Single cell analysis via mass cytometry of spontaneous intestinal perforation reveals alterations in small intestinal innate and adaptive mucosal immunity.

Introduction: Spontaneous intestinal perforation (SIP) is a poorly understood severe gastrointestinal complications of prematurity which is poorly understood. Extremely premature infants born prior to 28 weeks' gestation develop a localized perforation of the terminal ileum during the first week of life and therapy involves surgery and cessation of enteral feeds. Little is known regardj g the impact of mucosal immune dysfunction on disease pathogenesis. Methods: We performed mass cytometry time of flight (CyTOF) of small intestinal mucosa of patients with SIP (Gestational age (GA) 24 - 27 weeks, n=8) compared to patients who had surgery for non-SIP conditions (neonatal (GA >36 weeks, n=5 ) and fetal intestine from elective terminations (GA 18-21 weeks, n=4). CyTOF analysis after stimulation of T cells with PMA/Ionomycin was also performed. Results: We noted changes in innate and adaptive mucosal immunity in SIP. SIP mucosa had an expansion of ckit+ neutrophils, an influx of naïve CD4 and CD8 T cells and a reduction of effector memory T cells. SIP T cells were characterized by reduced CCR6 and CXCR3 expression and increased interferon gamma expression after stimulation. Discussion: These findings suggest that previously unrecognized immune dysregulation is associated with SIP and should be explored in future studies.

Delayed bowel perforation after instilling over warmed peritoneal dialysate.

BACKGROUND: Peritoneal dialysis (PD) is a safe and home-based treatment for end-stage renal disease (ESRD) patients. The direct thermal damage of abdominal organs is very rare. CASE PRESENTATION: We report a peritoneal dialysis patient presented abdominal pain and feculent effluent 3 weeks after he instilled hot dialysis solution. In spite of emergency exploratory laparotomy and active treatment, the patient died of septic shock. Biopsy revealed necrosis and perforation of the intestines. CONCLUSIONS: Delayed bowel perforation by hot fluid is very rare. Standardized performance is of the first importance for peritoneal dialysis patients.

Bowel perforation due to methotrexate therapeutic error: an insidious adverse reaction.

OBJECTIVE: Methotrexate (MTX) is widely used in the treatment of rheumatic and non-rheumatic disorders. Severe adverse effects are often associated with therapeutic errors, such as daily intake rather than weekly intake. Among them, the risk of bowel perforation is extremely rare (0.1%). We describe a case of bowel perforation, occurred following daily intake of MTX. CASE REPORT: A 68-year-old man was prescribed to take MTX 7,5 mg orally once a week, while waiting for switch to abatacept for a recent reactivation of rheumatoid arthritis. After 10 days he started having pharyngodynia, hematochezia and general malaise. At medical examination he presented oral and nasal mucositis; moreover, blood exams showed thrombocytopenia. The anamnesis revealed that he had been taken the prescribed dosage of MTX daily, instead of weekly. Therapy with Lederfolin 1000 mg (mg/m²/die) and urine alkalinization started. After 7 days of hospitalization, there was an abrupt worsening of clinical conditions and an emergency CT scan revealed millimetric gas bubbles indicating bowel perforation. The patient underwent an emergency exploratory laparotomy that resulted in peritoneal toilette and sigma resections. Anatomopathological findings were suggestive of MTX poisoning. CONCLUSIONS: The patient was discharged on the 17th day in good clinical condition.

A Novel Presentation of Tuberculosis with Intestinal Perforation in a Free-Ranging Australian Sea Lion (Neophoca cinerea).

