Clues to early diagnosis from clinical data- A clinicopathological analysis of primary malignant tumors of the small bowel

doi:10.21203/rs.3.rs-2202533/v1

Background

Primary malignant tumors of the small bowel (PMTSB) are relatively uncommon in gastrointestinal tumors. It is difficult to make an early diagnosis due to the atypical primary symptoms, special anatomical position and lack of effective diagnostic methods.

Objective

To improve the level of early diagnosis of PMTSB so as to speculate the pathological types and get better prognoses for patients.

Method

Clinicopathologic and follow-up data about 104 surgically treated patients with PMTSB (65 males and 39 females) at the median age of 58.1 years (range 23–85 years) were analyzed.

Result

The most common clinical features of the patients were anemia (73.1%), abdominal pain (62.5%), and weight loss (51.9%). Abdominal enhanced Computed Tomography (CT) had the highest detection rate (95.4%) and diagnosis rate (80%). Gastrointestinal hemorrhage, soft tissue mass on CT, no regional lymph nodes enlargement, and no intestinal obstruction were the independent predictors of diagnosis in GIST. Anemia, intestinal obstruction, without soft tissue mass on CT were the independent predictors of diagnosis in adenocarcinoma. Independent predictors of diagnosis of lymphoma included fever, and regional lymph nodes enlargement on CT.

Conclusion

Anemia, abdominal pain and weight loss were the main clinical manifestations for PMTSB, as CT was the most effective imaging examination. Based on clinical and imaging features, we analyzed several factors which related to diagnose the pathological classification, and expected to give patients the earlier diagnosis and better prognoses.

PMTSB

Small intestine

early diagnosis

Pathological classification

Clinical features

Imaging features

The small intestine represents 75% of the length and 90% of the absorptive surface area of the gastrointestinal tract, yet only approximately 5% of all gastrointestinal tumors occur at this site ¹. The primary malignant tumors of the small bowel (PMTSB) meanwhile account for 0.2–0.3% of all malignant tumors ^{2, 3}. However, the diagnosis of PMTSB is difficult while the symptoms and signs are nonspecific at presentation. At the same time because of the lack of accurate and reliable inspection methods, they are usually discovered at advanced stage. It was reported in the literature that the period from symptom onset to final diagnosis was about 7 months ⁴. Approximately 6–12% of patients with PMTSB were diagnosed as stage I, besides 27 ~ 37% were stage II, 21 ~ 27% were stage III, and 32 ~ 37% were stage IV based on AJCC staging criteria ^5–8. According to SEER data, the 5-year survival rate of the patients with PMTSB in early stage was 84.2%, and it went down to about 40% with metastases of regional lymph nodes and distant organs ^9–11. Thus, through analyzing clinical data of 104 patients with PMTSB, we aimed to investigate clinical symptoms, improve the level of early diagnosis, determine the pathological types of diseases, and further carry out effective clinical treatment.

Patients

Medical records of patients with pathologically proven as PMTSB treated by operation in our institution, Tianjin Medical University General Hospital, were analyzed between January 2005 to December 2020. Patients with tumor at the duodenum, and ileocecal valve and metastatic cancer were excluded from the study. Only those with primary tumor arising from the jejunum or ileum were included.

Methods

A complete medical record review was conducted to collect age, sex, clinical manifestations, initial diagnosis, imaging examination, pathological data, and prognosis of every enrolled patient. According to histological type, it was divided into the gastrointestinal stromal tumor (GIST), adenocarcinoma, and primary malignant lymphoma. By comparing the clinical characteristics and imaging data among the three types of patients with PMTSB, and analyzing their survival data, significant predictive factors for early diagnosis can be obtained.

Statistical analysis

All the calculations were performed using the SPSS 26.0 statistical software package. Kaplan-Meier method was used to calculate cumulative survival rate, and log-rank test was used to compare the difference of survival rate. Factors with P < 0.1 were incorporated into COX risk regression model to obtain independent prognostic risk factors. P < 0.05 was considered statistically significant.

