Use of Prognostic Factors and Scores in Selection of Patients with Colorectal Cancer Peritoneal Metastasis (CRPM) for Cytoreductive Surgery and Intraperitoneal Chemotherapy (CRS/IPC): Results of an International Survey Among Oncologic Clinicians.

BACKGROUND: No universally accepted guidelines exist for treatment of patients with colorectal cancer peritoneal metastases (CRPM) undergoing cytoreductive surgery and intraperitoneal chemotherapy (CRS/IPC). Several uncertainties remain concerning almost every aspect of this treatment modality, resulting in marked variability in patient management and likely outcomes. This survey aimed to define variations and trends in clinician decision making more clearly. METHODS: A 41-question web-based survey was distributed electronically via the Peritoneal Surface Oncology Group International (PSOGI), the International Society for the Study of Pleura and Peritoneum (ISSPP) as well as via social media (particularly Twitter). The survey sought to address and record clinician responses regarding patient workup/assessment, selection for preoperative systemic therapy, preoperative and intraoperative selection for CRS/IPC, and consideration of prognosis and complications. RESULTS: Complete responses were received from 60 clinicians from 45 centres in 22 countries. Upon assessment of survey responses, several interesting trends were noted in each section of the survey. Significant variability in surgeon practice and opinion were identified concerning almost every aspect of the treatment modality. CONCLUSION: This international survey provides the most comprehensive insight into clinician decision-making trends regarding patient assessment, selection and management. This should allow areas of variability to be more clearly defined and could potentially prompt development of initiatives for achieving consensus and standardisation of care in the future.

External validation of prognostic scores and comparison of predictive accuracy for patients with colorectal cancer with peritoneal metastases considered for cytoreductive surgery and intraperitoneal chemotherapy.

BACKGROUND AND OBJECTIVES: Prognostic scores are developed to facilitate the selection of patients with colorectal cancer peritoneal metastases (CRPM) for treatment with cytoreductive surgery (CRS) ± intraperitoneal chemotherapy (IPC). Three prominent prognostic scores are the Peritoneal Surface Disease Severity Score (PSDSS), the Colorectal Peritoneal Metastases Prognostic Surgical Score (COMPASS), and the modified COloREctal-Pc (mCOREP). We externally validate these scores and compare their predictive accuracy. METHODS: Data from consecutive CRPM patients who underwent CRS/IPC from 1996 to 2018 was used to externally validate COMPASS, PSDSS, and mCOREP. Analysis evaluated the efficacy of each score in predicting (1) open-close laparotomy-those found at laparotomy to not be eligible for curative intent CRS/IPC, (2) surgical futility-those who underwent open-close laparotomy, palliative debulking surgery, or had an overall survival of less than 12 months, and (3) overall and recurrence-free survival (OS, RFS). RESULTS: Prognostic scores were calculated for the 174-patient external validation cohort. COMPASS was most accurate in predicting open-close laparotomy, futile surgery, and survival (OS and RFS). Area under the curve (AUC) for open-close prediction was 0.78 (95% confidence interval, CI: 0.68-0.87), representing useful discrimination. However, AUC for futility prediction was 0.62 (95% CI: 0.52-0.71), and C-statistic for OS was 0.65 indicating only possibly helpful discrimination. C-statistic for RFS was 0.59 indicating poor discrimination. CONCLUSION: While COMPASS showed the best statistical behavior, accuracy for several clinically relevant outcomes remains low, and thus applicability to clinical practice limited.

Iterative cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy for colorectal peritoneal metastases: A multi-institutional experience.

BACKGROUND AND OBJECTIVES: The aims of this multi-institutional study were to assess the feasibility of iterative cytoreductive surgery (iCRS)/hyperthermic intraperitoneal chemotherapy, iCRS in colorectal peritoneal carcinomatosis (CRPC), evaluate survival, recurrence, morbidity and mortality outcomes, and identify prognostic factors for overall survival. METHODS: Patients with CRPC that underwent an iCRS, with or without intraperitoneal chemotherapy, from June 1993 to July 2016 at 13 institutions were retrospectively analyzed from prospectively maintained databases. RESULTS: The study comprised of 231 patients, including 126 females (54.5%) with a mean age at iCRS of 51.3 years. The iterative high-grade (3/4) morbidity and mortality rates were 23.4% and 1.7%, respectively. The median recurrence-free survival was 15.0 and 10.1 months after initial and iCRS, respectively. The median and 5-year survivals were 49.1 months and 43% and 26.4 months and 26% from the initial and iCRS, respectively. Independent negative predictors of survival from the initial CRS included peritoneal carcinomatosis index (PCI) > 20 ( P = 0.02) and lymph node positivity ( P = 0.04), and from iCRS, PCI > 10 ( P = 0.03 for PCI 11-20; P < 0.001 for PCI > 20), high-grade complications ( P = 0.012), and incomplete cytoreduction ( P < 0.001). CONCLUSION: iCRS can provide long-term survival benefits to highly selected colorectal peritoneal carcinomatosis patients with comparable mortality and morbidity rates to the initial CRS procedure. Careful patient selection is necessary to improve overall outcomes.

