Serial assessment of inflammatory parameters for prediction of septic complications following surgery for colorectal endometriosis

Summary Purpose To assess whether C‑reactive protein (CRP), white blood cell count (WBC) and body temperature changes are suitable parameters for the early detection of septic complications following resection of colorectal deep endometriosis (DE). Methods Retrospective data analysis of CRP, WBC and body temperature courses following colorectal surgery for DE at a tertiary referral center for endometriosis. Results Out of 183 surgeries performed, 10 major surgical complications were observed, including 4 anastomotic leakages (AL 2%) and 2 rectovaginal fistulae (RVF 1%). In the presence of a lower gastrointestinal tract (GIT)-related septic complication or abdominal wall abscess, serum CRP levels were increased starting at postoperative day 2–3. A cut-off value of 10 mg/dl on day 4 for prediction of early septic complications could be verified (area under the curve 0.94, obtained by receiver operating characteristics analysis, sensitivity 88%, specificity 90%, positive predictive value 32%, negative predictive value 99%). Additionally, most patients with early septic complications exhibited increased WBC levels starting mainly from day 3–4; however, increased inflammatory parameters could not be observed in one patient with an RVF. Body temperature did not prove useful for early discrimination between uncomplicated cases and those with early septic complications. Conclusion Relevant elevations of serum CRP and WBC levels were demonstrated in patients with early septic complications following surgery for colorectal DE starting at postoperative day 2–4. The cut-off value of 10 mg/dl for CRP levels may serve as an early predictor for lower GIT-related septic complications but should be used with caution in women with suspected RVF development.

DOP28 Medical and Surgical Outcomes in Isolated Internal Penetrating Crohn’s Disease: A Multi-Centre Experience

Background Isolated internal penetrating Crohn’s diseases (IIPCD) is the second most common fistulating phenotype yet remains poorly characterised in therapeutic trials. This study assessed long-term outcomes of IIPCD. Methods We performed a retrospective study on data collected from 6 IBD referral centres, screening imaging reports between January 2016 and April 2019, excluding perianal or enterocutaneous fistulation, resulting in 121 patients with IIPCD. Management was classified as no intervention, medical (new/optimised) or surgical. The primary endpoint was complete resolution (CR) of fistula at next two imaging reassessments, paired with symptom and nutrition status, as previously defined(Samimi et al., 2010). Secondary endpoint was combined CR and partial resolution (PR). Statistics: Fisher’s exact, Kaplan-Meier method (SPSS v.27). Results Of patients at IIPCD diagnosis, 21% had previous IBD-related surgery, 21% were on a current biologic, 41% immunomodulator and 41% no treatment. Fistulae were majority enteroenteric (55%) and enterocolonic (48%), minority genitourinary (7.4%), with median disease duration at IIPCD diagnosis of 64 months. Outcomes of 118 patients with ≥1 interval imaging were analysed. Initial management was: 25.4% (n=30) no intervention, 49.2% (n=59) medical, 25.4% (n=30) surgical. Of fistula characteristics, only abscess predicted surgery over medical management (OR 5.30, 95% CI 1.60–15.48 p=0.0061), Figure 1. At first reassessment, CR and PR for the three management cohorts was 13.3%, 12.1%, 66.7% and 20.0%, 46.6%, 26.7%, respectively. The cumulative probability of CR was significantly greater for surgery compared with no intervention and medical management (log-rank p<0.001), Figure 2, and sustained when excluding pre-existing biologic (log-rank p=0.007), Figure 3, or previous surgery history (log-rank p<0.001). As observed management was then adjusted, cohorts were re-stratified: 13.5% (n=16) no intervention only, 45.8% (n=54) any medical but no surgery, 40.7% (n=48) any surgery. At second reassessment, again surgery significantly predicted CR over other management (log-rank p<0.001), Figure 4, but this was lost using the less strict outcome of combined CR and PR (log-rank p=0.447). No baseline variables were predictive of CR by each management. 27.6% (16/58) and 6.7% (2/30) of initial medical and no intervention cohorts had subsequent surgery (median interval 6.7 and 50.1 months) but there was no significant difference in peri-operative parenteral nutrition or post-operative intra-abdominal septic complication rates between earlier or later surgery. Conclusion In this cohort, surgery increases the probability of resolution of IIPCD with medical therapy including biologics offering limited temporising effect.

