A modified Delphi process to establish research priorities in hernia surgery.

BACKGROUND: Abdominal wall hernia repair is one of the most commonly performed surgical procedures worldwide, yet despite this, there remains a lack of high-quality evidence to support best management. The aim of the study was to use a modified Delphi process to determine future research priorities in this field. METHODS: Stakeholders were invited by email, using British Hernia Society membership details or Twitter, to submit individual research questions via an online survey. In addition, questions obtained from a patient focus group (PFG) were collated to form Phase I. Two rounds of prioritization by stakeholders (phases II and III) were then completed to determine a final list of research questions. All questions were analyzed on an anonymized basis. RESULTS: A total of 266 questions, 19 from the PFG, were submitted by 113 stakeholders in Phase I. Of these, 64 questions were taken forward for prioritization in Phase II, which was completed by 107 stakeholders. Following Phase II analysis, 97 stakeholders prioritized 36 questions in Phase III. This resulted in a final list of 14 research questions, 3 of which were from the PFG. Stakeholders included patients and healthcare professionals (consultant surgeons, trainee surgeons and other multidisciplinary members) from over 27 countries during the 3 phases. CONCLUSION: The study has identified 14 key research priorities pertaining to abdominal wall hernia surgery. Uniquely, these priorities have been determined from participation by both healthcare professionals and patients. These priorities should now be addressed by well-designed, high-quality international collaborative research.

Indications and outcomes for repeat cytoreductive surgery and heated intra-peritoneal chemotherapy in peritoneal surface malignancy.

INTRODUCTION: Cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) is offered in specialist centres as a treatment for peritoneal surface tumours. Despite its demonstrated efficacy, intra-abdominal recurrence occurs in 31-57% of patients. The aim of this study is to review the early and long-term outcomes in patients who undergo repeat CRS/HIPEC. MATERIALS AND METHODS: A retrospective review of a prospectively maintained database of patients who had undergone repeat CRS/HIPEC for appendiceal neoplasms and colorectal peritoneal metastases (CRPM) from 2003 to 2019 was performed at a single specialist centre. Data pertaining to both short term outcomes and survival were evaluated. RESULTS: Of 1259 patients who had undergone CRS/HIPEC, 84(6.7%) underwent repeat surgery: 45(53.6%) had pseudomyxoma peritonei (PMP) secondary to low grade appendiceal mucinous neoplasms (LAMN), 21(25.0%) had appendix carcinoma and 18(21.4%) had CRPM. Demographics, intra-operative findings and short-term outcomes were comparable across tumour types and between procedures. Median (95% CI) interval between procedures was 22.7(18.9-26.6) months and was comparable between tumour types. Median (95%CI) overall survival was not reached for the cohort overall or for those with PMP, but was 61.0(32.6-89.4) months for those with appendix cancer and 76.9(47.4-106.4) months for CRPM (p=<0.001). Survival was favourable in the PMP group (HR [95%CI] 0.044 [0.008-0.262]; p = 0.000) and unfavourable in the CC2-3 at index CRS procedure group (HR [95%CI] 25.612 [2.703-242.703]; p = 0.005). CONCLUSION: Our findings demonstrate that repeat cytoredutive surgery with HIPEC can result in favourable survival, especially for patients with PMP when complete cytoreduction is achieved at index operation. We recommend that detailed patient assessment is performed through an expert multidisciplinary team meeting (MDT).

"What if I'm not trans enough? What if I'm not man enough?": Transgender young adults' experiences of gender-affirming healthcare readiness assessments in Aotearoa New Zealand.

Background: A growing body of transgender health research reports that transgender people often feel pressure to conform to a dominant narrative during gender-affirming readiness assessments. In New Zealand, however, no study to date has specifically examined transgender people's experiences of readiness assessments for gender-affirming healthcare. Aims: This study aimed to explore the experiences of transgender young adults (aged 16-30) during gender-affirming readiness assessments in New Zealand. We also sought participants' views on improving transgender healthcare provision. Methods: Thirteen transgender young adults took part in individual interviews or focus groups. Participants were asked to describe how they felt about the questions asked during readiness assessments and how the readiness assessment process could be improved. We used thematic analysis to identify patterns of meaning across the dataset. Results: We identified two themes. Firstly, proving gender explores participants' views of readiness assessments as designed to establish whether they were "trans enough" or "truly" transgender, and why readiness assessments are conducted in this manner. Secondly, the trans narrative describes the pressure participants felt to adhere to a dominant transgender narrative in order to gain access to the healthcare they needed. Discussion: Our findings call attention to the importance of a trans-affirmative approach and the need to clarify the purpose of gender-affirming healthcare readiness assessments in New Zealand.

