BACKGROUND:Selected high-risk appendiceal neoplasms with tumour perforation or T4 disease may be considered for risk-reducing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC), even without overt radiological peritoneal disease. Since 2012, our centre has offered laparoscopic CRS-HIPEC, and a robotic approach was recently introduced to enhance visualisation, dexterity, and precision while minimising surgical trauma. This study evaluates the feasibility, safety, and early outcomes of risk-reducing robotic CRS-HIPEC (RCRS-HIPEC) in selected patients with high-risk appendiceal neoplasms without radiological peritoneal disease. PATIENTS AND METHODS:This retrospective single-centre case series was conducted at a national referral centre for peritoneal surface malignancy. Eight patients underwent standardised RCRS-HIPEC. The cohort included low-grade appendiceal mucinous neoplasm ( n = 3), goblet cell carcinoma ( n = 4), and appendiceal adenocarcinoma ( n = 1). The standardised operative approach included omentectomy, falciform excision, umbilicectomy, and cholecystectomy or salpingo-oophorectomy where indicated, followed by closed HIPEC. Outcomes assessed included operative time, blood loss, complications, length of stay, histopathology, patient-reported recovery, and preliminary resource utilisation. RESULTS:Mean age was 65.8 years; there were 5 male and 3 female patients. Mean operative time was 6 h 19 min (±25 min), with minimal blood loss (<150 mL). No patient required epidural analgesia, parenteral nutrition, or prolonged critical care. Median time to first flatus was 3 days, and median hospital stay was 5 days. Two patients experienced Clavien-Dindo grade I morbidity, with no major complications. Histopathology demonstrated residual disease in two patients. Early electronic patient-reported outcome measures suggested favourable recovery, and preliminary Patient Level Information and Costing System data indicated potential NHS resource savings. CONCLUSIONS:RCRS-HIPEC is feasible and safe in carefully selected patients with high-risk appendiceal neoplasms without radiological peritoneal disease. A standardised robotic approach may promote reproducibility, support enhanced recovery, and reduce healthcare resource use. Larger comparative studies are warranted.
Pseudomyxoma Peritonei is characterised by peritoneal metastasis from appendiceal mucinous neoplasms (AMN). The PSOGI classification (2016) categorises PMP into acellular mucin (AM), low-grade mucinous carcinoma peritonei (LGMCP), and high-grade mucinous carcinoma peritonei (HGMCP). This study aimed to determine long-term prognosis based on this classification. Pathology review from PMP patients with AMNs undergoing cytoreductive surgery and heated intraperitoneal chemotherapy (CRS + HIPEC) with curative intent over a 15-year period (2006–2021) was undertaken. Patients underwent standardised surveillance. Cox proportional hazards regression models, log-rank test, and Kaplan–Meier method were used to assess overall (OS) and disease-free survival (DFS) based on histopathological peritoneal metastasis grade. DFS was only calculated for patients who had a complete cytoreduction. 290 PMP patients were identified (AM = 34
Introduction Low-grade appendiceal mucinous neoplasms (LAMNs) are classified as non-perforated (pTis, pT3) or perforated (pT4), and considered precursors of pseudomyxoma peritonei (PMP). This study aims to quantify the risk of developing PMP from pTis and pT3 LAMNs. Materials and Methods Retrospective analysis of a prospectively collected database identified LAMN patients referred to a specialist centre from 2004 to 2019. pT4 LAMNs and other appendix tumours were excluded. All patients had specialist review of their pathology, operation note, and a CT scan (at least 6 weeks post-operatively). Surveillance CTs were then performed at 6, 12, 24, 36, 48, & 60 months, with tumour markers (CEA, CA19-9, CA125). Results 193 pT3/pTis LAMN patients were included (pTis=153, pT3=40). Median follow-up=6.45 (3.91-22.13) years, M:F ratio=1:1.57, and median age=57 (23-83) years. Initial surgery included: appendicectomy (67%), appendicectomy + visceral resection (6%), and right hemicolectomy (27%). R1 resections were identified in 5/193 patients (2.5%). 3 R1 patients underwent re-operation (2 caecal pole excision and 1 ileocecectomy), none of which had residual tumour. 8/193 patients (4%) were lost to follow up. None of the remaining 185 developed PMP. Conclusion This is the largest reported series of pTis/pT3 LAMNs with standardised follow-up in the literature. LAMNs correctly classified as pT3/pTis (after careful specialist review of pathology, operation note, and a baseline post-operative CT) have negligible risk of developing PMP and should have low intensity surveillance. If completely excised, further surgery is not indicated. R1 resections should be considered on an individual basis at a specialist centre.
