Background

The mesentery is now recognized as a distinct organ. It is mostly made of adipose tissue but has other kinds of connective tissue.[1] Mesenteric panniculitis (MP) is a rare condition characterized by mesenteric fat inflammation. Its prevalence is less than 1% according to most studies. Its prevalence is much higher than before, likely due to the higher rate of CT scans performed and improvements in the technology. It is more common in men and in the 5th to 7th decades of life. [2,3,4,5].

There is a spectrum of mesenteric inflammation, and other terms are sclerosing mesenteritis, retractile mesenteritis, and mesenteric lipodystrophy. Authors have defined the terms as MP and mesenteric lipodystrophy for predominance of fatty inflammation (acute or chronic) and retractile or sclerosing mesenteritis for dominance of fibrosis (mostly chronic). MP mostly arises from the base of the small intestine mesentery (especially left-sided loops), but it can also involve the mesocolon and, rarely, the omentum, peripancreatic area and pelvic fat. [2, 6,7,8,9,10,11,12,13,14,15,16].

The symptoms are not specific and include abdominal pain, nausea and vomiting, diarrhea, weight loss, fever of unknown origin and mass sensation, and MP may cause intestinal obstruction. The duration of symptoms is variable. Many cases of MP are incidentally diagnosed on CT scans. [6, 10, 17,18,19,20,21] The diagnosis is usually based on CT scan, but the definitive diagnosis is based on surgery and histopathological examination. Mindelzun et al. described the CT scan findings of mesenteric panniculitis for the first time.[22] The CT findings were mesenteric fat stranding, thickening, lymph node enlargement, and well-circumscribed soft tissue nodules that surround vessels without signs of invasion. These features may include the presence of one or more soft tissue masses, mimicking mesenteric tumors, both benign and malignant. Signs such as a "fatty halo", "fat ring sign" or "tumoral pseudocapsule" are used for differentiating MP from similar conditions. [3, 4, 7, 8, 10, 20, 23,24,25,26,27,28,29,30,31] Histopathologic findings can range from lipid-laden macrophages in mesenteric fat with minimal signs of acute inflammation (mesenteric lipodystrophy) to inflammatory infiltration, slight thickening of bowel segments and lymphatic distention (panniculitis); the final stage is fibrosis (retractile/sclerosing).[32,33,34,35].

Its pathogenesis is unclear, but various factors, such as obesity, trauma, ischemia, previous surgery, infection, and autoimmune or collagen vascular disease, have been suggested. MP is associated with other idiopathic inflammatory conditions, such as carcinomatosis, sclerosing cholangitis, Riedel thyroiditis and orbital pseudotumors. Studies have investigated the relationship between MP and malignancies and have shown that the prevalence of MP is greater among cancer patients. The associated malignancies were lymphoma (mostly non-Hodgkin), breast cancer, melanoma, lung and colon cancers.[3, 7, 19, 24,25,26, 28, 36,37,38,39] Other Studies have shown that MP is neither paraneoplastic nor associated with cancer.[40, 41].

In our daily practice, we noticed a relatively high prevalence of MP among patients with urinary stones who did not have a history of malignancy, surgery or other predisposing factors.

Objectives

Most of the previous studies have investigated the association between MP and malignancies, and few studies have evaluated the association between MP and nonneoplastic diseases.[3, 25] In this study, according to our own daily experience, we examined the possibility of a relationship between MP and urolithiasis. We also investigated the potential increase in pain intensity in patients diagnosed with mesenteric panniculitis.

Patients and methods

This cross-sectional study was approved by the Research Ethics Committees of the School of Medicine, Iran University of Medical Sciences (IR.IUMS.FMD.REC.1401.185). The requirement for patient consent was waived due to the study design.

Patients and settings

Patients who were admitted to Shahid Hasheminejad Hospital, Tehran, Iran, in 2023 were included. A total of 500 patients who had undergone noncontrast abdominopelvic CT scans for acute abdominal pain and suspected urinary stones or other urinary symptoms were included. Studies with low-quality images or significant artifacts were excluded. One patient with mesenteric panniculitis who had both urolithiasis and malignancy (renal lymphoma) was excluded from the study due to the known cause of panniculitis.

The data were blindly collected and sorted by patient hospital numbers. Patient records, including demographic data, history of known or suspicious malignancy and history of previous surgery, were reviewed. The intensity of pain experienced by the patients was obtained from records according to the VAS (visual analog scale) and ranged from 1 (no pain) to 10 (worse pain ever). The CT scans were reviewed for urinary stones (kidney, ureter and bladder stones), mesenteric panniculitis and abdominal subcutaneous fat thickness. The prevalence of urinary stones, average subcutaneous fat thickness, underlying malignancy and history of surgery in people with mesenteric panniculitis were obtained. Then, patients were divided into two groups based on the presence or absence of urinary stones, and the prevalence of mesenteric panniculitis was compared between the two groups. Additionally, the average pain intensity of patients in each group was calculated and compared. Patients with panniculitis were interviewed for more information about related conditions and factors in their past medical history.