Long-term outcomes for patients with peritoneal acellular mucinosis secondary to low grade appendiceal mucinous neoplasms.

INTRODUCTION: Low grade appendiceal mucinous neoplasms (LAMN) are known to metastasise to the peritoneum resulting in pseudomyxoma peritonei (PMP). Literature suggests that the long-term outcome is dependent on the cellular grade of the peritoneal histology, less is known about the risk to patients with acellular mucinosis (AM) alone. This study aims to review long-term outcomes in patients with PMP treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (CRS/HIPEC), whose peritoneal histology was AM secondary to LAMN. METHODS: Pathological and treatment outcomes were collected from a prospectively maintained database between 2005 and 2019. Data was collected on patients with LAMN and AM diagnosed following CRS/HIPEC. A single institution performed the surgery and pathology reporting, samples reported by three different pathologists. RESULTS: Of the 2079 patients with any appendiceal neoplasm referred between 2005 and 2019, 809 underwent CRS/HIPEC, 67 (8%) of those had PMP with purely AM secondary to a LAMN. In the AM group the median age was 59, 37 (55%) were female, follow up was for a median 39 (2-145) months. Inpatient mortality occurred in 1 patient (1.5%), disease specific mortality in 2 (3%), recurrence in 2 (3%) and disease progression in 1 (1.5%). CONCLUSION: This study has identified AM secondary to LAMN as a low risk group for recurrence following CRS/HIPEC compared with epithelial pathology. Given such a low rate of recurrence we would recommend low intensity surveillance post CRS/HIPEC. Agreed standardised pathological assessment is required to exclude cellular material in specimens and diagnose AM.

Closure of the appendiceal stump in laparoscopic appendectomy: A systematic review of the literature.

BACKGROUND: Closure of the appendiceal stump is a key step performed during laparoscopic appendicectomy. Inadequate management of the appendiceal stump has the potential to cause significant morbidity. Several methods of stump closure have been described, however high-level evidence is limited. We performed a systematic review evaluating clinical outcomes and quality of the evidence for the methods of appendiceal stump closure. METHODS: A systematic literature search was performed using Medline, Embase, Cochrane Database and Google Scholar to identify studies comparing appendiceal stump closure methods in laparoscopic appendectomy for acute appendicitis from inception to October 2019. Data regarding operative duration, peri-operative complications, length of stay and costs were collated from all included studies. RESULTS: From 160 identified studies, 19 met the inclusion criteria. Endoloops and endoclips provide equivalent clinical outcomes at lower cost, while operative duration was shortest with endoclip closure. Endostapler devices have the lowest rate of peri-operative complications (3.56%), however their cost limits their regular use in many healthcare environments. Post-operative complication rate and length of stay were similar for all stump closure methods. Conclusion: Although there are no significant differences in method of stump closure in laparoscopic appendectomy, closure with endoclips provides the shortest operative duration. There is a need for robust and standardized reporting of cost data when comparing stump closure methods, together with higher level evidence in the form of multi-centre randomized controlled trials before firm conclusions can be drawn regarding the optimal method of stump closure.

What is the Operative Cost of Managing Acute Appendicitis in the NHS: The Impact of Stump Technique and Perioperative Imaging.

BACKGROUND: Acute appendicitis is a common surgical emergency that is typically managed with laparoscopic appendicectomy in UK centres. A number of variables influence the cost of managing this condition. Our aim was to identify the major influencing factors in our centre by performing a cumulative cost analysis. METHODS: We retrospectively analysed the costs associated with 99 cases of acute appendicitis managed with laparoscopic appendicectomy at Ninewells Hospital, Dundee, from January 2014 to February 2016. Costs were categorised according to blood tests, imaging, medications, operative costs and length of stay. RESULTS: Our cohort included 66 males, 33 females and 28 paediatric cases. The total cost was £220030.52 with a mean of £2222.53 per patient. The factor with the greatest influence on overall cost was operative time (53.2%) followed by length of stay (39.2%). There was no cost difference between adults and children (p = 0.24) or males and females (p = 0.38). Mean cost in adults ≥50 years was greater than those <50 years (£2899.32 vs £2152.97, p = 0.008) and greater in those who underwent imaging as opposed to no imaging (£2789.53 vs £2010.65, p = 0.0001). For appendiceal stump technique, polymer clips were cheaper (£1844.70) than ligatures (£2380.11, p = 0.006). CONCLUSIONS: Operative time (53.2%) and length of stay (39.2%) had the greatest impact on the cost in our cohort. Older patients have a greater overall cost, and this is associated with increased utilisation of imaging. Further studies assessing the safety and feasibility of methods to reduce operative time and to investigate the safety of reducing length of stay are required.

