Clinicopathological differences between patients with schistosomal appendicitis and non schistosomal appendicitis: A retrospectively study of past ten years

Abstract

BACKGROUND

Chronic schistosomiasis causes multiple organ and multiple system diseases, especially the digestive system. Schistosome eggs are mainly deposited in the stomach, liver and colorectal, but a few eggs are deposited in the appendix and cause disease. At present, there are few studies on schistosomal appendicitis.

AIM

To explore the differences in epidemiological, clinical and pathological characteristics between schistosomal appendicitis and non-schistosomal appendicitis over the past decade in order to assess the impact of schistosomiasis on appendicitis.

METHODS

The differences of general data, clinical data and laboratory examination data of patients with appendicitis from October 2013 to October 2023 were retrospectively analyzed. All patients were divided into two groups for analysis. There were 136 patients in schistosomal appendicitis group and 5418 patients in non-schistosomal appendicitis group.

RESULTS

Schistosomal appendicitis accounted for 2.45% of all patients with appendicitis, and the annual proportion in the past decade was 2.2%, 2.9%, 1.8%, 1.9%, 3.4%, 3.1%, 1.9%, 1.6%, 3%, 2.6%, respectively. The prevalence of schistosomal appendicitis was middle-aged and elderly males, with an average age of 61.73 ± 15.335 years. The main population of non-schistosomal appendicitis was middle-aged men, with an average age of 35.8 ± 24.013 years (P < 0.001). The distribution of pathological types of appendicitis was different between the two groups (P < 0.001). The incidence of acute suppurative appendicitis in non-schistosomal appendicitis was higher than that in schistosomal appendicitis [odds ratio (OR) = 0.504; 95% confidence interval (CI): 0.349-0.728; P < 0.001]. The proportion of acute attack of chronic appendicitis in schistosomal appendicitis was higher than that in non-schistosomal appendicitis (OR = 2.614; 95%CI: 1.815-3.763; P < 0.001). The proportion of schistosomal appendicitis patients complicated with colorectal cancer was higher than that of non-schistosomal appendicitis patients (OR = 5.087; 95%CI: 1.427-18.132; P = 0.012). There was no difference in clinical symptoms between the two groups. In the laboratory examination, there was a significant difference in white blood cells between schistosomal appendicitis and non-schistosomal appendicitis. The level of white blood cells in schistosomal appendicitis group was slightly higher than the upper limit of the normal range. Other statistically significant indicators were in the normal range.

CONCLUSION

Schistosomal appendicitis is a severe condition that is often associated with intestinal malignancies, potentially leading to a poor prognosis. Schistosomal appendicitis is more likely to be misdiagnosed and missed diagnosed in clinical work because of its nonspecific clinical manifestations and laboratory examination. It is crucial to differentiate schistosomal appendicitis in middle-aged and elderly male patients presenting with appendicitis, and to ensure early detection and treatment.

Key Words: Schistosomal appendicitis; Schistosomiasis; Appendix; Colorectal cancer; Clinicopathological characteristics

Core Tip: This is a retrospective single-center observational study to investigate clinical and pathological characteristics of schistosomal appendicitis. Schistosomal appendicitis is a serious disease, which is easy to be complicated with intestinal malignant tumors. Schistosomal appendicitis has no specific clinical manifestations and laboratory tests, and the prognosis may be poor. It is more likely to be misdiagnosed and missed diagnosis in clinical work. Although chronic schistosomiasis has decreased year by year, the proportion of schistosomal appendicitis has not decreased in the past decade.

