Abstract
Background
Klebsiella pneumoniae liver abscesses (KPLA) remain endemic to Taiwan. Hypervirulent strains in the gut can translocate across colonic mucosal defects into the portal circulation, causing subsequent liver abscesses. Occult colorectal cancer in patients with KPLA has been reported in a case series. Herein, we determined whether the diagnosis of KPLA serves as a harbinger of colorectal neoplasms.
Methods
Consecutive patients with KPLA treated at Taipei Veterans General Hospital in Taiwan between April 2011 and January 2024 were retrospectively enrolled. Hypervirulent K. pneumoniae strains were defined as those harboring mutations in rmpA or rmpA2. Patients who underwent colonoscopy within 6 months of diagnosis were included in the analysis. Logistic regression was used to assess the risk factors for colorectal adenomas and adenocarcinomas.
Results
A total of 489 patients with KPLA were identified during the study period, of which 114 (23.3%) underwent colonoscopy within 6 months of the diagnosis of KPLA. Most K. pneumoniae strains were hypervirulent (95.1%). Colonoscopy findings showed 48 (42.1%) cases of adenomas and 13 (11.4%) of adenocarcinomas. Age ≥ 50 years was the only independent factor for colorectal adenoma/adenocarcinoma (odds ratio = 5.728, 95% CI = 2.045–16.04, P = .001). During follow-up, most patients with adenocarcinoma (11/13, 84.6%) remained disease-free post-surgery. Of the 48 patients with adenomas, 2 developed colorectal cancer.
Conclusions
Colorectal adenomas and adenocarcinomas are common in patients with KPLA. Colonoscopy should be routinely performed in patients with KPLA, particularly those aged ≥ 50 years.
Keywords: colon cancer, Klebsiella pneumoniae, liver abscess
Upon diagnosis of Klebsiella pneumoniae liver abscess (KPLA), >50% of the patients had occult colorectal cancer or adenoma. Age ≥ 50 was the only independent risk factor. Our findings support the routine use of colonoscopy for patients with KPLA.
Pyogenic liver abscess (PLA) is a common disease in Taiwan, with an annual incidence that increased from 10.83 to 15.45 per 100 000 person-years between 2000 and 2011 [1]. In contrast to that in Western countries, Klebsiella pneumoniae is the most common cause of liver abscesses in Taiwan and other Asian countries [2]. K. pneumoniae liver abscess (KPLA) is an endemic disease in Taiwan, usually attributed to hypervirulent strains [3]. Hypervirulent K. pneumoniae strains, most of which belong to serotype K1/K2, can cause pyogenic infections, even in healthy individuals. Metastatic infections, such as meningitis and endophthalmitis, are often associated with KPLA, leading to severe complications [4].
Klebsiella pneumoniae liver abscess originates from K. pneumoniae colonizing the patient's own gastrointestinal tract [5], and hypervirulent strains may cross the compromised intestinal barrier, spread via portal circulation, and subsequently disseminate to the liver through hematogenous routes [6]. Our previous study has shown that the fecal carriage rate of hypervirulent K. pneumoniae (serotypes K1/K2) in healthy adults was 11.3% [7]. Another study from Korea reported a carriage rate of serotype K1 K. pneumoniae in stool samples from healthy adults of 21.1% [8]. The mechanisms underlying the interaction between K. pneumoniae and the host intestinal epithelium, as well as bacterial translocation, remain unclear.
Colorectal cancer is the most common malignancy and second most deadly cancer [9]. Most cancers originate from precancerous lesions or adenomatous polyps [10]. Colorectal neoplasms can compromise the mucosal barrier, creating a pathway for bacterial invasion of the portal venous system or systemic circulation, which can lead to liver abscess formation [6, 11, 12]. Studies from Korea conducted 20 years ago demonstrated that the rate of a hidden colorectal cancer in liver abscesses ranged from 7.4% to 16.2%; however, the number of patients undergoing colonoscopy was limited [12, 13].
In Taiwan, the endemic nature of KPLA presents a unique opportunity to study its association with underlying colorectal neoplasm. Therefore, in this study, we investigated whether the diagnosis of KPLA serves as a marker for occult colorectal neoplasms in Taiwan in the current era.
METHODS
Study Design
This retrospective study included adult hospitalized patients diagnosed with KPLA between January 2011 and January 2024 at Taipei Veterans General Hospital, a tertiary referral center with 3000 beds in Taipei, Taiwan. We excluded patients aged < 20 years and those diagnosed with colorectal cancer prior to KPLA. Data on age, sex, underlying diseases, imaging results (including abscess location, abscess size, gas formation, multiple liver abscesses, metastatic lesions, and concurrent bacteremia), day of hospitalization, treatment, and outcomes were collected from electronic medical charts. For the colonoscopy results, we only included data from colonoscopies performed within six months of KPLA diagnosis. The diagnosis of adenoma or adenocarcinoma based on colonoscopy was based on the pathological reports. Ethical approval for this study was granted by the Institutional Review Board of Taipei Veterans General Hospital, and the requirement for informed consent was waived because of the retrospective nature of the study.