BACKGROUND:Cytoreductive surgery (CRS) is effective for colorectal cancer peritoneal metastases (CRPM) at increasing overall survival (OS) compared to systemic anticancer treatment (SACT) alone. The addition of Oxaliplatin heated intraperitoneal chemotherapy (HIPEC) has been shown in a randomized controlled trial to result in increased complications without significant OS benefit. This study evaluates outcomes for CRPM patients undergoing CRS+HIPEC with Oxaliplatin (Ox) 368mg/m2 (30 min), versus Mitomycin C (MMC) 35mg/m2 (90min). METHODS: A prospective CRPM real-world database was used to collect outcomes for patients undergoing CRS+HIPEC at a single center. OS, recurrence-free (RFS), peritoneal RFS (PeRFS) were compared amongst all patients with histologically proven CRPM, those with completeness of cytoreduction (CC) score =0/1, and those with CC score=0/1 who were SACT naïve. RESULTS: Between April 2005 and April 2021, 409 patients underwent CRS+HIPEC: 271 (66%) had MMC, 138 (34%) Ox. Of these, 395 (97%) had histologically confirmed CRPM, 336 (85%) achieved CC=0/1, 188 (47%) were SACT naïve; median OS =39.5, 44.4, and 47.2 months respectively. MMC versus Ox median OS in CC0/1=43.7 (95% CI 35.9-48.3) versus 50.1 (39.7-70.2) months, P = .28; Median OS in SACT naïve=45.7 (39.4-65.9) versus 59.9 (38.3-82.0) months, P = .31; multivariable analysis for CC0/1, SACT naïve patients showed Ox was comparable to MMC: HR=0.90, (0.64-1.27) P = .55 versus HR=0.88, (0.53-1.44) P = .60, respectively. Ox resulted in a significantly improved PeRFS in CC0/1 patients (MMC=9.0 versus Ox=12.6months, P = .01). A multivariable model for PeRFS showed a HR=0.63, (0.43-0.95), P = .03 for Ox. CONCLUSION: This study suggests a role for Ox HIPEC in CRPM which should be explored further in clinical trials.
Treatment guidelines provided by PRODIGE-7 recommend perioperative systemic chemotherapy before cytoreductive surgery (CRS) for colorectal cancer peritoneal metastases (CRPM). Toxicity with multimodal treatment needs to be better defined. Chemotherapy response and impact on survival have not been reported. We assessed CRPM patients who received systemic oxaliplatin/irinotecan before CRS (preoperative) with Mitomycin C (35 mg/m2, 90 min) or Oxaliplatin (368 mg/m2, 30 min) heated intraperitoneal chemotherapy (HIPEC). Secondary analysis was performed from a prospective database. Overall survival (OS) in chemotherapy responders (R) and nonresponders (NR) was compared. Toxicity was assessed by rate of adverse events (AEs). From April 2005 to April 2021, 436 patients underwent CRS + HIPEC; 125 (29%) received preoperative chemotherapy. The 112 (90%) received oxaliplatin (64, 57%) or irinotecan (48, 43%). R, defined as complete (CR) or partial response on preoperative imaging and/or postoperative histology, was seen in 71, 63% (53.8-72.3); 16, 14% (8.4-22.2) had CR. Median OS in R versus NR was 43.7 months (37.9-49.4) versus 23.9 (16.3-31.4) p = 0.007, HR 0.51 (0.31-0.84). OS multivariable analysis showed HR 0.48 (0.25-0.95), p = 0.03 for chemotherapy response corrected by peritoneal cancer index, completeness of cytoreduction score. CRS led to 21% grade 3-4 AEs versus 4% for preoperative chemotherapy. HIPEC grade 3-4 AEs were 0.5%. Preoperative chemotherapy response is an independent predictor for OS in CRPM. Perioperative chemotherapy is used in the multimodal treatment of colorectal cancer peritoneal metastases (CRPM). Preoperative chemotherapy response is an independent predictor for overall survival in patients with CRPM. Grade 3-4 adverse events related to mitomycin C (35 mg/m2) and Oxaliplatin (368 mg/m2) heated intraperitoneal chemotherapy are rare (0.5%).