INTRODUCTION

Schistosomiasis is a zoonotic tropical disease, with up to 250 million people infected worldwide. When the human body is initially infected with Schistosoma japonicum, it is mainly characterized by fever, shivering, myalgia and other acute non-specific manifestations, which is defined as acute schistosomiasis (Pianshan syndrome), and then can develop into chronic schistosomiasis[1]. Schistosoma japonicum is one of the species causing chronic intestinal diseases in humans. Schistosome eggs are mostly found in the colon and rectum. With the further study, we found that schistosomiasis may even promote the occurrence and development of colorectal cancer by affecting the transformation of tumor-associated macrophages into the M2 phenotype[2]. Schistosoma japonicum and its eggs can spread through the bloodstream. Schistosome eggs can deposit in multiple systems and organs of the human body and cause disease, such as the nervous system, respiratory system, digestive system, urogenital system. In the digestive system, Schistosomiasis is most common in the liver and colorectal, and schistosome eggs are also found in the appendix. These Schistosome eggs are often discovered during appendectomy procedures performed for appendicitis[3]. In some developed areas, scholars have defined appendicitis caused by schistosomiasis entering the human body as schistosomal appendicitis (SA), but this kind of appendicitis is rare[4-6].

As early as 1987, Appendicular schistosomiasis was proposed as an ectopic Schistosomiasis. The main appendiceal lesions caused by Schistosoma japonicum are acute schistosomiasis granulomatous appendicitis and acute schistosomiasis obstructive appendicitis[7]. In 1909, SA was first proposed, with an incidence of about 0.175%-2%[8]. It has been reported that schistosomiasis may be a rare cause of appendicitis, but the specific pathogenesis of appendicular schistosomiasis and whether schistosomiasis can induce appendicitis are still unclear[9,10]. This study analyzed the differences between SA and non-SA (NSA) in epidemiology, laboratory examination and clinical pathological data, in order to explore the impact of schistosomiasis on appendicitis.

MATERIALS AND METHODS

Data collection

All clinical data were collected from 5554 patients with appendicitis treated in The First Affiliated Hospital of Wannan Medical College (Wuhu, Anhui Province, China) from October 2013 to October 2023. This study was approved by the medical ethics committee of Wannan Medical College [Research Proposal Notification of IRB Review Decision (2022) (No. 33)].

Of the total patients, 136 were diagnosed with SA (SA group), while 5418 had NSA (NSA group). All patients were from schistosoma japonicum endemic areas and underwent appendix biopsy and all patients with SA have a large amount of schistosome egg deposition in the appendix tissue. The diagnostic results were confirmed by more than two experienced pathologists. Patients with appendiceal foreign body obstruction or appendiceal tumors (such as carcinoid, adenocarcinoma, or cystic tumors) were excluded from the study.

This study has been approved by the ethics committee of Wannan Medical College and all patients included verbal consent. The general and pathological data of patients with appendicitis were collected. We collected 136 cases of SA patients’ personal history (smoking history, drinking history), disease history (hypertension, coronary heart disease, diabetes and malignant tumor), clinical symptoms (fever, nausea and vomiting, diarrhea, constipation, abdominal pain), laboratory examination. According to the gender and age distribution of 5418 patients with NSA, 136 cases were stratified sampled, and the above data were collected and analyzed.

Statistical analysis

Statistical analysis was conducted using international business machines corporation statistical product and service solutions (SPSS) statistics for Windows (version 26.0, SPSS Corporation, Armonk, NY, United States). Data were expressed as frequency (n), percentage (%), or mean ± SD, as appropriate. Categorical variables were analyzed using the χ² test and Fisher’s exact test. The normality of continuous data was assessed with the Kolmogorov-Smirnov test. Normally distributed data were analyzed by t test, while non-normally distributed data were analyzed using the Mann-Whitney U test. Binary Logistic regression analysis was used to calculate odds ratio (OR) and 95% confidence interval (CI). The difference was statistically significant (P < 0.05).