Patient characteristics:

From January 2005 to December 2020, 104 cases with PMTSB were collected. Among them, there were 65 males, 39 females, with median age was 58.1 years (range 23 to 85 years). The most common pathological type was GIST (57.7%), followed by adenocarcinoma (26.9%), and lymphoma (11.5%). Besides, neuroendocrine tumor (1.9%), inflammatory myofibroblastic tumor (1.0%) and anaplastic carcinoma (1.0%) were also included. (Supplementary Table. 1)

Clinical Features And Initial Diagnoses:

Clinical features of these 104 patients included anemia in 76 patients (73.1%), abdominal pain in 65 patients (62.5%), and weight loss in 54 patients (51.9%). Other clinical features included nausea and vomiting, abdominal mass, and fever but were relatively rare. Abdominal neoplasm (35.6%) was the most common initial diagnosis, followed by gastrointestinal hemorrhage (34.6%), intestinal obstruction (11.5%), and diffuse peritonitis (4.8%). (Table. 1)

Excluding the small number of cases contained neuroendocrine tumor, inflammatory myofibroblastic tumor, and anaplastic carcinoma, a total of 100 cases were included in the study and were divided into 3 groups according to histopathology, which were GIST (n = 60), adenocarcinoma (n = 28), and lymphoma (n = 12). The GIST had the lowest proportion of abdominal pain (P = 0.002) and the highest proportion of gastrointestinal hemorrhage (P = 0.002). The adenocarcinoma had the highest proportion of nausea and vomiting (P < 0.001), the same as intestinal obstruction (P < 0.001), but the lowest proportion of abdominal neoplasm (P = 0.001). The proportion of weight loss in the adenocarcinoma was significantly higher than that in the GIST (P = 0.001). (Supplementary Table. 2) The lymphoma had the highest proportion of fever (P = 0.001) and the lowest proportion of anemia (P = 0.001). (Table. 2)

Imaging Examination:

Abdominal CT scan was the most widely used imaging examination, among which enhanced CT had the relatively high detection rate (95.4%) and diagnosis rate (80.0%). Other examinations also included ultrasound, magnetic resonance imaging (MRI), enteroscopy and biopsy, and capsule endoscopy. (Table. 3)

A total of 91 patients who received CT routine scan and enhanced scan were divided into 3 groups by histological types, which were GIST (n = 55), adenocarcinoma (n = 25), and lymphoma (n = 11) respectively. In the GIST, the proportion of the intestinal lesions signs by CT was the lowest among the three groups (P < 0.001), while the proportion of soft tissue tumor signs was the highest (P < 0.001). Signs of regional lymph nodes enlargement were the highest in the lymphoma (P < 0.001). Adenocarcinoma had the highest incidence of signs of intestinal stenosis (P < 0.001). (Table. 4) Adenocarcinoma had the significantly higher proportion of intestinal obstruction than the GIST group (P < 0.001). (Supplementary Table. 3)

Analysis Of Clinicopathological Features Of Different Histological Types:

Logistic regression analysis showed that soft tissue mass on CT, gastrointestinal hemorrhage, no intestinal obstruction and no regional lymphadenopathy on CT were independent predictors for the diagnosis of GIST (P < 0.05). In adenocarcinoma group, anemia, intestinal obstruction, and absence of soft tissue mass on CT were independent predictors (P < 0.05). Fever and regional lymph nodes enlargement on CT were independent predictors for the diagnosis of lymphoma (P < 0.05). (Table. 5) (Supplementary Table. 4–9)

Survival Analysis:

A total of 60 patients with GIST were included in this study and 9 were lost to follow-up. The median follow-up time was 57 months. Of the 28 adenocarcinoma patients, we obtained follow-up data for 24 patients. 13 patients were died among these. The median follow-up time was 23 months. Of the 12 patients with lymphoma, 2 patients were lost to follow-up and 6 were died. The median follow-up time was 10 months. The 5-year cumulative survival rates of GIST and adenocarcinoma patients were 76.1% and 33.8%, respectively. And the 2-year cumulative survival rate of lymphoma patients was 40.0%. (Figure. 1)

There have been few studies performed on PMTSB so far in the world because it was a relatively rare disease compared to those occurring in the stomach and the colon. Tumors of the duodenal papilla belonged to peripancreatic tumors and were classified in the upper gastrointestinal tract, thus were excluded from our study. Perhaps due to the increased incidence of the tumor itself and the increasing diagnostic rate of evolving imaging techniques, the incidence of PMTSB was on rise. A large number of epidemiological investigations and studies had shown that, with an average annual increase of 1.9–2.4% in the past 10 years ^{10, 12, 13}. Therefore, a retrospective analysis of patients with PMTSB treated in our hospital during the past 15 years was conducted.

