Current status of the surgical training system in Japan: results of a nationwide questionnaire survey of graduating surgical trainees.

PURPOSE: To identify the problems trainees face during surgical training in Japan. METHODS: A nationwide online questionnaire survey was conducted targeting newly certified surgical trainees. RESULTS: The response rate was 53.8% (758/1410). Among those respondents, 25.6% were women, 71.4% were either married or had a partner, 41.3% had children, 72.7% had performed over 200 surgeries under general anesthesia, and 54.1% had chosen, before graduating from medical school, to become a surgeon. While 88.8% were interested in learning surgical techniques, 63.8% were hesitant to become a surgeon for fear of a compromised quality of private life (QOL). Conversely, only 1.4% chose their surgical training programs based on QOL. Overall, 84.6% of the trainees were satisfied with their training and this correlated with the number of surgeries performed. Only 29.9% received non-technical skill training. The average number of night shifts per month was 5.6, and 10.6% worked over 80 h per week. Harassment was reported by 41.5% of the respondents. Moreover, 33.0% had considered dropping out at some time, primarily because of their QOL (51.1%) or the harassment they had encountered (50.4%). CONCLUSION: This survey revealed that while trainees were satisfied with the overall training system, issues such as long working hours and harassment are prevalent. Working to improve these issues could make surgery more attractive for young trainees.

EPA, DHA, and resolvin effects on cancer risk: The underexplored mechanisms.

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) supplements have exhibited inconsistent effects on cancer risk, and their potential efficacy as cancer preventive agents has been increasingly questioned, especially in recent large randomized clinical trials. The role of host factors that govern EPA and DHA metabolism in relation to their impact on carcinogenesis remains understudied. Resolvins, the products of EPA and DHA oxidative metabolism, demonstrate intriguing antitumorigenic effects through mechanisms such as promoting macrophage phagocytosis of cell debris and inhibiting the production of proinflammatory chemokines and cytokines by tumor-associated macrophages (TAMs), which are crucial for cancer progression. However, clinical studies have not yet shown a significant increase in target tissue levels of resolvins with EPA and DHA supplementation. 15-Lipoxygenase-1 (ALOX15), a key enzyme in EPA and DHA oxidative metabolism, is often lost in various major human cancers, including precancerous and advanced colorectal cancers. Further research is needed to elucidate whether the loss of ALOX15 expression in colorectal precancerous and cancerous cells affects EPA and DHA oxidative metabolism, the formation of resolvins, and subsequently carcinogenesis. The findings from these studies could aid in the development of novel and effective chemoprevention interventions to reduce cancer risk.

Colorectal ALOX15 as a host factor determinant of EPA and DHA effects on colorectal carcinogenesis.

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), omega-3 polyunsaturated fatty acids (ω-3 PUFAs) derived from fish oil, are widely used as dietary supplements and FDA-approved treatments for hypertriglyceridemia. However, studies investigating the effects of EPA and DHA on colorectal carcinogenesis (CRC) have yielded conflicting results. The factors that determine these discrepant results remain unknown. Resolvins, oxidative metabolites of EPA and DHA, inhibit key pro-tumorigenic cytokine and chemokine signaling of colorectal cancer (e.g., IL-6, IL-1ß, and CCL2). 15-lipoxygenase-1 (ALOX15), a critical enzyme for resolvin generation is commonly lost during human CRC. Whether ALOX15 expression, as a host factor, modulates the effects of EPA and DHA on CRC remains unknown. Therefore, we evaluated the effects of ALOX15 transgenic expression in colonic epithelial cells on resolvin generation by EPA and DHA and CRC in mouse models representative of human CRC. Our results revealed that 1) EPA and DHA effects on CRC were diverse, ranging from suppressive to promotive, and these effects were occasionally altered by the formulations of EPA and DHA (free fatty acid, ethyl ester, triglyceride); 2) EPA and DHA uniformly suppressed CRC in the presence of intestinal ALOX15 transgenic expression, which induced the production of resolvins, decreased colonic CCL3-5 and CXCL-5 expression and tumor associated macrophages while increasing CD8 T cell abundance in tumor microenvironment; and 3) RvD5, the predominant resolvin produced by ALOX15, inhibited macrophage generation of pro-tumorigenic cytokines. These findings demonstrate the significance of intestinal ALOX15 expression as a host factor in determining the effects of EPA and DHA on CRC. Significance: Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are widely used as dietary supplements and FDA-approved treatments for hypertriglyceridemia. Studies of EPA and DHA effects on colorectal carcinogenesis (CRC) have revealed inconsistencies; factors determining the direction of their impact on CRC have remained unidentified. Our data show that EPA and DHA effects on CRC were divergent and occasionally influenced by their formulations. More importantly, intestinal 15-lipoxgenase-1 (ALOX15) expression modulated EPA and DHA effects on CRC, leading to their consistent suppression of CRC. ALOX15 promoted EPA and DHA oxidative metabolism to generate resolvins, which inhibited key pro-tumorigenic inflammatory cytokines and chemokines, including IL-6. IL-1ß, and CCL2. ALOX15 is therefore an important host factor in determining EPA and DHA effects on CRC.