We detail a novel presentation of tuberculosis associated with intestinal perforation in an endangered Australian sea lion (Neophoca cinerea) from South Australian waters and confirm the presence of this disease in the region of highest pup production. In February 2017, a 3-yr-old juvenile male died shortly after hauling out at the Kingscote beach on Kangaroo Island. On postmortem examination, we found a mid-jejunal intestinal perforation and partial obstruction (from a strangulating fibrous and granulomatous mesenteric mass), a marked multicentric abdominal fibrosing granulomatous lymphadenitis, and a large volume serosanguinous peritoneal effusion. Acid-fast bacteria were detected postmortem in cytologic preparations of the mesenteric lymph node and in histologic sections of jejunum and the encircling mass. Mycobacterial infection was confirmed by positive culture after 3 wk. Molecular typing using mycobacterial interspersed repetitive-unit-variable-number tandem-repeat typing with 12-locus analysis identified Mycobacterium pinnipedii. This case highlights the need for vigilance of zoonotic disease risk when handling pinnipeds, including in the absence of specific respiratory signs or grossly apparent pulmonary pathology. Increased serologic population surveillance is recommended to assess the species' risk from this and other endemic diseases, especially given its endangered status.

Gastrointestinal perforation in anti-NXP2 antibody-associated juvenile dermatomyositis: case reports and a review of the literature.

BACKGROUND: To summarize the characteristics of gastrointestinal (GI) perforation in anti-nuclear matrix protein 2 (NXP2) antibody-associated juvenile dermatomyositis (JDM). METHODS: Five patients with GI perforation from a JDM cohort of 120 cases are described. Relevant literature was reviewed. RESULTS: Five patients, including four females and one male, were included in the study. The age of onset of these patients ranged from 3.3 to 9.5 years with the median age of 5.0 years. When these patients were complicated by GI perforation, childhood myositis assessment score (CMAS) ranged from 1 to 5 with the median score of 2. Myositis-specific antibody (MSA) spectrum analysis indicated that the five patients were anti-NXP2 antibody positive. The initial symptoms of GI perforation were progressive abdominal pain and intermittent fever. Two patients also presented with ureteral calculus with hydronephrosis and ureteral stricture. Surgery was performed in four patients. One patient failed to undergo a repair as the perforation was high in position. For the other three patients, perforation repair was successful, of which two patients failed due to recurrent perforation. At 24 months postoperative follow-up, one patient was in complete remission on prednisone (Pred) and methotrexate (MTX) treatment, and her ureteral stricture had disappeared. The other four patients died. Adding these cases with 16 other patients described in the literature, the symptom at onset was progressive abdominal pain, which often occurred within 10 months after JDM was diagnosed. Perforation most commonly occurred in the duodenum, although it also occurred at multiple sites or was recurrent. The mortality rate of GI perforation in JDM was 38% (8/21). CONCLUSIONS: All the five perforation cases in our study subjected to MSA analysis were anti-NXP2 antibody positive. The symptom at onset was abdominal pain. The most common site of perforation was the duodenum in the retroperitoneum, and the lack of acute abdominal manifestations prevented early diagnosis. GI perforation may be a fatal complication in JDM, and early diagnosis is very important. More research is needed to determine the pathogenesis and predictive factors of GI perforation in JDM.

HARTMANN PROCEDURE OR RESECTION WITH PRIMARY ANASTOMOSIS FOR TREATMENT OF PERFORATED DIVERTICULITIS? SYSTEMATIC REVIEW AND META-ANALYSIS.

BACKGROUND: Mortality after emergency surgery in randomized controlled trials. The Hartmann procedure remains the treatment of choice for most surgeons for the urgent surgical treatment of perforated diverticulitis; however, it is associated with high rates of ostomy non-reversion and postoperative morbidity. AIM: To study the results after the Hartmann vs. resection with primary anastomosis, with or without ileostomy, for the treatment of perforated diverticulitis with purulent or fecal peritonitis (Hinchey grade III or IV), and to compare the advantages between the two forms of treatment. METHOD: Systematic search in the literature of observational and randomized articles comparing resection with primary anastomosis vs. Hartmann's procedure in the emergency treatment of perforated diverticulitis. Analyze as primary outcomes the mortality after the emergency operation and the general morbidity after it. As secondary outcomes, severe morbidity after emergency surgery, rates of non-reversion of the ostomy, general and severe morbidity after reversion. RESULTS: There were no significant differences between surgical procedures for mortality, general morbidity and severe morbidity. However, the differences were statistically significant, favoring primary anastomosis in comparison with the Hartmann procedure in the outcome rates of stoma non-reversion, general morbidity and severe morbidity after reversion. CONCLUSION: Primary anastomosis is a good alternative to the Hartmann procedure, with no increase in mortality and morbidity, and with better results in the operation for intestinal transit reconstruction.