Histology of portal vascular changes associated with idiopathic non-cirrhotic portal hypertension: nomenclature and definition.

Idiopathic non-cirrhotic portal hypertension (INCPH) is a rare vascular liver disease that has attracted new interest in recent years. It is characterised by clinical signs of portal hypertension in the absence of cirrhosis or severe fibrosis and any known cause of portal hypertension. As much uncertainty exists about INCPH pathophysiology, and no definite diagnostic tests are available, liver biopsy is an essential tool for achieving a definite diagnosis. Unfortunately, the histological diagnosis of INCPH is not always straightforward, as the characteristic lesions are unevenly distributed, vary greatly in their severity, are often very subtle, and are not all necessarily present in a single case. Furthermore, specifically for the characteristic portal vessel changes observed in INCPH, the terminology and definition are ambiguous, which adds complexity to the already complex clinicopathological scenario. An international study group of liver pathologists and hepatologists pursued a consensus on nomenclature for the portal vascular lesions of INCPH. Such standardisation may assist pathologists in the recognition of such lesions, and will possibly facilitate further advancement in this field.

Acute-on-chronic liver failure 2018: a need for (urgent) liver biopsy?

INTRODUCTION: 'Acute-on-Chronic-Liver Failure (ACLF)' entered hepatology practice by the end of the 20th century. Although we lack precise and universally agreed definitions, acute decompensation of chronic liver disease with jaundice and deranged clotting, multi-organ failure and high, short-term mortality are hallmarks of the syndrome. Timely recognition and and treatment, including urgent liver transplantation, may save the life of certain patients. The diagnosis and management are mostly based on clinical features, but some have suggested to incorporate histopathology (liver biopsy). This may add to the differentiation between acute and chronic disease, primary and concomitant etiologies, and identify prognostic determinants. Areas covered: A review of the literature on ACLF and the outcome of the discussions at a topical international meeting on specific histopathological aspects of diagnosis and prognosis of the syndrome. Expert commentary: There is a lack of standardized descriptions of histopathological features and there is limited prospective experience with the role of pathology of ACLF. It is important for the clinical hepatologist to understand the potential and limitations of (transjugular) liver biopsy in ACLF and for the pathologist to help address the clinical question and recognise the histopathological features that help to characterize ACLF, both in terms of diagnosis and prognosis.

CD4+ Th2 cells are directly regulated by IL-10 during allergic airway inflammation.

Interleukin-10 (IL-10) is an important regulatory cytokine required to control allergy and asthma. IL-10-mediated regulation of T cell-mediated responses was previously thought to occur indirectly via antigen-presenting cells. However, IL-10 can act directly on regulatory T cells and T helper type 17 (Th17) cells. In the context of allergy, it is therefore unclear whether IL-10 can directly regulate T helper type 2 (Th2) cells and whether this is an important regulatory axis during allergic responses. We sought to determine whether IL-10 signaling in CD4+ Th2 cells was an important mechanism of immune regulation during airway allergy. We demonstrate that IL-10 directly limits Th2 cell differentiation and survival in vitro and in vivo. Ablation of IL-10 signaling in Th2 cells led to enhanced Th2 cell survival and exacerbated pulmonary inflammation in a murine model of house dust mite allergy. Mechanistically, IL-10R signaling regulated the expression of several genes in Th2 cells, including granzyme B. Indeed, IL-10 increased granzyme B expression in Th2 cells and led to increased Th2 cell death, identifying an IL-10-regulated granzyme B axis in Th2 cells controlling Th2 cell survival. This study provides clear evidence that IL-10 exerts direct effects on Th2 cells, regulating the survival of Th2 cells and severity of Th2-mediated allergic airway inflammation.

MicroRNA-mediated regulation of immune responses to intestinal helminth infections.

