Background Randomised controlled trials (RCTs) for surgical interventions have often proven difficult with calls for innovative approaches. The Imperial Prostate (IP4) Comparative Health Research Outcomes of Novel Surgery in prostate cancer (IP4-CHRONOS) study aims to deliver level 1 evidence on outcomes following focal therapy which involves treating just the tumour rather than whole-gland surgery or radiotherapy. Our aim is to test the feasibility of two parallel RCTs within an overarching strategy that fits with existing patient and physician equipoise and maximises the chances of success and potential benefit to patients and healthcare services. Methods and design IP4-CHRONOS is a randomised, unblinded multi-centre study, including two parallel randomised controlled trials targeting the same patient population: IP4-CHRONOS-A and IP4-CHRONOS-B. IP4-CHRONOS-A is a 1:1 RCT and the other is a multi-arm, multi-stage (MAMS) RCT starting with three arms and a 1:1:1 randomisation. The two linked RCTs are discussed with patients at the time of consent and the choice of A or B is dependent on physician and patient equipoise. The primary outcome is the feasibility of recruitment, acceptance of randomisation and compliance to allocated arm. Results This paper describes the statistical analysis plan (SAP) for the feasibility study within IP4-CHRONOS given its innovative approach. Version 1.0 of the SAP has been reviewed by the Trial Steering Committee (TSC), Chief Investigator (CI), Senior Statistician and Trial Statistician and signed off. The study is ongoing and recruiting. Recruitment is scheduled to finish later in 2021. The SAP documents approved methods and analyses that will be conducted. Since this is written in advance of the analysis, we avoid bias arising from prior knowledge of the study data and findings. Discussion Our feasibility analysis will demonstrate if IP4-CHRONOS is feasible in terms of recruitment, randomisation and compliance, and whether to continue both A and B or just one to the main stage. Trial registration ISRCTN ISRCTN17796995. Registered on 08 October 2019

INTRODUCTION: Homeostasis of the GI mucosal environment depends on gut motility and normal gastric acid secretion. The autonomic nervous system plays an important role in these processes. Diabetes has been shown to injure the enteric nervous system, resulting in slowed motility. Gastroparesis and small intestinal bacterial overgrowth are two consequences of the enteric injury associated with diabetes. CASE DESCRIPTION/METHODS: A 23-year-old male with type 1 diabetes presented with 6 months of diffuse abdominal pain and diarrhea, which had recently worsened. He noted 4-6 loose bowel movements daily and vomiting after food. He had previously been seen by gastroenterology and had an unremarkable colonoscopy, EGD, and celiac testing. He had been trialed on rifaximin and neomycin, which improved his symptoms for a short period. He tried eluxadoline with little effect. On presentation, he was hemodynamically stable with labs significant only for mildly elevated AST (58 units/L). WBC, ESR, CRP, feces ova and parasites, and C. difficile Ag were all unremarkable. A gastric emptying study revealed moderate (24%) gastroparesis. A right upper quadrant ultrasound was unremarkable. Small intestinal bacterial overgrowth related to gastroparesis was suspected. A trial of rifaximin and metoclopramide improved his symptoms leading to empiric diagnosis of SIBO. DISCUSSION: Small intestinal bacterial overgrowth occurs when the normal homeostatic mechanisms that control bacterial populations are in some way disrupted. Frequently, this occurs with decreased gastric acid secretion or dysmotility of the small intestine. The most common symptoms of SIBO include bloating, abdominal discomfort and distention, chronic diarrhea, weight loss, and malabsorption. One proposed theory for SIBO in gastroparesis is the idea that phase 3 migratory motor complexes may be diminished in frequency or altogether absent. While the gold standard for diagnosis requires jejunal aspirate, lactulose and glucose breath testing have been used as indirect measures of SIBO. Multiple studies have been done to analyze the relationship between gastroparesis and SIBO with results showing up to 60-70% of study participants with gastroparesis test positive for SIBO via lactulose breath testing. Once the diagnosis of SIBO has been established, the goal of therapy is to correct the underlying cause, provide nutritional support, and treat overgrowth with a course of antibiotics.

INTRODUCTION: Peritoneal carcinomatosis (PC) is a metastatic feature in several gastrointestinal malignancies. As one of the most common presenting symptoms is new onset ascites, understanding the workup and typical findings of malignant ascites is crucial for appropriate and time sensitive diagnosis and treatment of such malignancies. CASE DESCRIPTION/METHODS: A 50-year-old female with past medical history significant for hypertension and alcohol abuse presented to the hospital with complaint of intermittent weakness and progressive abdominal fullness for one month. Her exam was notable for subconjunctival palor, abdominal ascites with generalized tenderness, and lower extremity edema. Labs showed leukocytosis and microcytic anemia, with hemoglobin of 5.9. CT abdomen/pelvis revealed cardiomegaly, moderate volume ascites, and diffuse body wall edema. Iron studies were obtained (low iron, low-normal ferritin) and the patient was transfused. A diagnostic paracentesis was completed with resultant SAAG of 0.6. Cytology revealed benign appearing mesothelial cells and histiocytes. Due to the patient's lack of insurance, GI was consulted for inpatient evaluation of iron deficiency. Colonoscopy showed a large (>10 cm) ulcerated lesion in the sigmoid colon with pathology consistent with moderately-differentiated adenocarcinoma. Repeat CT was obtained for staging purposes, showing diffuse peritoneal carcinomatosis, distal colon lesion, L4 vertebral sclerosis, and large volume ascites. The patient was discharged with plans to follow up with GI and oncology to discuss therapeutic options. DISCUSSION: Peritoneal carcinomatosis is defined as the dissemination of cancer cells throughout the periteoneum. About 8% of patients with colorectal cancer present with PC; most commonly with nonspecific symptoms such as fatigue, abdominal pain/fullness, and bowel obstruction. Since new onset ascites is common to PC, it is important to identify malignant ascitic fluid. Malignant ascites related to peritoneal carcinomatosis is mainly caused by subphrenic vessel obstruction and accounts for 7% of ascites cases. A diagnostic paracentesis is indicated, with typical fluid findings of WBC >500, SAAG <1.1, and total protein >2.5. Fluid cytology is important, however sensitivity is affected by the number and quality of specimens used, making the overall sensitivity only about 60-70%. After a diagnosis of malignant ascites is made, the patient should be counseled and referred for evaluation of available therapeutic options.