Laparoscopic cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for perforated low-grade appendiceal mucinous neoplasms.

INTRODUCTION: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is an established treatment for pseudomyxoma peritonei (PMP) from perforated low-grade appendiceal mucinous neoplasms (LAMN II). In a selected group of LAMN II patients without established PMP, CRS/HIPEC can be performed laparoscopically (L-CRS/HIPEC); however the short-term benefits and safety of this approach have yet to be determined. This study aims to determine the short-term outcomes from a series of L-CRS/HIPEC LAMN II patients compared to those who have undergone a similar open operation (O-CRS/HIPEC) for low-volume PMP. METHODS: LAMN II patients undergoing L-CRS/HIPEC at a UK national peritoneal tumour centre were compared to O-CRS/HIPEC patients (peritoneal cancer index ≤ 7). Outcomes of interest included Clavien-Dindo complication grade, operative time, blood transfusions, high dependency unit (HDU) admission, length of hospital stay, and histopathological findings. RESULTS: 55 L-CRS/HIPEC were compared to 29 O-CRS/HIPEC patients (2003-2017). Groups were matched for age, sex, and procedures. Median operative time was 8.8 (IQR 8.1-9.5) h for L-CRS/HIPEC versus 7.3 (IQR 6.7-8) h for O-CRS/HIPEC (Mann-Whitney test p < 0.001). Post-operative HDU admission was 56% versus 97% (OR 0.04 95% CI 0.01-0.34) and median length of stay = 6 (IQR 5-8) versus 10 (IQR 8-11) days (p < 0.001) for L- versus O-CRS/HIPEC. Despite a normal pre-operative CT scan, 13/55 (23.6%) L-CRS/HIPEC patients had acellular mucin and 2/55 (3.5%) had mucin with epithelium present in their specimens. Residual appendix tumour was identified in 2/55 patients (3.6%). Clavien-Dindo Grade 1-4 complications were similar in both groups with no mortality. CONCLUSION: L-CRS/HIPEC for LAMN II takes longer; however patients have significantly reduced length of HDU and overall stay, without increased post-operative complications. A significant proportion of LAMN II patients undergoing L-CRS/HIPEC have extra-appendiceal acellular mucin with some cases demonstrating residual cellular epithelium from the LAMN II. The risk of these patients developing PMP without surgery is under current review.

Temporal improvements in loco-regional failure and survival in patients with anal cancer treated with chemo-radiotherapy: treatment cohort study (1990-2014).

BACKGROUND: We evaluated oncological changes in patients with squamous cell carcinoma of the anus (SCCA) treated by chemoradiotherapy (CRT) from a large UK institute, to derive estimates of contemporary outcomes. METHODS: We performed a treatment-cohort analysis in 560 patients with non-metastatic SCCA treated with CRT over 25 years. The primary outcomes were 3-year loco-regional failure (LRF), 5-year overall survival (OS), and 5-year cancer-specific survival (CSS). We developed prediction models; and overlaid estimates on published results from historic trials. RESULTS: Age distributions, proportions by gender and cT stage remained stable over time. The median follow-up was 61 (IQR: 36-79) months. Comparing the first period (1990-1994) with the last period (2010-2014), 3-year LRF declined from 33 to 16% (Ptrends < 0.001); 5-year OS increased from 60% to 76% (Ptrends = 0.001); and 5-year CCS increased from 62% in to 80% (Ptrends = 0.001). For 2020, the models predicted a 3-year LRF of 14.7% (95% CIs: 0-31.3); 5-year OS of 74.7% (95% CIs: 54.6-94.9); and 5-year CSS of 85.7% (95% CIs: 75.3-96.0). Reported oncological outcomes from historic trials generally underestimated contemporary outcomes. CONCLUSIONS: Current and predicted rates for 3-year LRF and 5-year survivals are considerably improved compared with those in historic trials.

Predicting Survival After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Appendix Adenocarcinoma.

