applied them to detect ctDNA in 44 CRC patients, analysing a total of 260 plasma samples. We found that ctDNA detection correlated with clinical events – it is detectable in pre-operative but not post-operative plasma, and also in patients with recurrent CRC. We also detected ctDNA in 11 out of 15 cases at or before clinical or radiological recurrence of CRC, indicating the potential of our assay for early detection of metastasis. We further present data from a patient with multiple primary cancers to demonstrate the specificity of our assays to distinguish between CRC recurrence and a second primary cancer. Our approach can complement current methods for surveillance of CRC by adding an individualised biological component, allowing us not only to point to the presence of residual or recurrent disease, but also attribute it to the original cancer.

Laparoscopic liver resection has been increasingly adopted worldwide as a result of the rapid advancement in surgical techniques and equipment. This study aims to determine the factors associated with and outcomes of open conversion after laparoscopic minor hepatectomy (LMH) based on a single center multi-surgeon experience.This is a retrospective review of the first 147 consecutive LMH performed between 2006 and April 2014 at a single institution. Data on patient demographics, pathology results, perioperative outcomes, and operative results were collected. Factors associated with open conversion were analyzed via univariate analysis and a P value.05 was considered statistically significant.LMH was performed for malignancy in 114 (77.6%) patients of which hepatocellular carcinoma (n = 82) and colorectal metastases (n = 16) were the most common pathologies. Forty-one (27.9%) patients had cirrhotic livers and 18 (15.7%) had fibrotic livers. Fifty patients (44%) had concomitant surgery in addition to LMH. Twenty (13.6%) procedures required open conversion and the most common reason was for bleeding (n = 12). Twenty-five patients (17%) experienced postoperative complications. Univariate analyses demonstrated that only individual surgeon volume (n ≤ 10 cases) [15 (24.2%) vs 5 (5.9%), P = .001] and institution volume (n ≤ 25 cases) [8 (32%) vs 12 (9.8%), P = .003] were factors associated with open conversion. Open conversion was significantly associated with increased intra-operative blood loss, increased intra-operative blood transfusion, increased postoperative morbidity, and longer postoperative stay.Individual surgeon and institution volumes were important factors associated with open conversion after LMH. Open conversion after LMH resulted in poorer outcomes compared to procedures that were successfully completed laparoscopically.

Presently, the role of liver resection (LR) for multifocal hepatocellular carcinoma (HCC) remains controversial. However, in many regions worldwide, LR remains the only treatment modality available to such patients which offers the possibility of long-term cure. The aim of this study is to determine the outcomes and prognostic factors of patients with multifocal HCC after LR. This is a retrospective analysis of 110 patients who underwent potentially curative LR for pathologically proven multifocal HCC between 2000 and 2011. The median age was 64 (range, 18–84) years, and there were 88 males (80.0 %). Sixty-one patients underwent a major hepatectomy, and the overall postoperative mortality was 1.8 %. Sixty-eight patients had liver cirrhosis, of which, 58 were child’s A and 10 were child’s B. The 1- and 5-year overall survival (OS) was 82 and 44 %, respectively. The corresponding 1- and 5-year recurrence-free survival (RFS) was 57 and 19 %, respectively. Multivariate analysis demonstrated that the number of nodules (>3) and presence of microvascular invasion were associated with RFS. Number of nodules (>3), margin positivity, Child-Pugh status, and presence of microvascular invasion were independent prognostic factors of OS. LR followed by treatment of recurrences may result in reasonable long-term survival and should be considered in a selected group of patients with multifocal HCC. Number of nodules (>3), margin positivity, Child-Pugh status, and presence of microvascular invasion, but not tumor size, were independent negative predictors of OS. These findings have potential implications on the AJCC staging for multifocal HCC.