Synergistic antitumor activity by dual blockade of CCR1 and CXCR2 expressed on myeloid cells within the tumor microenvironment.

BACKGROUND: Chemokine signaling within the tumor microenvironment can promote tumor progression. Although CCR1 and CXCR2 on myeloid cells could be involved in tumor progression, it remains elusive what effect would be observed if both of those are blocked. METHODS: We employed two syngeneic colorectal cancer mouse models: a transplanted tumor model and a liver metastasis model. We generated double-knockout mice for CCR1 and CXCR2, and performed bone marrow (BM) transfer experiments in which sub-lethally irradiated wild-type mice were reconstituted with BM from either wild-type, Ccr1-/-, Cxcr2-/- or Ccr1-/-Cxcr2-/- mice. RESULTS: Myeloid cells that express MMP2, MMP9 and VEGF were accumulated around both types of tumors through CCR1- and CXCR2-mediated pathways. Mice reconstituted with Ccr1-/-Cxcr2-/- BM exhibited the strongest suppression of tumor growth and liver metastasis compared with other three groups. Depletion of CCR1+CXCR2+ myeloid cells led to a higher frequency of CD8+ T cells, whereas the numbers of Ly6G+ neutrophils, FOXP3+ Treg cells and CD31+ endothelial cells were significantly decreased. Furthermore, treatment with a neutralizing anti-CCR1 mAb to mice reconstituted with Cxcr2-/- BM significantly suppressed tumor growth and liver metastasis. CONCLUSION: Dual blockade of CCR1 and CXCR2 pathways in myeloid cells could be an effective therapy against colorectal cancer.

Downregulation of osteoprotegerin in colorectal cancer cells promotes liver metastasis via activating tumor-associated macrophage.

Osteoprotegerin (OPG) is a secreted cytokine that functions as a decoy receptor for receptor activator of nuclear factor kappa-B (RANK) ligand (RANKL). Anti-RANKL treatment for bone metastasis has been widely accepted for solid tumors. However, the mechanism of OPG-RANKL-RANK signaling in systemic colorectal cancer (CRC) metastasis remains unclear. In this study, we investigated the relevance and function of OPG expression in CRC liver metastasis. First, we performed in silico analysis using The Cancer Genome Atlas public database and found that lower OPG expression in CRC was associated with poor overall survival. Immunohistochemistry analyses using resected specimen from patients with CRC in our institute confirmed the result. Patient-matched primary CRC and liver metastases showed a significant downregulation of OPG expression in metastatic lesions. In CRC cell lines, OPG expression did not suppress cell proliferation and migration. However, OPG expression inhibited macrophage migration by suppressing the RANKL-RANK pathway. Moreover, in vivo mouse liver metastasis models showed that OPG expression in CRC cells suppressed liver metastases. In addition, treatment with an anti-RANKL neutralizing antibody also suppressed liver metastases. These results showed that downregulation of OPG expression in CRC cells promotes liver metastasis by activating tumor-associated macrophage, which can become a candidate for targeted therapy with anti-RANKL neutralizing antibody for CRC liver metastasis.

Neutrophil Extracellular Traps Promote Metastases of Colorectal Cancers through Activation of ERK Signaling by Releasing Neutrophil Elastase.