CEA to peritoneal carcinomatosis index (PCI) ratio is prognostic in patients with colorectal cancer peritoneal carcinomatosis undergoing cytoreduction surgery and intraperitoneal chemotherapy: A retrospective cohort study.

BACKGROUND AND OBJECTIVES: Serum tumor markers are prognostic in patients with colorectal cancer peritoneal carcinomatosis (CRPC) undergoing cytoreductive surgery (CRS) and intraperitoneal chemotherapy (IPC). Assessment of the ratio of tumor marker to volume, as depicted by peritoneal carcinomatosis index (PCI), and how this may affect overall (OS) and recurrence free survival (RFS) has not been reported. METHODS: Survival effect of this ratio was analyzed in patients with CRPC managed from 1996 to 2016 with CRS and IPC. RESULTS: Of 260 patients included, those with low CEA/PCI ratio (<2.3) had longer median OS (56 vs 24 months, P = 0.001) and RFS (13 vs 9 months, P = 0.02). The prognostic impact of CEA/PCI ratio was most pronounced in patients with PCI ≤ 10 (OS of 72 vs 30 months, P < 0.001; RFS of 21 vs 10 months, P = 0.002). In multivariable analysis, elevated CEA/PCI ratio was independently associated with poorer OS (adjusted HR 1.85, 95%CI 1.11-3.10, P = 0.02) and RFS (adjusted HR 1.58, 95%CI 1.04-2.41, P = 0.03). CONCLUSION: CEA/PCI ratio is an independent prognostic factor for OS and RFS in CRPC. This novel approach allows both tumor activity and volume to be accounted for in one index, thus potentially providing a more accurate indication of tumor biological behavior.

Extensive Resection for Treatment of Locally Advanced Primary Mucinous Adenocarcinoma Arising From Fistula-in-Ano.

We report a case of a 66-year-old male who presented with a locally advanced primary mucinous adenocarcinoma arising from a fistula-in-ano. The presentation was typical for perianal sepsis and fistula-in-ano with anal pain and chronic discharge. Initial treatments with fistula debridement and seton were performed. Subsequent review of histology revealed underlying adenocarcinoma, while magnetic resonance imaging (MRI) showed local invasion into the prostate. The patient received neoadjuvant chemoradiotherapy followed by pelvic exenteration to maximize the chance of achieving cure. Features of this case are discussed together with its implications, including treatment guidelines and typical MRI findings.

How to use a fan retractor in laparoscopic total mesorectal excision.

Obtaining exposure of the total mesorectal excision plane via a laparoscopic approach is technically challenging due to instrument limitations. Use of an articulating fan retractor is a relatively simple, cost-effective and easily accessible instrument that allows the surgeon to gain improved retraction and exposure in what is an otherwise technically challenging dissection.

The volume-time index (VTI) is prognostic in patients with colorectal cancer peritoneal metastases undergoing cytoreductive surgery and intraperitoneal chemotherapy.

BACKGROUND: Peritoneal cancer index (PCI) is an important prognostic factor in colorectal cancer peritoneal metastases (CRPM), however it fails to consider the time period over which disease burden develops. The volume-time index (VTI) is the ratio between PCI and time from primary tumour resection. METHODS: A retrospective cohort study of 182 patients managed from 1996 to 2017 was performed. RESULTS: As stratified by high vs low VTI groups, median overall survival (OS) was 23 months (95% 17-46) vs 44 months (95% 35-72) with a difference in 5-year OS of 20.3% (95%CI 10.2-40.4) vs 40.1% (95%CI 29.7-54.1), p = 0.002. No difference in 5-year recurrence free survival (RFS) exists. On multivariable analysis, an elevated VTI was independently associated with poorer OS (adjusted HR 3.20, 95%CI 1.64-6.23, p < 0.001) and RFS (adjusted HR 1.90, 95%CI 1.10-3.29, p = 0.02). CONCLUSION: VTI is an independent prognostic factor for OS and RFs in patients with CRPM undergoing CRS/IPC, behaving as a surrogate of tumour aggressiveness.

