Sanjeev Dayal

Complete cytoreduction for pseudomyxoma peritonei is optimal but maximal tumor debulking may be beneficial in patients in whom complete tumor removal cannot be achieved.

BACKGROUND: Pseudomyxoma peritonei is a diffuse peritoneal malignancy that generally originates form a perforated appendiceal tumor. Optimal treatment requires extensive surgical resection to achieve complete cytoreduction combined with hyperthermic intraperitoneal chemotherapy. In a proportion of patients this is impossible, in particular, owing to extensive irresectable small-bowel involvement. There is ongoing debate as to the role of maximal tumor debulking in such cases. OBJECTIVE:  The aim of this study was to assess the outcomes of patients who underwent major tumor debulking for pseudomyxoma peritonei of appendiceal origin and to compare outcomes with patients who had complete cytoreduction during the same period. DESIGN: This is a retrospective study. SETTINGS: This investigation was conducted at a tertiary referral center for peritoneal surface malignancy. PATIENTS: A prospective database of 953 consecutive patients with peritoneal malignancy undergoing surgery at a UK national referral center between 1994 and 2012 was analyzed. Of these patients, 748 (78%) had surgery for pseudomyxoma peritonei of appendiceal origin. MAIN OUTCOME MEASURES: Survival, morbidity, and mortality in both groups were compared. Univariate and multivariate analyses were performed to identify negative prognostic factors in the group that underwent major tumor debulking. RESULTS: Complete cytoreductive surgery was achieved in 543/748 (73%) patients, and 205 (27%) had maximal tumor debulking. Median age was 56 years (172 (31.7%) men) in the complete cytoreductive surgery group and 59 years (108 (52.7%) men) in the maximal tumor debulking group. Overall survival at 3, 5, and 10 years was 90%, 82%, and 64% in the complete cytoreductive group and 47%, 30%, and 22% in the maximal tumor debulking group. The median survival in the maximal tumor debulking group was 32.8 months (95% CI, 24.1–41.5). LIMITATIONS: The retrospective analysis of prospective data was a limitation of this study. CONCLUSIONS: Maximal tumor debulking may help patients with pseudomyxoma peritonei in whom complete cytoreduction cannot be achieved with almost half alive at 3 years with long-term survival in some.

Pre-operative tumour marker status predicts recurrence and survival after complete cytoreduction and hyperthermic intraperitoneal chemotherapy for appendiceal Pseudomyxoma Peritonei: Analysis of 519 patients

BACKGROUND Cytoreductive surgery (CRS) combined with Hyperthermic Intraperitoneal Chemotherapy (HIPEC) is the optimal treatment for Pseudomyxoma Peritonei (PMP). Despite treatment, disease often recurs and may not be amenable to further CRS. Clinical experience suggests a spectrum of disease which may correlate with tumour marker levels. The aim of this study was to analyse the influence of markers on recurrence and survival. METHODS The details of all patients undergoing surgery for PMP of appendiceal origin at a national centre for peritoneal malignancy were recorded in a dedicated prospective database. The data on all patients who had CRS and HIPEC between March 1994 and January 2012 was analysed and recurrence and survival correlated with pre-operative levels of CEA, CA-125 and CA19-9. RESULTS Overall, 519 (69%) of 752 consecutive patients, underwent complete CRS and HIPEC. The median (range) age was 56 (20-82) years with 342/519 (66%) females. The mean overall (OS) and disease free survival (DFS) in the 131/519 patients who had normal preoperative tumour markers was 168 (128-207) and 125 (114-136) months respectively, significantly higher when compared with the 109/519 (21%) who had all three tumour markers elevated (OS of 65 (42-88) and DFS of 55 (41-70) months respectively) (P = 0.002). CONCLUSIONS Elevated tumour markers predict an increased risk of recurrence and reduced survival after complete CRS. This may reflect cell biology in low grade tumours and is an independent prognostic feature. Further analysis may help to select patients for post-operative chemotherapy, second look procedures or stratification of follow up.

Peritoneal metastases from colorectal cancer: Patient selection for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy

Cytoreductive surgery (CRS) in combination with hyperthermic intraperitoneal chemotherapy (HIPEC) is an established treatment modality for patients with pseudomyxoma peritonei. The majority of patients with pseudomyxoma who have complete tumour removal and HIPEC are cured. Over the last decade CRS for peritoneal metastasis of colorectal origin has emerged as an effective treatment strategy in carefully selected patients. Although convincing evidence is limited, available data shows promising results. The key to a successful outcome is appropriate selection of patients. In patients with extensive peritoneal disease, where complete cytoreduction is not achieved, surgical treatment may not be beneficial and might impair quality of life. In this paper we discuss the challenges of selecting patients with colorectal peritoneal metastases who are likely to benefit from CRS with HIPEC.