Patients with PMTSB were mainly elderly male, and nearly half of them had the disease course for more than half a year. They had nonspecific clinical symptoms and signs, which brought difficulties to clinical diagnosis ^14–18.The most frequent symptoms were abdominal pain, abdominal mass, gastrointestinal hemorrhage and intestinal obstruction, which were similar to our findings ¹⁹. We also found that anemia, weight loss, nausea and vomiting, and fever were common clinical features of patients with PMTSB. Preoperative diagnosis of PMTSB was often difficult. It has previously been reported that the preoperative diagnosis rate was only 38% ²⁰. The initial diagnosis of patients was mainly abdominal neoplasm and gastrointestinal hemorrhage. Therefore, an early and accurate diagnosis is crucial to allow the surgeon to perform a curative radical surgery thereby achieving a better outcome for patients with PMTSB.

The most commonly used diagnostic technique was CT scan in our study. Among them, enhanced CT had the higher detection rate and diagnosis rate, and was also the most widely used. By contrast, ultrasound was easily hampered by luminal gas, which was prone to missed diagnosis and misdiagnosis. It has been reported to have a low sensitivity of no more than 26% ²¹. Enteroscopy was not widely accepted due to its high complications. Studies have shown that the retention rate of capsule endoscopy was high, and once retention occurred, it will increase the risk of missed diagnosis. In a large retrospective study, the missed diagnosis rate of capsule endoscopy in the diagnosis of PMTSB was approximately 20% ²². Although its detection rate was 100%, the diagnostic rate was not high due to the inability to take pathological biopsy or the small number of cases.

The malignant tumor was the most common disease in primary small intestinal disease, with a ratio of approximately 4:1 to benign diseases ^{3, 19}. Although carconoid tumor was one of the most commonly diagnosed in western countries, it was rarely diagnosed in eastern countries, and accounts for less than 2% of all primary small intestine tumors ^{16, 23, 24}. The 3 most commonly diagnosed PMTSB in China were adenocarcinoma, lymphoma, and GIST, and our study gave the similar results ³.

GIST is the most common primary mesenchymal tumor of the digestive tract. Although it may arise at any site, about 30–40% of cases occur in the small bowel ^{25, 26}. GIST of the small bowel showed a slight male predominance in our study, which was same as previously published studies ^27–29. Because most GISTs were exophytic, they rarely caused symptoms of intestinal obstruction such as nausea and vomiting et al. Generally, gastrointestinal hemorrhage associated with GIST of the small bowel usually arises from the ulcerated or necrotic component of the tumor ³⁰. Thus, it had a significantly higher incidence of gastrointestinal hemorrhage compared with other types. Zang et al ³¹ retrospectively analyzed 77 patients with intestinal hemorrhage and found that GIST was the most common cause of intestinal hemorrhage (about 62.3%). On CT, GIST tended to appear as the markedly enhancing soft tissue mass which could protrude into the cavity or grow outside the cavity. Joseph J et al ³² proposed that the appearance of regional lymph nodes enlargement was less common on CT in GIST because it rarely involved lymph nodes, which was consistent with our results. Because intestinal obstruction occurs less frequently in GIST, intestinal lesions such as intestinal stenosis and intestinal wall thickening were not easily seen on CT. The 5-year survival rate of GIST in this study was about 76.1%, which was similar to previously reported cases ³³.