Data Collection and Definitions
Klebsiella pneumoniae liver abscess was defined as the presence of ≥ 1 liver abscess(es) detected via ultrasonography or computed tomography and culture-confirmed K. pneumoniae isolated from an abscess or blood [14]. Multiple liver abscesses were defined as ≥ 3 abscesses in the liver parenchyma confirmed by imaging [14]. Metastatic infection was designated as a distant site of infection isolated with K. pneumoniae. Multidrug resistance was defined as K. pneumoniae isolate with non-susceptibility to at least one agent in ≥ 3 antimicrobial categories [15]. If the origin of the liver abscess was associated with the clinical features of cholecystitis/cholangitis or if extrahepatic biliary duct abnormalities were found on radiographic images, it was classified as having a biliary tract origin. The remaining liver abscesses were classified as cryptogenic in origin [14].
Microbiological Methods
Bacterial species were identified using a VITEKⓇ2 system (bioMérieux, Marcy-l’Étoile, France) or matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/MS) (bioMérieux). Capsular types of K. pneumoniae isolates were determined using polymerase chain reaction (PCR) to detect K serotype-specific alleles at the Wzy loci for the K1, K2, K5, K20, K54, and K57 types. Hypervirulent strains were defined as those with rmpA/rmpA2 genes [16].
Statistical Analysis
Continuous data are expressed as the mean ± standard deviation or the median (interquartile range [IQR]), depending on whether they are normally distributed. Chi-square and Fisher's exact tests were used to compare categorical data. Comparisons between groups were performed using the paired-sample t-test or Mann–Whitney U test, depending on whether the data were normally distributed. All variables with a P-value < .1 in the univariate analysis were included in the multivariate logistic regression model. Odds ratios (OR) with 95% CIs were calculated, and a P-value < .05 was considered statistically significant. Statistical analyses were performed using IBM SPSS Statistics (version 24.0; IBM Corp., Armonk, NY, USA).
RESULTS
Clinical Features of All Patients With KPLA
During the study period, 489 patients with KPLA met the inclusion criteria; among them, 114 underwent colonoscopy within 6 months of KPLA diagnosis. The clinical characteristics of 489 patients with KPLA are listed in Table 1. The mean age of the patients was 64.0 years, and 317 (64.8%) were males. Type 2 diabetes mellitus was the most common underlying condition, affecting 231 patients (47.2%). Most liver abscesses were cryptogenic (425/489, 86.9%) and predominantly located in the right lobe of the liver (343/489, 70.1%), with a median size of 5.5 cm (IQR 3.9–7.5). Gas-forming abscesses were observed in 42 patients (8.6%), while 81 (16.6%) had multiple abscesses, and 29 (5.9%) presented with metastatic infections. Approximately one-fifth of patients (n = 104, 21.3%) required admission to the intensive care unit. Nearly 90% of the patients underwent percutaneous drainage of the abscess as source control. Only 3 patients (0.6%) died during hospitalization.
Table 1.
Clinical Characteristics of Patients With KPLA Who Underwent Colonoscopy
| Characteristics | Total n = 489 |
Colonoscopy n = 114 (23.3) |
No Colonoscopy n = 375 (76.7) |
P Value |
|---|---|---|---|---|
| Male, n (%) | 317 (64.8) | 73 (64) | 244 (65.1) | .84 |
| Age, years (medium IQR) | 64 (54–75.5) | 60.5 (50.8–69) | 65 (55–77) | .001 |
| Age ≥50 years | 405 (82.8) | 88 (77.2) | 317 (84.5) | .069 |
| Body mass index, kg/m2 (medium IQR) | 25.1 (22.7–27.4) | 25.3 (22.6–28) | 25.1 (22.8–27.3) | .553 |
| Obesity (body mass index ≥24) | 285 (61.8) | 71 (65.7) | 214 (60.6) | .338 |
| Comorbidity, n (%) | ||||
| Diabetes mellitus | 231 (47.2) | 44 (38.6) | 187 (49.9) | .035 |
| Cancer | 50 (10.2) | 8 (7) | 42 (11.2) | .197 |
| Liver cirrhosis | 7 (1.4) | 1 (0.9) | 6 (11.2) | .487 |
| Congestive heart failure | 28 (5.7) | 4 (3.5) | 24 (6.4) | .245 |
| Chronic obstructive pulmonary disease | 12 (2.5) | 2 (1.8) | 10 (2.7) | .443 |
| Chronic kidney disease (eGFR < 60) | 34 (7) | 8 (7) | 26 (6.9) | .975 |
