Practical Management of Adult Ultra-Rare Primary Retroperitoneal Soft Tissue Sarcoma: A Focus on Perivascular Epithelioid Tumours and Extraosseous Ewing Sarcoma.

With the exception of well-differentiated liposarcoma, dedifferentiated liposarcoma, leiomyosarcoma, solitary fibrous tumour, malignant peripheral nerve sheath tumour, and undifferentiated pleomorphic sarcoma, the majority of the ≈70 histologic subtypes of retroperitoneal sarcoma are defined as 'ultra-rare' sarcomas, with an incidence of ≤1-5/1,000,000 persons/year. For most of these ultra-rare RPS subtypes, diagnosis and treatment follows international guidelines for the management of more common RPS histologies, with en bloc surgical resection as the mainstay of curative treatment, and enrolment in clinical trials where possible. Because the treatment of RPS is heavily driven by histology, the surgeon must be familiar with specific issues related to the diagnosis and management of ultra-rare sarcoma subtypes. Expert radiological and surgeon reviews are required to differentiate similarly presenting tumours where surgery can be avoided (e.g., angiomyolipoma), or where upfront systemic therapy is indicated (e.g., extraosseous Ewing's sarcoma). Thus, the management of all retroperitoneal sarcomas should occur at a sarcoma referral centre, with a multidisciplinary team of experts dedicated to the surgical and medical management of these rare tumours. In this focused review, we highlight how diagnosis and management of the ultra-rare primary RPS histologies of malignant perivascular epithelioid cell tumour (PEComa), extraosseous Ewing sarcoma (EES), extraosseous osteosarcoma (EOS), and rhabdomyosarcoma (RMS) critically diverge from the management of more common RPS subtypes.

Perioperative outcomes of cytoreductive surgery for tumours of colorectal or appendiceal origin with ovarian involvement.

BACKGROUND AND OBJECTIVES: Ovarian metastases (OM) are a common site for metastases in gastrointestinal tumours with peritoneal disease. This study aimed to evaluate perioperative complications between patients with and without OM following cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for appendiceal/colorectal cancer. METHODS: Female patients undergoing CRS ± HIPEC for appendiceal/colorectal tumours at a single centre from 2009 to 2020 were analysed. Patients were grouped according to presence or absence of OM at the time of CRS. RESULTS: The study included 318 patients, 72 (22.6%) had OM. Operation duration was longer for patients with OM (332 vs. 276 min, p < 0.0001). Patients with OM achieved higher rates of complete cytoreduction (93% vs. 79%, p = 0.006) despite a higher peritoneal carcinomatosis index (13 vs. 7, p < 0.001) and were more likely to require a blood transfusion (32% vs. 19%, p = 0.024) and a stoma (24% vs.10%, p = 0.005). Increasing age and presence of abdominal symptoms were independent predictors of major and all-cause morbidity, respectively. The presence of abdominal symptoms was independently associated with all-cause morbidity in the OM group. CONCLUSION: These results may assist with preoperative counselling. Prospective multicentre datasets are needed to evaluate morbidity in one- versus two-stage approaches for those with abdominal symptoms and OM.

Robotic pelvic side-wall lymph node dissection for rectal cancer: a systematic review of videos and application of the IDEAL 2A framework.

Lateral pelvic lymph node dissection (LPLND) in rectal cancer has gained increasing traction worldwide. Robotic LPLND is an emerging technique. Utilising the IDEAL (idea, development, exploration, assessment and long-term follow-up) framework for surgical innovation, robotic LPLND is currently at the IDEAL 2A stage (development) mainly limited to case reports, case series and videos. A systematic literature review was performed for videographic robotic LPLND. Pubmed, Ovid and Web of Science were searched with a predefined search strategy. The LapVEGAS score for peer review of video surgery was adapted for the robotic approach (RoVEGAS) and applied to measure video quality. Two reviewers independently reviewed videos and consensus reached on technical steps and learning points. Data are presented as a narrative synthesis of results. The IDEAL 2A framework was applied to videos to assess their content at the present stage of innovation. A total of 83 abstracts were identified. In accordance with the PRISMA statement, nine videos were analysed. Adherence to the complete IDEAL 2a framework was low. All videos demonstrated LPLND; however, reporting of clinical outcomes was heterogeneous and completed in six of nine videos. Histopathology was reported in six videos, with other outcomes variably reported. No videos presented patient-reported outcome measures. Two videos reported presence or absence of recurrence on follow-up. Video articles provide a valuable educational resource in dissemination and adoption of robotic techniques. Standardisation of reporting objectives are needed. Complete reporting of pathology and oncologic outcomes is required in videographic procedural-based publications to meet the IDEAL 2A framework criteria.

