The Role of Preoperative Inflammatory Markers in Pancreatectomy: a Norwegian Nationwide Cohort Study

Background and purpose Preoperative infammatory markers, such as Glasgow prognostic score, modifed Glasgow prognostic score and C-reactive protein to albumin ratio, were shown to be associated with prognosis in patients undergoing pancreatectomy for cancer. However, little is known about their predictive role in a Western population. Methods The Norwegian National Registry for Gastrointestinal Surgery (NORGAST) was used to capture all pancreatectomies performed within the study period (November 2015—April 2021). The association between the preoperative infammatory markers and postoperative outcomes was studied. Their impact on survival was examined in patients operated for pancreatic ductal adenocarcinoma. Results A total of 1554 patients underwent pancreatectomy in this period. Glasgow prognostic score, modifed Glasgow prognostic score and C-reactive protein to albumin ratio were associated with severe complications (Accordion grade≥III) in the univariable but not in the multivariable analysis. C-reactive protein to albumin ratio, but not Glasgow prognostic score and modifed Glasgow prognostic score, was linked to survival following pancreatectomy for ductal adenocarcinoma. In the multivariable model, age, neoadjuvant chemotherapy, ECOG score, C-reactive protein to albumin ratio and total pancreatectomy correlated with survival. Also, preoperative C-reactive protein to albumin ratio was signifcantly associated with survival after pancreatoduodenectomy. Conclusions Preoperative Glasgow prognostic score, modifed Glasgow prognostic score and C-reactive protein to albumin ratio have no role in predicting the complications after pancreatectomy. C-reactive protein to albumin ratio is a signifcant predictor for survival in ductal adenocarcinoma, yet its clinical relevance should be explored in conjunction with the pathology parameters and adjuvant therapy

Preoperative Inflammatory Markers in Liver Resection for Colorectal Liver Metastases: A National Registry-Based Study

Background Preoperative inflammatory markers were shown to be associated with prognosis following surgery for hepato-pancreato-biliary cancer. Yet little evidence exists about their role in patients with colorectal liver metastases (CRLM). This study aimed to examine the association between selected preoperative inflammatory markers and outcomes of liver resection for CRLM. Methods Data from the Norwegian National Registry for Gastrointestinal Surgery (NORGAST) was used to capture all liver resections performed in Norway within the study period (November 2015–April 2021). Preoperative inflammatory markers were Glasgow prognostic score (GPS), modified Glasgow prognostic score (mGPS) and C-reactive protein to albumin ratio (CAR). The impact of these on postoperative outcomes, as well as on survival were studied. Results Liver resections for CRLM were performed in 1442 patients. Preoperative GPS C 1 and mGPS C 1 were present in 170 (11.8%) and 147 (10.2%) patients, respectively. Both were associated with severe complications but became non-significant in the multivariable model. GPS, mGPS, CAR were significant predictors for overall survival in the univariable analysis, but only CAR remained such in the multivariable model. When stratified by the type of surgical approach, CAR was a significant predictor for survival after open but not laparoscopic liver resections. Conclusions GPS, mGPS and CAR have no impact on severe complications after liver resection for CRLM. CAR outperforms GPS and mGPS in predicting overall survival in these patients, especially following open resections. The prognostic significance of CAR in CRLM should be tested against other clinical and pathology parameters relevant for prognosis

A comprehensive framework for analysis of microRNA sequencing data in metastatic colorectal cancer

Although microRNAs (miRNAs) contribute to all hallmarks of cancer, miRNA dysregulation in metastasis remains poorly understood. The aim of this work was to reliably identify miRNAs associated with metastatic progression of colorectal cancer (CRC) using novel and previously published nextgeneration sequencing (NGS) datasets generated from 268 samples of primary (pCRC) and metastatic CRC (mCRC; liver, lung and peritoneal metastases) and tumor adjacent tissues. Differential expression analysis was performed using a meticulous bioinformatics pipeline, including only bona fide miRNAs, and utilizing miRNA-tailored quality control and processing. Five miRNAs were identified as upregulated at multiple metastatic sites Mir-210 3p, Mir191 5p, Mir-8-P1b 3p [mir-141–3p], Mir-1307 5p and Mir-155 5p. Several have previously been implicated in metastasis through involvement in epithelial-tomesenchymal transition and hypoxia, while other identified miRNAs represent novel findings. The use of a publicly available pipeline facilitates reproducibility and allows new datasets to be added as they become available. The set of miRNAs identified here provides a reliable starting-point for further research into the role of miRNAs in metastatic progression