RESULTS

Analysis of general data and pathological types of SA and NSA group

There were 136 patients in SA group. Pathological experts found different numbers of schistosome eggs in the appendix of these patients. A total of 5418 patients in NSA group. SA accounted for 2.45% of appendicitis patients in The First Affiliated Hospital of Wannan Medical College in the past decade. The annual proportions of SA were 2.2%, 2.9%, 1.8%, 1.9%, 3.4%, 3.1%, 1.9%, 1.6%, 3%, 2.6%, respectively (Table 1). There were 94 males (69.9%) and 42 females (30.1%) in SA group. There were 2818 males (52%) and 2600 females (48%) in the NSA group. The proportion of male patients with appendicitis in the two groups was higher than that in female patients, and the proportion of male patients in SA group was higher than that in NSA group. The difference in gender composition between the two groups was statistically significant (P < 0.001). The average age of patients in SA group was (61.73 ± 15.335) years old, which was significantly higher than that in NSA group (35.8 ± 24.013) years old (P < 0.001).

Table 1 Proportion of schistosomal appendicitis in total appendicitis treated in the First Affiliated Hospital of Wannan Medical College from October 2013 to October 2023.

Date	SA group (n)	NSA group (n)	SA proportion (%)
October 2013 to October 2014	11	495	2.20
October 2014 to October 2015	16	537	2.90
October 2015 to October 2016	9	487	1.80
October 2016 to October 2017	11	572	1.90
October 2017 to October 2018	20	565	3.40
October 2018 to October 2019	17	535	3.10
October 2019 to October 2020	11	568	1.90
October 2020 to October 2021	8	507	1.60
October 2021 to October 2022	17	555	3.00
October 2022 to October 2023	16	597	2.60

SA: Schistosomal appendicitis; NSA: Non schistosomal appendicitis.

In the pathological types, SA group had 12 cases of simple appendicitis (8.8%), 42 cases of suppurative appendicitis (39.8%), 37 cases of gangrenous or perforated appendicitis (27.2%), no cases of periappendiceal abscess, and 45 cases of acute attack of chronic appendicitis (33.1%). In NSA group, there were 677 cases (12.6%) of simple appendicitis, 2546 cases (47.2%) of suppurative appendicitis, 1303 cases (24.2%) of gangrenous or perforated appendicitis, 2 cases of periappendiceal abscess, and 862 cases (16%) of acute attack of chronic appendicitis. There was a statistical difference in the pathological types between the two groups (P < 0.001) (Table 2). The proportion of simple appendicitis in SA group was less than that in NSA group, and the proportion of gangrenous or perforated appendicitis in SA group was greater than that in NSA group, but the difference is not statistically significant. There was no difference in the incidence of periappendiceal abscess between the two groups. Acute suppurative appendicitis accounted for more of the pathological types of appendicitis in the two groups, but acute suppurative appendicitis in SA group was less than that in NSA group (OR = 0.504; 95%CI: 0.349-0.728; P < 0.001). The proportion of acute attack of chronic appendicitis in SA was higher than that in NSA (OR = 2.614; 95%CI: 1.815-3.763; P < 0.001) (See Tables 3, 4, 5, 6 and 7 for details).

Table 2 Analysis of general data and pathological types of schistosomal appendicitis and non schistosomal appendicitis, n (%).

Group	SA group (n = 136)	NSA group (n = 5418)	χ2/Z	P value
Gender			40.753	< 0.001
Female	42 (30.1)	2601 (48)
Male	94 (69.9)	2818 (52)
Age, mean ± SD (years)	61.73 ± 15.335	35.8 ± 24.013	-12.722	< 0.001
Classification			33.234	< 0.001
Acute simple appendicitis	12 (8.8)	677 (12.6)
Acute suppurative appendicitis	42 (39.8)	2546 (47.2)
Gangrenous or perforated appendicitis	37 (27.2)	1303 (24.2)
Periappendicular abscess	0 (0)	2 (0)
Acute attack of chronic appendicitis	45 (33.1)	862 (16)

SA: Schistosomal appendicitis; NSA: Non schistosomal appendicitis.

Table 3 Acute simple appendicitis.