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in small bowel adenocarcinoma with peritoneal metastasis: a systematic review.

Objectives: Small bowel adenocarcinoma (SBA) with peritoneal metastasis (PM) is rare and despite treatment with systemic chemotherapy, the prognosis is poor. However, there is emerging evidence that cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) may offer a survival benefit over systemic therapy alone. This systematic review will assess the effectiveness of CRS-HIPEC for SBA-PM. Content: Three databases were searched from inception to 11/10/21. Clinical outcomes were extracted and analysed. Summary: A total of 164 cases of SBA-PM undergoing CRS-HIPEC were identified in 12 studies. The majority of patients had neoadjuvant chemotherapy (87/164, 53%) and complete cytoreduction (143/164, 87%) prior to HIPEC. The median overall survival was 9-32 months and 5-year survival ranged from 25 to 40%. Clavien-Dindo grade III/IV morbidity ranged between 19.1 and 50%, while overall mortality was low with only 3 treatment-related deaths. Outlook: CRS-HIPEC has the potential to improve the overall survival in a highly selected group of SBA-PM patients, with 5-year survival rates comparable to those reported in colorectal peritoneal metastases. However, the expected survival benefits need to be balanced against the intrinsic risk of morbidity and mortality associated with the procedure. Further multicentre studies are required to assess the safety and feasibility of CRS-HIPEC in SBA-PM to guide best practice management for this rare disease.

Major vascular reconstruction in colorectal adenocarcinoma and retroperitoneal sarcoma: A retrospective study of safety and margins in a tertiary referral centre.

BACKGROUND: The role of en bloc vascular resection and reconstruction (EVRR) is controversial in colorectal adenocarcinoma (CRC), but well-established in retroperitoneal sarcoma (RPS). Sparse data exists regarding these complex procedures. METHODS: Patients undergoing curative intent EVRR for advanced CRC and RPS between 2014 and 2021 at a tertiary centre were included. Morbidity, margins, recurrence, and survival were evaluated. RESULTS: 24 patients underwent EVRR with 48 reconstructions (11 CRC and 13 RPS). For CRC, 100% of patients underwent Iliac system reconstructions. For RPS, inferior vena cava reconstructions were the most common (69.2%). There were 2 arterial and 1 venous graft thromboses. Primary graft patency was 89.4% arterial and 93.1% venous, while secondary patency was 100% arterial and 96.5% venous at last follow up. 1 venous and 1 arterial graft required reoperation for bleeding. There were no compromised limbs. Major complications occurred in 6 patients (25.0%) with no observed difference between CRC and RPS (OR 0.43 95%CI[0.60,3.19], P = 0.41). R1 margins occurred 1 CRC (90.9%) and 3 RPS (76.9%), with no R2 resections. All vascular resection margins were clear. There were 6 CRC (50%) and 4 RPS (33.3%) recurrences. Median recurrence time was 20.9 months for CRC and 'not yet reached' for RPS. Median follow-up was 19.4 months for CRC and 21.4 months for RPS. CONCLUSION: EVRR for locally advanced CRC or RPS is safe and achieves favorable R0 resection rates. CRC patients with major vascular invasion can still be considered for curative intent surgery. Larger cohorts with longer follow up are needed to assess oncologic outcomes.

A systematic review and meta-analysis of robotic resections for diverticular disease.