Laparoscopic versus open liver resection for intrahepatic cholangiocarcinoma: a multicenter propensity score-matched study

Background: The role of laparoscopy in the treatment of intrahepatic cholangiocarcinoma (ICC) remains unclear. This multicenter study examined the outcomes of laparoscopic liver resection for ICC. Methods: Patients with ICC who had undergone laparoscopic or open liver resection between 2012 and 2019 at four European expert centers were included in the study. Laparoscopic and open approaches were compared in terms of surgical and oncological outcomes. Propensity score matching was used for minimizing treatment selection bias and adjusting for confounders (age, ASA grade, tumor size, location, number of tumors and underlying liver disease). Results: Of 136 patients, 50 (36.7%) underwent laparoscopic resection, whereas 86 (63.3%) had open surgery. Median tumor size was larger (73.6 vs 55.1 mm, p¼ 0.01) and the incidence of bi-lobar tumors was higher (36.6 vs 6%, p< 0.01) in patients undergoing open surgery. After propensity score matching baseline characteristics were comparable although open surgery was associated with a larger fraction of major liver resections (74 vs 38%, p< 0.01), lymphadenectomy (60 vs 20%, p< 0.01) and longer operative time (294 vs 209 min, p< 0.01). Tumor characteristics were similar. Laparoscopic resection resulted in less complications (30 vs 52%, p¼ 0.025), fewer reoperations (4 vs 16%, p¼ 0.046) and shorter hospital stay (5 vs 8 days, p< 0.01). No differences were found in terms of recurrence, recurrence-free and overall survival. Conclusion: Laparoscopic resection seems to be associated with improved short-term and with similar long-term outcomes compared with open surgery in patients with ICC. However, possible selection criteria for laparoscopic surgery are yet to be defined

Deep learning-assisted survival prognosis in renal cancer: A CT scan-based personalized approach

This paper presents a deep learning (DL) approach for predicting survival probabilities of renal cancer patients based solely on preoperative CT imaging. The proposed approach consists of two networks: a classifier- and a survival- network. The classifier attempts to extract features from 3D CT scans to predict the ISUP grade of Renal cell carcinoma (RCC) tumors, as defined by the International Society of Urological Pathology (ISUP). Our classifier is a 3D convolutional neural network to avoid losing crucial information on the interconnection of slides in 3D images. We employ multiple procedures, including image augmentation, preprocessing, and concatenation, to improve the performance of the classifier. Given the strong correlation between ISUP grading and renal cancer prognosis in the clinical context, we use the ISUP grading features extracted by the classifier as the input to the survival network. By leveraging this clinical association and the classifier network, we are able to model our survival analysis using a simple DL-based network. We adopt a discrete LogisticHazard-based loss to extract intrinsic survival characteristics of RCC tumors from CT images. This allows us to build a completely parametric survival model that varies with patients' tumor characteristics and predicts non-proportional survival probability curves for different patients. Our results demonstrated that the proposed method could predict the future course of renal cancer with reasonable accuracy from the CT scans. The proposed method obtained an average concordance index of 0.72, an integrated Brier score of 0.15, and an area under the curve value of 0.71 on the test cohorts

Evolution of laparoscopic liver surgery: 20-year experience of a Norwegian high-volume referral center

Abstract Background Laparoscopic liver surgery has evolved to become a standard surgical approach in many specialized centers worldwide. In this study we present the evolution of laparoscopic liver surgery at a single high-volume referral center since its introduction in 1998. Methods Patients who underwent laparoscopic liver resection (LLR) between August 1998 and December 2018 at the Oslo University Hospital were analyzed. Perioperative outcomes were compared between three time periods: early (1998 to 2004), middle (2005 to 2012) and recent (2013–2018) . Results Up to December 2020, 1533 LLRs have been performed. A total of 1232 procedures were examined (early period, n  = 62; middle period, n  = 367 and recent period, n  = 803). Colorectal liver metastasis was the main indication for surgery (68%). The rates of conversion to laparotomy and hand-assisted laparoscopy were 3.2% and 1.4%. The median operative time and blood loss were 130 min [interquartile range (IQR), 85–190] and 220 ml (IQR, 50–600), respectively. The total postoperative complications rate was 20.3% and the 30-day mortality was 0.3%. The median postoperative stay was two (IQR, 2–4) days. When comparing perioperative outcomes between the three time periods, shorter operation time (median, from 182 to 120 min, p  &lt; 0.001), less blood loss (median, from 550 to 200 ml, p  = 0.023), decreased rate of conversions to laparotomy (from 8 to 3%) and shorter postoperative hospital stay (median, from 3 to 2 days, p  &lt; 0.001) was observed in the later periods, while the number of more complex liver resections had increased. Conclusion During the last two decades, the indications, the number of patients and the complexity of laparoscopic liver procedures have expanded significantly. Initially being an experimental approach, laparoscopic liver surgery is now safely implemented across our unit and has become the method of choice for surgical treatment of most liver tumors

Laparoscopic parenchyma-sparing liver resection for large (≥ 50 mm) colorectal metastases.