Over-the-scope clip closure indicated as first- line therapy for iatrogenic rectal perforation.

n/a.

Impact of rectal perforation on recurrence during rectal cancer surgery in a national population registry.

BACKGROUND: Incidental perforation in rectal cancer surgery is considered a risk factor for poorer oncological outcome. Most studies emanate from the era before total mesorectal excision when staging, neoadjuvant treatment and surgical technique were suboptimal. This study assessed the impact of incidental perforation on oncological outcome in a cohort of patients with optimized management. METHODS: Data from the Swedish Colorectal Cancer Registry for patients undergoing R0 abdominal surgery for TNM stage I-III rectal cancer between 2007 and 2012, with 5-year follow-up, were analysed. Multivariable analysis was performed. RESULTS: In total, 6176 patients were analysed (208 with and 5968 without perforation). The local recurrence rate was increased after perforation (7·2 per cent (15 of 208) versus 3·2 per cent (188 of 5968); P = 0·001), but there were no differences in rates of distant metastasis (16·3 per cent (34 of 208) versus 19·8 per cent (1183 of 5968); P = 0·215) and overall recurrence (20·7 per cent (43 of 208) versus 21·0 per cent (1256 of 5968); P = 0·897). The 5-year overall survival rate was lower after perforation (66·4 versus 75·5 per cent; P = 0·002), but the 5-year relative survival rate was no different (79·9 versus 88·2 per cent; P = 0·083). In multivariable analysis, perforation was a risk factor for local recurrence (hazard ratio 2·10, 95 per cent c.i. 1·19 to 3·72; P = 0·011), but not for the other outcomes. CONCLUSION: Incidental perforation remains a significant risk factor for LR, even with optimized management of rectal cancer. This must be considered when discussing adjuvant treatment and follow-up.

ANTECEDENTES: La perforación incidental durante la cirugía de cáncer de recto se considera un factor de riesgo de un peor resultado oncológico. La mayoría de los estudios proceden de la era previa a la exéresis total del mesorrecto cuando la estadificación, el tratamiento neoadyuvante y la técnica quirúrgica eran subóptimos. En este estudio se evalúa el impacto de la perforación incidental en el resultado oncológico en una cohorte de pacientes con un tratamiento óptimo. MÉTODOS: Se analizaron los datos del Registro Sueco de Cáncer Colorrectal para pacientes sometidos a cirugía abdominal R0 en estadios TNM I-III entre 2007-2012 con un seguimiento de 5 años. Se realizó un análisis multivariable. RESULTADOS: En total, se analizaron 6.176 pacientes (208 con perforación, 5.968 sin perforación). La tasa de recidiva local (local recurrence, LR) aumentó después de la perforación (7,2% (15/208) versus 3,2% (188/5.968); P = 0,001)), pero no se detectaron diferencias con respecto a las tasas de metástasis a distancia (16,3% (34/208) versus 19,8% (1.183/5.968); P = 0,215)) ni de recidiva global (20,7% (43/208) versus 21,0% (1.256/5.968); P = 0,897)). La tasa de supervivencia global a los 5 años fue menor después de la perforación (66,4% versus 75,5%; P = 0,002), pero la tasa de supervivencia relativa a los 5 años fue similar (79,9% versus 88,2%; P = 0,083). En el análisis multivariable, la perforación fue un factor de riesgo para la LR (cociente de riesgos instantáneos, hazard ratio, HR 2,10 (i.c. del 95% 1,19-3,72); P = 0,011], pero no fue un factor de riesgo para los otros resultados. CONCLUSIÓN: La perforación incidental sigue siendo un factor de riesgo significativo para la LR incluso con el tratamiento optimizado del cáncer de recto, lo que debe tenerse en cuenta al discutir la indicación de tratamiento adyuvante y el tipo de seguimiento.

