Int J Colorectal Dis DOI 10.1007/s00384-015-2138-5
LETTER TO THE EDITOR
Recurrent, spontaneous, postoperative small bowel perforations caused by invasive candidiasis Gaetano Luglio & Giovanni Domenico De Palma & Filomena Liccardo & Mariano Cesare Giglio & Viviana Sollazzo & Geremia Zito & Luigi Bucci
Accepted: 21 January 2015 # Springer-Verlag Berlin Heidelberg 2015
Dear Editor: Postoperative bowel perforations represent a serious medical condition with high morbidity and mortality. They are usually related to surgery itself; the anastomosis breakdown being considered the most common cause after bowel surgery; incidence may widely vary, depending on type of primary surgery, anastomosis level and comorbidities. Iatrogenic injuries after abdominal surgery are also well-recognised causes of postoperative perforations; prompt diagnosis of such situations and eventually early reoperation are key factors for better prognosis. On the other hand, spontaneous and no-traumatic perforations may represent even more challenging clinical conditions, due to both difficulties in diagnosis and management. Underlying medical conditions are usually recognised as predisposing factors of spontaneous bowel perforations, such as ulcerative colitis, Crohn’s disease, jejunal perforation in celiac disease (if complicated by lymphoma or collagenous sprue), other than metabolic and vascular diseases; thus, even more uncommon conditions associated with spontaneous bowel perforation have been described such as Ehlers-Danlos syndrome. In recent years, the wide adoption of biological medications, such as monoclonal antibodies, has also led to new G. Luglio (*) : G. D. De Palma : F. Liccardo : M. C. Giglio : V. Sollazzo : L. Bucci Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy e-mail: [email protected] G. Zito Department of Neurosciences, Reproductive and Odontostomatologic Sciences, University of Naples Federico II, Naples, Italy
records of spontaneous bowel perforations, the most emblematic example being represented from bevacizumab, an inhibitor of vascular endothelial growth factor, used for several malignancies; few reports sent a warning on the possibility of bowel perforation after bevacizumab adoption, with an estimated incidence of about 3 %. A further chapter to be considered is represented by the infectious-related perforation: Cytomegalovirus (CMV) infection has been recognised has a cause of bowel perforation especially in immunocompromised patients, other than other bacterial, parasitic or fungal infections [1]. We here describe the case of a 76-year-old woman, who underwent a right hemicolectomy for a colon cancer and then developed multiple spontaneous postoperative small bowel perforations, requiring multiple reoperations: the only suspected cause of this being represented by a Candida infection which finally led to death. The patient had no significant comorbidities; the only anamnestic record being represented by a gallbladder resection plus biliary tract exploration for gallstones, 30 years before. A right hemicolectomy was performed by our surgical team to treat the cancer; it was a straightforward procedure and an ileocolic stapled end-to-end anastomosis was fashioned in a standard manner. The only immediate complication was represented by a pneumothorax due to CVC insertion by the anaesthesiologist team, requiring a thoracic tube insertion and ICU admission. On the third postoperative day, a bilious-enteric fluid became apparent from surgical drain, associated with fever; after a CT scan, the patient was reoperated for a generalised peritonitis, due to a proximal ileal perforation which was taken out as an ileostomy; it was a small perforation (around 1.5 cm diameter), with raised edges, while all the surrounding gut wall seemed to be healthy.