AIM: Resection of diverticular disease can be technically challenging. Tissue planes can be difficult to identify intraoperatively due to inflammation or fibrosis. Robotic surgery may improve identification of tissue planes and dissection which can facilitate difficult minimally invasive resections. This systematic review and meta-analysis evaluates the role of robotic surgery compared to laparoscopic surgery in diverticular resection. METHODS: A systematic review and meta-analysis was performed in accordance with the PRISMA statement. The search was completed using PubMed, OVID MEDLINE and EMBASE. A total of 490 articles were retrieved, and studies reporting primary outcomes for robotic diverticular resection were included in the final analysis. A meta-analysis of studies comparing robotic and laparoscopic surgery was performed on rate of conversion to open surgery and complications. RESULTS: Fifteen articles (8 cohort studies and 7 case series) reporting 3711 robotic diverticular resections were analysed. In comparison to laparoscopic, robotic surgery for diverticular disease was associated with a reduced conversion to open and a longer operating time. Meta-analysis showed robotic resection was associated with a lower conversion rate compared to laparoscopic surgery (OR: 0.57; 95% CI: 0.49-0.66, p < 0.001). There was no significant difference in grade III and above complications (OR: 0.74; 95% CI: 0.49-1.13, p = 0.17). Operating time was longer with a robotic approach (Hedge's G: 0.43; 95% CI: 0.04-0.81, p = 0.03). CONCLUSION: Robotic resection is a feasible and safe option in diverticular disease. Although associated with a longer operating time, robotic surgery may render diverticular disease resectable with a minimally invasive approach that would have otherwise necessitated a laparotomy. Randomised controlled data is required to better define the role of robotic surgery for diverticular disease resections.

Retroperitoneal and Mesenteric Liposarcomas.

Retroperitoneal liposarcomas are a rare entity and are comprised mostly of the well-differentiated and dedifferentiated subtypes. Eight-year survival ranges from 30% to 80% depending on histologic subtype and grade. Surgery is the cornerstone of treatment and compartment resection is the current standard. Mesenteric liposarcomas are extremely rare and comprise more high-grade lesions, with poorer prognosis of 50% 5-year overall survival. They are managed with a similar aggressive surgical approach. This review presents the current management of retroperitoneal and mesenteric liposarcomas.

Preoperative imaging of gastric GISTs underestimates pathologic tumor size: A retrospective, single institution analysis.

BACKGROUND: How well imaging size agrees with pathologic size of gastric gastrointestinal stromal tumors (GISTs) is unknown. GIST risk stratification is based on pathologic size, location, and mitotic rate. To inform decision making, the size discrepancy between imaging and pathology for gastric GISTs was investigated. METHODS: Imaging and pathology reports were reviewed for 113 patients. Bland-Altman analyses and intraclass correlation (ICC) assessed agreement of imaging and pathology. Changes in clinical risk category due to size discrepancy were identified. RESULTS: Computed tomography (CT) (n = 110) and endoscopic ultrasound (EUS) (n = 50) underestimated pathologic size for gastric GISTs by 0.42 cm, 95% confidence interval (CI): (0.11, 0.73), p = 0.008 and 0.54 cm, 95% CI: (0.25, 0.82), p < 0.001, respectively. ICCs were 0.94 and 0.88 for CT and EUS, respectively. For GISTs ≤ 3 cm, size underestimation was 0.24 cm for CT (n = 28), 95% CI: (0.01, 0.47), p = 0.039 and 0.56 cm for EUS (n = 26), 95% CI: (0.27, 0.84), p < 0.0001. ICCs were 0.72 and 0.55 for CT and EUS, respectively. Spearman's correlation was ≥0.84 for all groups. For GISTs ≤ 3 cm, 6/28 (21.4% p = 0.01) on CT and 7/26 (26.9% p = 0.005) on EUS upgraded risk category using pathologic size versus imaging size. No GISTs ≤ 3 cm downgraded risk categories. Size underestimation persisted for GISTs ≤ 2 cm on EUS (0.39 cm, 95% CI: [0.06, 0.72], p = 0.02, post hoc analysis). CONCLUSION: Imaging, particularly EUS, underestimates gastric GIST size. Caution should be exercised using imaging alone to risk-stratify gastric GISTs, and to decide between surveillance versus surgery.

Perioperative blood transfusion is not an independent predictor for worse outcomes in retroperitoneal sarcoma surgery.

BACKGROUND: Surgery for retroperitoneal soft tissue sarcoma (RPS) is technically challenging, often requiring perioperative red blood cell transfusion (PBT). In other cancers, controversy exists regarding the association of PBT and oncologic outcomes. No study has assessed this association in primary RPS, or identified factors associated with PBT. METHODS: Data was collected on all resected primary RPS between 2006 and 2020 at The Ottawa Hospital (Canada) and University Hospital Birmingham (United Kingdom). 'PBT' denotes transfusion given one week before surgery until discharge. Multivariable regression (MVA) identified clinicopathologic factors associated with PBT and assessed PBT association with oncologic outcomes. Surgical complexity was measured using resected organ score (ROS) and patterns of resection. RESULTS: 192 patients were included with 98 (50.8%) receiving PBT. Median follow-up was 38.2 months. High tumour grade (OR 2.20, P = 0.048), preoperative anemia (OR 2.78, P = 0.020), blood loss >1000 mL (OR 4.89, P = 0.004) and ROS >2 (OR 2.29, P = 0.026) were associated with PBT on MVA. A direct linear relationship was observed between higher ROS and increasing units of PBT (ß = 0.586, P = 0.038). Increasingly complex patterns of resection were associated with increasing odds of PBT. PBT was associated with severe post-operative complications (P = 0.008) on MVA. Univariable association between PBT and 5-year disease-free or overall survival was lost upon MVA. CONCLUSIONS: Surgical complexity and high tumour grade are potentially related to PBT. Oncologic outcomes are not predicted by PBT but are better explained by tumour grade which subsequently may increase surgical complexity. Strategies to reduce PBT should be considered in primary RPS patients.

