This meta-analysis sought to evaluate the potential benefits and harms of laparoscopic gastrectomy with D2 lymphadenectomy for locally advanced gastric cancer versus open surgery.
A comprehensive ...search for randomized controlled studies that compared laparoscopic versus open gastrectomy with D2 lymphadenectomy for locally advanced gastric cancer published until December 31, 2018, was conducted. Operative outcomes, early postoperative outcomes, and long-term results were analyzed using a random effects model.
Five randomized controlled trials containing a collective total of 2157 patients were included. In comparison with open surgery, laparoscopic gastrectomy for locally advanced gastric cancer showed similar risks of short-term mortality and serious adverse events within 30 days after surgery. Regarding intraoperative outcomes, operative time was increased for the laparoscopic approach, whereas the estimated intraoperative blood loss tended to be less. However, the amount of evidence was low for most outcomes. In addition, the results for the length of hospital stay and time to first flatus did not show statistically significant differences. The number of harvested lymph nodes and compliance with D2 lymphadenectomy did not significantly differ between the two groups, indicating oncological equivalence of both approaches. However, long-term oncological results could not be evaluated due to a lack of relevant data in four of the trials.
Laparoscopic gastrectomy with D2 lymphadenectomy can be performed with equivalent overall short-term morbidity and mortality versus the open approach for locally advanced gastric cancer. However, further well-designed randomized controlled trials are necessary to assess the possible advantages and risks of the laparoscopic approach as well as the long-term results.
In colorectal cancer, oncogenic mutations transform a hierarchically organized and homeostatic epithelium into invasive cancer tissue lacking visible organization. We sought to define transcriptional ...states of colorectal cancer cells and signals controlling their development by performing single‐cell transcriptome analysis of tumors and matched non‐cancerous tissues of twelve colorectal cancer patients. We defined patient‐overarching colorectal cancer cell clusters characterized by differential activities of oncogenic signaling pathways such as mitogen‐activated protein kinase and oncogenic traits such as replication stress. RNA metabolic labeling and assessment of RNA velocity in patient‐derived organoids revealed developmental trajectories of colorectal cancer cells organized along a mitogen‐activated protein kinase activity gradient. This was in contrast to normal colon organoid cells developing along graded Wnt activity. Experimental targeting of EGFR‐BRAF‐MEK in cancer organoids affected signaling and gene expression contingent on predictive KRAS/BRAF mutations and induced cell plasticity overriding default developmental trajectories. Our results highlight directional cancer cell development as a driver of non‐genetic cancer cell heterogeneity and re‐routing of trajectories as a response to targeted therapy.
SYNOPSIS
Colorectal cancer (CRC) cells can adopt a range of transcriptomic states. This study uses single cell RNA sequencing of primary CRC tissue and organoids to identify patient‐overarching CRC cell transcriptome clusters. RNA metabolic labelling indicates preferred CRC cell developmental trajectories.
CRC cells of multiple patients clustered into six groups – termed TC1‐4, Goblet‐like, and stem‐like – characterized by differential transcriptional footprints of oncogenic signaling pathways.
CRC organoid cells develop along a decreasing MAPK gradient.
Experimental targeting of EGFR‐MAPK in CRC organoids re‐routes developmental trajectories.
Clinically relevant inhibition of EGFR‐MAPK can result in preferential CRC cell development towards endpoints expressing high levels of stem cell markers.
Colorectal cancer (CRC) cells can adopt a range of transcriptomic states. This study uses single cell RNA sequencing of primary CRC tissue and organoids to identify patient‐overarching CRC cell transcriptome clusters. RNA metabolic labelling indicates preferred CRC cell developmental trajectories.
Immune checkpoint therapy (ICT) has shown promising potential in the treatment of multiple solid tumors. However, the role of ICT in pancreatic ductal adenocarcinoma (PDAC) remains limited. Patterns ...of immune checkpoints (ICs) in PDAC represent the basis for establishing a potent ICT. The aim of this study is to create a profile of IC expression and its prognostic relevance in cancer cells of PDAC. Therefore, tumor cells from peripheral and central tissue microarray (TMA) spots from histologically confirmed PDAC of 68 patients after tumor resection were investigated in terms of expressions of TIM3, IDO, B7H4, LAG3, VISTA, and PD-L1 using immunohistochemistry. The presence of the respective ICs was compared to overall survival (OS). The presence of VISTA and PD-L1 significantly correlates with shorter OS (median OS: 22 months vs. 7 months and 22 months vs. 11 months, respectively,
< 0.05). For the presence of TIM3, IDO, B7H4, and LAG3, no difference in OS was observed (
> 0.05). The analysis of OS of combined subgroups for VISTA and PD-L1 (VISTA and PD-L1 neg., VISTA pos. and PD-L1 neg., VISTA neg. and PD-L1 pos., and VISTA and PD-L1 pos.) yielded overall statistical significance difference (
= 0.02). These results suggest that the presence of VISTA and PD-L1 is of prognostic relevance and potentially qualifies them as targets for ICT.