Case of Gut Necrosis in Adult-Onset Immunoglobulin A Vasculitis (Henoch-Schönlein Purpura).

Immunoglobulin A vasculitis (IgAV), formerly known as Henoch-Schönlein purpura, is an immune-mediated small vessel vasculitis characterized by palpable purpura, arthralgia, abdominal pain, and renal disease. It is primarily a childhood disease and usually resolves spontaneously with supportive therapy. Treatment of IgAV in adults is controversial with no clearly established guidelines. We report a rare case of IgAV in an adult male who developed gut necrosis and perforation while receiving glucocorticoid therapy for treatment of acute glomerulonephritis. A 44-year-old male was admitted with joint pain, leg swelling, mild abdominal pain, and a diffuse rash. Laboratory values revealed acute kidney injury with significant proteinuria and hematuria. The patient was started on glucocorticoid therapy for suspected IgAV nephritis, which was confirmed by kidney biopsy. Several days later, he complained of worsening abdominal pain. Imaging demonstrated bowel ischemia and perforation requiring multiple abdominal surgeries. The patient was critically ill in the intensive care unit with worsening renal failure requiring dialysis. He was discharged a month later after gradual recovery with stable but moderately impaired kidney function. IgAV is less common in adults; however, the disease is more severe with a higher risk of long-term complications. Adult patients with renal involvement may benefit from glucocorticoid therapy in preventing progression to end-stage renal disease. However, glucocorticoids may mask the symptoms of abdominal complications like gut necrosis and perforation causing delay in diagnosis and treatment. Therefore, vigilance to detect early signs of gut ischemia is imperative when treating an adult case of IgAV nephritis with glucocorticoids.

Multiple ulcerations and perforation in the small intestine after steroid treatment in eosinophilic granulomatosis with polyangiitis: a case report and literature review.

Eosinophilic granulomatosis with polyangiitis (EGPA), formerly called Churg-Strauss syndrome, is an uncommon disease with pathological features consisting of systemic necrotizing vasculitis, eosinophilic infiltration, and granulomatous or nongranulomatous extravascular eosinophilic inflammation. EGPA preferentially affects certain organ systems, including the airways, peripheral nerves, heart, kidney, and gastrointestinal tract. Although gastrointestinal involvement, such as ulcerations, is common in EGPA, gastrointestinal perforation is relatively uncommon and is associated with a poor prognosis. Ulceration, perforation, and stenosis of the gastrointestinal tract are assumed to be the result of ischemia caused by vasculitis. The histological finding in the biopsy specimens of EGPA is generally only eosinophil infiltration, and vasculitis is not often seen. Therefore, in biopsy specimens, it is difficult to distinguish eosinophilic gastroenteritis from the gastrointestinal involvement of EGPA. In addition, in general, steroid therapy is the first-choice treatment for EGPA, but some reports have described the frequent occurrence of acute ulcer or perforation of the gastrointestinal tract in association with steroid treatment. We herein report an EGPA patient who was treated with steroid therapy and subsequently developed perforation of the small intestine.

CT diagnosis of non-traumatic gastrointestinal perforation: an emphasis on the causes.