Neutrophil extracellular traps (NETs) play important roles in host immunity, as there is increasing evidence of their contribution to the progression of several types of cancers even though their role in colorectal cancers (CRCs) remains unclear. To investigate the clinical relevance of NETs in CRCs, we examined the expression of citrullinated histone H3 using immunohistochemistry and preoperative serum myeloperoxidase-DNA complexes in CRC patients using an enzyme-linked immunosorbent assay. High expression of intratumoral or systemic NETs was found to correlate with poor relapse-free survival (RFS), for which it is an independent prognostic factor. In vitro investigations of CRC cells (HCT116, HT29) revealed that NETs did not affect their proliferation but did promote the migration of CRC cells mediated by neutrophil elastase (NE) released during NETosis to increase extracellular signal-regulated kinase (ERK) activity. In vivo experiments using nude mice (KSN/slc) revealed that NE inhibition suppressed liver metastases in CRC cells, although it did not affect the growth of subcutaneously implanted tumors. Taken together, these results suggest that NET formation correlates with poor prognoses of patients with CRC and that the inhibition of NE could be a potential therapy for CRC metastases.

Single-incision laparoscopic partial cecectomy for appendiceal mucocele in a patient with porphyria photosensitivity.

Erythropoietic protoporphyria (EPP) is a rare hereditary subtype of cutaneous porphyria characterized by photosensitivity. Increased exposure to light irradiation may precipitate acute liver failure, and surgical light-induced intestinal burns and perforations are known to occur. We report a case of EPP in a patient who underwent laparoscopic partial cecectomy for appendiceal mucocele. A 55-year-old man with EPP was presented for treatment of appendiceal mucocele. A light test using two types of laparoscopes (Companies O and S) was performed preoperatively. Light from the laparoscope manufactured by Company O caused photosensitivity; this effect was not observed with light from the laparoscope manufactured by Company S. Therefore, we performed laparoscopic partial cecectomy through a single umbilical incision using the laparoscope from Company S. Except for the incision site, the patient's skin was completely covered using surgical drapes. No intra- or postoperative complications were observed. Histopathological examination of the resected specimen revealed a low-grade appendiceal mucinous neoplasm.

Dual blockade of macropinocytosis and asparagine bioavailability shows synergistic anti-tumor effects on KRAS-mutant colorectal cancer.

Mutations of KRAS gene are found in various types of cancer, including colorectal cancer (CRC). Despite intense efforts, no pharmacological approaches are expected to be effective against KRAS-mutant cancers. Macropinocytosis is an evolutionarily conserved actin-dependent endocytic process that internalizes extracellular fluids into large vesicles called macropinosomes. Recent studies have revealed macropinocytosis's important role in metabolic adaptation to nutrient stress in cancer cells harboring KRAS mutations. Here we showed that KRAS-mutant CRC cells enhanced macropinocytosis for tumor growth under nutrient-depleted conditions. We also demonstrated that activation of Rac1 and phosphoinositide 3-kinase were involved in macropinocytosis of KRAS-mutant CRC cells. Furthermore, we found that macropinocytosis was closely correlated with asparagine metabolism. In KRAS-mutant CRC cells engineered with knockdown of asparagine synthetase, macropinocytosis was accelerated under glutamine-depleted condition, and albumin addition could restore the glutamine depletion-induced growth suppression by recovering the intracellular asparagine level. Finally, we discovered that the combination of macropinocytosis inhibition and asparagine depletion dramatically suppressed the tumor growth of KRAS-mutant CRC cells in vivo. These results indicate that dual blockade of macropinocytosis and asparagine bioavailability could be a novel therapeutic strategy for KRAS-mutant cancers.

Disruption of CCR1-mediated myeloid cell accumulation suppresses colorectal cancer progression in mice.

Tumor-stromal interaction is implicated in tumor progression. Although CCR1 expression in myeloid cells could be associated with pro-tumor activity, it remains elusive whether disruption of CCR1-mediated myeloid cell accumulation can suppress tumor progression. Here, we investigated the role of CCR1 depletion in myeloid cells in two syngeneic colorectal cancer mouse models: MC38, a transplanted tumor model and CMT93, a liver metastasis model. Both cells induced tumor accumulation of CCR1+ myeloid cells that express MMP2, MMP9, iNOS, and VEGF. Lack of the Ccr1 gene in host mice dramatically reduced MC38 tumor growth as well as CMT93 liver metastasis. To delineate the contribution of CCR1+ myeloid cells, we performed bone marrow (BM) transfer experiments in which sub-lethally irradiated wild-type mice were reconstituted with BM from either wild-type or Ccr1-/- mice. Mice reconstituted with Ccr1-/- BM exhibited marked suppression of MC38 tumor growth and CMT93 liver metastasis, compared with control mice. Consistent with these results, administration of a neutralizing anti-CCR1 monoclonal antibody, KM5908, significantly suppressed MC38 tumor growth and CMT93 liver metastases. Our findings highlight the importance of the application of CCR1 blockade as a therapeutic strategy.