	β	SE	Wald	P value	95%CI
Schistosomal appendicitis	-0.389	0.305	1.626	0.202	0.678 (0.373-1.232)

CI: Confidence interval.

Table 4 Acute suppurative appendicitis.

	β	SE	Wald	P value	95%CI
Schistosomal appendicitis	-0.685	0.188	13.34	< 0.001	0.504 (0.349-0.728)

CI: Confidence interval.

Table 5 Gangrenous or perforated appendicitis.

	β	SE	Wald	P value	95%CI
Schistosomal appendicitis	0.166	0.195	0.721	0.396	1.180 (0.805-1.731)

CI: Confidence interval.

Table 6 Periappendicular abscess.

	β	SE	Wald	P value	95%CI
Schistosomal appendicitis	-13.299	3446.519	0	0.977	0 (0)

CI: Confidence interval.

Table 7 Acute attack of chronic appendicitis.

	β	SE	Wald	P value	95%CI
Schistosomal appendicitis	0.961	0.186	26.684	< 0.001	2.614 (1.815-3.763)

CI: Confidence interval.

Analysis of general situation and past history of patients with SA and NSA

There were 136 cases in SA group. According to the age and gender distribution of NSA patients treated in The First Affiliated Hospital of Wannan Medical College in recent 10 years, 136 patients were stratified selected and included in the NSA group. There were 94 males and 42 females in SA group, with an average age of 61.73 ± 15.335 years. There were 71 males and 65 females in NSA group, with an average age of 33.21 ± 22.974 years. The male proportion in the two groups was more than that in the female, the male proportion in the SA group was higher than that in the NSA group, and the former was older than the latter, the differences were statistically significant (P < 0.05). In the past history of patients in the two groups, SA group had more drinkers than NSA group (P = 0.048), but there were no significant difference in smoking history, hypertension history, diabetes history and coronary heart disease history (P > 0.05) (Table 8).

Table 8 Analysis of general situation and past history of patients with schistosomal appendicitis and non schistosomal appendicitis, n (%).

Group	SA group (n = 136)	NSA group (n = 136)	χ2/Z	P value
Gender			8.15	0.004
Female	42 (30.9)	65 (47.8)
Male	94 (69.1)	71 (52.2)
Age, mean ± SD (years)	61.73 ± 15.335	33.21 ± 22.974	-9.519	< 0.001
Smoking history	9 (7.5)	6 (4.4)	1.102	0.294
Drinking history	7 (5.8)	1 (0.7)	3.919	0.048
Hypertension history	16 (13.3)	10 (7.4)	2.499	0.114
Coronary heart disease history	9 (7.5)	5 (3.7)	1.803	0.179
Diabetes history	2 (1.7)	2 (1.7)	0	1

SA: Schistosomal appendicitis; NSA: Non schistosomal appendicitis.

Clinical characteristics of SA and NSA

The clinical symptoms of the two groups were collected, such as fever, nausea and vomiting, abdominal pain, diarrhea and constipation. There were no significant difference in clinical symptoms between the two groups (P > 0.05) (Table 9). Complications, such as peritonitis and colorectal cancer. There was no significant difference in the incidence of peritonitis between the two groups, but there were 14 cases of SA group combined with colorectal cancer and 3 cases of NSA group combined with colorectal cancer. There was significant difference in the incidence of colorectal cancer between the two groups (OR = 5.087; 95%CI: 1.427-18.132; P = 0.012) (See Table 10 for details).

Table 9 Analysis of clinical symptoms and complications of schistosomal appendicitis and non schistosomal appendicitis, n (%).

