Presacral Neuroendocrine Neoplasms: A Multi-site Review of Surgical Outcomes.

INTRODUCTION: Presacral neuroendocrine neoplasms (PNENs) are rare tumors, with limited data on management and outcomes. METHODS: A retrospective review of institutional medical records was conducted to identify all patients with PNENs between 2008 and 2022. Data collection included demographics, symptoms, imaging, surgical approaches, pathology, complications, and long-term outcomes. RESULTS: Twelve patients were identified; two-thirds were female, averaging 44.8 years of age, and, for the most part, presenting with back pain, constipation, and abdominal discomfort. Preoperative imaging included computed tomography scans and magnetic resonance images, with somatostatin receptor imaging and biopsies being common. Half of the patients had metastatic disease on presentation. Surgical approach varied, with anterior, posterior, and combined techniques used, often involving muscle transection and coccygectomy. Short-term complications affected one-quarter of patients. Pathologically, PNENs were mainly well-differentiated grade 2 tumors with positive synaptophysin and chromogranin A. Associated anomalies were common, with tail-gut cysts prevalent. Mean tumor diameter was 6.3 cm. Four patients received long-term adjuvant therapy. Disease progression necessitated additional interventions, including surgery and various chemotherapy regimens. Skeletal, liver, thyroid, lung, and pancreatic metastases occurred during follow-up, with no mortality reported. Kaplan-Meier analysis showed a 5-year local recurrence rate of 23.8%, disease progression rate of 14.3%, and de novo metastases rate of 30%. CONCLUSION: The study underscores the complex management of PNENs and emphasizes the need for multicenter research to better understand and manage these tumors. It provides valuable insights into surgical outcomes, recurrence rates, and overall survival, guiding future treatment strategies for PNEN patients.

Contemporary perioperative outcomes after total abdominal colectomy for ulcerative colitis in a tertiary referral centre.

OBJECTIVE: Colectomy for ulcerative colitis (UC) is common despite therapeutic advances. Post-operative morbidity and mortality demonstrate an association between hospital volumes and outcomes. This single-centre retrospective study examines outcomes after emergency colectomy for UC. METHODS: Patient demographics, perioperative variables and outcomes were collected in Beaumont Hospital between 2010 and 2023. Univariant analysis was used to assess relationships between perioperative variables and morbidity and length of stay (LOS). RESULTS: A total of 115 patients underwent total abdominal colectomy with end ileostomy for UC, 8.7 (±3.8) per annum. Indications were refractory acute severe colitis (88.7%), toxic megacolon (6.1%), perforation (4.3%), or obstruction (0.9%). Over 80% of cases were performed laparoscopically. Pre-operative steroid (93%) and biologic (77.4%) use was common. Median post-operative LOS was 8 days (interquartile range 6-12). There were no 30-day mortalities, and 30-day post-operative morbidity was 38.3%. There was no association between time to colectomy ( P  = 0.85) or biologic use ( P  = 0.24) and morbidity. Increasing age was associated with prolonged LOS ( P  = 0.01). Laparoscopic approach (7 vs. 12 days P  =0.01, 36.8% vs. 45% P  = 0.66) was associated with reduced LOS and morbidity. CONCLUSION: This study highlights contemporary outcomes after emergency colectomy for UC at a specialist high-volume, tertiary referral centre, and superior outcomes after laparoscopic surgery in the biologic era.

Thinking outside the pelvis: benign peritoneal multicystic mesothelioma of the ascending colon.

Benign peritoneal multicystic mesothelioma is a rare tumor of the visceral peritoneum. The authors present an atypical case of a 74-year-old man who presented with a multicystic mesothelioma of the ascending colon.

A prospective evaluation of the effect of transanal minimally invasive surgery (TAMIS) on low anterior resection syndrome.

PURPOSE: Transanal minimally invasive surgery (TAMIS) is a surgical alternative to transanal endoscopic microsurgery (TEM), transanal excision and proctectomy in the management of benign rectal polyps and early rectal cancers. Low anterior resection syndrome (LARS) describes the constellation of symptoms which result from and are common after distal colorectal resection. Symptoms include incontinence, frequency, urgency and evacuatory dysfunction. The aim of the current study was to prospectively evaluate pre- and post-operative LARS in patients who undergo TAMIS. METHODS: We conducted a prospective analysis of a consecutive series of patients who underwent TAMIS at our institution between January 2021 and February 2022. A LARS questionnaire was undertaken preoperatively, at 1 month and at 6 months post-operatively. RESULTS: Twenty patients were recruited to this pilot study. The mean age was 63 ± 12 years, 11 of the patients were male, mean pre-operative BMI was 29 ± 6 kg/m2, and 30% (n = 6) of patients underwent TAMIS for an invasive rectal cancer, with all patients receiving an R0 resection. Mean distance from the anal verge was 5.7 ± 3.2 cm, and mean lesion diameter was 46 ± 20.5 mm. A statistically significant interval reduction was observed between preoperative (20.3 ± 12.9) and 6-month post-operative (12.6 ± 9.7) LARS scores (p = 0.02) and also between 1-month (18.2 ± 10.6) and 6-month post-operative scores (p = 0.01). CONCLUSIONS: We noted a high prevalence of LARS across our cohort preoperatively, and this had improved significantly at 6-month review post-TAMIS. This study reaffirms the safety and efficacy of TAMIS for the treatment of early rectal neoplasia.