Abdominal CT scans

All CT scans were obtained by a General Electronics 16-slice CT scanner and were reported by experienced radiologists. In the case of indeterminate findings, revision was performed by another radiologist so that the interobserver variability was negligible. CT findings for mesenteric panniculitis included fat stranding and thickening and regional well-circumscribed soft tissue nodules in the mesenteric root that wrapped but did not displace the mesenteric vessels. Figure 1 shows imaging findings in a non contrast CT scan of a patient with both panniculitis and urolithiasis. The thickness of subcutaneous fat was measured in terms of the mean thickness of subcutaneous fat in the bilateral paraumbilical regions. CT scans of patients with panniculitis were reviewed for related conditions such as retroperitoneal fibrosis, signs of (potential) malignancies and sites of inflammation.

Fig. 1
figure 1

Mesenteric panniculitis in a patient with urolithiasis. Axial nonenhanced CT scan (A) showing the soft tissue nodules (prominent mesenteric lymph nodes) associated with stranding and haziness of mesenteric fat in the root of mesentery (B) showing kidney stone in the same patient

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Statistical analysis

For descriptive results, numbers and percentages were used for qualitative variables, while means and standard deviations were used for quantitative variables. Comparisons between groups were performed by Fisher’s exact test. P values lesser than 0.05 indicated statistically significant associations. Statistical analyses were performed using IBM SPSS Statistics for Windows, version 22.0 (IBM Corp., Armonk, N.Y., USA).

Results

Descriptives:

Five hundred patients (346 men and 154 women) were included. Their ages ranged from 18 to 88 years (average age: 45.90 ± 14.33 years).

Table 1 presents the findings and their prevalence among the study patients. Five (1%) patients had a history of malignancy, and 10.2% mentioned a history of surgery (except head and neck or facial surgery). 355 people (71%) had urolithiasis, and ureteral stones were detected in 261 of them (55.2%).

Table 1 patient findings in CT scans and records
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Mesenteric panniculitis was found in CT scans of 10 patients (2% of all patients). Nine of them had concurrent urinary stones, and the other patient had a history of recent ureteral stones and extracorporeal shock wave lithotripsy (ESWL) two weeks prior according to the records. Seventy percent of patients with panniculitis were male, and their average age was 53.6 years. Ureteral stones were observed in all of the patients, and kidney stones were present in 7 patients at the same time. None of these patients had a history of surgery or malignancy (Table 2). To investigate related conditions, such as retroperitoneal fibrosis, previous surgery and proinflammatory conditions, patients with panniculitis were interviewed, and CT scans were reviewed. Except for age-related heart problems in a few patients, there was no relevant point in the patients' past medical history.

Table 2 characteristics of patients with panniculitis
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Comparison between groups:

The prevalence of panniculitis was significantly greater in the group with urolithiasis (2.8%) than in the group without urolithiasis (0%) (p = 0.035). (Table 3).

Table 3 The contingency table of the study: Comparing prevalence of mesenteric panniculitis between groups based on presence of urolithiasis
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Table 4 shows the mean intensity of pain experienced by the patients on a scale ranging from 1 (no pain) to 10 (worst pain). Patients with urolithiasis and concurrent panniculitis experienced slightly greater pain intensity than patients with urinary stones but without panniculitis; however, the difference was not significant (p = 0.929).

Table 4 Pain intensity in groups
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Patients without urolithiasis had slightly thicker subcutaneous fat, but the difference was not significant (p = 0.732). In the urolithiasis group, subcutaneous fat thickness was greater in patients with panniculitis, although the difference was not statistically significant (p = 0.275). The mean thickness of the subcutaneous fat in the different groups is shown in Table 5.

Table 5 Subcutaneous fat thickness
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Discussion

In this study, 500 patients were included. The mean age was 45.90 ± 14.33 years, and 69.2% of them were men. MP was found in 10 patients (2%) who all had urolithiasis or a recent history of urolithiasis, and MP was not found in patients without urolithiasis. In our study, MP was significantly greater among patients with urolithiasis. None of the patients with MP had a history of previous abdominal surgery, malignancy or autoimmune or autoinflammatory diseases. It should be noted that none of the patients with MP in our study mentioned the use of medicine for urolithiasis, and MP does not seem to be related to side effects of drugs. Additionally, as mentioned, only a few cases of heart disease related to age could be mentioned in their past medical histories.

In patients with urolithiasis, we found a greater mean subcutaneous fat thickness (29 ± 6.93 mm) in patients with panniculitis than in those without MP (26.37 ± 9.8 mm). This trend could be due to the possible association of panniculitis with obesity. The difference was not statistically significant. In the comparison between the two groups based on the presence of urinary stones, the mean fat thickness was similar (26.32 ± 9.04 mm in the urolithiasis group versus 26.85 ± 11.25 mm in the group without urolithiasis), and we do not believe that obesity can account for the high association of panniculitis with urinary stones in our study. Studies on similar patients have shown similar mean fat thicknesses.[42] In a study by Unlu et al., findings of MP were incidentally identified in 80 patients. Their body mass indices were relatively high, and most of them were considered obese.[26].