Intestinal helminth infections are highly prevalent in the developing world, often resulting in chronic infection and inflicting high host morbidity. With the emergence of drug-resistant parasites, a limited number of chemotherapeutic drugs available and stalling vaccine efforts, an increased understanding of antihelminth immunity is essential to provide new avenues to therapeutic intervention. MicroRNAs are a class of small, nonprotein coding RNAs which negatively regulate mRNA translation, thus providing finite control over gene expression in a plethora of biological settings. The miRNA-mediated coordinated control of gene expression has been shown to be essential in infection and immunity, in promoting and fine-tuning the appropriate immune response. This review gathers together and discusses observations of miRNA-mediated effects on the immune system and the subsequent impact on our understanding of antihelminth immunity.

Role of aetiology in the progression, regression, and parenchymal remodelling of liver disease: implications for liver biopsy interpretation.

Clinicopathological concepts on acute and chronic liver disease have evolved rapidly during the last few years, with advances in general and specific treatment options and improved patient outcomes. The old paradigm of 'irreversibility' of cirrhosis had been challenged in major ways, and the validity of the usage of the term 'cirrhosis' has come into question. This paper addresses aetiology-based clinicopathological concepts and features that may deserve attention because they may determine disease outcome and, specifically, patterns of regression and remodelling. A variety of therapeutic interventions may influence remaining disease features after elimination of damaging agents (virus, alcohol, etc.), and determine the final clinical outcome including the risk of hepatocellular carcinoma (HCC). New concepts create new responsibilities and opportunities for the pathologist to contribute to the understanding of liver pathology and communicate this with clinical colleagues and researchers.

IL-4-producing ILC2s are required for the differentiation of TH2 cells following Heligmosomoides polygyrus infection.

Immunity to many human and murine gastrointestinal helminth parasites requires interleukin-4 (IL-4)-directed type 2 helper (TH2) differentiation of CD4+ T cells to elicit type-2 immunity. Despite a good understanding of the inflammatory cascade elicited following helminth infection, the initial source of IL-4 is unclear. Previous studies using the rat helminth parasite Nippostronglyus brasiliensis, identified an important role for basophil-derived IL-4 for TH2 differentiation. However, basophils are redundant for TH2 differentiation following infection with the natural helminth parasite of mice Heligmosomoides polygyrus, indicating that other sources of IL-4 are required. In this study using H. polygyrus, which is controlled by IL-4-dependent immunity, we identified that group-2 innate lymphoid cells (ILC2s) produced significant amounts of IL-4 and IL-2 following H. polygyrus infection. Leukotriene D4 was sufficient to stimulate IL-4 secretion by ILC2s, and the supernatant from activated ILC2s could potently drive TH2 differentiation in vitro in an IL-4-dependent manner. Furthermore, specific deletion of IL-4 from ILC2s compromised TH2 differentiation in vivo. Overall, this study highlights a previously unrecognized and important role for ILC2-derived IL-4 for TH2 differentiation in a natural TH2-dependent model of human helminthiasis.

Documentation of Pregnancy Status, Gynaecological History, Date of Last Menstrual Period and Contraception Use in Emergency Surgical Admissions: Time for a Change in Practice?

OBJECTIVE: To determine whether pregnancy status, gynaecological history, date of last menstrual period and contraceptive use are documented in emergency female admissions of reproductive age admitted to general surgery. DESIGN: This is a retrospective study. SETTING: This study was conducted in the United Kingdom. POPULATION: Females of reproductive age (12-50 years) admitted as an emergency to general surgery with abdominal pain were considered in this study. METHODS: Retrospective analysis of medical notes of emergency female admissions with abdominal pain between January and September 2012. We recorded whether a pregnancy test result was documented (cycle 1). Results were analysed and a prompt added to the medical clerk-in document. We re-audited (cycle 2) between January and June 2013 looking for improvement. MAIN OUTCOME MEASURES: Documented pregnancy status within 24 h of admission and prior to any surgical intervention. RESULTS: 100 case notes were reviewed in stage 1. 30 patients (30 %) had a documented pregnancy status. 32 (32 %), 25 (25 %) and 29 (29 %) had a documented gynaecology history, contraceptive use and date of last menstrual period (LMP), respectively. 24 patients underwent emergency surgery, 6 (25 %) had a documented pregnancy status prior to surgery. Of 50 patients reviewed in stage 2, 37 (75.0 %) had a documented pregnancy status (p < 0.001), with 41 (82 %) having both gynaecological history (p < 0.0001) and contraceptive use (p < 0.0001) documented. 40 patients (80 % had a documented LMP (p < 0.0001). 7 patients required surgery, of whom 6 (85.7 %) had a documented pregnancy test prior to surgery (p = 0.001). All pregnancy tests were negative. CONCLUSIONS: A simple prompt in the surgical admission document has significantly improved the documentation of pregnancy status and gynaecological history in our female patients, particularly in those who require surgical intervention. A number of patient safety concerns were addressed locally, but require a coordinated, interdisciplinary discussion and a national guideline. A minimum standard of care, in females of reproductive age, should include mandatory objective documentation of pregnancy status, whether or not they require surgical intervention.