Small bowel adenocarcinoma occurs most often in the duodenum, and its incidence decreases with distance from Treitz ligament ³⁴. Adenocarcinoma patients in this study accounted for 26.9% of the total. They had no significant gender difference, and the average age at diagnosis was 60 years old. Patients often present with local complications of the tumor, such as abdominal discomfort, abdominal pain, and hidden gastrointestinal hemorrhage. At the same time, due to chronic consumption, patients will be accompanied by significant anemia and weight loss ^{35, 36}. Adenocarcinoma was dominated by intestinal lesions, mainly manifested as intestinal wall thickening and lumen stenosis, which could lead to partial or complete intestinal obstruction. Therefore, the incidence of intestinal obstruction of adenocarcinoma was higher than other types, and also the same as nausea and vomiting caused by intestinal obstruction. On CT, it was more likely to manifest as a segmental bowel disease, including circumferential or eccentric thickening of the bowel wall, irregular lumen narrowing, or bowel lumen dilatation. If the tumor progressed locally, CT could show tumor infiltration into adjacent adipose tissue and local mesentery, and signs of regional lymph nodes enlargement may be present ³⁷. In our study, 92.0% of adenocarcinoma patients had signs of intestinal lesions, which were mainly characterized by intestinal stenosis, and 28.0% had signs of increased fat density and regional lymph nodes enlargement. Michael J et al ³⁸ reported that the survival rate of adenocarcinoma patients was low, and the 5-year survival rate was about 14%-33%, which was 33.8% in our series.

Primary gastrointestinal non-Hodgkin’s lymphoma is the most common extranodal lymphoma, occurring in about 75% of cases in the stomach and only about 15% in the small intestine. The cell type was dominated by diffuse large B-cell lymphoma ^{39, 40}. Abdominal pain was the most common symptom of lymphoma. It was reported to be the first symptom in about 45–65% of patients, compared to 75% in our study ^{41, 42}. Patients often had fever, which was one of the characteristics different from other tumors ⁴¹. Normal mucosal folds were disrupted when lymphomas involved the intestine and often result in full-thickness intestinal infiltration. Therefore, signs of bowel disease were often seen on CT, manifested as infiltrative masses or diffuse thickening of the bowel wall. At the same time, tumors were more likely to involve lymph nodes while they originated in lymph nodes or lymphoid tissue, and regional lymph nodes enlargement was more likely to appear on CT. The prognosis of lymphoma patients was related to histological type, postoperative chemotherapy, etc. It was reported that the 5-year survival rate was about 50%-70% ³⁹. In our series, probably due to the small sample size, the 2-year survival rate was 40%.

Our observations suggest that malignant tumors should be considered if small intestinal disease is under consideration, and further examinations should be taken as soon as possible to assure or exclude small intestinal malignant tumor. Therefore, it is necessary to confirm the diagnosis in different clinical data so as to speculate the pathological types. Among them, preoperative classification is the difficulty of clinical diagnosis and treatment which has been focused on by few studies in the past. The histological type confirmed in clinical work is mainly through pathological biopsy, but there are situations that biopsy cannot be taken or too late. We hope to conduct relatively accurate classification of patients with PMTSB by studying clinical manifestations and examination results. In this way, patients would receive optimum management through the early diagnosis and early treatment strategy, and thus prognosis would be significantly improved. And this study also had some limitations, including the relatively small sample size and the fact that the study was undertaken at a single center, which may have introduced some study bias. We expect to obtain multicenter clinical data for validation and analysis.

Through the above analysis, we get the following conclusions. If the patients have gastrointestinal hemorrhage with soft tissue mass signs on CT, but no intestinal obstruction and signs of regional lymph nodes enlargement, it is more likely to suggest small bowel GIST. The presence of anemia with intestinal obstruction but the absence of CT signs of soft tissue mass is often suggestive of small bowel adenocarcinoma. Fever with CT showing regional lymph nodes enlargement are evidences of small bowel lymphoma.

Availability of data and materials

Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.

Acknowledgements

None

Consent for publication

Written informed consent for publication of their clinical data was obtained from the patients.

Conflict of Interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Author Contributions

Xinyang Nie and Dongjie Liu performed the manuscript writing and the literature collecting, and these authors contributed equally to this article. Tong Liu and Weidong Li conceived, designed, and supervised all studies and the drafting and editing of the manuscript, they are co-corresponding authors. Yuxin Teng, Zhufeng Li and Li Lu helped the collection of clinical data of patients. All the authors have read and approved the final manuscript.

Funding

This study is supported by grant from the Fundamental Scientific Research Project of Tianjin Universities of China (No. 2017KJ191).

Ethics approval and consent to participate

We have passed the ethics approval by Tianjin Medical University General Hospital and been agreed to participate.