Acute midgut volvulus in a septuagenarian with secondary jejunoileal diverticulitis and undiagnosed congenital malrotation: an unusual presentation.

A 79-year-old male presented with abdominal pain, incidental umbilical hernia and acute midgut volvulus that was not detected until surgical exploration. When he presented to hospital, computed tomography (CT) findings indicated perforated jejunoileal diverticulitis; however, in the operating room clockwise volvulization of the jejunum and ileum, secondarily inflamed jejunoileal diverticula, incomplete malrotation (right-sided duodenojejunal flexure), right retroperitoneal adhesions (Ladd's bands) and numerous other congenital adhesive bands were found. A modified Ladd's procedure and umbilical hernia repair were completed including detorsion, division of Ladd's bands with medialization of the cecum and lysis of other congenital adhesions without appendectomy. The patient recovered to baseline function by 3 weeks postoperatively. Acute midgut volvulus is a life-threatening surgical emergency that is exceptionally rare in the elderly. CT is relatively insensitive, so misdiagnosis is common. A high index of suspicion is required, especially in patients with a history of congenital gastrointestinal abnormalities. Prompt surgical exploration for correction and prevention is crucial.

Prospective randomised controlled trial using the REthinking Clinical Trials (REaCT) platform and National Surgical Quality Improvement Program (NSQIP) to compare no preparation versus preoperative oral antibiotics alone for surgical site infection rates in elective colon surgery: a protocol.

INTRODUCTION: Despite 40 randomised controlled trials (RCTs) investigating preoperative oral antibiotics (OA) and mechanical bowel preparation (MBP) to reduce surgical site infection (SSI) rate following colon surgery, there has never been an RCT published comparing OA alone versus no preparation. Of the four possible regimens (OA alone, MBP alone, OA plus MBP and no preparation), randomised evidence is conflicting for studied groups. Furthermore, guidelines vary, with recommendations for OA alone, OA plus MBP or no preparation. The National Surgical Quality Improvement Program (NSQIP) has automated data collection for surgical patients. Similarly, the 'REthinking Clinical Trials' (REaCT) platform increases RCT enrolment by simplifying pragmatic trial design. In this novel RCT protocol, we combine REaCT and NSQIP to compare OA alone versus no preparation for SSI rate reduction in elective colon surgery. To our knowledge, this is the first published RCT protocol that leverages NSQIP for data collection. In our feasibility study, 67 of 74 eligible patients (90%) were enrolled and 63 of 67 (94%) were adherent to protocol. The 'REaCT-NSQIP' trial design has great potential to efficiently generate level I evidence for other perioperative interventions. METHODS AND ANALYSIS: SSI rates following elective colorectal surgery after preoperative OA or no preparation will be compared. We predict 45% relative rate reduction of SSI, improvement in length of stay, reduced costs and increased quality of life, with similar antibiotic-related complications. Consent, using the 'integrated consent model', and randomisation on a mobile device are completed by the surgeon in a single clinical encounter. Data collection for the primary end point is automatic through NSQIP. Analysis of cost per weighted case, cost utility and quality-adjusted life years will be done. ETHICS AND DISSEMINATION: This study is approved by The Ontario Cancer Research Ethics Board. Results will be disseminated in surgical conferences and peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03663504; Pre-results, recruitment phase.

Current developments in the tissue engineering of autologous heart valves: moving towards clinical use.

