The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

Aim: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. Methods: This was an international prospective cohort study of consecutive colorectalcancer patients with a decision for curative surgery (January–April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision,in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored theeffects of delay in elective patients only. The impact of longer delays was explored in asensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. Results: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operatedpatients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks.Delayed patients were more likely to be older, men, more comorbid, have higher bodymass index and have rectal cancer and early stage disease. Delayed patients had higherunadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates ofemergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90–1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69–1.27, P = 0.672). Longer delays were not associated with poorer outcomes. Conclusion: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long- term survival attributable to delays is likely to be due to micro-metastatic disease

Novel surgical technique for complete traumatic rupture of the pancreas: A case report

<p>Abstract</p> <p>Introduction</p> <p>Complete pancreatic rupture is a rare injury. The typical mechanism by which this occurs is overstretching of the pancreas across the vertebral column during blunt abdominal trauma. The management of this injury depends on the location and extent of the injury.</p> <p>Case presentation</p> <p>A 45-year-old Caucasian woman presented with blunt abdominal trauma after she fell onto the end of a handlebar during a bicycle accident. She arrived in the emergency room with stable vital signs and an isolated bruise just above the umbilicus. A computed tomography scan revealed a complete rupture of the pancreas, just ventral to her superior mesenteric vein, and an accompanying hematoma but no additional injuries. An emergency laparotomy was performed; the head of the pancreas was oversewn with interrupted sutures and this was followed by a two-layer pancreaticojejunostomy with the tail of the pancreas. The recovery after surgery was completely uneventful.</p> <p>Conclusions</p> <p>Isolated complete pancreatic rupture is a rare injury that can be managed with complete organ preservation. The combination of suturing the pancreatic head and two-layer pancreaticojejunostomy with the pancreatic tail is a feasible technique to manage this condition.</p

Quality of life in peritoneal carcinomatosis: A prospective study in patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC)

BACKGROUND/AIMS Cytoreductive surgery and hyperthermic intraperitoneal chemoperfusion (HIPEC) can improve survival in selected patients with peritoneal carcinomatosis, but bear a significant risk of perioperative morbidity. The aim of this study was to prospectively evaluate the quality of life (QoL) following cytoreduction and HIPEC. METHODS In this study including 40 patients (65% females) with different primary tumors, the EORTC QLQ-C30 questionnaire was applied prior to CS and HIPEC as well as 3, 9, and 18 months postoperatively. RESULTS Global health status was not impaired significantly following HIPEC. Scales and symptom scores that deteriorated 3 months postoperatively (p < 0.05), that is, physical, role, and social functions as well as fatigue, pain, dyspnea, insomnia, and diarrhea, all returned to preoperative values within 9 months. CONCLUSIONS Following cytoreductive surgery and HIPEC, QoL returns to preoperative levels within 9 months. Selected patients that are likely to benefit oncologically from HIPEC should not be denied this option for fear of reduced postoperative QoL

Over-the-scope clip (OTSC (R)) closure of a recto-acetabular fistula

A 25-year-old male Syrian refugee presented in our hospital with recurrent hip infections after having undergone hip arthroplasty abroad following destruction of his right hip joint by shell splinters in the Syrian civil war. The patient underwent hip arthroplasty revision with implantation of a cement spacer. CT-scan with rectal contrast media filling revealed a rectoacetabular fistula. Consecutively, the patient underwent ileostomy formation. The fistula was then successfully closed by endoscopic over-the-scope clipping (OTSC (R)). Fistulas between intestines and joints rarely develop and in the few cases published mostly extensive abdominal rescue surgery has been performed. Here, we present a case of a traumatic rectoacetabular fistula that was successfully closed by OTSC. This innovative method could represent a safe and suitable option to effectively close fistulas between joints and intestines thereby avoiding extensive rescue surgery with bowel resection or permanent ostomy

Effect of suture technique on the occurrence of incisional hernia after elective midline abdominal wall closure: study protocol for a randomized controlled trial