Loss of SMAD4 Promotes Colorectal Cancer Progression by Recruiting Tumor-Associated Neutrophils via the CXCL1/8-CXCR2 Axis.

PURPOSE: SMAD4 is a key transcriptional factor of TGFß signaling and acts as a tumor suppressor in colorectal cancer. In the present study, we explored the immunologic effect of SMAD4 on the tumor microenvironment. EXPERIMENTAL DESIGN: Using 99 clinical specimens and human colorectal cancer cell lines, we investigate the relationship between SMAD4 expression and neutrophil accumulation. We immunohistochemically analyzed expression of SMAD4, CXCL1, CXCL8, CXCR2, and other proteins with clinical specimens. Finally, we determined the serum levels of CXCL1 and CXCL8 in 125 patients with colorectal cancer. RESULTS: SMAD4 knockdown from human colorectal cancer cells upregulated the expression of CXCL1 and CXCL8, which recruited neutrophils to colorectal cancer tumor via CXCR2. In turn, when neutrophils were exposed to the supernatant of SMAD4-negative colorectal cancer cells, they produced a large amount of CXCL1 and CXCL8 by themselves in vitro. In human clinical specimens, we found that neutrophil infiltration into the peritumoral stroma was more marked in SMAD4-negative colorectal cancer compared with that in SMAD4-positive colorectal cancer, and that both CXCL1 and CXCL8 were abundantly expressed in the tumor-infiltrating neutrophils. Neutrophils isolated from primary colorectal cancer expressed significantly higher levels of CXCL1 and CXCL8 than did those isolated from peripheral blood. Furthermore, tumor-infiltrating neutrophils expressed MMP2 and MMP9 in addition to ARG1 and IDO. Serum CXCL8 level was significantly higher in colorectal cancer patients, especially those at stage II/III, and statistical analysis indicated a high CXCL8 level was associated with a shorter overall survival and relapse-free survival. CONCLUSIONS: Blockade of the CXCL1/8-CXCR2 axis could be a novel therapeutic approach against SMAD4-negative colorectal cancer.

The Role of Tumor-Associated Neutrophils in Colorectal Cancer.

Colorectal cancer (CRC) is one of the most common causes of cancer deaths worldwide and the number of CRC patients is increasing progressively. Despite the improvement of the surgical techniques and chemotherapy, we have not completely overcome this disease yet due to the metastases. Therefore, understanding the mechanisms through which metastasis occurs is important for overcoming CRC. Normal host cells in the tumor microenvironment, such as macrophages and fibroblasts, have been reported to promote the growth of CRCs. Although neutrophils were originally considered to have defensive functions against tumor cells, it has been revealed that some populations of neutrophils, called as tumor-associated neutrophils (TANs), have tumor-supportive functions. The plasticity between tumor-suppressive and -supportive neutrophils are regulated by transforming growth factor (TGF)-ß and Interferon-ß signaling. Some studies have demonstrated that TANs promote the spread of cancer cells to distant organs. TANs contribute to the tumor invasion and angiogenesis through the production of matrix metalloproteinase-9 (MMP9), vascular endothelial growth factor (VEGF), and hepatocyte growth factor (HGF) in the primary and metastatic sites. Neutrophils also promotes tumor cell dissemination by capturing circulating tumor cells using neutrophil extracellular traps and promote their migration to distant sites. The neutrophil-to-lymphocyte ratio is a well-defined predictive marker for CRC patients. In this review, we highlight the molecular signaling between TANs and CRC cells and the possibility of TANs as a potential target for cancer therapy.

Huge rectovesical fistula due to long-term retention of a rectal foreign body: A case report and review of the literature.