Robotic-assisted ventral hernia repair with surgical mesh: how I do it and case series of early experience.

BACKGROUND: Laparoscopic ventral hernia repair provides several benefits over the open approach. Intraperitoneal surgical mesh placement without fascial defect closure is associated with increased seroma formation and other adverse hernia-site outcomes. Transfascial sutures and tacs for fascial closure and surgical mesh fixation are associated with greater post-operative pain. Robotic-assisted ventral hernia repair (rVHR) may afford benefits of the laparoscopic approach while facilitating a more robust and less painful repair. METHODS: Consecutive patients managed by rVHR from May 2015 to August 2018 were identified from a prospectively maintained robotic database. Retrospective review of this data was performed. RESULTS: Fifty patients underwent rVHR during the study period. Median body mass index was 31 (interquartile range (IQR) 29-34). Forty-eight had previous abdominal surgery. Forty-seven hernias were midline and three were lateral. Regarding hernia width, 15 were <4 cm wide, 32 were 4-10 cm and three were >10 cm. Median total anaesthetic time, docking time and surgical console time were 214 min (IQR 182-252), 5 min (IQR 4-8) and 144 min (IQR 104-174), respectively. No major intra-operative complications occurred. No documented cases of adhesional complications or chronic post-operative pain have occurred. To date, two recurrences have occurred in our series. Median length of hospital stay was 3 days (IQR 2-4). CONCLUSION: We describe our rVHR technique and report on our series and early experience, showing that rVHR can be performed safely with good patient outcomes. We demonstrate a team approach to achieving a safe transition to new technology.

Intraoperative packed red blood cell transfusion (iPRBT) and PCI-normalised iPRBT rates (iPRBT/PCI ratio) negatively affect short- and long-term outcomes of patients undergoing cytoreductive surgery and intraperitoneal chemotherapy - An analysis of 880 patients.

BACKGROUND: Most studies on the effects of intraoperative packed red blood cell transfusions (iPRBT) on patients undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have shown deleterious outcomes. It is unclear if this is a result of the transfusion itself or because iPRBTs serve as a surrogate of more advanced disease. METHODS: A retrospective analysis of 880 patients treated from 1996 to 2017. The effect of any exposure to iPRBT as well as the effect of peritoneal cancer index (PCI)-normalised iPRBT rates (ratio of iPRBT/PCI) on patients short- and long-term outcomes (recurrence-free (RFS) and overall survival (OS)) were assessed. Equally, the prognostic effect of postoperative PRBTs was analysed and adjusted for. RESULTS: Of the 880 patients included, only 26.4% had no iPRBT whereas 59.2% of patients had no postoperative PRBT. Patients with no iPRBTs had significantly lower PCIs, less high-grade complications, shorter ICU and hospital length of stay, as well as improved RFS and OS. Furthermore, high PCI-normalised iPRBTs resulted in worse perioperative and long-term outcomes, with a median OS of 41 months vs. 103 months (5-year survival rate 36.6% vs. 66.1%; p < 0.001) and median RFS of 13 months vs. 30 months (5-year RFS rate 18.3% vs. 37.6% p < 0.001) compared to those with a low iPRBT/PCI ratio. This independent effect was confirmed upon multivariable Cox regression analysis which corrected for important confounders including complexity of procedures and postoperative PRBTs (adjusted HR [aHR]2.04, 95%CI 1.36-3.04, p = 0.001 for OS; aHR 1.38, 95%CI 1.06-1.81, p = 0.017 for RFS). However, subgroup analysis (stratified by histopathologic disease entities) revealed that this independent prognostic effect was seen in high-grade mucinous appendiceal neoplasms, whereas PCI-normalised IPRBTs were not significantly prognostic in other histopathologic subgroups. CONCLUSION: iPRBTs significantly and independently impact perioperative and long-term outcomes of patients undergoing CRS/HIPEC. However, this effect mainly seems to occur in patients with high-grade mucinous neoplasms, whereas it may only be of borderline prognostic significance in other patient groups. The development of blood-sparing protocols may help improve outcomes of patients undergoing this complex oncologic procedure.