Background: Based on a recent meta-analysis, a continuous suture technique with a suture to wound length ratio of at least 4: 1, using a slowly absorbable monofilament suture material, is recommended for primary median laparotomy closure. Incisional hernia, which develops in 9 to 20% of patients, remains the major complication of abdominal wall closure. Current clinical data indicate that the incidence of incisional hernias increases by 60% between the first and the third year after median laparotomy, implicating that a follow-up period of 1 year postoperatively is too short with regard to this common complication. Trauma to the abdominal wall can be reduced by improvements in suture technique as well as suture material. Several factors, such as stitch length, suture tension, elasticity, and tensile strength of the suture material are discussed and currently under investigation. A Swedish randomized controlled trial showed a significant reduction in the incisional hernia rate by shortening the stitch length. However, a non-elastic thread was used and follow-up ended after 12 months. Therefore, we designed a multicenter, international, double-blinded, randomized trial to analyze the influence of stitch length, using an elastic, extra-long term absorbable monofilament suture, on the long term clinical outcome of abdominal wall closure. Methods: In total, 468 patients undergoing an elective, median laparotomy will be randomly allocated to either the short stitch or the long stitch suture technique for abdominal wall closure in a 1: 1 ratio. Centers located in Germany and Austria will participate. The primary endpoint measure is the incisional hernia rate 1 year postoperatively, as verified by ultrasound. The frequency of short term and long term complications as well as costs, length of hospital stay and patients' quality of life (EQ-5D-5 L) will be considered as secondary parameters. Following hospital discharge, patients will be examined after 30 days and 1, 3, and 5 years after surgery. Discussion: This study will provide further evidence on whether a short stitch suture technique in combination with an elastic, extra-long term absorbable monofilament suture can prevent incisional hernias in the long term, compared with the long stitch suture technique

Association of differential miRNA expression with hepatic vs. peritoneal metastatic spread in colorectal cancer

Background: Though peritoneal carcinomatosis reflects a late stage of colorectal cancer (CRC), only few patients present with synchronous or metachronous liver metastases alongside their peritoneal carcinomatosis. It is hypothesized that this phenomenon may be causally linked to molecular characteristics of the primary CRC. This study used miRNA profiling of primary CRC tissue either metastasized to the liver, to the peritoneum or not metastasized at all thus to identify miRNAs potentially associated with defining the site of metastatic spread in CRC. Methods: Tissue of the primary tumor stemming from CRC patients diagnosed for either liver metastasis (LM; n = 10) or peritoneal carcinomatosis (PER; n = 10) was analyzed in this study. Advanced CRC cases without metastasis (M0; n = 3) were also included thus to select on those miRNAs most potentially associated with determining metastatic spread in general. miRNA profiling of 754 different miRNAs was performed in each group. MiRNAs being either differentially expressed comparing PER and LM or even triple differentially expressed (PER vs. LM vs. M0) were identified. Differentially expressed miRNAs were further validated by in silico and functional analysis. Results: Comparative analysis identified 41 miRNAs to be differentially expressed comparing primary tumors metastasized to the liver as opposed to those spread to the peritoneum. A set of 31 miRNAs was significantly induced in primary tumors that spread to the peritoneum (PER), while the remaining 10 miRNAs were found to be repressed. Out of these 41 miRNAs a number of 25 miRNAs was triple-differentially expressed (i.e. differentially expressed comparing LM vs. PER vs. M0). The latter underwent in silico analysis. Finally, we demonstrated that miR-31 down-regulated c-MET in DLD-1 colon cancer cells. Conclusions: This study demonstrates that CRC primary tumors spread to the peritoneum vs. metastasized to the liver display significantly different miRNA profiles. Larger patient cohorts will be needed to validate whether determination of e.g. miR-31 may aid to predict the course of disease and whether this may help to create individualized follow up or treatment protocols. To determine whether certain miRNAs may be involved in regulating the metastatic potential of CRC, functional studies will be essential

The potential role of T-cells and their interaction with antigen-presenting cells in mediating immunosuppression following trauma-hemorrhage