The use of tissue-engineering methods to create autologous heart valve constructs has the potential to overcome the fundamental drawbacks of more traditional valve prostheses. Traditional mechanical valves, while durable, increase the risk for endocarditis and thrombogenesis, and require the recipient to continue lifelong anticoagulant therapy. Homograft or xenograft heart valve prostheses are associated with immune reaction and progressive deterioration with limited durability. Most importantly, neither option is capable of growth and remodeling in vivo and both options place the patient at risk for valve-related complications and reoperation. These shortcomings have prompted the application of tissue-engineering techniques to create fully autologous heart valve replacements. Future clinically efficacious tissue-engineered autologous valves should be nonthrombogenic, biocompatible, capable of growth and remodeling in vivo, implantable with current surgical techniques, hemodynamically perfect, durable for the patient's life and most importantly, significantly improve quality of life for the patient. In order to meet these expectations, the nature of the ideal biochemical milieu for conditioning an autologous heart valve will need to be elucidated. In addition, standardized criteria by which to quantitatively evaluate a tissue-engineered heart valve, as well as noninvasive analytical techniques for use in long-term animal models, will be required. This article highlights the advances, challenges and future clinical prospects in the field of tissue engineering of autologous heart valves, focusing on progress made by studies that have investigated a fully autologous, tissue-engineered pulmonary valve replacement in vivo.

Both Nramp1 and DMT1 are necessary for efficient macrophage iron recycling.

OBJECTIVE: Divalent metal transporter 1 (DMT1) and natural resistance-associated macrophage protein 1 (Nramp1) are iron transporters that localize, respectively, to the early and late endosomal compartments. DMT1 is ubiquitously expressed, while Nramp1 is found only within macrophages and neutrophils. Our previous studies have identified a role for Nramp1 during macrophage erythrophagocytosis; however, little is known about the function of DMT1 during this process. MATERIALS AND METHODS: Wild-type RAW264.7 macrophages (RAW), and those stably transfected with Nramp1 (RAW/Nramp1) were treated with either DMT1-small interfering RNA, or with ebselen, a selective inhibitor of DMT1. RESULTS: Although macrophages lacking either functional DMT1 or Nramp1 experienced a moderate reduction in iron recycling efficiency, the ability of macrophages lacking both functional DMT1 and Nramp1 to recycle hemoglobin-derived iron was severely compromised. Compared to macrophages singly deficient in either DMT1 or Nramp1 transport ability, macrophages where DMT1 and Nramp1 were both compromised exhibited an abrogated increase in labile iron pool content, released less iron, and experienced diminished upregulation of ferroportin and heme-oxygenase 1 levels following erythrophagocytosis. CONCLUSIONS: These results suggest that although the loss of either Nramp1 or DMT1 transport ability results in minor impairment after erythrophagocytosis, the simultaneous loss of both Nramp1 and DMT1 iron transport activity is detrimental to the iron recycling capacity of the macrophage.

Nramp1 promotes efficient macrophage recycling of iron following erythrophagocytosis in vivo.

Natural resistance-associated macrophage protein 1 (Nramp1) is a divalent metal transporter expressed exclusively in phagocytic cells. We hypothesized that macrophage Nramp1 may participate in the recycling of iron acquired from phagocytosed senescent erythrocytes. To evaluate the role of Nramp1 in vivo, the iron parameters of WT and KO mice were analyzed after acute and chronic induction of hemolytic anemia. We found that untreated KO mice exhibited greater serum transferrin saturation and splenic iron content with higher duodenal ferroportin (Fpn) and divalent metal transporter 1 (DMT1) expression. Furthermore, hepatocyte iron content and hepcidin mRNA levels were dramatically lower in KO mice, indicating that hepcidin levels can be regulated by low-hepatocyte iron stores despite increased transferrin saturation. After acute treatment with the hemolytic agent phenylhydrazine (Phz), KO mice experienced a significant decrease in transferrin saturation and hematocrit, whereas WT mice were relatively unaffected. After a month-long Phz regimen, KO mice retained markedly increased quantities of iron within the liver and spleen and exhibited more pronounced splenomegaly and reticulocytosis than WT mice. After injection of (59)Fe-labeled heat-damaged reticulocytes, KO animals accumulated erythrophagocytosed (59)Fe within their liver and spleen, whereas WT animals efficiently recycled phagocytosed (59)Fe to the marrow and erythrocytes. These data imply that without Nramp1, iron accumulates within the liver and spleen during erythrophagocytosis and hemolytic anemia, supporting our hypothesis that Nramp1 promotes efficient hemoglobin iron recycling in macrophages. Our observations suggest that mutations in Nramp1 could result in a novel form of human hereditary iron overload.