Siegel RL, Miller KD, Fuchs HE and Jemal A. Cancer Statistics, 2021. CA Cancer J Clin. 2021;71:7–33.
Chen CC, Neugut AI and Rotterdam H. Risk factors for adenocarcinomas and malignant carcinoids of the small intestine: preliminary findings. Cancer Epidemiol Biomarkers Prev. 1994;3:205–7.
Cao J, Zuo Y, Lv F, Chen Z and Li J. Primary small intestinal malignant tumors: survival analysis of 48 postoperative patients. J Clin Gastroenterol. 2008;42:167–73.
Nutu OA, Marcacuzco Quinto AA and Jimenez Romero LC. Primary malignant tumors of the small intestine: A retrospective analysis of 15 years experience. Med Clin (Barc). 2017;149:129–130.
Bilimoria KY, Bentrem DJ, Wayne JD, et al. Small bowel cancer in the United States: changes in epidemiology, treatment, and survival over the last 20 years. Ann Surg. 2009;249:63–71.
Duerr D, Ellard S, Zhai Y, Taylor M and Rao S. A Retrospective Review of Chemotherapy for Patients with Small Bowel Adenocarcinoma in British Columbia. J Cancer. 2016;7:2290–2295.
Nicholl MB, Ahuja V, Conway WC, et al. Small bowel adenocarcinoma: understaged and undertreated? Ann Surg Oncol. 2010;17:2728–32.
Overman MJ, Hu CY, Kopetz S, et al. A population-based comparison of adenocarcinoma of the large and small intestine: insights into a rare disease. Ann Surg Oncol. 2012;19:1439–45.
Aparicio T, Zaanan A, Svrcek M, et al. Small bowel adenocarcinoma: epidemiology, risk factors, diagnosis and treatment. Dig Liver Dis. 2014;46:97–104.
Bojesen RD, Andersson M, Riis LB, Nielsen OH and Jess T. Incidence of, phenotypes of and survival from small bowel cancer in Denmark, 1994–2010: a population-based study. J Gastroenterol. 2016;51:891–9.
Lu Y, Frobom R and Lagergren J. Incidence patterns of small bowel cancer in a population-based study in Sweden: increase in duodenal adenocarcinoma. Cancer Epidemiol. 2012;36:e158-63.
Small Intestine Cancer — Cancer Stat Facts[EB/OL]. [2021/8/13]. https://seer.cancer.gov/statfacts/html/smint.html.
Small intestine cancer statistics | Cancer Research UK[EB/OL].. [2021/8/13]. .https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/small-intestine-cancer.
Alvarado-Cabrero I, Vázquez G, Sierra Santiesteban FI, Hernández-Hernández DM and Pompa AZ. Clinicopathologic study of 275 cases of gastrointestinal stromal tumors: the experience at 3 large medical centers in Mexico. Ann Diagn Pathol. 2007;11:39–45.
Egberts JH, Scharrer ML, Hinz S, et al. Small bowel cancer: single-centre results over a period of 12 years. Hepatogastroenterology. 2007;54:129–34.
Hatzaras I, Palesty JA, Abir F, et al. Small-bowel tumors: epidemiologic and clinical characteristics of 1260 cases from the connecticut tumor registry. Arch Surg. 2007;142:229–35.
Martin RG. Malignant tumors of the small intestine. Surg Clin North Am. 1986;66:779–85.
Pătraşcu T, Doran H, Strâmbu V and Vîlcu M. [Small bowel tumors. Clinical course and therapeutic aspects]. Chirurgia (Bucur). 2006;101:477–81.
Zhan J, Xia ZS, Zhong YQ, et al. Clinical analysis of primary small intestinal disease: A report of 309 cases. World J Gastroenterol. 2004;10:2585–7.
Mussi C, Caprotti R, Scaini A, et al. Management of small bowel tumors: personal experience and new diagnostic tools. Int Surg. 2005;90:209–14.
