Overview
Infection of the pancreas with Candida spp. is another form of intra-abdominal candidiasis that was considered extremely unusual for many years but now it is being recognized as an important, albeit infrequent, problem. All cases of pancreatic candidiasis are related to some form of pancreatic injury. Indeed, its retroperitoneal location seems to protect the pancreas from hematogenous or contiguous infections, but once some type of injury has occurred a predisposition to this type of complication becomes manifest. Bacterial infections are much more frequent in this setting, with enteric microorganisms being the ones usually recovered. Cultures show a polymicrobial flora in up to 50% of cases. Candidal infection may occur either as part of a mixed infection or by itself.
The presence of Candida in pancreatic cultures, especially when part of a mixed flora, has often been disregarded [1178]. However, evidence of the importance of this organism in pancreatic infection processes continues to grow [902, 1052].
Candida spp. have been implicated in some cases of the following varieties of pancreatic diseases:
Acute Pancreatitis
This may occur in pancreatitis of any etiology, including gallstone pancreatitis, alcoholic, traumatic, post-surgical, post-traumatic or idiopathic. Candidal infection may be superimposed as well on any of the possible complications of pancreatitis, including:
- Necrotizing Pancreatitis [902, 1052]
- Pancreatic Pseudocysts [434, 680, 754, 1884]
- Pancreatic Abscesses [742, 1072, 1178, 1923].
Intraductal pancreatic obstruction (Fungus ball) [442].
The route of infection is not always clear, but the most likely alternatives include exposure to a colonized gastrointestinal tract, including contaminated bile (via reflux), exposure to exterior sources via abdominal drains or opened packing/marsupialization, and hematogenous dissemination during an episode of candidemia.
Epidemiology
Very few data exist on the incidence of pancreatic candidiasis, as the literature on this topic consist almost exclusively on anecdotal case reports. Two retrospective series reported rates of pancreatic candidiasis of 35 and 41%, in periods of 5 and 4 years respectively [52, 1052]. The only published prospective study was performed by Grewe et al. and reported a 12% incidence of candidal pancreatic infection among 57 patients with necrotizing pancreatitis during a two year period [902].
Risk factors
Patients with pancreatitis are frequently exposed to several of the (A):usual risk factors for invasive candidiasis, especially:
- Use of multiple & broad spectrum antibiotics
- Central venous lines
- Multiple deep abdominal surgeries. Recent pancreatic surgery has been specifically associated with pancreatic candidiasis [361, 1178, 2457].
- Total parenteral nutrition
Both endoscopic retrograde cholangiopancreatography (ERCP) [902, 1112] and pancreatic transplant [284, 377, 1042] have (not surprisingly) been associated with candidal infection of the pancreas.
Candida species and Pancreatic Candidiasis
Although very few data has been published on this condition, the clear preponderance of Candida albicans is evident.
| Author, Year (Reference) | N | Frequency (%) | ||||
|---|---|---|---|---|---|---|
| C. albicans | C. glabrata | C tropicalis | C. parapsilosis | Other Species | ||
| Keiser, 1992 [1178] | 9(1) | 100 | 0 | 0 | 0 | 0 |
| Hoerauf, 1998 [1052] | 17(2) | 94 | 0 | 6 | 0 | 0 |
| Grewe, 1999 [902] | 6(1) | 83 | 17 | 0 | 0 | 14 |
- One additional case was identified by histopathology characteristic of yeast
- Candida spp. was considered to be pathogenic only in 13 of these cases
Pulling this type of data from case reports imposes a major bias in that rare species may be more frequently reported. However, just to be complete, two cases of infection with Candida glabrata and one case due to Candia pelliculosa have also been reported [680, 1636, 1884].
Clinical Manifestations
The clinical presentations of pancreatic candidiasis are the same as in cases not related to this fungal infection. The most common findings are abdominal pain and persistent fever. These signs are, of course, completely non-specific.
Specific Diagnostic Strategies
In addition to the classic biochemical abnormalities seen in pancreatic inflammatory processes and the commonly accompanied leukocytosis, the diagnosis of pancreatic candidiasis is made based on the isolation of Candida from a pancreatic source. The sample should be taken during surgery, as culture samples from drains are less reliable and may reflect contamination. However, ideal circumstances are rare and one generally feels compelled to treat with an antifungal agent if Candida spp. are isolated from either type of specimen [1178].
But, as is common with many forms of candidiasis, a positive culture for Candida spp. is also not definite proof of invasive infection. Calandra et al. have suggested that demonstration of heavier organism load by semiquantitative studies might be more suggestive of infection [361], but the correlation is quite loose.
Histopathologic confirmation of tissue invasion is the only convincing proof of pancreatic candidiasis [1178]. The surgeon is encouraged to send samples for fungal stains, particularly in patients with persistent fever and candidal colonization.
Therapies
Limited data on therapeutic strategies for this condition are available. Based on published cases, and small series, the following recommendations are given:
Surgical procedures
Extensive surgical debridement of retroperitoneal tissue with scheduled re-explorations is recommended for the treatment of necrotizing pancreatitis and pancreatic abscesses [45, 314, 2381]. A few authors have reported success when performing CT-guided drainage of small abscesses or pseudocysts infected with Candida [434, 742].
Antifungal therapy
A review of the literature on candidal pancreatic abscesses described 100% mortality in four patients who did not receive antifungal therapy for this condition. In contradistinction, six other patients in the same report were treated with surgery plus Amphotericin B, and all six survived [1178]. Pointing in the same direction, Hoerauf et al. described a clear association between death and lack of antifungal therapy in a series of 13 patients with acute necrotizing pancreatitis and Candida pancreatic infection [1052].
The limited published experience on antifungal treatment for pancreatic candidiasis mostly focuses on use of amphotericin B. Precise doses and length of therapy have not been studied, but we would recommend doses of at least 0.5 mg/kg/day for 10-14 days.
Because of its favorable pharmacokinetics and toxicity profile, fluconazole is an attractive alternative. However, very limited experience exists on the use of this agent for pancreatic candidiasis.