| Cerebrovascular accident | 32 (6.5) | 1 (0.9) | 31 (8.3) | .005 |
| Autoimmune disease | 8 (1.6) | 0 | 8 (2.1) | .118 |
| Origin of K. pneumoniae liver abscessa | ||||
| Cryptogenic | 425 (86.9) | 105 (92.1) | 320 (85.3) | .06 |
| Biliary | 64 (13.1) | 9 (7.9) | 55 (14.7) | .06 |
| Abscess locationb | ||||
| Right lobes | 343 (70.1) | 82 (71.9) | 261 (69.9) | .634 |
| Left lobes | 89 (18.2) | 22 (19.3) | 67 (17.9) | .729 |
| Both lobes | 56 (11.5) | 9 (7.9) | 47 (12.5) | .173 |
| Abscess size (medium IQR) | 5.5 (3.9–7.5) | 5.1 (3.5–7.3) | 5.7 (4–7.6) | .123 |
| Abscess size > 5 cm | 280 (57.3) | 59 (51.8) | 221 (58.9) | .175 |
| Gas forming | 42 (8.6) | 6 (5.3) | 36 (9.6) | .148 |
| Multiple liver abscessc | 81 (16.6) | 11 (9.6) | 70 (18.7) | .023 |
| Metastatic lesion | 29 (5.9) | 6 (5.3) | 23 (6.1) | .73 |
| Bacteremia | 228 (46.6) | 55 (48.2) | 173 (46.1) | .692 |
| Hospital days (medium IQR) | 22 (15–31) | 17 (10–28.3) | 23 (16–32) | <.001 |
| Intensive care unit admission | 104 (21.3) | 19 (16.7) | 85 (22.7) | .170 |
| Mortality in hospital | 3 (0.6) | 0 | 3 (0.8) | .450 |
| Treatment | ||||
| Antibiotic and drainage | 422 (86.3) | 98 (86) | 324 (86.4) | .906 |
| Antibiotic and operation | 8 (1.6) | 1 (0.9) | 7 (1.9) | .409 |
| Only antibiotic | 62 (12.7) | 15 (13.2) | 47 (12.5) | .861 |
| Microbiological characteristics of K. pneumoniae isolates | ||||
| rmpA or rmpA2 positive | 405/426 (95.1) | 106 (98.1) | 299 (94) | .087 |
| Capsular type (with rmpA n = 426) | ||||
| K1 and K2 | 315 (73.9) | 75 (69.4) | 240 (75.5) | .333 |
| K1 | 238 (56.3) | 62 (57.9) | 176 (55.7) | .685 |
| K2 | 77 (18.2) | 14 (13.1) | 63 (19.9) | .112 |
| K5 | 24 (5.7) | 7 (6.5) | 17 (5.4) | .653 |
| K20 | 9 (2.1) | 4 (3.7) | 5 (1.6) | .239 |
| K54 | 13 (3.1) | 3 (2.8) | 10 (3.2) | .574 |
| K57 | 12 (2.8) | 6 (5.6) | 6 (1.9) | .083 |
| K1, K2, K5, K20, K54, and K57 | 373 (88.2) | 96 (89.7) | 277 (87.7) | .568 |
| Any drug resistance | 23 (4.7) | 3 (2.6) | 20 (5.3) | .233 |
| Multidrug resistance | 16 (3.3) | 0 | 16 (4.3) | .013 |
Data are presented as n (%) of patients unless stated otherwise.
aCryptogenic KPLA was defined as those cases without obvious extrahepatic source of infection; biliary KPLA was defined when the clinical features of cholecystitis/cholangitis or extrahepatic biliary. Ductal abnormalities were identified by image studies.
bOne patient underwent colonoscopy, revealing an abscess located in the caudate lobe.
cDefined as >2 abscesses on imaging.
A total of 426 K. pneumoniae isolates (426/489, 87.1%) were available for microbiological analysis; most of them (405/426, 95.1%) were hypervirulent strains. Capsular types K1, K2, K5, K20, K54, and K57 accounted for 88.2% (373/426) of hypervirulent K. pneumoniae strains. K1 was the most common capsular type (238/426, 56.3%), followed by K2 (77/426, 18.2%), K5 (24/426, 5.7%), K54 (13/426, 3.1%), K57 (12/426, 2.8%), and K20 (9/426, 2.1%).
The clinical characteristics of patients who underwent colonoscopy (n = 114) were similar to those who did not (n = 375), except for younger age, a lower proportion of underlying cerebrovascular accidents, diabetes, multiple liver abscesses, and multiple-drug resistant strains, and shorter hospital stay in patients who underwent colonoscopy (Table 1).
Comparison of Clinical Characteristics of Patients With KPLA With or Without Colorectal Adenoma or Adenocarcinoma
Among 114 patients with KPLA who have undergone colonoscopy within 6 months of diagnosis, as high as 72 (63.2%) had colorectal polyps and/or cancer and underwent polypectomies for polyps or cancer biopsies. Pathological findings revealed adenoma in 48 patients and adenocarcinoma in 13 patients. The remaining 11 had hyperplastic polyps (n = 8), inflammatory polyps (n = 2), or sessile serrated lesions (n = 1). We compared the clinical characteristics of the patients with and without adenoma/adenocarcinoma (Table 2). Patients with adenomas or adenocarcinomas were older (65, IQR = 56–74.5 vs 55, IQR = 43.5–66, P < .001) and had a higher proportion of males (73.6% vs 55.7%, P = .048) compared to those without.
Table 2.