Masselli G, Casciani E, Polettini E, Laghi F and Gualdi G. Magnetic resonance imaging of small bowel neoplasms. Cancer Imaging. 2013;13:92–9.
Lewis BS, Eisen GM and Friedman S. A pooled analysis to evaluate results of capsule endoscopy trials. Endoscopy. 2005;37:960–5.
Yang YS, Huang QY, Wang WF, Sun G and Peng LH. Primary jejunoileal neoplasmas: a review of 60 cases. World J Gastroenterol. 2003;9:862–4.
Kusumoto H, Takahashi I, Yoshida M, et al. Primary malignant tumors of the small intestine: analysis of 40 Japanese patients. J Surg Oncol. 1992;50:139–43.
Joensuu H. Gastrointestinal stromal tumor (GIST). Ann Oncol. 2006;17 Suppl 10:x280-6.
Zhou L, Liao Y, Wu J, et al. Small bowel gastrointestinal stromal tumor: a retrospective study of 32 cases at a single center and review of the literature. Ther Clin Risk Manag. 2018;14:1467–1481.
Baheti AD, Shinagare AB, O'neill AC, et al. MDCT and clinicopathological features of small bowel gastrointestinal stromal tumours in 102 patients: a single institute experience. Br J Radiol. 2015;88:20150085.
Wu TJ, Lee LY, Yeh CN, et al. Surgical treatment and prognostic analysis for gastrointestinal stromal tumors (GISTs) of the small intestine: before the era of imatinib mesylate. BMC Gastroenterol. 2006;6:29.
Xing GS, Wang S, Sun YM, et al. Small Bowel Stromal Tumors: Different Clinicopathologic and Computed Tomography Features in Various Anatomic Sites. PLoS ONE. 2015;10:e0144277.
Fletcher CD, Berman JJ, Corless C, et al. Diagnosis of gastrointestinal stromal tumors: A consensus approach. Hum Pathol. 2002;33:459–65.
Zang L, Hu WG, Yan XW, et al. Laparoscopic treatment for small intestinal bleeding: a report of 77 cases. J Laparoendosc Adv Surg Tech A. 2010;20:521–5.
Kim JJ, Lim JY and Nguyen SQ. Laparoscopic resection of gastrointestinal stromal tumors: Does laparoscopic surgery provide an adequate oncologic resection? World J Gastrointest Endosc. 2017;9:448–455.
Giuliano K, Nagarajan N, Canner J, et al. Gastric and small intestine gastrointestinal stromal tumors: Do outcomes differ? J Surg Oncol. 2017;115:351–357.
Halfdanarson TR, Mcwilliams RR, Donohue JH and Quevedo JF. A single-institution experience with 491 cases of small bowel adenocarcinoma. Am J Surg. 2010;199:797–803.
Negoi I, Paun S, Hostiuc S, et al. Most small bowel cancers are revealed by a complication. Einstein (Sao Paulo). 2015;13:500–5.
Zhang S, Zheng C, Chen Y, et al. Clinicopathologic features, surgical treatments, and outcomes of small bowel tumors: A retrospective study in China. Int J Surg. 2017;43:145–154.
Jasti R and Carucci LR. Small Bowel Neoplasms: A Pictorial Review. Radiographics. 2020;40:1020–1038.
Overman MJ. Rare but real: management of small bowel adenocarcinoma. Am Soc Clin Oncol Educ Book. 2013:189–93.
Lu PW, Fields AC, Yoo J, et al. Surgical Management of Small Bowel Lymphoma. J Gastrointest Surg. 2021;25:757–765.
Olszewska-Szopa M and Wrobel T. Gastrointestinal non-Hodgkin lymphomas. Adv Clin Exp Med. 2019;28:1119–1124.
Lightner AL, Shannon E, Gibbons MM and Russell MM. Primary Gastrointestinal Non-Hodgkin's Lymphoma of the Small and Large Intestines: a Systematic Review. J Gastrointest Surg. 2016;20:827–39.
Shirwaikar Thomas A, Schwartz M and Quigley E. Gastrointestinal lymphoma: the new mimic. BMJ Open Gastroenterol. 2019;6:e000320.