BACKGROUND:Genetic biomarkers guide systemic anti-cancer treatment (SACT) in metastatic colorectal cancer. It has been suggested they have a role in selecting patients with colorectal peritoneal metastases (CRPM) for cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). This study aims to quantify the effect of mutation status on overall survival (OS), adjusting for confounders such as pre-operative systemic anticancer treatment (SACT). PATIENTS AND METHODS:Retrospective analysis of patients undergoing CRS/HIPEC for CRPM at a national peritoneal tumour centre (2004-2017) was performed. Demographics, treatment history and operative data were extracted. Known biomarker gene mutation status was noted including: KRAS, NRAS, BRAF, PIK3CA and MMR. Cox regression analysis and Kaplan-Meier curves were used to determine overall survival. RESULTS:One hundred ninety-five patients were included. Median follow-up time was 34.7 months (range 5.4-184.9 months) and median OS was 38.7 months (95% CI 32.4-44.9 months). Biomarker status was as follows: KRAS (n = 114), NRAS (n = 85), BRAF (n = 44), PIK3CA (n = 15) and MMR (n = 21). Mutation rates were 45.6%, 3.5%, 13.6%, 13.3% and 14.3%, respectively. Seventy-four per cent underwent complete cytoreduction (CC = 0), 81% received SACT pre-CRS/HIPEC and 65% post-CRS/HIPEC. RAS (p = 0.21) or BRAF (p = 0.109) mutation status did not predict OS. Nodal involvement, extramural vascular invasion, Peritoneal Cancer Index (PCI) score, CC score, SACT post-HIPEC and NRAS mutation were significant negative predictors of OS in univariate analysis (p < 0.05). Multivariate Cox regression confirmed CC-score > 1 (HR: 7.599, 95% CI 3.402-16.974, p < 0.0001) as a negative predictor of OS. RAS mutation status did not affect outcome (HR: 1.682, 95% CI 0.995-2.843, p = 0.052). CONCLUSIONS:RAS mutation status should not in isolation be used to select patients for CRS/HIPEC.
Introduction: Traditionally patients with colorectal peritoneal metastases (CRPM) were offered palliative chemotherapy and best supportive care. With the introduction of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), patients in the UK have been referred to nationally approved centres. This study describes the pattern of referral and outcomes of patients managed through one UK centre. Methods: and Methods: A prospective register recorded referrals, demographics, prior treatment pathways, and specialist multidisciplinary team (MDT) decisions (2002-2015). Peritoneal cancer index (PCI) was recorded intra-operatively; complete cytoreduction was deemed when a CC0/1 was achieved. Complications were classified using NCI CTCAE. v.4. Median overall survivals (OS) were described for those treated by CRS/HIPEC and in derived estimates for patients with isolated peritoneal metastases treated by chemotherapy alone in the ARCAD trials consortium. Results: Two-hundred-eighty-six patients with CRPM were referred. Despite increasing numbers of referrals annually, the proportion of patients selected for CRS/HIPEC decreased from 64.5%, to 40%, and to 37.1% for 2002-09, 2010-12, and 2013-15, respectively (p < 0.017). CRS/HIPEC was undertaken in 117 patients with a median PCI of 7 and CC0/1 achieved in 86.3%. NCI CTCAE grade 3/4 complication rates were 9.4%; 30-day mortality was 0.85%. Median OS following CRS/HIPEC was 46.0 months: that for patients not receiving CRS/HIPEC was 13.2 months. Conclusion: The evolution of the national peritoneal treatment centre over 14 years has been associated with increased referral numbers, refinement of selection for major surgery, matched with achievements of low complication rates and survival advantages in selected patients compared with traditional nonsurgical treatments. (C) 2019 Elsevier Ltd, BASO similar to The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.
BACKGROUND:Low-grade appendiceal mucinous neoplasm (LAMN) is a precursor lesion of pseudomyxoma peritonei, which, if treated suboptimally, may later disseminate throughout the abdominal cavity. We previously demonstrated the role of cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) to reduce the dissemination risk. Here we describe the feasibility and safety of minimal access cytoreductive surgery (MACRS) and HIPEC as an alternative to the open approach.METHODS:We evaluated patients with LAMNs at risk of dissemination (known as LAMN II) who were referred to a national treatment centre between 2010 and 2012 and comparison is made between this group and patients undergoing open CRS and HIPEC for the same pathology over the same time period.RESULTS:Of the 39 patients with LAMN II, 10 patients were treated by MACRS and HIPEC and 7 were treated by an open approach. Among the MACRS procedures, there were no conversions to open surgery; median procedure length, median length of stay, and complication rates were similar between groups and there were no 30-day deaths. After 3- and 11-months median follow-up respectively, no patients have evidence of disease progression.CONCLUSIONS:The present series demonstrates that MACRS and HIPEC is a feasible and safe alternative to the open procedure with the advantage of smaller abdominal wounds and comparable morbidity and inpatient stay. Longer follow-up is needed to assess the impact on disease progression.