Comparison of Clinical Characteristics of Patients With KPLA With or Without Colorectal Adenoma or Adenocarcinoma
| Characteristics | Total n = 114 |
Adenoma Or Adenocarcinoma n = 61 (53.5) |
Not Adenoma/adenocarcinoma n = 53 (46.5) |
P Value |
|---|---|---|---|---|
| Male, n (%) | 73 (64) | 34 (55.7) | 39 (73.6) | .048 |
| Age, years (medium IQR) | 60.5 (15.8–69) | 65 (56–74.5) | 55 (43.5–66) | <.001 |
| Age ≥50 years | 88 (77.2) | 55 (90.2) | 33 (62.3) | <.001 |
| Body mass index, kg/m2 (medium IQR) | 25.3 (22.6–28) | 25.4 (22.6–27.8) | 25.1 (22.5–28.4) | .702 |
| Obesity (body mass index ≥24) | 71 (65.7) | 39 (66.1) | 32 (65.3) | .931 |
| Comorbidity, n (%) | ||||
| Diabetes mellitus | 44 (38.6) | 26 (42.6) | 18 (34) | .343 |
| Cancer | 8 (7) | 5 (8.2) | 3 (5.7) | .722 |
| Liver cirrhosis | 1 (.9) | 1 (1.6) | 0 | 1.000 |
| Congestive heart failure | 4 (3.5) | 2 (3.3) | 2 (3.8) | 1.000 |
| Chronic obstructive pulmonary disease | 2 (1.8) | 2 (3.3) | 0 | .498 |
| Chronic kidney disease (eGFR < 60) | 8 (7) | 5 (8.2) | 3 (5.7) | .722 |
| Cerebrovascular accident | 1 (0.9) | 1 (1.6) | 0 | 1.000 |
| Origin of K. pneumoniae liver abscessa | ||||
| Cryptogenic | 105 (92.1) | 57 (93.4) | 48 (90.6) | .731 |
| Biliary | 9 (7.9) | 4 (6.6) | 5 (9.4) | .731 |
| Abscess locationb | ||||
| Right lobes | 82 (71.9) | 40 (65.6) | 42 (79.2) | .105 |
| Left lobes | 22 (19.3) | 14 (23) | 8 (15.1) | .289 |
| Both lobes | 9 (7.9) | 6 (9.8) | 3 (5.7) | .5 |
| Abscess size (medium IQR) | 5.1 (3.5–7.3) | 5 (3.5–7.5) | 5.2 (3.5–6.7) | .517 |
| Abscess size > 5 cm | 59 (51.8) | 30 (49.2) | 29 (54.7) | .555 |
| Gas forming | 6 (5.3) | 3 (4.9) | 3 (5.7) | 1.000 |
| Multiple liver abscessc | 12 (10.5) | 5 (8.2) | 7 (13.2) | .385 |
| Metastatic lesion | 6 (5.3) | 3 (4.9) | 3 (5.7) | 1.000 |
| Bacteremia | 54 (47.4) | 27 (44.3) | 27 (50.9) | .476 |
| Length of stay (medium IQR) | 17 (10–28.3) | 19 (13–31.5) | 14 (9–24.5) | .052 |
| Intensive care unit admission | 19 (16.7) | 10 (16.4) | 9 (17) | .933 |
| Treatment | ||||
| Antibiotic and drainage | 98 (86) | 52 (85.2) | 46 (86.8) | .813 |
| Antibiotic and operation | 1 (0.9) | 1 (1.6) | 0 | 1.000 |
| Only antibiotic | 15 (13.2) | 8 (13.1) | 7 (13.2) | .988 |
Data are presented as n (%) of patients unless stated otherwise.
aCryptogenic KPLA was defined as those cases without obvious extrahepatic source of infection; biliary KPLA was defined when the clinical features of cholecystitis/cholangitis or extrahepatic biliary. Ductal abnormalities were identified by image studies.
bOne patient underwent colonoscopy, revealing an abscess located in the caudate lobe.
cDefined as >2 abscesses on imaging.
Among the 13 patients diagnosed with adenocarcinoma, 2 did not undergo surgery due to the very early stage of cancer, while 11 did. Finally, 11 patients achieved disease-free survival. A 58-year-old female underwent surgery for cancer and showed no recurrence during the follow-up period; however, she died of pneumonia 1 year later. Another 60-year-old male received chemotherapy after surgery for colorectal cancer but died of septic shock 3 years later. Among the 48 patients who underwent polypectomy for adenoma, 2 were later diagnosed with colorectal cancer during the 1–3 year follow-up period. Both patients underwent surgery for colorectal cancer and have survived disease-free to date. Other patients did not have a diagnosis of colorectal cancer during the 1–6 years of follow-up period. Among the 53 patients without colorectal adenoma or adenocarcinoma, 1 died of pneumonia 1 year following diagnosis of KPLA. Eight patients underwent follow-up colonoscopy within 1–9 years following KPLA, and only 2 were found to have tubular adenomas.
The analysis of the risk factors for colorectal adenoma or adenocarcinoma in patients is shown in Table 3. In the multivariate analysis, age ≥ 50 years (OR = 5.728, 95% CI = 2.045–16.04; P = .001) was the only independent predictor of colorectal adenoma or adenocarcinoma in patients with KPLA.
Table 3.
Risk Factors for Colorectal Adenoma or Adenocarcinoma in Patients With KPLA
| Variables | Univariate Analysis | Multivariate Analysis | ||
|---|---|---|---|---|
| OR (95% CI) | P value | OR (95% CI) | P value | |
| Age > 50 | 5.556 (2.025–15.242) | .001 | 5.728 (2.045–16.04) | .001 |
| Gender | 0.452 (0.205–0.999) | .005 | 0.513 (0.22–1.2) | .124 |
CI, confidence interval; OR, odds ratio.