Gastrointestinal tract (GI) perforations can occur due to various causes such as trauma, iatrogenic factor, infectious condition, peptic ulcer, inflammatory disease, or a neoplasm. Because GI perforations represent an emergency and life-threatening condition, prompt diagnosis and surgical treatment are required in most cases. However, according to the underlying causes of GI perforations, additional treatment strategies may be needed. Adjuvant chemotherapy or immunotherapy may be required in various GI neoplasms such as adenocarcinoma, lymphoma or gastrointestinal stromal tumor. Inflammatory bowel disease is a chronic disease repeating cycle of intermittent, thus appropriate medical treatment and periodic follow-up are also required. Moreover, vascular intervention may have a role in some cases of mesenteric ischemia associated with mesenteric artery occlusion. Recently, computed tomography (CT) has been the first choice for patients with suspected GI perforations, because CT plays an important role in the accurate assessment of the perforation site, the pathology causing the perforation and the ensuing complications. This review will illustrate characteristic CT findings that differentiate underlying pathologies causing GI perforations to help clinicians decision-making regarding an optimal treatment plan.

Hartmann procedure or resection with primary anastomosis for treatment of perforated diverticulitis? systematic review and meta-analysis / Procedimento de hartmann ou ressecção com anastomose primária para tratamento da diverticulite perfurada? revisão sistematizada e metanálise

ABSTRACT Background: The Hartmann procedure remains the treatment of choice for most surgeons for the urgent surgical treatment of perforated diverticulitis; however, it is associated with high rates of ostomy non-reversion and postoperative morbidity. Aim: To study the results after the Hartmann vs. resection with primary anastomosis, with or without ileostomy, for the treatment of perforated diverticulitis with purulent or fecal peritonitis (Hinchey grade III or IV), and to compare the advantages between the two forms of treatment. Method: Systematic search in the literature of observational and randomized articles comparing resection with primary anastomosis vs. Hartmann's procedure in the emergency treatment of perforated diverticulitis. Analyze as primary outcomes the mortality after the emergency operation and the general morbidity after it. As secondary outcomes, severe morbidity after emergency surgery, rates of non-reversion of the ostomy, general and severe morbidity after reversion. Results: There were no significant differences between surgical procedures for mortality, general morbidity and severe morbidity. However, the differences were statistically significant, favoring primary anastomosis in comparison with the Hartmann procedure in the outcome rates of stoma non-reversion, general morbidity and severe morbidity after reversion. Conclusion: Primary anastomosis is a good alternative to the Hartmann procedure, with no increase in mortality and morbidity, and with better results in the operation for intestinal transit reconstruction.

RESUMO Racional: O procedimento a Hartmann permanece sendo o tratamento de escolha da maioria dos cirurgiões para o tratamento cirúrgico de urgência da diverticulite perfurada, entretanto está associado com altas taxas de não reversão da ostomia e de morbidade pós-operatória. Objetivo: Estudar os resultados após o procedimento de Hartmann vs. ressecção com anastomose primária, com ou sem ileostomia, para o tratamento da diverticulite perfurada com peritonite purulenta ou fecal (grau de Hinchey III ou IV), e comparar as vantagens entre as duas formas de tratamento. Método: Busca sistemática na literatura de artigos observacionais e randomizados comparando ressecção com anastomose primária vs. procedimento de Hartmann no tratamento de urgência da diverticulite perfurada. Analisar como desfechos primários a mortalidade após a operação de urgência e a morbidade geral após ela; como desfechos secundários, a morbidade severa após a operação de urgência, as taxas de não reversão da ostomia, a morbidade geral e severa após a reversão. Resultados: Não houve diferenças significativas entre os procedimentos cirúrgicos para mortalidade, morbidade geral e morbidade severa. Contudo, as diferenças foram significativas estatisticamente favorecendo anastomose primária na comparação com procedimento de Hartmann nos desfechos taxas de não reversão do estoma, morbidade geral e morbidade severa após reversão. Conclusão: A anastomose primária apresenta-se como boa alternativa ao procedimento de Hartmann, sem aumento de mortalidade e morbidade, e com melhores resultados na operação de reconstrução do trânsito intestinal.