Int J Colorectal Dis
Anastomosis and all the bowel loops were also checked and were found to be OK. In the perioperative time, the patient being still hospitalised in the ICU, some hemocultures were taken, together with cultures from pleural and abdominal drains: all were found to be positive for Candida albicans. Specific antibiotic and antifungal therapy was obviously soon undertaken. The next postoperative period was complicated by an episodic state of delirium and severe thrombocytopenia. On the other hand, surgical recovery seemed to be uneventful with the ileostomy normally working. Nevertheless, 10 days after the second operation, a new septic state due to peritonitis became evident and, after CT confirmation, the patient was reoperated again: three more perforations on the defunctioned ileum were found, the first ileocolic anastomosis still being fine; a bowel resection was performed, and a new proximal diversion was fashioned. Again, 7 days later, abdominal drains showed signs of a subsequent perforation: the patient was taken again in theatre, two more perforations were found, one on the afferent, the other on the efferent ileostomy limb; all these perforations showed the same macroscopic appearance as the first one. A subtotal enterectomy with a high terminal jejunostomy was performed as a last chance. The patient died 8 days later in the ICU. Histopathology of all the specimens (including the right hemi one) showed the significant presence of Candida albicans; the tissue surrounding the ulcers/perforations showed a full thickness coagulation necrosis, vessels thrombosis, hyphae, pseudo-hyphae and mycelial spores. It is still to be emphasised that the patient also received an aggressive antifungal therapy from the beginning, as she was soon put on high dose of echinocandins and lastly on Amphotericin B. Invasive candidiasis represents a serious public health problem, being the leading cause of mycosis-associated mortality in the USA. Candida albicans remains the main cause of invasive candidiasis, followed by Candida glabrata. Candida represents a commensal fungus in healthy individuals; nevertheless, invasive infections, especially in immunocompromised patients or after major surgical procedures, may potentially cause extensive ulceration and tissue necrosis. Despite the wide usage of antimitotic agents, less common Candida species are probably emerging, resistant to common antifungal medications. One of the most alarming aspect is that mortality for invasive candidiasis has not declined over the last two decades, differently from aspergillosis trend; 30-day mortality was estimated to be of about 38 %, according to the results of a European survey [2].
Bowel, oesophageal or gastric perforation caused by an unusual presentation of Candida infection is very rare, the mechanism being often not fully understood [3]. L. Yan et al. [4] in their review article try to elucidate the complex mechanism of Candida enterogenic infections, including the formation of a biofilm on the intestinal surface in which Candida can switch from yeast to hyphal form, starting a sequential process involving adherence, proliferation and penetration in the bowel wall; at the same time, Candida can disrupt the mucous layer, neutralise the chemical barrier and interact with both immune (gut-associated lymphoid tissue (GALT)) and microbial barrier. Some reports emphasise the role of echinocandins in invasive Candida infections, especially in patients who had recently undergone abdominal surgery, presenting recurrent gastrointestinal perforations, ventilated etc., sometimes also showing a favourable outcome. Very few data regarding small bowel perforations after Candida infection come from literature; we believe the present case is even more peculiar: to our knowledge, it is the only report describing an invasive candidiasis in an immunocompetent woman, who developed multiple, spontaneous, recurrent small bowel perforations which finally led the patient to death despite an early, aggressive medical and surgical treatment. Reasons of such failure remain unclear; gastrointestinal tract perforations due to invasive candidiasis is certainly a rare complication, but true incidence is probably underestimated and the small number of cases reported prevented the possibility to establish a validated treatment model and achieve better outcomes. Conflict of interest Drs Gaetano Luglio, Giovanni Domenico De Palma, Filomena Liccardo, Mariano Cesare Giglio, Viviana Sollazzo, Geremia Zito and Luigi Bucci have no conflicts of interest, financial ties or ethical issues to disclose.