Colorectal cancer is one of the most common malignancies worldwide. There is an urgent need for simple and fast methods to improve tumor detection in the diagnostic and intraoperative setting to ...avoid complications and provide objective information in distinguishing malignant and benign colorectal tissue. Optical spectroscopy methods have recently shown a great potential for this discrimination in different organs.
In this pilot study, fluorescence emission spectra (excitation: 473 nm) and diffuse reflectance spectra (DRS) of normal and tumor tissues from resected colorectal cancer specimen were measured using fiber optical probes in an ex vivo setting, and the data were subjected to multivariate analysis.
Substantial spectral differences were found in the fluorescence and DRS spectra of colorectal cancer tissue in comparison to benign tissue. The diagnostic potential of a multimode optical system combining both spectroscopic methods was investigated by mathematical combination. Compared with the individual techniques, a higher sensitivity of the joint DRS-fluorescence optical system in the discrimination between malignant and benign colorectal tissue could be observed.
In the pilot study presented herein, a quick and reliable method to differentiate malignant and benign colorectal tissue ex vivo with different spectroscopic techniques using spectral fiber probes could be established. Joint fluorescence and near-infrared spectroscopy had a higher sensitivity in tissue discrimination and showed to be a promising combination of two spectroscopic methods. Further studies using the synergic effect of fluorescence and DRS spectroscopy are needed to transfer these findings into the in vivo situation.
Purpose
Prolonged postoperative ileus (PPOI) is common after bowel resections, especially in Crohn’s disease (CD). The pathophysiology of PPOI is not fully understood. PPOI could affect only the ...upper or lower gastrointestinal (GI) tract. The aim of this study was to assess risk factors for diverse types of PPOI, particularly to differentiate PPOI of upper and lower GI tract.
Methods
A retrospective analysis of 163 patients with CD undergoing ileocecal resection from 2015 to 2020 in a single center was performed. PPOI of the upper GI tract was predefined as the presence of vomiting or use of nasogastric tube longer than the third postoperative day. Lower PPOI was predefined as the absence of defecation for more than three days. Independent risk factors were identified by multivariable logistic regression analysis.
Results
Overall incidence of PPOI was 42.7%. PPOI of the upper GI tract was observed in 30.7% and lower PPOI in 20.9% of patients. Independent risk factors for upper PPOI included older age, surgery by a resident surgeon, hand-sewn anastomosis, prolonged opioid analgesia, and reoperation, while for lower PPOI included BMI ≤ 25 kg/m
2
, preoperative anemia, and absence of ileostomy.
Conclusion
This study identified different risk factors for upper and lower PPOI after ileocecal resection in patients with CD. A differentiated upper/lower type approach should be considered in future research and clinical practice. High-risk patients for each type of PPOI should be closely monitored, and modifiable risk factors, such as preoperative anemia and opioids, should be avoided if possible.
Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the TNF superfamily. TRAIL has historically been distinct from the Fas ligand and TNFα in terms of selective ...apoptosis induction in tumor cells and has a nearly non-existent systemic toxicity. Consequently, in the search for an ideal drug for tumor therapy, TRAIL rapidly drew interest, promising effective tumor control with minimal side effects. However, euphoria gave way to disillusionment as it turned out that carcinoma cells possess or can acquire resistance to TRAIL-induced apoptosis. Additionally, studies on models of inflammation and autoimmunity revealed that TRAIL can influence immune cells in many different ways. While TRAIL was initially found to be an important player in tumor defense by natural killer cells or cytotoxic T cells, additional effects of TRAIL on regulatory T cells and effector T cells, as well as on neutrophilic granulocytes and antigen-presenting cells, became focuses of interest. The tumor-promoting effects of these interactions become particularly important for consideration in cases where tumors are resistant to TRAIL-induced apoptosis. Consequently, murine models have shown that TRAIL can impair the tumor microenvironment toward a more immunosuppressive type, thereby promoting tumor growth. This review summarizes the current state of knowledge on TRAIL's interactions with the immune system in the context of cancer.