Comparison of Clinical Characteristics of Patients With KPLA With or Without Colorectal Adenocarcinoma
We compared the clinical characteristics of patients with and without adenocarcinoma (Table 4). Patients with adenocarcinoma had a higher proportion of those aged ≥ 50 years. The analysis of the risk factors for patients with colorectal adenocarcinoma is shown in Table 5. In multivariate analysis, both male sex (P = .058) and bilateral lobe involvement (P = .059) were marginally significantly associated with colorectal adenocarcinoma in patients with KPLA.
Table 4.
Comparison of Clinical Characteristics of Patients With KPLA With or Without Colorectal Adenocarcinoma
| Characteristics | Total n = 114 |
Adenocarcinoma n = 13 (11.4) |
Not Adenocarcinoma n = 101 (88.6) |
P Value |
|---|---|---|---|---|
| Male, n (%) | 73 (64) | 5 (38.5) | 68 (67.3) | .063 |
| Age, years (medium IQR) | 60.5 (15.8–69) | 68 (59–74.5) | 60 (49–68) | .062 |
| Age ≥50 years | 88 (77.2) | 13 (100) | 75 (74.3) | .038 |
| Body mass index, kg/m2 (medium IQR) | 25.3 (22.6–28) | 24.1 (21.7–26.2) | 25.5 (22.7–28.4) | .182 |
| Obesity (body mass index ≥24) | 71 (65.7) | 7 (53.8) | 64 (67.4) | .362 |
| Comorbidity, n (%) | ||||
| Diabetes mellitus | 44 (38.6) | 7 (53.8) | 37 (36.6) | .23 |
| Cancer | 8 (7) | 2 (15.4) | 6 (5.9) | .226 |
| Liver cirrhosis | 1 (0.9) | 0 | 1 (1) | 1.000 |
| Congestive heart failure | 4 (3.5) | 0 | 4 (4) | 1.000 |
| Chronic obstructive pulmonary disease | 2 (1.8) | 1 (7.7) | 1 (1) | .216 |
| Chronic kidney disease (eGFR < 60) | 8 (7) | 2 (15.4) | 6 (5.9) | .226 |
| Cerebrovascular accident | 1 (0.9) | 1 (7.7) | 0 | .114 |
| Origin of K. pneumoniae liver abscessa | ||||
| Cryptogenic | 105 (92.1) | 12 (92.3) | 93 (92.1) | 1.000 |
| Biliary | 9 (7.9) | 1 (7.7) | 8 (7.9) | 1.000 |
| Abscess locationb | ||||
| Right lobes | 82 (71.9) | 8 (61.5) | 74 (73.3) | .512 |
| Left lobes | 22 (19.3) | 1 (7.7) | 21 (20.8) | .457 |
| Both lobes | 9 (7.9) | 3 (23.1) | 6 (5.9) | .066 |
| Abscess size (medium IQR) | 5.1 (3.5–7.3) | 5 (4.7–6.4) | 5.2 (3.4–7.5) | .915 |
| Abscess size > 5cm | 59 (51.8) | 6 (46.2) | 53 (52.5) | .668 |
| Gas forming | 6 (5.3) | 1 (7.7) | 5 (5) | .525 |
| Multiple liver abscessc | 12 (10.5) | 2 (15.4) | 10 (9.9) | .626 |
| Metastatic lesion | 6 (5.3) | 2 (15.4) | 4 (4) | .139 |
| Bacteremia | 54 (47.4) | 5 (38.5) | 49 (48.5) | .494 |
| Length of stay (medium IQR) | 17 (10–28.3) | 22 (14.5–39.5) | 17 (10–27.5) | .111 |
| Intensive care unit admission | 19 (16.7) | 2 (15.4) | 17 (16.8) | 1.000 |
| Treatment | ||||
| Antibiotic and drainage | 98 (86) | 10 (76.9) | 88 (87.1) | .39 |
| Antibiotic and operation | 1 (0.9) | 1 (7.7) | 0 | .114 |
| Only antibiotic | 15 (13.2) | 2 (15.4) | 13 (12.9) | .68 |
Data are presented as n (%) of patients unless stated otherwise.
aCryptogenic KPLA was defined as those cases without obvious extrahepatic source of infection; biliary KPLA was defined when the clinical features of cholecystitis/cholangitis or extrahepatic biliary. Ductal abnormalities were identified by image studies.
bOne patient underwent colonoscopy, revealing an abscess located in the caudate lobe.
cDefined as >2 abscesses on imaging.
Table 5.