The Sendai Consensus Guidelines (SCG) was formulated in 2006 to guide the management of intraductal papillary mucinous neoplasms (IPMN). The main area of controversy is the criteria for selection of branch duct (BD)-IPMN for resection. Although these guidelines have gained widespread acceptance, there is limited data to date supporting its use. This systematic review is performed to evaluate the utility of the Sendai Consensus Guidelines (SCG) for BD-IPMN. Studies evaluating the clinical utility of the SCG in surgically resected neoplasms were identified. The SCG were retrospectively applied to all resected neoplasms in these studies. BD-IPMNs which met the criteria for resection were termed SCG+ve and those for surveillance were termed SCG−ve. Twelve studies were included, of which, 9 were suitable for pooled analysis. There were 690 surgically resected BD-IPMNs, of which, 24 % were malignant. Five hundred one BD-IPMNs were classified as SCG+ve and 189 were SCG−ve. The positive predictive value (PPV) of SCG+ve neoplasms ranged from 11 to 52 % and the NPV of SCG−ve neoplasms ranged from 90 to 100 %. Overall, there were 150/501 (29.9 %) of malignant BD-IPMNs in the SCG+ve group and 171/189 (90 %) of benign BD-IPMNs in the SCG−ve group. Of the 18 reported malignant (11 invasive) BD-IPMNs in the SCG−ve group, 17 (including all 11 invasive) were from a single study. When the results from this single study were excluded, 170/171 (99 %) of SCG−ve BD-IPMNs were benign. The results of this review confirm the limitations of the SCG for BD-IPMN. The PPV of the SCG in predicting a malignant BD-IPMN was low and some malignant lesions may be missed based on these guidelines.

A method is proposed for the bonding of quartz to anodic aluminum oxide by means of the localized heating effect induced by a focused laser beam. The characteristics of the bonding region are investigated by means of SEM, EDX and XRD. It is shown that given a laser power of 2 W, the bonding strength is equal to approximately 8 kg, and is thus higher than that achieved in a typical thermal bonding method (~5 kg). Overall, the results show that the proposed laser-bonding method provides a simple solution for the rapid and selective area bonding of quartz to anodic aluminum oxide.

The impact of different carcinogenic exposures on the specific patterns of somatic mutation in human tumors remains unclear. To address this issue, we profiled 209 cholangiocarcinomas (CCAs) from Asia and Europe, including 108 cases caused by infection with the liver fluke Opisthorchis viverrini and 101 cases caused by non-O. viverrini-related etiologies. Whole-exome sequencing (n = 15) and prevalence screening (n = 194) identified recurrent somatic mutations in BAP1 and ARID1A, neither of which, to our knowledge, has previously been reported to be mutated in CCA. Comparisons between intrahepatic O. viverrini-related and non-O. viverrini-related CCAs demonstrated statistically significant differences in mutation patterns: BAP1, IDH1 and IDH2 were more frequently mutated in non-O. viverrini CCAs, whereas TP53 mutations showed the reciprocal pattern. Functional studies demonstrated tumor suppressive functions for BAP1 and ARID1A, establishing the role of chromatin modulators in CCA pathogenesis. These findings indicate that different causative etiologies may induce distinct somatic alterations, even within the same tumor type.

Background Ewing sarcomas are highly aggressive malignant tumours occurring predominantly in the long bones of the extremities in children and young adults. About 20 % of patients will present with metastases at diagnosis with the commonest sites being the lungs, bone and bone marrow. Cases of primary small bowel Ewing sarcomas have been described but are nonetheless exceedingly rare, even more so cases of metastasis to the small bowel. Case Presentation We describe a case of vertebral Ewing sarcoma in a 44 year-old female which metastasized to the jejunum causing intussusception. Conclusions Ewing’s sarcoma is highly aggressive and presence of metastases, overt or subclinical, is thought to be present in almost all patients at diagnosis. As evidenced by our patient, metastatic disease can progress rapidly to cause further complications and confer a poorer survival. The possibility of metastasis, no matter how rare or unlikely the site is, should be considered and actively investigated to expedite treatment of the primary disease.

Widely dehisced abdominal wounds present as challenging surgical cases often incurring multiple complications such as bowel desiccation, perforation, and enterocutaneous fistula [1], equating a mortality of 25% [2]. With the extensive usage of topical negative pressure dressings, these complications have reduced. However these abdomens are now presenting as open wounds with incarcerated edges, necessitating skin grafting on bowel. We present an effective approach to the closure of open abdomens using a combination of topical negative pressure and elastic sutures improvised from silicone tubing. The elastic sutures stretch the skin and prevent wound edges from bedding down prematurely, thereby allowing primary closure.