Abstract Background Traditionally, patients with large liver tumors (≥ 50 mm) have been considered for anatomic major hepatectomy. Laparoscopic resection of large liver lesions is technically challenging and often performed by surgeons with extensive experience. The current study aimed to evaluate the surgical and oncologic safety of laparoscopic parenchyma-sparing liver resection in patients with large colorectal metastases. Methods Patients who primarily underwent laparoscopic parenchyma-sparing liver resection (less than 3 consecutive liver segments) for colorectal liver metastases between 1999 and 2019 at Oslo University Hospital were analyzed. In some recent cases, a computer-assisted surgical planning system was used to better visualize and understand the patients’ liver anatomy, as well as a tool to further improve the resection strategy. The surgical and oncologic outcomes of patients with large (≥ 50 mm) and small (&lt; 50 mm) tumors were compared. Multivariable Cox-regression analysis was performed to identify risk factors for survival. Results In total 587 patients met the inclusion criteria (large tumor group, n  = 59; and small tumor group, n  = 528). Median tumor size was 60 mm (range, 50–110) in the large tumor group and 21 mm (3–48) in the small tumor group ( p  &lt; 0.001). Patient age and CEA level were higher in the large tumor group (8.4 μg/L vs. 4.6 μg/L, p  &lt; 0.001). Operation time and conversion rate were similar, while median blood loss was higher in the large tumor group (500 ml vs. 200 ml, p  &lt; 0.001). Patients in the large tumor group had shorter 5 year overall survival (34% vs 49%, p  = 0.027). However, in the multivariable Cox-regression analysis tumor size did not impact survival, unlike parameters such as age, ASA score, CEA level, extrahepatic disease at liver surgery, and positive lymph nodes in the primary tumor. Conclusion Laparoscopic parenchyma-sparing resections for large colorectal liver metastases provide satisfactory short and long-term outcomes. Graphical abstrac

Outcome a decade after laparoscopic and open Nissen fundoplication in children: results from a randomized controlled trial

Abstract Background Randomized controlled trials (RCT) comparing long-term outcome after laparoscopic (LF) and open fundoplication (OF) in children are lacking. Here we report recurrence rates and time to recurrence, frequency of re-interventions, use of antisecretory drugs, gastrointestinal symptoms, and patient/parental satisfaction a decade after children were randomized to LF or OF. Methods Cross-sectional long-term follow-up study of a two-center RCT that included patients during 2003–2009. Patients/parents were interviewed and medical charts reviewed for any events that might be related to the fundoplication. If suspicion of recurrence, further diagnostics were performed. Informed consent and ethical approval were obtained. Clinicaltrials.gov: NCT01551134. Results Eighty-eight children, 56 (64%) boys, were randomized (LF 44, OF 44) at median 4.4 [interquartile range (IQR) 2.0–8.9] years. 46 (52%) had neurological impairment. Three were lost to follow-up before first scheduled control. Recurrence was significantly more frequent after LF (24/43, 56%) than after OF (13/42, 31%, p  = 0.004). Median time to recurrence was 1.0 [IQR 0.3–2.2] and 5.1 [IQR 1.5–9.3] years after LF and OF, respectively. Eight (19%) underwent redo fundoplication after LF and three (7%) after OF ( p  = 0.094). Seventy patients/parents were interviewed median 11.9 [IQR 9.9–12.8] years postoperatively. Among these, use of anti-secretory drugs was significantly decreased from preoperatively after both LF (94% vs. 35%, p  &lt; 0.001) and OF (97% vs. 19%, p  &lt; 0.001). Regurgitation/vomiting were observed in 6% after LF and 3% after OF ( p  = 0.609), and heartburn in 14% after LF and 17% after OF ( p  = 1.000). Overall opinion of the surgical scars was good in both groups (LF: 95%, OF: 86%, p  = 0.610). Patient/parental satisfaction with outcome was high, independent of surgical approach (LF: 81%, OF: 88%, p  = 0.500). Conclusions The recurrence rate was higher and recurrence occurred earlier after LF than after OF. Patient/parental satisfaction with outcome after both LF and OF was equally high. Graphical abstrac