Intraoperative macroscopic tumour consistency is associated with overall survival after cytoreductive surgery and intraperitoneal chemotherapy for appendiceal adenocarcinoma with peritoneal metastases: A retrospective observational study.

BACKGROUND: This study examines the impact of intraoperative macroscopic tumour consistency on short-term and long-term outcomes after cytoreductive surgery (CRS) with intraperitoneal chemotherapy (IPC) for appendiceal adenocarcinoma with peritoneal metastases. METHODS: Macroscopic intraoperative tumour consistency was classified in three groups as soft (jelly-like geltatinous tumours), hard (hard tumour nodules without gelatinous features) and intermediate (both soft and hard features). In-hospital mortality, major morbidity, intensive care unit (ICU), high dependency unit (HDU) and total hospital stay, disease-free survival (DFS) and overall survival (OS) were compared. RESULTS: The three groups had similar perioperative short-term outcomes. Patients with soft, intermediate and hard tumours revealed differences in OS (p < 0.001) and DFS (p = 0.03). Multivariable analysis revealed a shorter OS for patients with hard versus soft tumours (HR for hard tumours = 4.43, 95%CI 2.19-9.00). CONCLUSIONS: Intraoperative macroscopic tumour consistency may be used as a prognostic marker for survival in patients with appendiceal adenocarcinoma with peritoneal metastases.

Left Paraduodenal Hernia: A Rare Complication following Laparoscopic Appendectomy.

Paraduodenal hernias are rare congenital internal hernias accounting for <2% of intestinal obstruction. Left paraduodenal hernias (LPDHs) into the fossa of Landzert are the more common type and result from abnormal rotation of the midgut and failure of peritoneal fusion. Sequelae of these hernias usually occur spontaneously in the 4th or 5th decade of life and are more common in males and have a significant risk of incarceration and subsequent strangulation. We describe a case of a 15-year-old female who develops a LPDH following laparoscopic appendectomy, resulting in jejunal incarceration and subsequent small intestinal obstruction. The patient discussed is from an atypical demographic, being young and female. In addition, the precipitating event prompting incarceration of the hernia appears to be the application of pneumoperitoneum, placement in the Trendelenburg position, and manipulation of small intestine for the purpose of facilitating laparoscopic appendectomy. To our knowledge, this is the first reported case of LPDH exacerbated by laparoscopic procedure.

CA 19-9 to peritoneal carcinomatosis index (PCI) ratio is prognostic in patients with epithelial appendiceal mucinous neoplasms and peritoneal dissemination undergoing cytoreduction surgery and intraperitoneal chemotherapy: A retrospective cohort study.

BACKGROUND: Serum tumour levels have been shown to be prognostic in patients with epithelial appendiceal mucinous neoplasms with peritoneal dissemination (pseudomyxoma peritonei (PMP)). A singular index which incorporates both tumour activity (as depicted by serum tumour marker levels) and tumour volume (as depicted by peritoneal carcinomatosis index (PCI)), may give a more precise surrogate of tumour biological behaviour. The prognostic implication of this index has not yet been reported. METHODS: A retrospective cohort study of all patients with PMP managed from 1996 to 2016 with cytoreductive surgery (CRS) and intraperitoneal chemotherapy (IPC) was performed by analysing the survival effect of the ratio of preoperative serum CEA, CA19.9 and CA125 to PCI. RESULTS: Three hundred and eighty-six patients were included. In patients with low-grade PMP, elevated CA19-9/PCI ratio resulted in poorer median overall survival times (104 months vs NR, 95%CI 83 - NR, log-rank p < 0.001) and was an independent predictor of reduced overall survival on multivariable analysis (adjusted HR 5.60, 95%CI 1.60-19.68, p = 0.007). In patients with high-grade PMP, no statistically significant difference in survival was recognised. CONCLUSION: CA19-9/PCI ratio is an independent prognostic factor for overall survival in patients with low-grade PMP undergoing CRS and IPC. By accounting for both tumour activity and tumour volume simultaneously, this novel index behaves as a surrogate of tumour biology and provides a useful adjunct for decisions regarding treatment allocation in this patient group.