Table. 1 Clinical characteristics of patients with PMTSB

	Number	Proportion (%)
Clinical features
Anemia	76	73.1
Abdominal pain	65	62.5
Weight loss	54	51.9
Nausea and vomiting	30	28.8
Abdominal mass	15	14.4
Fever	12	11.5
Initial diagnosis
Abdominal neoplasm	37	35.6
Gastrointestinal hemorrhage	15	14.4
Intestinal obstruction	12	11.5
Diffuse peritonitis	5	4.8

Table. 2 General condition and clinical characteristics of three histological types

	Major histological types of PMTSB			P value
	GIST (n=60)	Adenocarcinoma (n=28)	Lymphoma (n=12)	P value
Gender				0.553
male	39（65.0%）	15（53.6%）	8（66.7%）
female	21（35.0%）	13（46.4%）	4（33.3%）
Age	56.4 ± 13.7	60.2 ± 12.3	61.6 ± 11.1	0.281
Clinical features
anemia	44（73.3%）	25（89.3%）	4（33.3%）	0.001
abdominal pain	29（48.3%）	22（78.6%）	11 (91.7%）	0.002
weight loss	24（40.0%）	22（78.6%）	6（50.0%）	0.003
nausea and vomiting	6（10.0%）	20（71.4%）	3（25.0%）	<0.001
abdominal mass	9（15.0%）	2（7.1%）	4（33.3%）	0.114
fever	6（10.0%）	0（0.0%）	5（41.7%）	0.001
Initial diagnosis
abdominal neoplasm	26（43.3%）	2（7.1%）	7（58.3%）	0.001
gastrointestinal hemorrhage	29（48.3%）	7（25.0%）	0（0.0%）	0.002
intestinal obstruction	4（6.7%）	17（57.1%）	3（25.0%）	<0.001
diffuse peritonitis	1（1.7%）	2（7.1%）	2（16.7%）	0.055

Table. 3 Types of imaging examination

	Detection rate (%)	Diagnosis rate (%)
Abdominal ultrasound	79.2（19/24）	8.3（2/24）
Abdominal CT routine scan	65.5（36/55）	21.8（12/55）
Abdominal CT enhanced scan	95.4（62/65）	80.0（52/65）
Abdominal MRI	81.8（9/11）	81.8（9/11）
Enteroscopy and biopsy	81.8（9/11）	72.7（8/11）
Capsule endoscopy	100.0（5/5）	40.0（2/5）

Detection rate: The ratio of the number of positive cases to the total number of cases examined.

Diagnosis rate: The ratio of the number of positive results and the final pathological diagnosis of the cases to the total number of cases examined.

Table. 4 CT appearances of three major histological types of PMTSB

	Major histological types of PMTSB			P value
	GIST (n=55)	Adenocarcinoma (n=25)	Lymphoma (n=11)	P value
Intestinal lesion signs	12（21.8%）	23（92.0%）	7（63.6%）	<0.001
extra-intestinal mass	7（12.7%）	0（0.0%）	0（0.0%）	0.128
intestinal stenosis	0（0.0%）	16（64.0%）	2（18.2%）	<0.001
thickening of bowel wall	3（5.5%）	10（40.0%）	7（63.6%）	<0.001
Soft tissue mass	49（89.1%）	4（16.0%）	6（54.5%）	<0.001
Increased fat density	9（16.4%）	7（28.0%）	5（45.5%）	0.089
Regional lymph nodes enlargement	4（7.3%）	7（28.0%）	8（72.7%）	<0.001
Intestinal obstruction	3（5.5%）	13（52.0%）	2（18.2%）	<0.001

Table. 5 Multivariate logistic regression analysis of three major histological types

Clinical information	OR	95%CI	P value
GIST
gastrointestinal hemorrhage	6.978	1.213-40.134	0.030
intestinal obstruction	0.156	0.034-0.709	0.016
soft tissue mass on CT	10.168	2.501-41.338	0.001
regional lymph nodes enlargement on CT	0.098	0.021-0.446	0.003
Adenocarcinoma
anemia	22.131	2.726-179.676	0.004
intestinal obstruction	17.662	3.332-93.630	0.001
soft tissue mass on CT	0.063	0.014-0.278	<0.001
Lymphoma
fever	10.428	1.551-70.094	0.016
regional lymph nodes enlargement	19.524	3.653-104.341	0.001

No competing interests reported.

Supplementarymaterial.docx

Clues to early diagnosis from clinical data- A clinicopathological analysis of primary malignant tumors of the small bowel

Status:

Version 1

Abstract

Background

Objective

Method

Result

Conclusion

Figures

Introduction

Methods

Results

Patient characteristics:

Clinical Features And Initial Diagnoses:

Imaging Examination:

Analysis Of Clinicopathological Features Of Different Histological Types:

Survival Analysis:

Discussion

Conclusion

Declarations

References

Tables

Additional Declarations

Supplementary Files

Status:

Version 1