Group	SA group (n = 136)	NSA group (n = 136)	χ2/Z	P value
Fever	1 (0.8)	6 (4.4)	1.871	0.171
Nausea and vomiting	30 (25)	36 (26.5)	0.072	0.788
Abdominal pain	106 (88.3)	125 (91.9)	0.926	0.336
Diarrhea	0	1 (0.7)	0	1
Constipation	2 (1.7)	1 (0.7)	0.012	0.913
Peritonitis	76 (63.3)	83 (61)	0.144	0.705
Colorectal cancer	14 (11.7)	3 (2.2)	9.204	0.002

SA: Schistosomal appendicitis; NSA: Non schistosomal appendicitis.

Table 10 Colorectal cancer.

	β	SE	Wald	P value	95%CI
Schistosomal appendicitis	1.627	0.648	6.294	0.012	5.087 (1.427-18.132)

CI: Confidence interval.

Analysis of laboratory examination of SA and NSA

The blood routine, liver function, renal function, blood lipid, C-reactive protein and procalcitonin of the two groups were collected. The differences of white blood cells, red blood cells, lymphocytes, monocytes, eosinophils and hematocrit in the two groups were statistically significant (P < 0.05). The white blood cells in SA group: 10.142 ± 3.638 × 10⁹/L exceeded the upper limit of the normal range, while the white blood cells in NSA group: 9.382 ± 3.637 × 10⁹/L were lower than those in SA group, and within the normal range. Other statistically significant indicators such as red blood cells, neutrophils, lymphocytes, monocytes, eosinophils, hemoglobin and hematocrit were within the normal range. In terms of renal function, urea in SA group: 5.316 ± 4.435 μmol/L was higher than that in NSA group: 4.807 ± 3.120 μmol/L (P = 0.028). Urea in both groups were in the normal range (Table 11).

Table 11 Analysis of laboratory examination of schistosomal appendicitis and non schistosomal appendicitis, mean ± SD.

Group	SA group (n = 136)	NSA group (n = 136)	Z/t	P value
WBC (109/L)	10.142 ± 3.638	9.382 ± 3.637	-2.033	0.042
RBC (1012/L)	3.432 ± 0.645	3.949 ± 0.587	-6.28	< 0.001
NEU (109/L)	8.691 ± 4.217	7.288 ± 3.3	-2.95	0.003
LYM (109/L)	1.185 ± 0.558	0.921 ± 0.492	-3.544	< 0.001
MO (109/L)	0.696 ± 0.366	0.571 ± 0.283	-2.68	0.007
EO (109/L)	0.115 ± 0.127	0.057 ± 0.283	-4.428	< 0.001
BA (109/L)	0.003 ± 0.018	0.01 ± 0.032	-1.83	0.067
HGB (g/L)	116.02 ± 16.829	120.81 ± 15.978	2.336	0.020
PLT (109/L)	196.40 ± 87.267	202.96 ± 67.237	-1.046	0.295
HCT	0.344 ± 0.048	0.358 ± 0.061	-2.045	0.041
TP (g/L)	61.839 ± 6.703	62.909 ± 6.57	1.154	0.250
ALB (g/L)	33.719 ± 5.279	36.515 ± 5.635	3.657	< 0.001
ALT (U/L)	19.13 ± 15.389	20.08 ± 16.346	-0.66	0.509
AST (U/L)	19.258 ± 8.855	22.184 ± 15.582	-1.789	0.074
Cr (μmol/L)	61.785 ± 16.525	56.303 ± 19.990	-0.679	0.498
Bun (μmol/L)	5.316 ± 4.435	4.807 ± 3.120	-2.204	0.028
UA (μmol/L)	274.439 ± 84.443	265.027 ± 96.503	-0.717	0.414
TC (mmol/L)	3.775 ± 0.776	21.747 ± 95.122	-1.192	0.233
TG (mmol/L)	1.164 ± 0.516	1.245 ± 0.560	-0.506	0.613
C-reactive protein (mg/L)	60.932 ± 46.672	61.546 ± 45.350	-0.443	0.658
PCT (ng/L)	1.15	0.273 ± 0.118	-1.414	0.4

WBC: White blood cells; RBC: Red blood cells; NEU: Neutrophils; LYM: Lymphocyte; MO: Monocyte; EO: Eosinophil; BA: Basophil; HGB: Haemoglobin; PLT: Platelet; HCT: Haematocrit; TP: Total proteins; ALB: Albumin; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; Cr: Creatinine; Bun: Blood urea nitrogen; UA: Uric acid; TC: Total cholesterol; TG: Triglyceride; PCT: Procalcitonin.

