Single centre guidelines for radiological follow-up based on 775 patients treated by cytoreductive surgery and HIPEC for appendiceal pseudomyxoma peritonei.

AIM: Pseudomyxoma peritonei (PMP) is an uncommon malignancy, generally originating from a ruptured epithelial tumour of the appendix. Despite successful cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), some patients recur. Currently there are no guidelines on the methods, frequency and intensity of follow-up. METHODS: Between 1994 and 2016, 1070 patients underwent surgery for a perforated epithelial tumour of the appendix, predominantly with PMP. Overall (OS) and Disease Free Survival (DFS) were documented by annual CT scanning and evaluated according to the Kaplan-Meier method. The influence of histological differentiation was investigated. RESULTS: Overall, 775/1070 (72%) had complete cytoreductive surgery (CCRS) and HIPEC. Histological classification was low grade PMP in 615 (79.4%), high grade PMP in 134 (17.3%) and adenocarcinoma in 26 (3.4%). DFS and OS were significantly worse for high grade disease, with the steepest decline for both in the first three years. DFS curves, for low as well as high grade PMP, levelled off at year 6 at approximately 60% and 20% respectively. Thereafter there were few recurrences in either group. CONCLUSION: Annual CT of the abdomen and pelvis in the first six years appears to be adequate follow-up for low grade PMP. In high grade PMP, additional imaging of the chest and more frequent surveillance, during the first three years postoperatively, may detect recurrent disease earlier. From year 6 on, reduced frequency of follow-up is proposed, independent of the histology. This long-term follow-up in a large number of patients gives insight into tumour behavior after CCRS and HIPEC for PMP and guides intensity of surveillance.

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.

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.

A Consensus for Classification and Pathologic Reporting of Pseudomyxoma Peritonei and Associated Appendiceal Neoplasia: The Results of the Peritoneal Surface Oncology Group International (PSOGI) Modified Delphi Process.

Pseudomyxoma peritonei (PMP) is a complex disease with unique biological behavior that usually arises from appendiceal mucinous neoplasia. The classification of PMP and its primary appendiceal neoplasia is contentious, and an international modified Delphi consensus process was instigated to address terminology and definitions. A classification of mucinous appendiceal neoplasia was developed, and it was agreed that "mucinous adenocarcinoma" should be reserved for lesions with infiltrative invasion. The term "low-grade appendiceal mucinous neoplasm" was supported and it was agreed that "cystadenoma" should no longer be recommended. A new term of "high-grade appendiceal mucinous neoplasm" was proposed for lesions without infiltrative invasion but with high-grade cytologic atypia. Serrated polyp with or without dysplasia was preferred for tumors with serrated features confined to the mucosa with an intact muscularis mucosae. Consensus was achieved on the pathologic classification of PMP, defined as the intraperitoneal accumulation of mucus due to mucinous neoplasia characterized by the redistribution phenomenon. Three categories of PMP were agreed-low grade, high grade, and high grade with signet ring cells. Acellular mucin should be classified separately. It was agreed that low-grade and high-grade mucinous carcinoma peritonei should be considered synonymous with disseminated peritoneal adenomucinosis and peritoneal mucinous carcinomatosis, respectively. A checklist for the pathologic reporting of PMP and appendiceal mucinous neoplasms was also developed. By adopting the classifications and definitions that were agreed, different centers will be able to use uniform terminology that will allow meaningful comparison of their results.

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.

Total mesorectal excision results in low local recurrence rates in lymph node-positive rectal cancer.

PURPOSE: Most series report lymph node involvement as the main predictor for local recurrence. The principal lymphatic drainage of the rectum is to nodes in the mesorectum and then nodes along the superior rectal and inferior mesenteric arteries. If total mesorectal excision provides adequate block dissection of the lymphatics of the rectum, good local control with low rates of local recurrence should be achieved even in node-positive disease. METHODS: Prospective data on all rectal cancers have been collected since 1978; 170 patients with Dukes C rectal cancer have undergone anterior resection and total mesorectal excision. We did not perform any internal iliac node dissections. Follow-up data were analyzed for local recurrence and distant recurrence. RESULTS: The local recurrence rate was 2 percent for Dukes A cases, 4 percent for Dukes B, and 7.5 percent for Dukes C ( P = 0.0127). The systemic recurrence rate was 8 percent for Dukes A, 18 percent for Dukes B, and 37 percent for Dukes C ( P = 0.0001). CONCLUSIONS: If surgical priority is given to the difficult task of excision of the whole mesorectum, anterior resection with total mesorectal excision in node-positive rectal cancer, local recurrence rates of < 10 percent can be achieved.

The etiology, clinical presentation, and management of pseudomyxoma peritonei.

PMP is a rare condition, which, although of "borderline malignancy," is invariably fatal. Difficulties exist with the definition of PMP. It has been broadly applied to include a heterogenous group of pathologic lesions that present clinically with "jelly belly" due to mucinous ascites. The relatively few reports in the literature commonly use different pathologic definitions, and there is no consensus on the point of separation between PMP and carcinomatosis secondary to a mucinous adenocarcinoma. Sugarbaker has suggested "the term pseudomyxoma peritonei syndrome be strictly applied to a pathologically and prognostically homogenous group of cases characterized by histologically benign peritoneal tumors that are frequently associated with an appendiceal mucinous adenoma." This definition excludes all cases with mucinous adenocarcinoma. The optimal treatment is undoubtedly complete tumor excision, by complex surgical peritonectomy procedures, taking on average 10 hours. Surgery is usually combined with intraperitoneal, and now intraoperative heated chemotherapy. These techniques have a high morbidity and mortality. The rarity of the condition, together with the risks associated with definitive treatment, suggests that such treatment ought to be centralized in a few centers, covering a large population. The search continues for safer, less aggressive treatments, but is hampered by a lack of hard evidence and the absence of experimental animal or human models to evaluate emerging strategies.