Performances of a magnetic particle driven micromixer are predicted numerically. This micromixer takes advantages of mixing enhancements induced by alternating actuation of magnetic particles suspended in the fluid. Effects of magnetic actuation force, switching frequency and channel’s lateral dimension have been investigated. Numerical results show that the magnetic particle actuation at an appropriate frequency causes effective mixing and the optimum switching frequency depends on the channel’s lateral dimension and the applied magnetic force. The maximum efficiency is obtained at a relatively high operating frequency for large magnetic actuation forces and narrow microchannels. If the magnetic particles are actuated with a much higher or lower frequency than the optimum switching frequency, they tend to add limited agitation to the fluid flow and do not enhance the mixing significantly. The optimum switching frequency obtained from the present numerical prediction is in good agreement with the theoretical analysis. The proposed mixing scheme not only provides an excellent mixing, even in simple microchannel, but also can be easily applied to lab-on-a-chip applications with a pair of external electromagnets.

The p16 gene, encodes a key checkpoint protein p16 in the cell cycle, has been reported inactivation in a wide variety of human cancers. We have previously demonstrated high frequency of p16 alterations in primary nasopharyngeal carcinoma (NPC), xenografts and cell lines. The finding implied that inactivation of the p16 gene may play an important role in the NPC development. To investigate the tumour suppressor function of p16 in NPC, we tranfected p16-deficient NPC cell line, NPC/HK-1, with a wild-type p16 expression construct, and evaluated growth and tumorigenic properties of the clones stably expressing exogenous p16. Expression of the exogenous wild-type p16 significantly inhibited cell growth by more than 70% when compared to that of the parental and empty vector-transfected cells. This growth inhibition was attributable to a significant proportion of p16-expressing cells arrested at G1 phase in the cell cycle as revealed by flow cytometric analysis. By anchorage-independent colony forming assay, we found that the ability to form colonies in soft agar was highly reduced in cells expressing p16. NPC/HK1 cells expressing functional p16 also showed suppressed tumorigenicity in athymic nude mice. Taken together, our results provide strong evidence for a tumour suppressor role of p16 in NPC. © 1999 Cancer Research Campaign

Decompression retinopathy following laser peripheral iridoplasty for acute primary angle-closure

Turbulent heat transfer from a sudden expansion pipe subjected to an externally convective boundary condition is studied numerically using the proposed modified turbulence model. Both HYBRID and QUICK schemes are employed for comparison purposes. The calculated velocity distribution and turbulent kinetic energy show a significant improvement over the existing model solutions. The present results of center-line velocity, temperature distribution and Nusselt number under a limiting condition compare well with the available experimental data.

Optical time-stretch imaging enables the continuous capture of non-repetitive events in real time at a line-scan rate of tens of MHz—a distinct advantage for the ultrafast dynamics monitoring and high-throughput screening that are widely needed in biological microscopy. However, its potential is limited by the technical challenge of achieving significant pulse stretching (that is, high temporal dispersion) and low optical loss, which are the critical factors influencing imaging quality, in the visible spectrum demanded in many of these applications. We present a new pulse-stretching technique, termed free-space angular-chirp-enhanced delay (FACED), with three distinguishing features absent in the prevailing dispersive-fiber-based implementations: (1) it generates substantial, reconfigurable temporal dispersion in free space (>1 ns nm−1) with low intrinsic loss (