Risk Factors for Colon Cancer (Adenocarcinoma) in Patients With KPLA
| Variables | Univariate Analysis | Multivariate Analysis (Forward Selection) | ||
|---|---|---|---|---|
| OR (95% CI) | P value | OR (95% CI) | P value | |
| Gender | 0.303 (0.092–0.999) | .05 | 0.309 (0.092–1.042) | .058 |
| Both lobes | 4.75 (1.027–21.968) | .046 | 4.75 (1.027–21.968) | .059 |
| Age | 1.040 (0.994–1.089) | .088 | ||
DISCUSSION
Among the 114 patients who underwent colonoscopy within 6 months of KPLA diagnosis, 48 had colorectal adenoma and 13 had colorectal adenocarcinoma. Age ≥ 50 years was the only independent predictor for colorectal adenoma/adenocarcinoma. Our findings indicate that underlying colorectal neoplasia is prevalent among patients with KPLA, underscoring the importance of routine colonoscopy following a KPLA diagnosis.
Previous studies have reported an association between liver abscesses and subsequent colorectal cancer and revealed that patients with liver abscesses had an increased risk of colorectal cancer during the long-term follow-up period [17–19]. A population-based study in Taiwan reported that patients with cryptogenic liver abscesses between 2000 and 2004 had a significantly higher incidence of colorectal cancer than the general population (5.5% vs 1.8%) during a 5-year follow-up period [17]. Kao et al [18] conducted another nationwide cohort study in Taiwan between 2000 and 2007 and found that 40 out of 1257 patients (3.2%) developed colorectal cancer during the follow-up period, but the follow-up period was not specified. Huang et al [19] also conducted a retrospective cohort study at a medical center in northern Taiwan, involving 1194 patients diagnosed with KPLA between 2000 and 2009. Over an 11-year follow-up period, 42 patients with KPLA (3.4%) were diagnosed with colorectal cancer. Most liver abscesses in Taiwan are caused by K. pneumoniae [20–23], and the aforementioned 3 Taiwanese studies showed an increased risk of colorectal cancer in patients with KPLA during extended follow-up periods.
Most liver abscesses in Korea are also caused by K. pneumoniae [24]. Koo et al retrospectively analyzed 163 patients with cryptogenic liver abscesses at a single institute in Korea between 2001 and 2010; 121 patients underwent colonoscopy. The authors found a colorectal cancer prevalence of 7.4% (12/163); this study was also limited by the unknown timing of colonoscopy after liver abscess in 121 patients [12]. Jeong et al reported a colorectal cancer detection rate of 16.2% (6/37) among patients with liver abscesses diagnosed between 2003 and 2010 who underwent colonoscopy within 6 weeks of PLA diagnosis. To the best of our knowledge, this is the only study focusing on occult colorectal cancer for the diagnosis of KPLA. However, the limited number (37 cases) of colonoscopy cases restricts the implications of these results [13]. In addition, a United States retrospective cohort study followed 8286 patients with PLA and 23 201 matched controls for up to 10 years and diagnosed colorectal cancer in a significantly higher proportion of PLA patients than controls (1.9% vs 0.8%; P < .001). However, K. pneumoniae was identified as the etiology in 20% of these cases. Notably, this study also suggested that undiagnosed colorectal cancer is a likely cause of cryptogenic PLA [25]. These aforementioned studies usually focused on the incidence of colorectal cancer during long-term follow-up in patients with liver abscesses and do not indicate whether colorectal cancer was already present at the time of liver abscess diagnosis. Meanwhile, in our study, colonoscopy was performed within 6 months of KPLA diagnosis, and our findings, which identified colorectal cancer in 11.4% of patients, emphasize the significant role of colonoscopic screening in the diagnosis of KPLA.
The adenoma–carcinoma sequence theory indicates that colorectal cancer develops through stepwise progression from normal to dysplastic epithelium to carcinoma [26]. The literature suggests that the removal of adenomas during colonoscopy can reduce colorectal cancer mortality by as much as 53% [27]. A high detection rate of colorectal adenoma in the diagnosis of KPLA has not yet been reported; only a few case reports from Taiwan and Korea have addressed this finding [28–32]. In our study of 48 patients who underwent polypectomy for adenoma, only 2 were diagnosed with colorectal cancer during the follow-up period. All 48 patients had disease-free survival. Among the 13 patients with colorectal cancer, 11 had disease-free survival. In contrast to previous studies, our study period spans 2011–2024, which is representative of the real-world situation in the current era. No professional guidelines recommend colorectal cancer screening for patients diagnosed with KPLA. Our findings underscore the high prevalence of occult colorectal neoplasia in patients with KPLA, and we strongly recommend routine colonoscopic evaluations in these patients.
In the current study, we had provided microbiological information of K. pneumoniae strains and demonstrated most of them were hypervirulent strains. However, diagnostic capacity may vary across different regions, and molecular diagnostics are not readily available in resource-constrained setting. Hypervirulent K. pneumoniae strains are frequently associated with a hypermucoviscous phenotype, and the string test may serve as a practical screening method to identify hypervirulent strains [33]. Our study had some limitations. First, this was a retrospective analysis conducted at a single tertiary referral center, which may limit the generalizability of the findings. Second, the number of patients who underwent colonoscopy following KPLA diagnosis was limited; however, our case numbers are the largest in the literature. Third, although our findings strongly support the high detection rate of colorectal neoplasia in patients with KPLA, they may be limited by a lack of comparison with patients without KPLA.
In conclusion, our study demonstrated that patients with KPLA have a high detection rate of underlying colorectal neoplasia, including both adenomas and adenocarcinomas. Age ≥ 50 years is a risk factor for adenoma and cancer. Our findings emphasize the importance of routine colonoscopy in patients with KPLA, particularly in those aged ≥ 50 years.