Interactions of occult tumor spread and surgical technique on overall and disease-free survival in patients operated for stage I and II right-sided colon cancer

Purpose To determine if “medial to lateral” (ML) dissection with devascularization first is superior to “lateral to medial” (LM) dissection regarding numbers of lymph node micro metastases (MM) and isolated tumor cells (ITC) as well as 5-year disease-free (5YDFS) and 5-year overall survival (5YOS) in stage I/II right-sided colon cancer. Methods Two datasets are used. ML group consists of consecutive stage I/II patients from a prospective trial. LM group is the original dataset from a previous publication. All harvested lymph nodes are examined with monoclonal antibody CAM 5.2 (immunohistochemically). Lymph node harvest and 5YOS/5YDFS were compared between ML/LM groups, stage I/II tumors and MM/ITC presence/absence. Results 117 patients included ML:51, LM:66. MM/ITC positive in ML 37.3% (19/51), LM 31.8% (21/66) p = 0.54. The 5YDFS for patients in ML 70.6% and LM 69.7%, p = 0.99, 5YOS: 74.5% ML and 71.2% LM (p = 0.73). No difference in 5YDFS/5YOS between groups for Stage I/II tumors; however, LM group had an excess of early tumors (16) when compared to ML group, while lymph node harvest was significantly higher in ML group (p < 0.01) 15.1 vs 26.7. 5YDFS and 5YOS stratified by MM/ITC presence/absence was 67.5%/71.4%, p = 0.63, and 75.0%/71.4%, p = 0.72, respectively. Death due to recurrence in MM/ITC positive was significantly higher than MM/ITC negative (p = 0.012). Conclusion Surgical technique does not influence numbers of MM/ITC or 5YDFS/5YOS. Presence of MM/ITC does not affect 5YOS/5YDFS but can be a potential prognostic factor for death due to recurrence. Clinical trial Safe Radical D3 Right Hemicolectomy for Cancer through Preoperative Biphasic Multi-Detector Computed Tomography (MDCT) Angiography” registered at http://clinicaltrials.gov/ct2/show/NCT01351714

Reconstructing topography and extent of injury to the superior mesenteric artery plexus in right colectomy with extended D3 mesenterectomy: a composite multimodal 3‑dimensional analysis

Background Superior mesenteric artery plexus (SMAP) injury is reported to cause postoperative intractable diarrhea after pancreatic/colonic surgery with extended lymphadenectomy. This study aims to describe the SMAP microanatomy and extent of injury after right colectomy with extended D3 mesenterectomy for cancer. Methods Three groups (I) anatomical dissection, (II) postmortem histology, and (III) surgical specimen histology were included. Nerve count and area were compared between groups II and III and paravascular sheath thickness between groups I and II. 3D models were generated through 3D histology, nanoCT scanning, and finally through 3D printing. Results A total of 21 specimens were included as follows: Group (I): 5 (3 females, 80–93 years), the SMAP is a complex mesh surrounding the superior mesenteric artery (SMA), branching out, following peripheral arteries and intertwining between them, (II): 7 (5 females, 71–86 years), nerve count: 53 ± 12.42 (38–68), and area: 1.84 ± 0.50 mm2 (1.16–2.29), and (III): 9 (5 females, 55–69 years), nerve count: 31.6 ± 6.74 (range 23–43), and area: 0.889 ± 0.45 mm2 (range 0.479–1.668). SMAP transection injury is 59% of nerve count and 48% of nerve area at middle colic artery origin level. The median values of paravascular sheath thickness decreased caudally from 2.05 to 1.04 mm (anatomical dissection) and from 2.65 to 1.17 mm (postmortem histology). 3D histology models present nerve fibers exclusively within the paravascular sheath, and lymph nodes were observed only outside. NanoCT-derived models reveal oblique nerve fiber trajectories with inclinations between 35° and 55°. Two 3D-printed models of the SMAP were also achieved in a 1:2 scale. Conclusion SMAP surrounds the SMA and branches within the paravascular sheath, while bowel lymph nodes and vessels lie outside. Extent of SMAP injury on histological slides (transection only) was 48% nerve area and 59% nerve count. The 35°–55° inclination range of SMAP nerves possibly imply an even larger injury when plexus excision is performed (lymphadenectomy). Reasons for later improvement of bowel function in these patients can lie in the interarterial nerve fibers between SMA branche