During the course of immunizing balb/c mice with eye muscle (EM) or thyroid (THY) membranes for monoclonal antibody (MCAB) production their sera frequently contain antibodies which react against both EM and THY membranes in enzyme-linked immunosorbent assay (ELISA) and SDS-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blotting. In order to further study this phenomenon we have analyzed sera from 27 balb/c mice, including 10 that were studied serially, and their tissues examined histologically at sacrifice. Following immunization serum and, in some cases, the corresponding MCAB produced by fusion of the mouse spleen cells with a mouse myeloma cell line, were tested for EM and THY cross-reactivity in an ELISA and by immunoblotting. The number of antibodies demonstrated in Western blotting identified as bands of reactivity, and ELISA levels, expressed as optical density — increased with time, each peaking at around 10–12 weeks. THY and EM antibody cross-reactivity was demonstrated in the majority of mice, serum from mice immunized with THY membranes reacting with these membranes as well as with pig EM membranes in both ELISA and immunoblotting and, conversely, sera from mice immunized with pig EM membranes also reacting with THY membranes in the two tests. In Western blotting a variety of THY and EM-reactive antibodies were demonstrated including those directed against a 64 kDa protein, shown to be an important autoantigen in thyroid-associated ophthalmopathy. There was also some cross-reactivity with brain membranes, used as control antigen in both tests and in immunization, although to a lesser degree, but very little to liver and orbital connective tissue membrane. While there were several exceptions there was, overall, a fairly close correlation between serum reactivities and tissue specificities of the corresponding MCAB. No mouse demonstrated significant lymphocytic infiltration in THY or orbital tissues and none developed features of an ophthalmopathy although the experimental protocol was not optimised for the production of autoimmunity. This is the first report of the production of antibodies reactive against putative THY and EM shared epitopes in experimental animals and provides further support for the notion that the mechanism for the association of ophthalmopathy with autoimmune THY disorders in humans may be immunological cross-reactivity.

Multivariate statistical analyses have been extensively applied to geochemical measurements to analyze and aid interpretation of the data. Estimation of the covariance matrix of multivariate observations is the first task in multivariate analysis. However, geochemical data for the rare elements, especially Ag, Au, and platinum-group elements, usually contain observations the below detection limits. In particular, Instrumental Neutron Activation Analysis (INAA) for the rare elements produces multilevel and possibly extremely high detection limits depending on the sample weight. Traditionally, in applying multivariate analysis to such incomplete data, the observations below detection limits are first substituted, for example, each observation below the detection limit is replaced by a certain percentage of that limit, and then the standard statistical computer packages or techniques are used to obtain the analysis of the data. If a number of samples with observations below detection limits is small, or the detection limits are relatively near zero, the results may be reasonable and most geological interpretations or conclusions are probably valid. In this paper, a new method is proposed to estimate the covariance matrix from a dataset containing observations below multilevel detection limits by using the marginal maximum likelihood estimation (MMLE) method. For each pair of variables, sayY andZ whose observations containing below detection limits, the proposed method consists of three steps: (i) for each variable separately obtaining the marginal MLE for the means and the variances,\(\widetilde{\widetilde\mu }_Y \),\(\widetilde{\widetilde\mu }_Z \),\(\widetilde{\widetilde\sigma }_{YY} \), and\(\widetilde{\widetilde\sigma }_{ZZ} \) forY andZ: (ii) defining new variables by\(C = (Y - \widetilde{\widetilde\mu }_Y )/\sqrt {\widetilde{\widetilde\sigma }_{YY} } \) and\(D = (Z - \widetilde{\widetilde\mu }_Z )/\sqrt {\widetilde{\widetilde\sigma }_{ZZ} } \) and lettingA=C+D andB=C−D, and obtaining MLE for variances,\(\widetilde\sigma _ + \) and\(\widetilde\sigma _ - \) forA andB; (iii) estimating the correlation coefficient ϱYZ by\(\widetilde\rho _{YZ} = (\widetilde\sigma _ + - \widetilde\sigma _ - )/(\widetilde\sigma _ + + \widetilde\sigma _ - )\) and the covariance σYZ by\(\widetilde\sigma _{YZ} = \bar \rho _{YZ} \sqrt {\widetilde{\widetilde\sigma }_{YY} \widetilde{\widetilde\sigma }_{YY} .} \). The procedure is illustrated by using a precious metal geochemical data set from the Fox River Sill, Manitoba, Canada.

Some new confidence bands are established for the quantile function from randomly censored data. The method does not require estimation of the density function. As an application, we construct bands for the quantile function of the length of fractures in the granitic plutons near Lac du Bonnet, Manitoba, where an Underground Research Laboratory is being built for the nuclear waste disposal program in Canada.