Notes
Acknowledgements. The preliminary data of this study were presenting ID week 2024 as a paper poster. We sincerely thank Medical Science and Technology Building of the Taipei Veterans General Hospital for providing experimental space and facilities.
Author Contributions. T. E. L. performed the data collection and analysis and wrote the original draft of the manuscript. C. C. contributed to study design and data analysis. Y. T. L. contributed to the study design, data collection, data analysis, and manuscript revision. S. H. C. contributed to the laboratory experiments. S. Y. L., Y. C. H., and W. C. revised the manuscript. All authors have reviewed and approved the final manuscript.
Ethical Approval. Ethical approval was obtained from the Institutional Review Board of the Taipei Veterans General Hospital. The requirement for informed consent was waived due to the retrospective nature of the study.
Data availability. Due to the sensitive nature of the questions asked in this study, survey respondents were assured that the raw data would remain confidential and would not be shared.
Financial support. This work was supported by grants from the National Science and Technology Council (NSTC 112-2314-B-A49-029 and NSTC 114-2314-B-A49-079-MY3) of Taiwan, the Taipei Veterans General Hospital (V112C-102, V113C-073, V114C-047, V115C-170 and V115B-001), the Szu-Yuan Research Foundation of Internal Medicine, and Y.L. Lin Hung Tai Education Foundation. The funders had no role in the study design, data collection, and interpretation, or decision to submit the work for publication.
Contributor Information
Tsen-En Liao, Institute of Emergency and Critical Care Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Center for Infection Control, Taipei Veterans General Hospital, Taipei, Taiwan.
Chien Chuang, Division of Infectious Diseases, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
Szu-Yu Liu, Division of Infectious Diseases, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
Yu-Chien Ho, Division of Infectious Diseases, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Department of Medicine, Kinmen Hospital, Ministry of Health and Welfare, Kinmen, Taiwan.
Wan Chin, Division of Infectious Diseases, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
Sheng-Hua Chou, Institute of Emergency and Critical Care Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Center for Infection Control, Taipei Veterans General Hospital, Taipei, Taiwan.
Yi-Tsung Lin, Institute of Emergency and Critical Care Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Center for Infection Control, Taipei Veterans General Hospital, Taipei, Taiwan; Division of Infectious Diseases, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
References
- 1. Chen YC, Lin CH, Chang SN, Shi ZY. Epidemiology and clinical outcome of pyogenic liver abscess: an analysis from the national health insurance research database of Taiwan, 2000-2011. J Microbiol Immunol Infect 2016; 49:646–53. [DOI] [PubMed] [Google Scholar]
- 2. Lin YT, Liu CJ, Yeh YC, Chen TJ, Fung CP. Ampicillin and amoxicillin use and the risk of Klebsiella pneumoniae liver abscess in Taiwan. J Infect Dis 2013; 208:211–7. [DOI] [PubMed] [Google Scholar]
- 3. Yeh KM, Kurup A, Siu LK, et al. Capsular serotype K1 or K2, rather than magA and rmpA, is a major virulence determinant for Klebsiella pneumoniae liver abscess in Singapore and Taiwan. J Clin Microbiol 2007; 45:466–71. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4. Siu LK, Yeh KM, Lin JC, Fung CP, Chang FY. Klebsiella pneumoniae liver abscess: a new invasive syndrome. Lancet Infect Dis 2012; 12:881–7. [DOI] [PubMed] [Google Scholar]
- 5. Fung CP, Lin YT, Lin JC, et al. Klebsiella pneumoniae in gastrointestinal tract and pyogenic liver abscess. Emerg Infect Dis 2012; 18:1322–5. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6. Tu YC, Lu MC, Chiang MK, et al. Genetic requirements for Klebsiella pneumoniae-induced liver abscess in an oral infection model. Infect Immun 2009; 77:2657–71. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7. Lin YT, Siu LK, Lin JC, et al. Seroepidemiology of Klebsiella pneumoniae colonizing the intestinal tract of healthy Chinese and overseas Chinese adults in Asian countries. BMC Microbiol 2012; 12:13. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8. Chung DR, Lee H, Park MH, et al. Fecal carriage of serotype K1 Klebsiella pneumoniae ST23 strains closely related to liver abscess isolates in Koreans living in Korea. Eur J Clin Microbiol Infect Dis 2012; 31:481–6. [DOI] [PubMed] [Google Scholar]
- 9. Xi Y, Xu P. Global colorectal cancer burden in 2020 and projections to 2040. Transl Oncol 2021; 14:101174. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10. Druliner BR, Rashtak S, Ruan X, et al. Colorectal cancer with residual polyp of origin: a model of malignant transformation. Transl Oncol 2016; 9:280–6. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11. Cohen JL, Martin FM, Rossi RL, Schoetz DJ Jr. Liver abscess. The need for complete gastrointestinal evaluation. Arch Surg 1989; 124:561–4. [DOI] [PubMed] [Google Scholar]