Objective: Trauma-hemorrhage results in depressed immune responses of antigen-presenting cells (APCs) and T-cells. Recent studies suggest a key role of depressed T-cell derived interferon (IFN)-g in this complex immune cell interaction. The aim of this study was to elucidate further the underlying mechanisms responsible for dysfunctional T-cells and their interaction with APCs following trauma-hemorrhage. Design: Adult C3H/HeN male mice were subjected to trauma-hemorrhage (3-cm midline laparotomy) followed by hemorrhage (blood pressure of 35�5mmHg for 90 min and resuscitation) or sham operation. At 24 h thereafter, spleens were harvested and T-cells (by Microbeads) and APCs (via adherence) were Isolated. Co-cultures of T-cells and APCs were established for 48 h and stimulated with concanavalin A and lipopolysaccharide. T-Cell specific cytokines known to affect APC function (i.e. interleukin(IL)-2, IL-4 and granulocyte-macrophage colony-stimulating factor (GM-CSF)) were measured in culture supernatants by Multiplex assay. The expression of MHC class II as well as co-stimulatory surface molecules on T-cells and APCs was determined by flow cytometry. Results: The release of IL-4 and GM-CSF by T-cells was suppressed following trauma-hemorrhage, irrespective of whether sham or trauma-hemorrhage APCs were present. Antigen-presenting cells from animals subjected to trauma-hemorrhage did not affect T-cell derived cytokine release by sham T-cells. In contrast, T-cells from traumahemorrhage animals depressed MHC class II expression of CD11c(þ) cells, irrespective of whether APCs underwent sham or trauma-hemorrhage procedure. Surprisingly, co-stimulatory molecules on APCs (CD80, CD86) were not affected by trauma-hemorrhage. Conclusions: These results suggest that beside IFN-g other T-cell derived cytokines contribute to immunosuppression following trauma-hemorrhage causing diminished MHC II expression on APCs. Thus, T-cells appear to play an important role in this interaction at the time-point examined. Therapeutic approaches should aim at maintenance of T-cell function and their interaction with APCs to prevent extended immunosuppression following trauma-hemorrhage

Expression Patterns of TOP2A and SIRT1 Are Predictive of Survival in Patients with High-Risk Soft Tissue Sarcomas Treated with a Neoadjuvant Anthracycline-Based Chemotherapy

Simple Summary High-risk soft tissue sarcomas (HR-STS) account for less than 1% of all malignancies in adults. Despite optimal local treatment, almost half of patients will die within five years of their diagnosis. Chemoresistance is a major responsible mechanism for treatment failure in advanced tumor stages. In contrast to other cancer types, molecular predictors of response to chemotherapy and survival have not been identified and put into clinical practice by now. We analyzed the predictive value of two molecules involved in the working and resistance mechanisms to doxorubicin, TOP2A and SIRT1, in a large cohort of locally advanced HR-STS who underwent a neoadjuvant anthracycline-based chemotherapy with a long-term follow-up. Our results show sarcoma subtype-specific patterns of TOP2A and SIRT1 expression. We demonstrate significant differences in overall survival according to the TOP2A and SIRT1 expression status. Both markers can be used as clinically significant predictive indicators for HR-STS patients scheduled for neoadjuvant anthracycline-based chemotherapy. Abstract Molecular predictors of response to chemotherapy and survival have not been put into clinical practice in high-risk soft tissue sarcomas (HR-STS) by now. The expression of TOP2A and SIRT1 has implications for the mechanism of action of doxorubicin, which is the backbone of chemotherapy in HR-STS. Pre-treatment samples of 167 patients with HR-STS were collected. Protein expression levels of TOP2A and SIRT1 were evaluated with tissue microarrays and immunohistochemistry and correlated with clinicopathological parameters, including overall survival (OS). The expression of TOP2A and SIRT1 was seen in 47% and 60% of patients with HR-STS, respectively. TOP2A expression was associated with higher tumor grading and shorter 5-year OS. The expression of SIRT1 was correlated with a better 5- and 10-year OS. The combination of high SIRT1 and low TOP2A (“Top survivors”) significantly predicted a better OS compared to other biomarker combinations. A multivariate analysis confirmed the expression of SIRT1 and the “Top survivor” biomarker combination as independent predictive factors of OS. This is the first study to associate SIRT1 overexpression with a statistically significant prolongation of OS in HR-STS. Both individual markers and their combination can be used as predictive indicators for HR-STS patients scheduled for neoadjuvant anthracycline-based chemotherapy