INTRODUCTION: Most patients with foreign bodies in their rectums present to medical institutions within a few days. In this report, we describe a foreign body in the rectum in situ for 5 months that resulted in a huge rectovesical fistula 4cm in diameter, requiring emergency laparotomy. PRESENTATION OF CASE: A 59-year-old man, who had undergone rectal foreign body extraction via the anal canal without any complications 7 years previously, presented with abdominal pain and diarrhea. Computed tomography revealed a cup-shaped rectal foreign body and huge rectovesical fistula. We performed an emergency laparotomy. There was no contaminated ascites. The adhesion around the fistula was too stiff to be dissected. We incised the rectal wall, excised the ceramic cup-shaped foreign body, and detected a fistula approximately 4cm in diameter. We performed sigmoid colostomy, and the incised rectal wall and the bladder wall were sutured, and the residual rectum was supposed to function as a part of the bladder. After the surgery, no severe complications occurred. The patient told us that he inserted the foreign body himself 5 months earlier, and urine had appeared in the stool in the previous month. DISCUSSION: A long-term retained rectal foreign body is very rare and could create an abnormal huge fistula between the pelvic organs because of prolonged pressure on the walls of the pelvic organs. CONCLUSION: In patients with a long-term retained rectal foreign body, we should prepare for surgical treatment of not only the rectum but also the other pelvic organs.

Transanal approach for intersphincteric resection of rectal cancer in a patient with a huge prostatic hypertrophy.

The gold standard of surgical technique for rectal cancer is total mesorectal excision (TME). Laparoscopic TME has been proven to provide surgical safety and oncological outcomes equivalent to open TME. However, dissection of the lower rectum has some inherent difficulties related to a narrow pelvic space. The challenge of TME in the lower rectum was confirmed by the Colorectal Cancer Laparoscopic or Open Resection (COLOR) II trial showing a 9% positive circumferential margin (CRM) rate in laparoscopic TME and a 22% positive CRM rate in open TME. Recently, transanal TME has attracted intense attention as a promising alternative to laparoscopic TME. In this video article, we show the performance of a transanal approach for intersphincteric resection (ISR) of rectal cancer in a patient with a huge prostatic hypertrophy.

Laparoscopic ventral rectopexy with sacrocolpopexy for coexisting pelvic organ prolapse and external rectal prolapse.

OBJECTIVES: Pelvic organ prolapse (POP) POP is defined as the protrusion of pelvic organs from the vaginal canal. POP often coexists with internal rectal prolapse or external rectal prolapse (ERP). A series of patients with coexisting POP and ERP who underwent laparoscopic ventral rectopexy (LVR) combined with laparoscopic sacrocolpopexy (LSC) are reported here. METHODS: Seven patients underwent LVR and LSC together. Fecal incontinence was assessed by the Fecal Incontinence Severity Index (FISI), constipation was assessed by the Constipation Scoring System (CSS), and urinary incontinence was assessed by the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF). Anatomical disorders were assessed by Pelvic Organ Prolapse Quantification (POP-Q) and defecography. RESULTS: The patients' median age was 81 (60-88) years. The median operative time was 380 (282-430) minutes. The median postoperative hospital stay was 3 (1-5) days. There were no postoperative complications. The FISI, CSS, POP-Q, and defecography findings improved postoperatively; however, the ICIQ-SF deteriorated in 2 of 5 patients. CONCLUSIONS: LVR combined with LSC for coexisting POP and ERP is feasible.

Recovery of gastric ileus following laparoscopic ventral rectopexy within an enhanced recovery protocol.

PURPOSE: The enhanced recovery after surgery (ERAS) protocol has had limited adoption in laparoscopic ventral rectopexy (LVR), and the extent of gastric ileus shortly after LVR remains unknown. This study was designed to assess the degree of gastric emptying shortly after LVR within an ERAS protocol. METHODS: From August 2012 to June 2014, 40 patients diagnosed with external or internal rectal prolapse were recruited. All patients underwent LVR within an ERAS protocol. Carbohydrate solution (CS) was administered before and 5 h after surgery on the same day. The pyloric area (PA) was measured using ultrasonography before and after each CS intake. RESULTS: The PA was measured in 34 patients. The PA measured prior to CS intake, before surgery, was not significantly different from that after surgery. The rate of increase in the PA, which was calculated by the PA measured 1 h after CS intake divided by the PA measured prior to CS intake before surgery, was not significantly different from that after surgery. The postoperative hospital stay was 1 (1-2) day, and 36 patients (90 %) were discharged on the first postoperative afternoon. CONCLUSION: Postoperative gastric ileus was resolved in most cases within 5 h after LVR under an ERAS protocol.