Risk of definitive stoma after surgery for peritoneal malignancy in 958 patients: Comparative study between complete cytoreductive surgery and maximal tumor debulking

INTRODUCTION Complete cytoreductive surgery (CRS) can achieve cure or long-term survival in selected patients with peritoneal malignancy. In selected patients, due to extensive disease, complete tumour removal is impossible and optimal strategy may be maximal tumour debulking (MTD). We analysed the stoma related outcome in a series of patients undergoing surgery in a National Peritoneal Malignancy Referral Centre. METHODS All patients who underwent CRS, with or without, intra-operative hyperthermic intraperitoneal chemotherapy (HIPEC) between 1994 and 2012 were included. Data was collected prospectively in an institutional database and analysed retrospectively. RESULTS CRS was performed in 958 patients (female: 595, male: 363) of whom 781 (81.5%) had a primary appendix tumour, 63 (6.6%) had a colorectal primary, 47 (4.9%) peritoneal mesothelioma, 38 (4%) an ovarian tumour and 29 patients (3%) other tumours. Complete CRS was achieved in 72% (693/958). Overall 352/958 (37%) had a stoma, which was permanent in 165/958 (17.2%). The median time interval from CRS to reversal of stoma was 4.4 months (range: 1.4-13.8). Stomas were created in 113/265 (42.6%) at MTD (permanent: n = 105 (93%), temporary: n = 8 (7%)), and 239/693 (34.5%) at complete CRS (permanent: n = 60 (25%), temporary: n = 179 (75%)) (p = 0.020). All temporary stomas in the 168/693 (24.4%) of patients who had complete CRS were subsequently reversed. CONCLUSION To achieve complete CRS for peritoneal malignancy a stoma is often required and in a proportion this will be permanent. Overall over one third had a stoma at surgery with almost half subsequently reversed.

Evolution of Surgical Treatment for Rectal Cancer: a Review

Surgery that produces an optimal total mesorectal excision (TME) resection specimen remains the cornerstone of curative rectal cancer management. In the modern era, despite the results of recent randomised trials, laparoscopic TME is a crucial technique in the TME surgery armamentarium. Laparoscopic surgery offers the benefit of magnified views that aid sharp and precise dissection. However operating in the confines of a narrow pelvis, particularly when the mesorectum is bulky, requires significant technical skill. This is compounded by limited angulation of laparoscopic instruments and staplers. The final challenge is to preserve the integrity of the mesorectum during delivery of the specimen. The principles of TME surgery, on which Bill Heald founded the Basingstoke Colorectal unit, can equally be applied to laparoscopic, transanal and robotic TME, but great care must be taken to preserve the key principle—that no steps are taken that have the potential to shed tumour cells or compromise the quality of the mesorectal specimen.

The modified Glasgow prognosis score predicts for overall and disease-free survival following cytoreductive surgery and HIPEC in patients with pseudomyxoma peritonei of appendiceal origin

BACKGROUND The modified Glasgow prognostic score (incorporating C-reactive protein and albumin) predicts survival in patients with gastro-intestinal tract cancer but has not been evaluated in patients with peritoneal malignancy. The aim was to evaluate the modified Glasgow score preoperatively in patients undergoing complete cytoreductive surgery (CCRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) for pseudomyxoma peritonei (PMP) of appendiceal origin. METHODS Prospectively collected data from patients with PMP of appendiceal origin following CCRS and HIPEC between January 2007 and December 2011 were analysed. The mGPS was calculated from preoperative C-reactive protein and albumin. Predicted overall survival (OS) and disease-free survival (DFS) for each mGPS score were calculated using the Kaplan-Meier model. In a separate analysis, a comparison was made between mGPS and Tumour Markers (TM). RESULTS 260 patients were included in the study. The mGPS of 0, 1, and 2 were found in 111, 130, and 19 patients respectively. The median follow-up was 48 months. For mGPS-0, -1, and -2, the predicted OS was 82.2, 73.7, and 69.2 months and the DFS was 73.5, 62.9, and 54.4 months respectively. As mGPS increases, there is a reduction in long-term survival. There was no difference between mGPS and TM. CONCLUSION Preoperative mGPS may be a cost effective prognostic tool for predicting OS and DFS in patients following complete CRS-HIPEC, and performs well compared to TM for predicting patients at high risk of recurrence.

The pre-operative neutrophil–lymphocyte ratio predicts overall and disease-free survival following cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with pseudomxyoma peritonei of appendiceal origin

Abstract Aim: The neutrophil–lymphocyte ratio (NLR) and other inflammation-based scores have been used as a prognostic tool to predict survival in solid tumours including pseudomyxoma peritonei (PMP). The aim was to evaluate the prognostic value of this marker and risk stratify PMP patients undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Methods: Retrospective analysis was conducted of a prospectively collected database of patients with PMP who underwent CRS and HIPEC between 1994 and 2015. The NLR was calculated by dividing the pre-operative neutrophil count by lymphocyte count. Predicted overall survival (OS) and disease-free interval (DFI) were calculated using a Kaplan–Meier survival model. Results: The study included 699 patients, stratified into four groups as defined by their NLR. Group A: 200 (28.6%) patients (NLR = 0.10–2.00), Group B: 160 (22.8%) patients (NLR = 2.10–2.78), Group C: 184 (26.3%) patients (NLR = 2.79–4.31) and Group D: 155 (22.2%) patients (NLR ≥ 4.32). The median follow-up for this cohort was 36 months. The predicted DFI was 132.2, 113.1, 84.4 and 47.9 months and the OS was 141.1, 117.6, 88.7 and 51.2 months for Groups A, B, C and D, respectively. As the NLR increases, there is a reduction in long-term survival. Conclusion: The pre-operative NLR is cost effective and has equivalent prognostic value to pre-operative tumour markers for patients with PMP treated with CRS and HIPEC. The NLR is a reliable tool that may have a role in predicting outcomes following CRS and HIPEC for patients with PMP of appendiceal origin.