DISCUSSION

SA has two manifestations, one is schistosomiasis granulomatous acute appendicitis, the other is schistosomiasis obstructive acute appendicitis[7]. Weber et al[11] proposed two kinds of pathogenesis of appendiceal schistosomiasis, obstructive or granulomatous. Parasitic infection caused local tissue granuloma reaction, destroyed local tissue, and led to the occurrence of appendicitis.

SA is rare, most of the reports of SA are presented in the form of case reports. In this study, 136 cases of SA were collected and analyzed. Through a large number of samples, we found that the incidence of SA was mainly middle-aged and elderly men aged about 60 years old, which was significantly different from NSA in the distribution of the incidence population. According to the classification of appendicitis, the two groups of appendicitis patients in this study were mainly suppurative appendicitis, but the results showed that the SA group had more acute attack of chronic appendicitis than the NSA group. We speculate that the deposition of schistosome eggs in the appendix may induce acute attack of appendicitis and aggravate the condition of appendicitis. We believe that patients with SA may be in a serious condition.

Valluru et al[12] concluded that the incidence of suppurative, perforated and peripheral abscesses in SA was high, which was the same as our study. These results show that SA is more serious. At the same time, we also found that patients with SA had a higher incidence of intestinal malignant tumors, and patients with SA complicated with intestinal malignant tumors tended to have a poor prognosis. This also suggests that we should pay more attention to the diagnosis of schistosomiasis appendicitis, early detection and early treatment.

SA has the same clinical symptoms as most appendicitis[12]. In this study, there was no significant difference in clinical symptoms between the two groups, whether it was SA group or NSA group. In laboratory examination, the white blood cells in SA group were slightly higher than the upper limit of the normal range, while the other inflammatory cells and liver function and kidney function indexes were within the normal range although there were differences. Middle aged and elderly men with appendicitis need to be vigilant against SA, but SA has no specific clinical manifestations and laboratory tests, so it is difficult to distinguish from NSA only from clinical manifestations. Schistosomiasis appendicitis is misdiagnosed in clinical practice.

According to the literature in different regions of the world, the prevalence of SA is 0.2%-13.1%[6,13-22]. This study collected the histopathological data of appendicitis in recent ten years, including 136 cases of SA and 5418 cases of NSA. SA accounted for 2.45% of all patients with appendicitis, and the annual proportion of SA fluctuated between 1.6% and 3.4%. Although there are fewer and fewer patients with acute schistosomiasis, there is no trend to reduce the number of patients with SA in chronic schistosomiasis endemic areas.

Although the sample size of this study is large, there are also some limitations, that is, the lack of single center research and imaging data analysis. In future studies, we aim to expand the multi center case data and supplement the imaging data. At present, the pathogenesis of SA remains unclear, and it needs to be further explored from the perspective of pathogenesis in future research.

CONCLUSION

The classification of SA is mainly concentrated in suppurative appendicitis, and acute attack of chronic appendicitis is a common pathological type of SA. Additionally, SA is often associated with intestinal malignant tumors, contributing to its severity and poor prognosis. Due to its nonspecific clinical manifestations and laboratory findings, SA is more likely to be misdiagnosed or overlooked in clinical practice. It is crucial to differentiate SA in middle-aged and elderly males with appendicitis and ensure early detection and treatment.

ACKNOWLEDGEMENTS

Thank you for your efforts on this manuscript and the help provided by pathology experts. Thank you for the data support provided by the First Affiliated Hospital of Wannan Medical College.