References 1. Freeman HJ (2014) Spontaneous free perforation of the small intestine in adults. World J Gastroenterol 20(29):9990–9997 2. Tortorano AM et al (2004) Epidemiology of candidaemia in Europe: results of 28-month European Confederation of Medical Mycology (ECMM) hospital-based surveillance study. Eur J Clin Microbiol Infect Dis 23(4):317–22 3. Schlossberg D et al (1977) Bowel perforation with candidiasis. JAMA 238(23):2520–1 4. Yan L, Yang C, Tang J (2013) Disruption of the intestinal mucosal barrier in Candida albicans infections. Microbiol Res 168(7):389–95
LETTER TO THE EDITOR
Recurrent, spontaneous, postoperative small bowel perforations caused by invasive candidiasis Gaetano Luglio & Giovanni Domenico De Palma & Filomena Liccardo & Mariano Cesare Giglio & Viviana Sollazzo & Geremia Zito & Luigi Bucci
Accepted: 21 January 2015 # Springer-Verlag Berlin Heidelberg 2015
Dear Editor: Postoperative bowel perforations represent a serious medical condition with high morbidity and mortality. They are usually related to surgery itself; the anastomosis breakdown being considered the most common cause after bowel surgery; incidence may widely vary, depending on type of primary surgery, anastomosis level and comorbidities. Iatrogenic injuries after abdominal surgery are also well-recognised causes of postoperative perforations; prompt diagnosis of such situations and eventually early reoperation are key factors for better prognosis. On the other hand, spontaneous and no-traumatic perforations may represent even more challenging clinical conditions, due to both difficulties in diagnosis and management. Underlying medical conditions are usually recognised as predisposing factors of spontaneous bowel perforations, such as ulcerative colitis, Crohn’s disease, jejunal perforation in celiac disease (if complicated by lymphoma or collagenous sprue), other than metabolic and vascular diseases; thus, even more uncommon conditions associated with spontaneous bowel perforation have been described such as Ehlers-Danlos syndrome. In recent years, the wide adoption of biological medications, such as monoclonal antibodies, has also led to new G. Luglio (*) : G. D. De Palma : F. Liccardo : M. C. Giglio : V. Sollazzo : L. Bucci Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy e-mail: [email protected] G. Zito Department of Neurosciences, Reproductive and Odontostomatologic Sciences, University of Naples Federico II, Naples, Italy
records of spontaneous bowel perforations, the most emblematic example being represented from bevacizumab, an inhibitor of vascular endothelial growth factor, used for several malignancies; few reports sent a warning on the possibility of bowel perforation after bevacizumab adoption, with an estimated incidence of about 3 %. A further chapter to be considered is represented by the infectious-related perforation: Cytomegalovirus (CMV) infection has been recognised has a cause of bowel perforation especially in immunocompromised patients, other than other bacterial, parasitic or fungal infections [1]. We here describe the case of a 76-year-old woman, who underwent a right hemicolectomy for a colon cancer and then developed multiple spontaneous postoperative small bowel perforations, requiring multiple reoperations: the only suspected cause of this being represented by a Candida infection which finally led to death. The patient had no significant comorbidities; the only anamnestic record being represented by a gallbladder resection plus biliary tract exploration for gallstones, 30 years before. A right hemicolectomy was performed by our surgical team to treat the cancer; it was a straightforward procedure and an ileocolic stapled end-to-end anastomosis was fashioned in a standard manner. The only immediate complication was represented by a pneumothorax due to CVC insertion by the anaesthesiologist team, requiring a thoracic tube insertion and ICU admission. On the third postoperative day, a bilious-enteric fluid became apparent from surgical drain, associated with fever; after a CT scan, the patient was reoperated for a generalised peritonitis, due to a proximal ileal perforation which was taken out as an ileostomy; it was a small perforation (around 1.5 cm diameter), with raised edges, while all the surrounding gut wall seemed to be healthy.