30-Day and 1-year mortality in emergency general surgery laparotomies: an area of concern and need for improvement?

AIMS: Emergency surgery is associated with poorer outcomes and higher mortality with recent studies suggesting the 30-day mortality to be 14-15%. The aim of this study was to analyse the 30-day mortality, age-related 30-day mortality and 1-year mortality following emergency laparotomy. We hope this will encourage prospective data collection, improvement of care and initiate strategies to establish best practice in this area. METHODS: This was a retrospective study of patients who underwent emergency laparotomy from June 2010 to May 2012. The primary end point of the study was 30-day mortality, age-related 30-day mortality and 1-year all-cause mortality. RESULTS: 477 laparotomies were performed in 446 patients. 57% were aged <70 and 43% aged >70 years. 30-day mortality was 12, 4% in those aged <70 years and 22% in those >70 years (p < 0.001). 1-year mortality was 25, 15% in those aged under 70 years and 38% in those aged >70 years (p < 0.001). CONCLUSIONS: Emergency laparotomy carries a high rate of mortality, especially in those over the age of 70 years, and more needs to be done to improve outcomes, particularly in this group. This could involve increasing acute surgical care manpower, early recognition of patients requiring emergency surgery, development of clear management protocols for such patients or perhaps even considering centralisation of emergency surgical services to specialist centres with multidisciplinary teams involving emergency surgeons and care of the elderly physicians in hospital and related community outreach services for post-discharge care.

Elucidating the prognostic significance of KRAS, NRAS, BRAF and PIK3CA mutations in Chinese patients with metastatic colorectal cancer.

AIM: The prognostic significance of KRAS, NRAS, PIK3CA and BRAF mutations was evaluated in Chinese patients with metastatic colorectal cancer (CRC). METHOD: Tumor samples from 183 patients were retrospectively tested for KRAS, NRAS, PIK3CA and BRAF mutations. Multivariate analysis was performed to determine the relationship between mutational status, drug response and survival. RESULT: Over 70% of patients received two or more lines of chemotherapy, 50% had cetuximab and 18% had bevacizumab. The prevalence of KRAS, NRAS, BRAF and PIK3CA mutations was 45, 3.2, 5 and 20%, respectively. For the entire cohort, the median overall survival was 24 months (95% confidence interval [CI] = 20.4-26.4 months). Of the genes tested, only KRAS mutation was an independent prognostic factor with a multivariate hazard ratio of 1.5 (95% CI = 1.05-2.16, P = 0.03). In the subgroup of patients who received cetuximab-based therapy in the first-line setting, KRAS mutation was associated with a lack of response to chemotherapy (28% vs 66%, chi-square, P = 0.01). Patients with KRAS mutant tumors (or KRAS wild-type tumors that harbored BRAF and/or PIK3CA mutations) tended to have lower response rates to chemotherapy and/or cetuximab (P = not significant). The number of NRAS mutant cases was too small to allow any statistical analysis. CONCLUSION: The prevalence of KRAS, NRAS, BRAF and PIK3CA mutations in this cohort is consistent with reports from non-Asian populations, and KRAS mutation has both prognostic and predictive significance in Chinese patients with metastatic CRC.

Xanthogranulomatous inflammation of terminal ileum: report of a case with small bowel involvement.

Xanthogranulomatous inflammation is a rare pathological condition most frequently detected in the kidney and gallbladder. Reported herein is a case of xanthogranulomatous inflammation in a 51-year-old male presenting as a mass-forming lesion in the terminal ileum with mucosal ulceration. Diagnostic laparoscopy followed by ileocecectomy was performed due to intra-operative suspicion of carcinoma of appendix. This is a report of the condition involving the terminal ileum with mucosal ulceration and full-thickness involvement of bowel wall which are uncommon features of xanthogranulomatous inflammation in previously reported lower gastro-intestinal tract lesions.

Giant condylomata acuminata of Buschke and Lowenstein: A peristomal variant.

