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.

Robotic versus laparoscopic proctectomy: a comparative study of short-term economic and clinical outcomes.

BACKGROUND: Although several studies compare the clinical outcomes and costs of laparoscopic and robotic proctectomy, most of them reflect the outcomes of the utilisation of older generation robotic platforms. The aim of this study is to compare the financial and clinical outcomes of robotic and laparoscopic proctectomy within a public healthcare system, utilising a multi-quadrant platform. METHODS: Consecutive patients undergoing laparoscopic and robotic proctectomy between January 2017 and June 2020 in a public quaternary centre were included. Demographic characteristics, baseline clinical, tumour and operative variables, perioperative, histopathological outcomes and costs were compared between the laparoscopic and robotic groups. Simple linear regression and generalised linear model analyses with gamma distribution and log-link function were used to determine the impact of the surgical approach on overall costs. RESULTS: During the study period, 113 patients underwent minimally invasive proctectomy. Of these, 81 (71.7%) underwent a robotic proctectomy. A robotic approach was associated with a lower conversion rate (2.5% versus 21.8%;P = 0.002) at the expense of longer operating times (284 ± 83.4 versus 243 ± 89.8 min;P = 0.025). Regarding financial outcomes, robotic surgery was associated with increased theatre costs (A$23,019 ± 8235 versus A$15,525 ± 6382; P < 0.001) and overall costs (A$34,350 ± 14,770 versus A$26,083 ± 12,647; P = 0.003). Hospitalisation costs were similar between both approaches. An ASA ≥ 3, non-metastatic disease, low rectal cancer, neoadjuvant therapy, non-restorative resection, extended resection, and a robotic approach were identified as drivers of overall costs in the univariate analysis. However, after performing a multivariate analysis, a robotic approach was not identified as an independent driver of overall costs during the inpatient episode (P = 0.1). CONCLUSION: Robotic proctectomy was associated with increased theatre costs but not with increased overall inpatient costs within a public healthcare setting. Conversion was less common for robotic proctectomy at the expense of increased operating time. Larger studies will be needed to confirm these findings and examine the cost-effectiveness of robotic proctectomy to further justify its penetration in the public healthcare system.

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.

Contemporary Neoadjuvant Therapies for High-Risk Melanoma: A Systematic Review.

Despite advances in adjuvant immuno- and targeted therapies, the risk of relapse for stage III melanoma remains high. With 43 active entries on clinicaltrials.gov (8 July 2020), there is a surge of interest in the role of contemporary therapies in the neoadjuvant setting. We conducted a systematic review of trials performed in the last decade evaluating neoadjuvant targeted, immuno- or intralesional therapy for resectable stage III or IV melanoma. Database searches of Medline, Embase, and the Cochrane Central Register of Controlled Trials were conducted from inception to 13 February 2020. Two reviewers assessed titles, abstracts, and full texts. Trials investigating contemporary neoadjuvant therapies in high-risk melanoma were included. Eight phase II trials (4 randomized and 4 single-arm) involving 450 patients reported on neoadjuvant anti-BRAF/MEK targeted therapy (3), anti-PD-1/CTLA-4 immunotherapy (3), and intralesional therapy (2). The safest and most efficacious regimens were dabrafenib/trametinib and combination ipilimumab (1 mg/kg) + nivolumab (3 mg/kg). Pathologic complete response (pCR) and adverse events were comparable. Ipilimumab + nivolumab exhibited longer RFS. Contemporary neoadjuvant therapies are not only safe, but also demonstrate remarkable pCR and RFS-outcomes which are regarded as meaningful surrogates for long-term survival. Studies defining predictors of pCR, its correlation with oncologic outcomes, and phase III trials comparing neoadjuvant therapy to standard of care will be crucial.

Morbidity and Outcomes After Distal Pancreatectomy for Primary Retroperitoneal Sarcoma: An Analysis by the Trans-Atlantic Australasian Retroperitoneal Sarcoma Working Group.

BACKGROUND: Multi-visceral resection often is used in the treatment of retroperitoneal sarcoma (RPS). The morbidity after distal pancreatectomy for primary pancreatic cancer is well-documented, but the outcomes after distal pancreatectomy for primary RPS are not. This study aimed to evaluate morbidity and oncologic outcomes after distal pancreatectomy for primary RPS. METHODS: In this study, 26 sarcoma centers that are members of the Trans-Atlantic Australasian Retroperitoneal Sarcoma Working Group (TARPSWG) retrospectively identified consecutive patients who underwent distal pancreatectomy for primary RPS from 2008 to 2017. The outcomes measured were 90-day severe complications (Clavien-Dindo ≥ 3), postoperative pancreatic fistula (POPF) rate, and oncologic outcomes. RESULTS: Between 2008 and 2017, 280 patients underwent distal pancreatectomy for primary RPS. The median tumor size was 25 cm, and the median number of organs resected, including the pancreas, was three. In 96% of the operations, R0/R1 resection was achieved. The 90-day severe complication rate was 40 %. The grades B and C POPF complication rates were respectively 19% and 5% and not associated with worse overall survival. Administration of preoperative radiation and factors to mitigate POPF did not have an impact on the risk for the development of a POPF. The RPS invaded the pancreas in 38% of the patients, and local recurrence was doubled for the patients who had a microscopic, positive pancreas margin (hazard ratio, 2.0; p = 0.042). CONCLUSION: Distal pancreatectomy for primary RPS has acceptable morbidity and oncologic outcomes and is a reasonable approach to facilitate complete tumor resection.

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.