BACKGROUND: Appendix adenocarcinomas are rare tumors with propensity for peritoneal metastasis. Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy is an established treatment with curative intent, but, to date, studies reporting survival have been heterogeneous with regard to their patient groups (including other tumor types), interventions (not all patients receiving intraperitoneal chemotherapy), and follow-up (varying surveillance protocols). OBJECTIVE: The aim of this study is to quantify the impact of this intervention on survival in a homogeneous group of patients with appendix adenocarcinoma receiving standardized treatment and follow-up, and to determine the impact of prognostic indicators on survival. DESIGN: This is a retrospective analysis of a prospective database at a national peritoneal tumor center where all patients had their appendix pathology reviewed and management planned by a specialized peritoneal tumor multidisciplinary team. MAIN OUTCOME MEASURES: Data were extracted on prognostic indicators including peritoneal cancer index, completeness of cytoreduction score, preoperative tumor markers, and histological features. Overall and disease event-free survival from the date of intervention were evaluated using Kaplan Meier curves and univariate Cox proportional hazards regression analysis. RESULTS: A total of 65 patients underwent cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for appendix adenocarcinoma between 2005 and 2015. Median follow-up was 44.3 months. The overall survival was 55.5% and disease event-free survival was 36.1% (5-year rate). Peritoneal Cancer Index <7, complete cytoreduction score of 0, and preoperative CEA of <6 were all associated with significantly higher overall and disease event-free survival. CA19-9 <38 and CA125 <31 were not associated with a significantly higher overall or disease event-free survival. LIMITATIONS: The sample size was limited because of the rarity of this tumor type. CONCLUSIONS: This study quantifies the impact of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy on overall and disease event-free survival for appendix adenocarcinoma, identifying key prognostic indicators that may guide treatment. It supports the referral of these rare tumors to specialist centers with appropriate expertise for initial management and follow-up. See Video Abstract at http://links.lww.com/DCR/A595.

Long-term Quality of Life After Cytoreductive Surgery and Heated Intraperitoneal Chemotherapy for Pseudomyxoma Peritonei: A Prospective Longitudinal Study.

BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are an established treatment for pseudomyxoma peritonei (PMP), but it is a major surgical procedure and may be associated with long-term morbidity. To date, health-related quality-of-life (HRQL) data among survivors are lacking. METHODS: A two-period qualitative study investigated patients undergoing CRS-HIPEC for PMP at a national peritoneal tumor center between 2003 and 2011. First, the European Organization for Research and Treatment (EORTC)-QLQ C30 HRQL questionnaire was used longitudinally preoperatively and at postoperative months 3, 6, 9, 12, 18, and 24, then yearly thereafter. Second, it was updated in 2016 as a cross-sectional study. Both studies were compared with age- and sex-matched reference populations (one-way t tests). RESULTS: A total of 553 longitudinal HRQL questionnaires were completed for 137 patients, truncated at 60 months. In the 2016 update, 85 responses were received from 103 survivors (mean follow-up period, 8.11 years). Patients' physical, role, and social function scores were impaired until 12 months postoperatively, after which the scores did not differ significantly from those of with reference populations. Similarly, fatigue, appetite loss, insomnia, and financial difficulties worsened significantly compared with reference populations in the first 12-months and then normalized. In contrast, impaired cognitive function (82.3 vs 88.5; P = 0.017), constipation (13.7 vs 7.3; P = 0.032), and diarrheal symptoms (15.1 vs 4.9; P = 0.0006) persisted through both periods. Global health scores did not differ significantly from those of the reference population. CONCLUSIONS: Beyond 12 months postoperatively, CRS-HIPEC for PMP is associated with a good quality of life except for some cognitive functional impairment and bowel disturbances.

Watch-and-wait approach versus surgical resection after chemoradiotherapy for patients with rectal cancer (the OnCoRe project): a propensity-score matched cohort analysis.