Acute Rheumatic Fever: Where Do We Stand? An Epidemiological Study in Northern Italy

Acute rheumatic fever (ARF) is a non-septic complication of group A β-hemolytic streptococcal (GAS) throat infection. Since 1944, ARF diagnosis relies on the Jones criteria, which were periodically revised. The 2015 revision of Jones criteria underlines the importance of knowing the epidemiological status of its own region with updated data. This study aims to describe ARF features in a retrospective cohort retrieved over a 10-year timespan (2009–2018) and to report the annual incidence of ARF among children in the Province of Monza-Brianza, Lombardy, Italy during the same period. This is a multicentric cross-sectional/retrospective study; 70 patients (39 boys) were diagnosed with ARF. The median age at diagnosis was 8.5 years (range, 4–14.2 years). Overall, carditis represented the most reported major Jones criteria followed by arthritis and chorea (40, 27, and 20 cases, respectively). In order to calculate the annual incidence of ARF, only children resident in the Province of Monza-Brianza were included in this part of the analysis. Therefore, 47 patients aged between 5 and 14 years were identified. The median incidence during the study time was 5.7/100,000 (range, 2.8–8.3/100,000). In the Province of Monza-Brianza, we found an incidence rate of ARF among children aged 5–14 years constantly above the threshold of low-risk area as defined in the 2015 revision of Jones criteria. Therefore, the diagnosis of ARF should be based on the moderate–high-risk set of Jones criteria. However, given the burden of secondary prophylaxis, expert opinion is advisable when the diagnosis of ARF is uncertain.

Hypoalbuminemia, Not Biologic Exposure, is Associated with Postoperative Complications in Crohn’s Disease Patients Undergoing Ileocolic Resection

Background There is limited data on the postoperative outcomes in Crohn’s disease patients exposed to preoperative ustekinumab or vedolizumab. We hypothesized preoperative biologic use in Crohn’s disease is not associated with postoperative complications after ileocolic resection. Methods Crohn’s disease patients who underwent ileocolic resection between 2009-2019 were identified at a large regional health system. Preoperative biologic use within 12 weeks surgery was categorized as no biologic, anti-tumor necrosis factor, vedolizumab, or ustekinumab. The primary endpoint was 90-day intra-abdominal septic complication. Risk factors included preoperative medical therapies, demographics, disease characteristics, laboratory values, and surgical approach. Regression models assessed the association of biologic use with intra-abdominal septic complication. Results 815 Crohn’s disease patients who underwent an ileocolic resection were included (62% no biologic, 31.4% anti-tumor necrosis factor, 3.9% vedolizumab, 2.6% ustekinumab). Primary anastomosis was performed in 85.9% of patients (side-to-side 48.8%, end-to- side 26%, end-to-end 25%) in primarily a stapled (77.2%) manner. Minimally invasive approach was used in 41.4%. The 90-day postoperative intra-abdominal sepsis rate of 810 patients was 12%, abscess rate was 9.6%, and anastomotic leak rate was 3.2%. Multivariable regression modeling controlling for confounding variables demonstrated that preoperative biologic use with anti-tumor necrosis factor (P=0.21), vedolizumab (P=0.17), or ustekinumab (P=0.52) was not significantly associated with intra-abdominal septic complication. Preoperative albumin <3.5 g/dl was independently associated with intra-abdominal septic complication (OR 1.76 [1.03-3.01]). Conclusions In Crohn’s disease patients undergoing ileocolic resection, preoperative biologics are not associated with 90-day postoperative intra-abdominal septic complication. Preoperative biologic exposure should not delay necessary surgery.