The NR4A agonist, Cytosporone B, attenuates pro-inflammatory mediators in human colorectal cancer tissue ex vivo.

Inflammation is a pivotal pathological factor in colorectal cancer (CRC) initiation and progression, and modulating this inflammatory state has the potential to ameliorate disease progression. NR4A receptors have emerged as key regulators of inflammatory pathways that are important in CRC. Here, we have examined the effect of NR4A agonist, Cytosporone B (CsnB), on colorectal tissue integrity and its effect on the inflammatory profile in CRC tissue ex vivo. Here, we demonstrate concentrations up 100 µM CsnB did not adversely affect tissue integrity as measured using transepithelial electrical resistance, histology and crypt height. Subsequently, we reveal through the use of a cytokine/chemokine array, ELISA and qRT-PCR analysis that multiple pro-inflammatory mediators were significantly increased in CRC tissue compared to control tissue, which were then attenuated with the addition of CsnB (such as IL-1ß, IL-8 and TNFα). Lastly, stratification of the data revealed that CsnB especially alters the inflammatory profile of tumours derived from males who had not undergone chemoradiotherapy. Thus, this study demonstrates that NR4A agonist CsnB does not adversely affect colon tissue structure or functionality and can attenuate the pro-inflammatory state of human CRC tissue ex vivo.

Salcaprozate sodium (SNAC) enhances permeability of octreotide across isolated rat and human intestinal epithelial mucosae in Ussing chambers.

Octreotide is approved as a one-month injectable for treatment of acromegaly and neuroendocrine tumours. Oral delivery of the octapeptide is a challenge due mainly to low intestinal epithelial permeability. The intestinal permeation enhancer (PE) salcaprozate sodium (SNAC) has Generally Regarded As Safe (GRAS) status and is a component of an approved oral peptide formulation. The purpose of the study was to examine the capacity of salcaprozate sodium (SNAC), to increase its permeability across isolated rat intestinal mucosae from five regions and across human colonic mucosae mounted in Ussing chambers. Apical-side buffers were Kreb's-Henseleit (KH), fasted simulated intestinal fluid (FaSSIF-V2), rat simulated intestinal fluid (rSIF), and colonic simulated intestinal fluid (FaSSCoF). The basal apparent permeability coefficient (Papp) of [3H]-octreotide was equally low across rat intestinal regional mucosae in KH, rSIF, and FaSSIF-V2. Apical addition of 20 mM SNAC increased the Papp across rat tissue in KH: colon (by 3.2-fold) > ileum (3.4-fold) > upper jejunum (2.3-fold) > duodenum (1.4-fold) > stomach (1.4-fold). 20 mM and 40 mM SNAC also increased the Papp by 1.5-fold and 2.1-fold respectively across human colonic mucosae in KH. Transepithelial electrical resistance (TEER) values were reduced in the presence in SNAC especially in colonic regions. LC-MS/MS analysis of permeated unlabelled octreotide across human colonic mucosae in the presence of SNAC indicated that [3H]-octreotide remained intact. No gross damage was caused to rat or human mucosae by SNAC. Attenuation of the effects of SNAC was seen in rat jejunal mucosae incubated with FaSSIF-V2 and rSIF, and also to some extent in human colonic mucosae using FaSSCoF, suggesting interaction between SNAC with buffer components. In conclusion, SNAC showed potential as an intestinal permeation enhancer for octreotide, but in vivo efficacy may be attenuated by interactions with GI luminal fluid contents.

Modern surgery for ulcerative colitis.

Ulcerative colitis (UC) is a chronic inflammatory disorder of poorly understood aetiology. While medical treatment is first-line management, approximately 10% of patients with UC will require a colectomy either as an emergency or elective procedure. There are multiple surgical options available in the current era and the choice of operation(s) is highly dependent on the clinical presentation, patient preference and individual surgeon or institutional practice. We present a review of modern surgical practices in ulcerative colitis, addressing some current controversies and diversities.

Activated systemic inflammatory response at diagnosis reduces lymph node count in colonic carcinoma.

AIM: To investigate a link between lymph node yield and systemic inflammatory response in colon cancer. METHODS: A prospectively maintained database was interrogated. All patients undergoing curative colonic resection were included. Neutrophil lymphocyte ratio (NLR) and albumin were used as markers of SIR. In keeping with previously studies, NLR ≥ 4, albumin < 35 was used as cut off points for SIR. Statistical analysis was performed using 2 sample t-test and χ(2) tests where appropriate. RESULTS: Three hundred and two patients were included for analysis. One hundred and ninety-five patients had NLR < 4 and 107 had NLR ≥ 4. There was no difference in age or sex between groups. Patients with NLR of ≥ 4 had lower mean lymph node yields than patients with NLR < 4 [17.6 ± 7.1 vs 19.2 ± 7.9 (P = 0.036)]. More patients with an elevated NLR had node positive disease and an increased lymph node ratio (≥ 0.25, P = 0.044). CONCLUSION: Prognosis in colon cancer is intimately linked to the patient's immune response. Assuming standardised surgical technique and sub specialty pathology, lymph node count is reduced when systemic inflammatory response is activated.