BACKGROUND: Induction of a clinical complete response with chemoradiotherapy, followed by observation via a watch-and-wait approach, has emerged as a management option for patients with rectal cancer. We aimed to address the shortage of evidence regarding the safety of the watch-and-wait approach by comparing oncological outcomes between patients managed by watch and wait who achieved a clinical complete response and those who had surgical resection (standard care). METHODS: Oncological Outcomes after Clinical Complete Response in Patients with Rectal Cancer (OnCoRe) was a propensity-score matched cohort analysis study, that included patients of all ages diagnosed with rectal adenocarcinoma without distant metastases who had received preoperative chemoradiotherapy (45 Gy in 25 daily fractions with concurrent fluoropyrimidine-based chemotherapy) at a tertiary cancer centre in Manchester, UK, between Jan 14, 2011, and April 15, 2013. Patients who had a clinical complete response were offered management with the watch-and-wait approach, and patients who did not have a complete clinical response were offered surgical resection if eligible. We also included patients with a clinical complete response managed by watch and wait between March 10, 2005, and Jan 21, 2015, across three neighbouring UK regional cancer centres, whose details were obtained through a registry. For comparative analyses, we derived one-to-one paired cohorts of watch and wait versus surgical resection using propensity-score matching (including T stage, age, and performance status). The primary endpoint was non-regrowth disease-free survival from the date that chemoradiotherapy was started, and secondary endpoints were overall survival, and colostomy-free survival. We used a conservative p value of less than 0·01 to indicate statistical significance in the comparative analyses. FINDINGS: 259 patients were included in our Manchester tertiary cancer centre cohort, 228 of whom underwent surgical resection at referring hospitals and 31 of whom had a clinical complete response, managed by watch and wait. A further 98 patients were added to the watch-and-wait group via the registry. Of the 129 patients managed by watch and wait (median follow-up 33 months [IQR 19-43]), 44 (34%) had local regrowths (3-year actuarial rate 38% [95% CI 30-48]); 36 (88%) of 41 patients with non-metastatic local regrowths were salvaged. In the matched analyses (109 patients in each treatment group), no differences in 3-year non-regrowth disease-free survival were noted between watch and wait and surgical resection (88% [95% CI 75-94] with watch and wait vs 78% [63-87] with surgical resection; time-varying p=0·043). Similarly, no difference in 3-year overall survival was noted (96% [88-98] vs 87% [77-93]; time-varying p=0·024). By contrast, patients managed by watch and wait had significantly better 3-year colostomy-free survival than did those who had surgical resection (74% [95% CI 64-82] vs 47% [37-57]; hazard ratio 0·445 [95% CI 0·31-0·63; p<0·0001), with a 26% (95% CI 13-39) absolute difference in patients who avoided permanent colostomy at 3 years between treatment groups. INTERPRETATION: A substantial proportion of patients with rectal cancer managed by watch and wait avoided major surgery and averted permanent colostomy without loss of oncological safety at 3 years. These findings should inform decision making at the outset of chemoradiotherapy. FUNDING: Bowel Disease Research Foundation.

Successful Management of Jejunal Perforation in Burkitt's Lymphoma: A Case Report.

Burkitt's lymphoma (BL) is rare, rapidly growing, and highly aggressive. Urgent commencement of chemotherapy is vital to prevent complications and promote a favourable prognosis. Any factor causing a delay in the initiation of chemotherapy will affect prognosis significantly. Intestinal perforation is a well-known complication with devastating consequences. It inevitably leads to a delay in the initiation of chemotherapy. There are few reports in the literature that discuss this complication. Furthermore, there are no reports of patients that have survived intestinal perforation occurring prior to the commencement of chemotherapy. We present a case of a 55-year-old male who survived perforation of advanced sporadic BL of the jejunum occurring prior to the commencement of chemotherapy. Critical aspects of the patients care are discussed.

Adhesions after abdominal surgery in children.