- 12. Koo HC, Kim YS, Kim SG, et al. Should colonoscopy be performed in patients with cryptogenic liver abscess? Clin Res Hepatol Gastroenterol 2013; 37:86–92. [DOI] [PubMed] [Google Scholar]
- 13. Jeong SW, Jang JY, Lee TH, et al. Cryptogenic pyogenic liver abscess as the herald of colon cancer. J Gastroenterol Hepatol 2012; 27:248–55. [DOI] [PubMed] [Google Scholar]
- 14. Chuang C, Fan WC, Lin YT, Wang FD. The emergence of Klebsiella pneumoniae liver abscess in non-diabetic patients and the distribution of capsular types. Gut Pathog 2016; 8:46. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15. Magiorakos AP, Srinivasan A, Carey RB, et al. Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect 2012; 18:268–81. [DOI] [PubMed] [Google Scholar]
- 16. Turton JF, Payne Z, Coward A, et al. Virulence genes in isolates of Klebsiella pneumoniae from the UK during 2016, including among carbapenemase gene-positive hypervirulent K1-ST23 and ‘non-hypervirulent’ types ST147, ST15 and ST383. J Med Microbiol 2018; 67:118–28. [DOI] [PubMed] [Google Scholar]
- 17. Lai HC, Lin HC. Cryptogenic pyogenic liver abscess as a sign of colorectal cancer: a population-based 5-year follow-up study. Liver Int 2010; 30:1387–93. [DOI] [PubMed] [Google Scholar]
- 18. Kao WY, Hwang CY, Chang YT, et al. Cancer risk in patients with pyogenic liver abscess: a nationwide cohort study. Aliment Pharmacol Ther 2012; 36:467–76. [DOI] [PubMed] [Google Scholar]
- 19. Huang WK, Chang JC, See LC, et al. Higher rate of colorectal cancer among patients with pyogenic liver abscess with Klebsiella pneumoniae than those without: an 11-year follow-up study. Colorectal Dis 2012; 14:e794–801. [DOI] [PubMed] [Google Scholar]
- 20. Wu PF, Chang YY, Lin YT, Wang FD, Chan YJ, Fung CP. Clinical characteristics and economic consequence of Klebsiella pneumoniae liver abscess in Taiwan. J Microbiol Immunol Infect 2015; 48:190–7. [DOI] [PubMed] [Google Scholar]
- 21. Lin YT, Wang FD, Wu PF, Fung CP. Klebsiella pneumoniae liver abscess in diabetic patients: association of glycemic control with the clinical characteristics. BMC Infect Dis 2013; 13:56. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22. Lin YT, Cheng YH, Chuang C, et al. Molecular and clinical characterization of multidrug-resistant and hypervirulent Klebsiella pneumoniae strains from liver abscess in Taiwan. Antimicrob Agents Chemother 2020; 64:e00174-20. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23. Chuang C, Chou SH, Wang FD, Huang YH, Tsai TH, Lin YT. Fluoroquinolones as an alternative treatment for Klebsiella pneumoniae liver abscess and impact on hospital length of stay. Int J Antimicrob Agents 2020; 56:106120. [DOI] [PubMed] [Google Scholar]
- 24. Chung D, Lee S, Lee H, et al. Emerging invasive liver abscess caused by K1 serotype Klebsiella pneumoniae in Korea. J Infect 2007; 54:578–83. [DOI] [PubMed] [Google Scholar]
- 25. Suzuki H, Kidder I, Tanaka T, Goto M. Incidence of colorectal cancer in patients diagnosed with pyogenic liver abscess. JAMA Netw Open 2023; 6:e2348218. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26. Leslie A, Carey F, Pratt N, Steele R. The colorectal adenoma–carcinoma sequence. Br J Surg 2002; 89:845–60. [DOI] [PubMed] [Google Scholar]
- 27. Zauber AG, Winawer SJ, O'Brien MJ, et al. Colonoscopic polypectomy and long-term prevention of colorectal-cancer deaths. N Engl J Med 2012; 366:687–96. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28. Lai HC, Chan CY, Peng CY, Chen CB, Huang WH. Pyogenic liver abscess associated with large colonic tubulovillous adenoma. World J Gastroenterol 2006; 12:990–2. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29. Hsu WH, Yu FJ, Chuang CH, Chen CF, Lee CT, Lu CY. Occult colon cancer in a patient with diabetes and recurrent Klebsiella pneumoniae liver abscess. Kaohsiung J Med Sci 2009; 25:98–103. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30. Kang MK, Kwon HJ, Kim MC. Gastric cancer and adenomatous colorectal polyp concomitant with pyogenic liver abscess and bacteremia. Yeungnam Univ J Med 2020; 37:246–9. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 31. Kim HY, Kim CW, Kim DR, et al. Recurrent pyogenic liver abscess as a presenting manifestation of colorectal cancer. Korean J Intern Med 2017; 32:174–7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 32. Park JG, Suh JI, Kim YU. Gastric heterotopia of colon found cancer workup in liver abscess: a case report. World J Clin Cases 2022; 10:5012–7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 33. Shon AS, Bajwa RP, Russo TA. Hypervirulent (hypermucoviscous) Klebsiella pneumoniae: a new and dangerous breed. Virulence 2013; 4:107–18. [DOI] [PMC free article] [PubMed] [Google Scholar]