Laparoscopic ventral rectopexy for rectoanal intussusception: postoperative evaluation with proctography.

BACKGROUND: Laparoscopic ventral rectopexy can relieve symptoms of obstructed defecation and fecal incontinence in patients with rectoanal intussusception. However, pelvic floor imaging after surgery has not been reported. OBJECTIVE: This study was designed to assess the outcome of patients who underwent laparoscopic ventral rectopexy for rectoanal intussusception, with special reference to the postoperative findings on evacuation proctography. DESIGN: This study was a retrospective analysis of prospectively collected data. SETTING: The study was conducted from 2012 to 2013 at the Department of Surgery, Kameda Medical Center, Japan. PATIENTS: We included 26 patients with symptomatic rectoanal intussusception. INTERVENTION: Laparoscopic ventral rectopexy was performed. MAIN OUTCOME MEASURE: Evacuation proctography was performed before and 6 months after the procedure. Defecatory function was evaluated using the Constipation Scoring System and Fecal Incontinence Severity Index. RESULTS: Of 26 patients with rectoanal intussusception preoperatively, 22 had symptoms of obstructed defecation and 21 complained of fecal incontinence. Postoperatively, rectoanal intussusception was eliminated in all patients, though 8 developed recto rectal intussusception. There was an overall reduction in both grade 2 rectocele size (median preop 26 mm vs. postop 11 mm; p < 0.0001) and pelvic floor descent (median preop 26 mm vs. postop 20 mm; p < 0.0001). 6 months after surgery, a reduction of at least 50% was observed in the Constipation Scoring System score for 9 patients (41%) with obstructive defecation and in the Fecal Incontinence Severity Index score for 14 incontinent patients (67%). LIMITATIONS: This was a preliminary study with a small sample size, no control group, and short follow-up time. CONCLUSION: Evacuation proctography showed anatomical correction in patients with rectoanal intussusception who underwent laparoscopic ventral rectopexy. However, the data also indicate that such correction does not necessarily result in meaningful symptomatic relief.

Comparison of the early results of transanal hemorrhoidal dearterialization and hemorrhoidectomy using an ultrasonic scalpel.

PURPOSE: Doppler-guided transanal hemorrhoidal dearterialization and mucopexy (THD surgery) is a new approach for treating hemorrhoids. The early results of the procedure are presented and compared with those of hemorrhoidectomy using an ultrasonic scalpel (US surgery). METHODS: Thirty-six patients with grade III hemorrhoids underwent the THD surgery and were compared with a cohort of 30 patients with grade III or IV hemorrhoids who were assigned to US surgery in a previous randomized trial. RESULTS: The pain scores were significantly lower in the THD patients on days 6 and 7 after the operation. The number of analgesic tablets consumed during the first postoperative week in the THD patients was significantly lower than that in the US patients. The blood loss was significantly greater in the THD patients. The hospital stay and length of time until the first defecation after surgery were both significantly shorter in the THD patients. The postoperative complications were comparable between the two groups of patients. CONCLUSION: The THD surgery was as effective as the US surgery for the treatment of hemorrhoids in the short term. THD surgery might be a preferred treatment because it is associated with a similar complication rate and short-term results, but results in lower postoperative pain and analgesic requirements compared with the US surgery.

Acute cholecystitis with bacteremia caused by Pasteurella multocida.

BACKGROUND: Pasteurella multocida is a commensal organism present in the oral cavities of many animals. It can cause various infections including soft tissue, joint, and respiratory infections in human beings, but intra-abdominal infection by P. multocida is rare. We report our experience with a case of acute cholecystitis with bacteremia caused by P. multocida. CASE REPORT: The patient was a 39-year-old female who underwent emergency laparoscopic cholecystectomy for acute cholecystitis. The patient's blood and bile cultures were positive for P. multocida. She kept a dog and a cat as pets, but denied having had any bites or major scratches. Our investigation did not find that she had any sign of other potential sources of infection. CONCLUSION: Acute cholecystitis can be a primary source of Pasteurella bacteremia in a previously healthy, young patient.