Purpose
Myopenia and myosteatosis have been proposed to be prognostic factors of surgical outcomes for various diseases, but their exact role in Crohn’s disease (CD) is unknown. The aim of this study ...is to evaluate their impact on anastomotic leakage, CD recurrence, and postoperative complications after ileocecal resection in patients with CD.
Methods
A retrospective analysis of CD patients undergoing ileocecal resection at our tertiary referral center was performed. To assess myopenia, skeletal muscle index (skeletal muscle area normalized for body height) was measured using an established image analysis method at third lumbar vertebra level on MRI cross-sectional images. Muscle signal intensity was measured to assess myosteatosis index.
Results
A total of 347 patients were retrospectively analyzed. An adequate abdominal MRI scan within 12 months prior to surgery was available for 223 patients with median follow-up time of 48.8 months (IQR: 20.0–82.9). Anastomotic leakage rate was not associated with myopenia (SMI:
p
= 0.363) or myosteatosis index (
p
= 0.821). Patients with Crohn’s recurrence had a significantly lower SMI (
p
= 0.047) in univariable analysis, but SMI was not an independent factor for recurrent anastomotic stenosis in multivariable analysis (OR 0.951, 95% CI 0.840–1.078;
p
= 0.434). Postoperative complications were not associated with myopenia or myosteatosis.
Conclusion
Based on the largest cohort of its kind with a long follow-up time, we could provide some data that MRI parameters for myopenia and myosteatosis may not be reliable predictors of postoperative outcome or recurrence in patients with Crohn’s disease undergoing ileocecal resection.
Crohn's disease (CD) is associated with changes in the microbiome. The role of these changes and their precise association with disease course and activity remain ambiguous. In this prospective ...single-center study, the mucosal microbiome of surgical CD and non-CD patients was compared at the time of surgery. Microbial analyses were individually performed for ileal and colonic tissue samples obtained during surgery using 16S-rRNA-gene amplicon sequencing. Three groups out of the 46 included patients were formed: 1) a study group of CD of patients who received ileocecal resection due to CD involvement (CD study, n=10); 2) a control group of non-CD of patients who received intestinal resection due to indications other than CD (non-CD control, n=27); and 3) a second control group of CD who underwent resection of the intestine not affected by CD (CD non-affected control, n=9). Species richness and Shannon diversity were not different between all formed groups and regions analyzed (p>0.05). Several significant taxonomic differences were seen at the phylum-, order-, and genus-levels between the formed groups, such as a decrease of
(phylum-level) and an increase of
and
(genus-level) in CD study - colon vs. the non-CD control - colon (p ≤ 0.05). The CD non-affected control presented the largest amount of differentially abundant taxa in comparison to the other groups. These results underline that CD is accompanied by changes in affected and non-affected intestinal regions compared to non-CD controls. This study contributes the mucosal microbiome of a well-defined subset of surgical CD patients without confounding aspects of the fecal microbiome or regional microbial differences to the existing literature.
Background
Different tumor-specific prognostic factors have been identified in recent years for patients who undergo surgery due to pancreatic head cancer, but the results often were inconsistent. ...Furthermore, the impact of postoperative complications on patient long-term survival has not been described.
Methods
The long-term outcome of 428 patients who underwent resection of pancreatic head cancer at our center during a 17-year period was evaluated. Perioperative details, including postoperative complications, as well as the follow-up of all patients who left the hospital postoperatively were collected in a prospective database. Univariate and multivariate models were used to identify potential prognostic factors and to evaluate the impact of postoperative complications on long-term survival.
Results
The median survival was 15.5 months with a postoperative complication rate (grade I–IV) of 32.7%. Independent prognostic significance was detected for grading (
P
< 0.001), R status (
P
= 0.001), and lymph node status (
P
= 0.003). The occurrence of severe postoperative complications (grade III–IV) was associated with a significantly shortened survival (16.5 vs. 12.4 months;
P
= 0.002) and was identified as an independent prognostic factor (
P
= 0.002).
Conclusions
This large study demonstrates that severe postoperative complications have a strong impact on the long-term survival of patients with pancreatic head cancer comparable to tumor characteristics, such as lymph node status, grading, or R status. As a result, the improvement of surgical procedures in specialized centers might lead to a survival benefit in these patients.
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