PURPOSE: The objective of this study is to quantify the overall burden (operative and nonoperative) of small bowel obstruction caused by adhesions after laparotomy in children. METHODS: Data from the Scottish National Health Service Medical Record Linkage database were used to assess risk of an adhesion-related readmission in the 5 years after open abdominal surgery in children and adolescents younger than 16 years from April 1996 to March 1997. RESULTS: A total of 1581 children underwent abdominal surgery (ie, from duodenum downward). Patients undergoing surgery on the ileum had the highest risk of readmission because of adhesions in the subsequent 5 years after surgery (9.2%)--formation/closure of ileostomy had the greatest risk (25%); 6.5% of children were readmitted after general laparotomy, 4.7% after duodenal surgery, and 2.1% after colonic surgery. The incidence of readmissions was 0.3% after appendicectomy. The overall readmission rate was 5.3% (if appendicectomy was excluded) and 1.1% (if appendicectomy was included). CONCLUSION: This population-based study has demonstrated that children have a high incidence of readmissions owing to adhesions after lower abdominal surgery. The risks are related to the site and the type of the original surgery. The risk of further readmissions was highest in the first year but continued with time. The data enable surgeons to target antiadhesion strategies at procedures that lead to a high risk of adhesions.

Human peritoneal adhesions show evidence of tissue remodeling and markers of angiogenesis.

PURPOSE: This study was designed to investigate the vascular structure and angiogenic activity of human peritoneal adhesions. METHODS: Adhesions were collected from patients undergoing laparotomy (n=32). Histologic features were documented and the distribution of mature and immature vascular markers were determined by immunolocalization and quantified by image analysis. The three-dimensional organization of blood vessels was investigated by confocal microscopy. Expression of vascular endothelial growth factor A, its receptor flk-1, and proliferating cell nuclear antigen were assessed by immunohistochemistry as indicators of angiogenic activity. RESULTS: Adhesions were found to be vascularized structures comprising bundles of collagen, interspersed with varying amounts of adipose tissue. Functional blood vessels expressed recognized vascular markers (vWF, CD34, alpha-SMA, and CD105) and formed a branching network similar to that of the peritoneum. Those adhesions expressing vascular endothelial growth factor A and its receptor showed significantly higher numbers of immature vessels as defined by expression of CD105. Omental adhesions (n=16) contained significantly more adipose tissue (P<0.05) and displayed a higher microvessel density (P<0.01) but lower cellularity (P<0.05) compared with nonomental adhesions (n=16). CONCLUSIONS: All adhesions contained functional blood vessels and most showed evidence of cell proliferation. The presence of vascular endothelial growth factor A and its receptor in human adhesions suggests ongoing angiogenic activity. This study demonstrates that adhesions are vascular structures with evidence of tissue remodeling and suggests potential for new prevention strategies involving antiangiogenic therapies.

Population-based analysis of the risk of adhesion-related readmissions after abdominal surgery in children.

PURPOSE: The aim of this study was to quantify the risk of adhesion-related readmissions after abdominal surgery in children. METHODS: This was a population-based study. One thousand five hundred eighty-one children younger than 16 years underwent laparotomy in 1996. Patients were identified from the Scottish Morbidity Records database and followed up for 4 years. RESULTS: In children younger than 5 years, 4.2% had a readmission "directly" owing to adhesions. In children younger than 16 years, 1.1% had a readmission directly owing to adhesions. The highest risk of readmission followed surgery on the small intestine (9.3%), followed by abdominal wall surgery (5.8%), duodenal surgery (2.6%), colonic surgery (2.1%), and appendicectomy (0.3%). 55% of all readmissions occurred in the first year. CONCLUSION: There was no difference in readmission rates between younger and older children when comparing the organ on which surgery was initially performed. The highest readmission rate followed small intestinal surgery and the lowest followed appendicectomy. The risk of readmission was highest in the first year.