Abstract 16648: Covid-19 at the ICU: A Multiorgan Challenge

Introduction: About 5% of all COVID-19 patients require intensive care, mostly because of respiratory failure. Little is known about concomitant multi-organ manifestation under these circumstances. Methods: Retrospective observational study using routine data sets of 13 COVID-19 patients requiring mechanical ventilation in the Regiomed Hospital Coburg, Germany, between March 1 st and June 15 th , 2020. Results: Of 13 patients eligible for this study, all were intubated and ventilated mechanically, with signs of infiltration in chest radiographs. 4 suffered from renal failure and needed dialysis; 3 of these patients died, but none without renal failure. Proteinuria was found in all and microhematuria in all but one patients tested (n=11). All developed metabolic alkalosis (BEmax 9.75±0.99, mean ±SEM), and 6 afterwards polyuria (6.75 ±2.45l per day); both conditions resolved in all surviving patients but 1 spontaneously and were not related to prior renal failure. Liver enzymes were elevated in all patients (γGT 506 ±78U/l), but bilirubin levels only in 4; 2 of these died shortly after. Bacterial superinfection was found in 8 patients, and in all 3 ones finally dying. Rhabdomyolysis affected 12 patients (CKmax 1604±542U/l) and resolved later. All patients had slightly elevated troponin T (0.059 ±0.013ng/ml), and 7 had elevated nt-pro-BNP levels (3566±2359pg/ml), indicating cardiac COVID-19, and elevated d-dimer levels (18.1 ±6.68mg/dl) representing disseminated intravascular coagulation. No thromboembolic was observed. The need of catecholamines was low (<1mg/h norepinephrine), as long as there was no septic complication. Conclusions: Our data indicate that severe COVID-19 is a multi-organ disease, even though ARDS is the leading problem; renal involvement - together with bacterial superinfection - seems to be a major risk factor for unfavorable disease development. Especially metabolic alkalosis and polyuria without overt renal failure have not been studied yet and require close clinical attention.

Causes and Prognosis of Intestinal Failure in Crohn’s Disease: An 18-year Experience From a National Centre

Background and Aims Intestinal failure [IF] is a feared complication of Crohn’s disease [CD]. Although cumulative loss of small bowel due to bowel resections is thought to be the dominant cause, the causes and outcomes have not been reported. Methods Consecutive adult patients referred to a national intestinal failure unit over 2000–2018 with a diagnosis of CD, and subsequently treated with parenteral nutrition during at least 12 months, were included in this longitudinal cohort study. Data were extracted from a prospective institutional clinical database and patient records. Results A total of 121 patients were included. Of these, 62 [51%] of patients developed IF as a consequence of abdominal sepsis complicating abdominal surgery; small bowel resection, primary disease activity, and proximal stoma were less common causes [31%, 12%, and 6%, respectively]. Further, 32 had perianastomotic sepsis, and 15 of those had documented risk factors for anastomotic dehiscence. On Kaplan-Meier analysis, 40% of all patients regained nutritional autonomy within 10 years and none did subsequently; 14% of patients developed intestinal failure-associated liver disease. On Kaplan-Meier analysis, projected mean age of death was 74 years.2 Conclusions IF is a severe complication of CD, with 60% of patients permanently dependent on parenteral nutrition. The most frequent event leading directly to IF was a septic complication following abdominal surgery, in many cases following intestinal anastomosis in the presence of significant risk factors for anastomotic dehiscence. A reduced need for abdominal surgery, an increased awareness of perioperative risk factors, and structured pre-operative optimisation may reduce the incidence of IF in CD.

Functional outcome of surgical treatment of adults with extremity osteosarcoma after megaprosthetic reconstruction—single-center experience

Background Osteosarcoma is the most common primary malignant bone tumor in adults and is usually located in the long bones. Standard treatment consists of perioperative chemotherapy and radical surgical resection. Limb-sparing surgery using a variety of reconstructive techniques remains the gold standard. Methods In our study, we retrospectively analyzed 90 adult patients operated at our institution between 2000 and 2017 for extremity osteosarcoma that underwent limb-sparing reconstruction with the megaprosthesis. Sixty-one patients underwent resection and reconstruction of the distal femur, 9 patients—proximal femur, 7 patients—proximal tibia, 5 patients—total femoral resection and reconstruction, 5 patients—proximal humeral resection, and 3 patients—other types of resection with endoprosthetic reconstruction. The median follow-up time was 41 months, median overall survival was 86 months (3–225 months), and progression-free survival was 81 months (1–86 months). Functional assessment was made on 48 out of 56 living patients, after endoprosthetic reconstruction. The assessment was made according to MSTS functional scale. Results In 14 cases (15%), the endoprosthesis had to be explanted, or amputation was performed for local recurrence or septic complication. Due to a mechanical failure of the implant, we had to perform a revision in 5 patients (5%). Eighteen out of 74 patients with endoprosthesis died of the disease. The median MSTS score was 84% (53–100%), and the best result of 85% was achieved in patients after distal femoral resection with endoprosthetic reconstruction. Conclusion Careful planning of the treatment of patients with extremity osteosarcoma that is performed at the referral centers gives the possibility of long-term survival with a good and excellent functional result.