Objective. To estimate adhesiolysis rates at cesarean delivery (CD) and to estimate costs and clinical implications of performing adhesiolysis at repeat CD. Design. Retrospective cohort using secondary data. Setting. Over 500 acute care hospitals in the USA. Population . Women ≥15 years old with a medical claim for CD between 1 January 2007 and 31 December 2008 who were treated in a hospital that contributed data to the Premier Perspective™ database. Methods. Using data from hospital discharge records, rates of adhesiolysis at the time of CD were calculated. Among patients with repeat CD, a propensity score was used to create matched cohorts with and without adhesiolysis. Unadjusted rates and means were compared between these cohorts. Main outcome measures. Cost, length of stay and selected clinical complications between repeat CD patients with and without adhesiolysis. Results. Adhesiolysis was performed in 0.5% of primary and 6.1% of repeat CD patients. Using propensity scores, 10 261 women who experienced repeat CD with adhesiolysis were matched to 10 261 control women. Hospital cost ($5739 vs. $5448), length of stay (2.97 vs. 2.88 days) and operative time (84.0 vs. 74.2 min) were significantly greater in the adhesiolysis than in the non-adhesiolysis group ( p < 0.01 for all comparisons), as was the overall complication rate (6.3 vs. 3.5%). Conclusions. Adhesiolysis rates were higher in repeat compared with primary CD. Among repeat CD patients, costs and complications were higher in the adhesiolysis group. Reducing adhesion formation after primary CD could reduce cost and complications at the time of repeat CD.
Objective. To estimate adhesiolysis rates at cesarean delivery (CD) and to estimate costs and clinical implications of performing adhesiolysis at repeat CD. Design. Retrospective cohort using secondary data. Setting. Over 500 acute care hospitals in the USA. Population. Women ≥15 years old with a medical claim for CD between 1 January 2007 and 31 December 2008 who were treated in a hospital that contributed data to the Premier Perspective™ database. Methods. Using data from hospital discharge records, rates of adhesiolysis at the time of CD were calculated. Among patients with repeat CD, a propensity score was used to create matched cohorts with and without adhesiolysis. Unadjusted rates and means were compared between these cohorts. Main outcome measures. Cost, length of stay and selected clinical complications between repeat CD patients with and without adhesiolysis. Results. Adhesiolysis was performed in 0.5% of primary and 6.1% of repeat CD patients. Using propensity scores, 10 261 women who experienced repeat CD with adhesiolysis were matched to 10 261 control women. Hospital cost ($5739 vs. $5448), length of stay (2.97 vs. 2.88 days) and operative time (84.0 vs. 74.2 min) were significantly greater in the adhesiolysis than in the non‐adhesiolysis group (p < 0.01 for all comparisons), as was the overall complication rate (6.3 vs. 3.5%). Conclusions. Adhesiolysis rates were higher in repeat compared with primary CD. Among repeat CD patients, costs and complications were higher in the adhesiolysis group. Reducing adhesion formation after primary CD could reduce cost and complications at the time of repeat CD.
BACKGROUND:Adhesions are fibrous bands of scar tissue, often a result of surgery, that form between internal organs and tissues, joining them together abnormally. Postoperative adhesions frequently occur following abdominal surgery, and are associated with a large economic burden. This study examines the inpatient burden of adhesiolysis in the United States (i.e., number and rate of events, cost, length of stay [LOS]).METHODS:Hospital discharge data for patients with primary and secondary adhesiolysis were analyzed using the 2005 Healthcare Cost and Utilization Project's Nationwide Inpatient Sample. Procedures were aggregated by body system.RESULTS:We identified 351,777 adhesiolysis-related hospitalizations: 23.2% for primary and 76.8% for secondary adhesiolysis. The average LOS was 7.8 days for primary adhesiolysis. We found that 967,332 days of care were attributed to adhesiolysis-related procedures, with inpatient expenditures totaling $2.3 billion ($1.4 billion for primary adhesiolysis; $926 million for secondary adhesiolysis). Hospitalizations for adhesiolysis increased steadily by age and were higher for women. Of secondary adhesiolysis procedures, 46.3% involved the female reproductive tract, resulting in 57,005 additional days of care and $220 million in attributable costs.CONCLUSIONS:Adhesiolysis remain an important surgical problem in the United States. Hospitalization for this condition leads to high direct surgical costs, which should be of interest to providers and payers.