INTRODUCTION: Giant condylomata acuminata (GCA) is a rare, locally invasive tumour that may undergo malignant transformation. It was first described a HPV-induced penile tumour which clinically resembled both a squamous cell carcinoma and condyloma acuminatum, often arising from a pre-existing warty lesion. We describe a case of peri-stomal GCA transformation into invasive squamous cell carcinoma (SCC), which is, to our knowledge, the first report of this in the literature. PRESENTATION OF CASE: A 74 year old gentleman developed an acuminate, papillomatous peristomal eruption around a fifty year old ileostomy, with biopsies of the eruption showing reactive changes. Two years later, he developed ulcerating plaques affecting the previously papillomatous areas and an erythematous nodular lesion involving the superior part of the ileostomy and adjacent skin. Histological examination of the ileostomy lesion showed focal small islands of atypical squamous epithelium, and moderately differentiated invasive squamous cell carcinoma was shown in the excised tissue subsequently. Human papillomavirus (HPV type 16), p16 and p53 tumour suppressors were positive in the peri-stomal skin sample. DISCUSSION AND CONCLUSIONS: Recurring, changing papillomatous lesions in the peristomal area should be reviewed with a high index of suspicion in relation to GCA tumours as they can progress to invasive squamous cell carcinomas.

Microbial biogeochemistry of Boiling Springs Lake: a physically dynamic, oligotrophic, low-pH geothermal ecosystem.

Boiling Springs Lake (BSL) in Lassen Volcanic National Park, California, is North America's largest hot spring, but little is known about the physical, chemical, and biological features of the system. Using a remotely operated vessel, we characterized the bathymetry and near-surface temperatures at sub-meter resolution. The majority of the 1.2 ha, pH 2.2 lake is 10 m deep and 50-52 °C, but temperatures reach 93 °C locally. We extracted DNA from water and sediments collected from warm (52 °C) and hot (73-83 °C) sites separated by 180 m. Gene clone libraries and functional gene microarray (GeoChip 3.0) were used to investigate the BSL community, and uptake of radiolabeled carbon sources was used to assess the relative importance of heterotrophic vs. autotrophic production. Microbial assemblages are similar in both sites despite the strong temperature differential, supporting observations of a dynamic, convectively mixed system. Bacteria in the Actinobacteria and Aquificales phyla are abundant in the water column, and Archaea distantly related to known taxa are abundant in sediments. The functional potential appears similar across a 5-year time span, indicating a stable community with little inter-annual variation, despite the documented seasonal temperature cycle. BSL water-derived DNA contains genes for complete C, N, and S cycles, and low hybridization to probes for N and S oxidation suggests that reductive processes dominate. Many of the detected genes for these processes were from uncultivated bacteria, suggesting novel organisms are responsible for key ecosystem services. Selection imposed by low nutrients, low pH, and high temperature appear to result in low diversity and evenness of genes for key functions involved in C, N, and S cycling. Conversely, organic degradation genes appear to be functionally redundant, and the rapid assimilation of radiolabeled organic carbon into BSL cells suggests the importance of allochthonous C fueling heterotrophic production in the BSL C cycle.

Classification of and cytoreductive surgery for low-grade appendiceal mucinous neoplasms.

BACKGROUND: Low-grade appendiceal mucinous neoplasm (LAMN) is a precursor lesion for pseudomyxoma peritonei (PMP), which, if treated suboptimally, may later disseminate throughout the abdominal cavity. The role of cytoreductive surgery for these relatively early lesions is unclear. METHODS: Clinicopathological details and treatment outcomes of patients with a LAMN and disease limited to the appendix or immediate periappendiceal tissues, referred to a national treatment centre between 2002 and 2009, were evaluated prospectively. RESULTS: Of 379 patients with a diagnosis of PMP, 43 (median age 49 years) had LAMNs localized to the appendix and periappendiceal tissue. Thirty-two patients initially presented with symptoms of acute appendicitis or right iliac fossa pain. Two distinct lesions were identified: type I (disease confined to the appendiceal lumen) and type II (mucin and/or neoplastic epithelium in the appendiceal submucosa, wall and/or periappendiceal tissue, with or without perforation). Type I lesions were managed by a watch-and-wait surveillance policy with serial measurement of tumour markers and computed tomography in 14 of 16 patients. Seventeen of 27 patients with type II lesions underwent risk-reducing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy with low morbidity. After a median follow-up of 40 months, there was no disease progression in either treatment pathway. CONCLUSION: This study identified two LAMN subtypes. Type II lesions have pathological features of increased risk for dissemination and should be considered for risk-reducing cytoreductive surgery.