Treating of duodenal perforation following endoscopic retrograde transpapillary manipulations

Objective: valuation of diff erent duodenal perforation surgical management following endoscopic retrograde transpapillary manipulations. Materials and methods: thirty-one patients with duodenal perforation following transpapillary manipulations (17 own observations, 14 — admission from other hospitals). Th e 14 (45.2 %) cases had a diagnosis less than 24 hours, 17 (54.8 %) — more than 24 hours aft er injury. Twenty patients had the primary reconstruction of duodenum with various drainage options of zone of injury. Sixteen patients had a two-stage surgery procedure: 5 cases aft er of primary reconstruction of duodenum and 11 — like a primary surgery (more than a day aft er injury). Results: aft er primary of duodenum reconstruction 11 patients (55.0 %) had no complications, 5 (25.0 %) — were re-operated, 4 (20.0 %) — were died. Aft er two-stage surgery procedure 9 patients (56.3 %) had no complications, fi ve (31.2 %) had surgical complications, 2 (12.5 %) were died. Conclusion: the primary of duodenum reconstruction can be performing, when the duodenal perforation there is less than a day. When there is a clinic of septic complication of retroperitoneum and abdominal cavity, two-stage surgery procedure is justifi ed.

Clinical Implications of MYD88 and CXCR4 in Patients with Waldenström's Macroglobulinemia

Background Waldenström's macroglobulinemia (WM) is a rare B-cell neoplasm defined as lymphoplasmacytic lymphoma with bone marrow infiltration and monoclonal IgM in the serum. More than 90% of WM patients carry a point mutation L265P in the MYD88 gene and concurrently, almost one third of MYD88L265P-positive patients harbor frameshift (WHIM-FS) or non-sense (WHIM-NS) mutation in gene CXCR4. The mutations in CXCR4 result in premature stop codons and in shortening of CXCR4 protein product. Incomplete C-terminal domain of CXCR4 chemokine receptor is known to hyperactivate CXCR4-mediated signalization. The presence and type of mutation in genes MYD88 and CXCR4 appears to be significant in diagnostics and prognostic stratification of WM patients and it also influences the clinical manifestation of the disease. Aims To analyze mutational status of MYD88 and CXCR4 genes in patients with WM, to compare our results with laboratory parameters and to evaluate the prognostic stratification of the patients according to MYD88 and CXCR4 mutational status. Methods Analyzed DNA was isolated from mononuclear fraction of bone marrow or peripheral blood cells at the time of diagnosis. Mutational status of analyzed genes was determined using allele-specific PCR (in the case of MYD88) and using direct Sanger sequencing (in the case of CXCR4). All found mutations were confirmed by specific cleavage with restriction endonucleases at defined conditions. Results We analyzed 23 patients with WM. All patients were MYD88L265P-positive (100 %), and 7 of them (30,4%) were also CXCR4 mutants (1 patient harbored WHIM-FS mutation and 6 harbored WHIM-NS mutation). CXCR4 mutations were associated with more aggressive disease: higher ISSWM score (low 0/intermediate 1/ high 6 risk), anemia (7/7), hyperviscosity syndrome (2/7) at time of diagnosis. CXCR4WHIM-WT patients were often asymptomatic (5/16) with lower ISSWM score (low 5/intermediate 5/ high 6 risk) but with common adenopathy (11/16). CXCR4 mutations were also associated with worse treatment response (2 CXCR4WHIM-MUT patients were refractory to initial therapy and needed 2nd line treatment, 3 patients had only partial response to first-line therapy, one patient died after 2nd cycle due to abdominal septic complication and only one patient reached VGPR). Progression-free survival in treated patients was 32 vs. 8 months in CXCR4 mutants. Conclusion/summary The mutational analysis of MYD88 and CXCR4 genes is essential for the diagnostics and prognostic stratification of patients with WM and it allows a deeper understanding of the molecular pathogenesis of the diseases. CXCR4 mutations were found in nearly one third of WM patients. In accordance with published data, we confirmed that CXCR4 mutations are associated with more aggressive disease presentation and thus affect treatment outcome. On the contrary CXCR4WHIM-WT patients have more indolent course of the disease. This work was supported by grant IGA-LF-2018-004 and MH CR - RVO (FNOL, 00098892). Disclosures No relevant conflicts of interest to declare.