Our patient illustrates two important clinical issues with respect to C. perfringens infection. First, C. perfringens should be suspected when treating a post-PD patient with a rapidly developing gas-producing abdominal abscess and/or sepsis with massive intravascular hemolysis. Second, prompt drainage is required for suspected C. perfringens abscesses.
Despite improvements in surgical techniques and perioperative care, the postoperative morbidity rate for PD remains at 40–50% [3,4,5]. Hepatic abscess is a relatively rare complication of PD, the reported frequency being 2.4–3.4% . The pathogens most commonly responsible for post-PD hepatic abscesses are Enterococcus species, Escherichia coli, and Klebsiella pneumoniae ; there are few reports implicating C. perfringens . C. Perfringens, an anaerobic gram-positive bacillus, is widely distributed in soil and sewage; however, it is also resident in the human digestive tract and genitourinary system. In addition, C. perfringens is reportedly present in the bile of up to 18% of patients undergoing biliary surgery . It is known that these bacteria use extrinsic and intrinsic routes to cause infection. The former, which includes food poisoning and trauma, causes soft tissue infection (gas gangrene), whereas the latter causes non-traumatic sepsis as a result of bacterial translocation [8, 9]. C. perfringens sepsis rarely occurs in healthy individuals, being more likely to occur in patients with underlying disorders such as diabetes mellitus, malignancies, or immunosuppression, such as that related to chemotherapy [8, 9]. Therefore, in our patient, the hepatic abscess caused by C. perfringens may have been attributable to immunosuppression caused by surgical stress in addition to bacterial translocation from the intestinal tract, because there was no stenosis of the biliary anastomosis, which could be a cause of cholangitis, in the postoperative DIC-CT.
Early diagnosis of C. perfringens infection is difficult, because the symptoms are non-specific in the early phase. They include disturbed consciousness, epigastric pain, vomiting, and nausea . In our patient, we initially diagnosed mild postoperative retrograde cholangitis associated with biliary reconstruction. In the future, greater availability of rapid polymerase chain reaction-based testing should assist with diagnosis . Once sepsis has progressed in a patient with C. perfringens infection, α-toxin produced by these bacteria causes massive intravascular hemolysis, which can result in sudden death. Bunderen et al. reviewed 40 cases of C. perfringens sepsis with intravascular hemolysis reported after 1990, 32 (80%) of whom died, the median time to death being 8 h . Our patient may have survived, because he was diagnosed rapidly and treated appropriately after development of sepsis. In addition, the focus of infection was relatively small.
Prompt drainage is vital for suspected C. perfringens abscesses. In a review of patients with C. perfringens septicemia, Kurasawa et al.  reported a 90% mortality in 30 patients with C. perfringens hepatic abscesses. Three of the six patients (50%) who underwent debridement or drainage survived. These authors advocated aggressive treatment of the infection focus when C. perfringens is suspected. Our patient’s abscess was in an accessible liver location (S6), enabling expeditious imaging-guided percutaneous drainage. After drainage of his abscess, his vital signs improved dramatically, enabling weaning off vasopressors within 24 h. Considering that mortality is so high and can occur within several hours [1, 9, 11,12,13], we believe that the focus of infection should be drained as quickly as possible, even in high-risk patients.
We consider that our patient’s rapidly progressive anemia was caused by α-toxin produced by C. perfringens. Although hemophagocytic syndrome associated with C. perfringens infection is a possible differential diagnosis , the presence of hemoglobinuria and indirect hyperbilirubinemia, and the absence of pancytopenia and hepatosplenomegaly suggest that his rapidly progressive anemia was caused by α-toxin produced by C. perfringens. Alpha-toxin, a zinc metalloenzyme composed of 370 amino acids, is the most important cause of hemolysis and gas gangrene among the six major C. perfringens toxin types [15, 16]. Alpha-toxin binds to host cell membranes in the presence of calcium ions  and directly hydrolyzes phosphatidylcholine and sphingomyelin proteins, which disrupts the cell membrane . An additional effect of α-toxin is indirect activation of the mitogen-activated protein kinase kinase/extracellular-signal-regulated kinase pathway , which is involved in generating reactive oxygen species and tumor necrosis factor-α. These then activate the intrinsic pathway of apoptosis and promote inflammation [15, 19]. Although there is no established antimicrobial regimen for treating C. perfringens infection , clindamycin, metronidazole, and rifampicin are more effective than penicillin at reducing α-toxin release in mice . In addition, erythromycin pretreatment reportedly reduced tumor necrosis factor-α release from activated neutrophils in a C. perfringens gas gangrene mouse model .