We report on the OMVPE growth and characterization of AlGalnN and its heterostructures, including measurements of electrical properties (Hall), optical properties (photo- and cathodo- luminescence), structural characteristics (x-ray diffraction and TEM); and also the emission of InGaN/AlGaN heterostructures subject to optical and electrical pumping.

In this paper present experimental results on the quality of AIGaAs material after high concentrations of impurities have been introduced for the purpose of impurity induced disordering. A comparison between Zn and Si diffusion is presented, and the nature of the transition region between uniform alloy and as-grown periodic structure has been characterized both experimentally and theoretically. Device implications of these observations is discussed.

Balaji Yegneswaran, University of Toronto, University Health Network, Toronto, ON, Canada; Balaji Yegneswaran, University of Toronto, University Health Network; Sharon Chung, University of Toronto, University Health Network; A Khajehdehi, University of Toronto, University Health Network; S Islam, University of Toronto, University Health Network; C Shapiro, University of Toronto, University Health Network; F Chung, University of Toronto, University Health Network

Balaji Yegneswaran, University of Toronto, University Health Network, Toronto, ON, Canada; Balaji Yegneswaran, University of Toronto, University Health Network; Peter Liao, University of Toronto, University Health Network; S Vairavanathan, University of Toronto, University Health Network; A Zaki, University of Toronto, University Health Network; F Chung, University of Toronto, University Health Network

Buffon's needle problem is generalized to a grid of unequally spaced parallel strips and a needle with a preferred orientation. This generalization is useful to determine the spacing of flight lines for locating anomalies by airborne geophysical surveys.

Several regression models can be used for explaining discovered occurrences and estimating undiscovered occurrences of mineral deposits of a given type from geological data quantified for equal-area cells. All the models are based on the assumption that the occurrences of mineral deposits in an area are estimable as a function of the mapable geological attributes in the area. Depending upon further assumptions made with respect to the dependent variable, that is, the occurrence of mineral deposits, different regression techniques such as logistic and Poisson regression analysis can be employed. In this paper, a jackknife method was used to estimate the variances of the regression coefficient and the occurrences. The effect of undiscovered deposits on the regression models was considered by treating the known deposits separately (Separate Event Method). As an illustrative example, the occurrence of volcanogenic massive sulfide deposits has been expressed in terms of the geological framework in parts of the island of Newfoundland. Each of the models provides a similar and relatively stable pattern that explains the occurrence of the known deposits in a study area of 6000 km 2.The methods presented for calculating the variances of the estimated values are meaningful because they can be used to test whether or not an estimated probability or frequency value for any one cell is significantly greater than zero. The logistic model is used to indicate cells outside the study area where undiscovered deposits are likely to occur.

Geological and geophysical data digitized by Fabbri (1981)are augmented by eleven lakesediment geochemical variables in a quantitative study of the Kasmere Lake—Whiskey Jack Lake area, NW Manitoba. Each of 33 geological map units (Archean and Aphebian igneous and metamorphic rocks)have a fairly distinct multivariate geochemical and geophysical signal, as shown by discriminant analysis which is able to “recover” the geological map from the geophysical and geochemical data. Autocorrelation analysis of the geochemical variables, after removing a quadratic trend, indicate that copper, nickel, uranium, and cobait have a zone of influence from 15 to 30 km or more, with a marked anisotropy parallel to geological, geophysical, and structural trends which run NE-SW, parallel to the Wollaston fold belt. The observed uranium autocorrelation coefficients are modeled as a two-dimensional exponential function with elliptical contours. A trend-signal-noise model is applied to the lake-sediment uranium using kriging on residuals from the quadratic trend. A map comparing the resulting lake-sediment uranium signal with radiometric uranium/thorium patterns indicates considerable overlap and a generally good prediction of known uranium occurrences. In areas with a strong lake-sediment uranium signal, Aphebian metasediments have a somewhat different multivariate geochemical character from Archean and Hudsonian igneous and metamorphic rocks, suggesting a method of removing areas from the signal underlain by granites that may be economically uninteresting. Logistic and stepwise regression experiments based on a control area which includes most of the presently reported occurrences are used to predict areas favorable for uranium exploration.