In a study by Gunes et al., which aimed to investigate the relationship between MP and nonneoplastic conditions, metabolic syndrome and urolithiasis were significantly more common in patients with MP, similar to our study.[3] Tekin et al. reported mesenteric inflammation in 62 out of 434 patients (14.2%) with ureteral stones, which was related to thickening of the perirenal fasciae and periureteral fat stranding.[43] In a study by Conyigit et al. investigating the prevalence of MP, urolithiasis was found in 10 out of 51 patients, with MP as an associated factor.[30].

As mentioned, the mesentery is an organ mostly made of adipose tissue. Studies have investigated the similarities between adipocytes and macrophages and the ability of adipocyte progenitors to convert to macrophages. Adipose tissue can be considered a part of the innate immune system and can cause the costimulation of immune cells. Studies have also suggested that an imbalance between proinflammatory and anti-inflammatory cytokines released by macrophages can result in low-grade chronic inflammation, leading to mesenteric panniculitis as a component of Crohn’s disease. However, the exact etiology of MP is still unknown. MP histologic findings are nonspecific and include a range of chronic inflammatory changes, fat necrosis and fibrosis of adipose tissue.[1, 33, 44,45,46,47,48,49] Since the proposed pathologic mechanisms can lead to other inflammatory diseases involving the mesentery, the imaging findings of mesenteric panniculitis has also been observed in patients with diseases such as crohn's disease.[50] The exact pathogenesis of MP in patients with urolithiasis has not been investigated, but it may be related to inflammatory factors and cytokines released related to urolithiasis. The right ureter is behind the third part of the duodenum in its proximal part and crosses the ileocolic vessels and the root of the mesentery in its course. The left ureter is also crossed by the left colic vessels, and at the pelvic brim, it is close to the sigmoid mesocolon. Studies have suggested that urinary obstruction and potential urine leakage may be linked to the presence of MP. Despite these anatomical relations, the ureter is located in the retroperitoneum, and the leaked urine(urinoma) is not in direct contact with the peritoneal structures. As mentioned, it is likely that the inflammation caused by stone passage is related to mesenteric inflammation, not direct contact with urine. [32, 43].

Among the patients in our study, seven were men (70%), and the mean age was 53.6 years. Five out of the 10 patients were older than 50 years. The observed trend is in agreement with previous studies.

In our study, 71% of patients had urolithiasis, and the most common site was the ureter (55.2%). According to previous reports, the most common symptom among MP patients was abdominal pain. We also investigated pain intensity and found no significant differences between the different groups. Mesenteric panniculitis does not seem to change the pain intensity experienced by the patient. Like in most previous reports, MP was coincidentally found on CT scans aimed at other conditions, such as urinary conditions and trauma.

Five patients had a history of malignancy, but none of them had features of MP in their CT scans. Authors have investigated MP as a paraneoplastic syndrome, a precursor of malignancy, a mimicker of malignancy or a common associated finding in imaging. Studies have shown that MP is a coincidental finding in the imaging of patients diagnosed with cancer. [51, 52] Scheer et al. retrospectively studied CT scans of MP patients, and oncologic disease was confirmed in 74.8% of them. The most common tumor was non-Hodgkin lymphoma.[36].

In the study by Gunes et al., unlike others, no significant relationship was detected between MP and malignancy.[3] Gultekin also reported a greater rate of malignancy in MP patients, but the difference was not significant.[41] In a case control study by Gogebakan et al., which aimed to investigate MP as a paraneoplastic phenomenon, there was no association between MP degree and malignancy development or stage.[40]Mesenteric panniculitis may mimic mesenteric neoplasm, and it is related to malignancies as well. Therefore, many studies have recommended routine follow-up CT scans for possible malignancies in MP patients.[53, 54].

This study also had a number of limitations. For example, our sample included 500 patients; 10 patients were identified to have MP, and all of them also had urolithiasis. The difference in the prevalence of MP among the groups based on the presence of urinary stones was significant, but the number of subjects studied did not allow us to investigate other possible cases of MP without urinary stones. This could be caused by the low prevalence of mesenteric panniculitis. The authors hypothesize that there may be a relationship between the type of stone (its content) and panniculitis. Since urinary stones are treated regardless of the type of stone, information on the type of urinary stone was not available. The authors suggest that studies should be conducted to investigate the relationship between the occurrence of panniculitis and the type of stone.

Conclusion

Our study revealed a correlation between mesenteric panniculitis and urolithiasis. We detected MP in 2% of patients who had a history of urolithiasis, and no MP was detected in patients without urolithiasis. The average thickness of subcutaneous fat was greater in the group with panniculitis, although the observed trend was not statistically significant. Pain intensity was not significantly different among patients with MP, which implies that MP alone does not change pain intensity.

Conflict of interest:

The authors declare that they have no conflict of interest.