Int J Colorectal Dis
Anastomosis and all the bowel loops were also checked and were found to be OK. In the perioperative time, the patient being still hospitalised in the ICU, some hemocultures were taken, together with cultures from pleural and abdominal drains: all were found to be positive for Candida albicans. Specific antibiotic and antifungal therapy was obviously soon undertaken. The next postoperative period was complicated by an episodic state of delirium and severe thrombocytopenia. On the other hand, surgical recovery seemed to be uneventful with the ileostomy normally working. Nevertheless, 10 days after the second operation, a new septic state due to peritonitis became evident and, after CT confirmation, the patient was reoperated again: three more perforations on the defunctioned ileum were found, the first ileocolic anastomosis still being fine; a bowel resection was performed, and a new proximal diversion was fashioned. Again, 7 days later, abdominal drains showed signs of a subsequent perforation: the patient was taken again in theatre, two more perforations were found, one on the afferent, the other on the efferent ileostomy limb; all these perforations showed the same macroscopic appearance as the first one. A subtotal enterectomy with a high terminal jejunostomy was performed as a last chance. The patient died 8 days later in the ICU. Histopathology of all the specimens (including the right hemi one) showed the significant presence of Candida albicans; the tissue surrounding the ulcers/perforations showed a full thickness coagulation necrosis, vessels thrombosis, hyphae, pseudo-hyphae and mycelial spores. It is still to be emphasised that the patient also received an aggressive antifungal therapy from the beginning, as she was soon put on high dose of echinocandins and lastly on Amphotericin B. Invasive candidiasis represents a serious public health problem, being the leading cause of mycosis-associated mortality in the USA. Candida albicans remains the main cause of invasive candidiasis, followed by Candida glabrata. Candida represents a commensal fungus in healthy individuals; nevertheless, invasive infections, especially in immunocompromised patients or after major surgical procedures, may potentially cause extensive ulceration and tissue necrosis. Despite the wide usage of antimitotic agents, less common Candida species are probably emerging, resistant to common antifungal medications. One of the most alarming aspect is that mortality for invasive candidiasis has not declined over the last two decades, differently from aspergillosis trend; 30-day mortality was estimated to be of about 38 %, according to the results of a European survey [2].
Bowel, oesophageal or gastric perforation caused by an unusual presentation of Candida infection is very rare, the mechanism being often not fully understood [3]. L. Yan et al. [4] in their review article try to elucidate the complex mechanism of Candida enterogenic infections, including the formation of a biofilm on the intestinal surface in which Candida can switch from yeast to hyphal form, starting a sequential process involving adherence, proliferation and penetration in the bowel wall; at the same time, Candida can disrupt the mucous layer, neutralise the chemical barrier and interact with both immune (gut-associated lymphoid tissue (GALT)) and microbial barrier. Some reports emphasise the role of echinocandins in invasive Candida infections, especially in patients who had recently undergone abdominal surgery, presenting recurrent gastrointestinal perforations, ventilated etc., sometimes also showing a favourable outcome. Very few data regarding small bowel perforations after Candida infection come from literature; we believe the present case is even more peculiar: to our knowledge, it is the only report describing an invasive candidiasis in an immunocompetent woman, who developed multiple, spontaneous, recurrent small bowel perforations which finally led the patient to death despite an early, aggressive medical and surgical treatment. Reasons of such failure remain unclear; gastrointestinal tract perforations due to invasive candidiasis is certainly a rare complication, but true incidence is probably underestimated and the small number of cases reported prevented the possibility to establish a validated treatment model and achieve better outcomes. Conflict of interest Drs Gaetano Luglio, Giovanni Domenico De Palma, Filomena Liccardo, Mariano Cesare Giglio, Viviana Sollazzo, Geremia Zito and Luigi Bucci have no conflicts of interest, financial ties or ethical issues to disclose.
References 1. Freeman HJ (2014) Spontaneous free perforation of the small intestine in adults. World J Gastroenterol 20(29):9990–9997 2. Tortorano AM et al (2004) Epidemiology of candidaemia in Europe: results of 28-month European Confederation of Medical Mycology (ECMM) hospital-based surveillance study. Eur J Clin Microbiol Infect Dis 23(4):317–22 3. Schlossberg D et al (1977) Bowel perforation with candidiasis. JAMA 238(23):2520–1 4. Yan L, Yang C, Tang J (2013) Disruption of the intestinal mucosal barrier in Candida albicans infections. Microbiol Res 168(7):389–95