Clinical presentation, diagnosis, classification and management of peritoneal mesothelioma: a review

Peritoneal mesothelioma (PM) is an uncommon but a serious, and often, fatal primary peritoneal tumour, with increasing incidence worldwide. Conventional systemic chemotherapy, generally based on experience with pleural mesothelioma, usually has disappointing results considering PM as a terminal condition. Patients usually present with non-specific symptoms of abdominal distension and pain making the diagnosis challenging. As PM is confined to the abdomen for all, or much, of its clinical course, a multimodality treatment combining cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has emerged as a new standard of care, and has been reported to achieve promising survival outcomes and local disease control in selected patients with PM. This review updates the presentation, diagnosis, classification and treatment strategies for PM.

Preserving fertility in pseudomyxoma peritonei, a novel approach

Abstract Background Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is the gold standard treatment for patients with pseudomyxoma peritonei (PMP) but involves routine bilateral salpingo-oophorectomy. Young women wishing to maintain fertility may be reluctant to pursue this. An alternative strategy in women with low-grade PMP has been explored in the form of laparoscopic evacuation of pelvic and ovarian mucin with resection of the appendiceal tumour. Methods Between January 2012 and January 2015, four young women (aged 28–35 years) with PMP seeking to maintain fertility underwent laparoscopy, appendicectomy and pelvic mucinous evacuation and washout. Data regarding intra-operative and histopathological findings were collected. Endpoints were fertility-related outcomes and oncological follow-up. Results Infertility was a presenting symptom in three of the four women. All four had significant pelvic mucinous disease on radiological imaging and were offered CRS and HIPEC as definitive treatment, but chose laparoscopy with appendicectomy and copious irrigation and washout of the pelvis with stripping of mucinous disease off the ovarian surfaces. Postoperative histology demonstrated a low-grade appendiceal mucinous neoplasm (LAMN) in all patients with acellular mucin or low-grade mucinous carcinoma peritonei in the peritoneal cavity. All patients successfully conceived subsequently and gave birth to healthy babies. After 12–29 months follow-up, all women are well with no radiological or laparoscopic evidence of disease recurrence. Conclusions In patients with low-grade PMP, initial therapeutic laparoscopy can restore fertility, whilst providing short- to medium-term disease control. This modality in young women wishing to have children appears to be a feasible alternative to immediate CRS and HIPEC.

Risk of Ovarian Involvement in Advanced Colorectal or Appendiceal Tumors Involving the Peritoneum

BACKGROUND: Ovarian metastases of GI tumors grow rapidly and are relatively resistant to systemic chemotherapy. They may be unilateral or bilateral and macroscopic or occult. The risk of macroscopic ovarian involvement or occult involvement of macroscopically normal ovaries is unquantified. OBJECTIVE: This study aims to quantify the risks of ovarian involvement in patients with peritoneal malignancy undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy. DESIGN: This was a retrospective analysis of a dedicated prospective malignancy database. SETTINGS: This study was conducted at a high-volume tertiary referral center for peritoneal malignancy. PATIENTS: Female patients with at least 1 remaining ovary, undergoing complete cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for appendiceal tumors or colorectal peritoneal metastases between January 2010 and March 2015 were included. OUTCOME MEASURES: Data regarding ovarian involvement was extracted from surgical and histological records. RESULTS: Two hundred fifty-eight female patients with at least 1 ovary underwent complete cytoreduction and hyperthermic intraperitoneal chemotherapy during the study period. In total, 141 of 258 (54.7%) patients had ovarian tumor involvement, and 80% with at least 1 macroscopically abnormal ovary had bilateral involvement. Of 40 patients with 1 macroscopic ovarian metastasis, microscopic involvement of the contralateral ovary was found in 18 of 40 (45.0%). Of 141 patients in whom both ovaries were macroscopically normal, 24 of 141 (17.0%) patients had microscopic ovarian involvement. LIMITATIONS: The retrospective nature limits the interpretation of these results. CONCLUSIONS: Occult malignancy was present in 17% when both ovaries looked macroscopically normal and in 45% of contralateral normal-looking ovaries if the other ovary was macroscopically involved. These results help to inform preoperative consent and intraoperative decision making in patients with advanced appendiceal and colorectal malignancy, and are of benefit in managing advanced lower GI tract malignancy.