Prevalence and risk factors of phlebosclerosis in the great saphenous vein.

OBJECTIVES: Phlebosclerosis is a fibrous degeneration of the vein wall, predominantly the intima, with or without calcification. The prevalence and etiology of phlebosclerosis of the great saphenous vein are not well documented. This study aimed to estimate the prevalence and define the risk factors of phlebosclerosis of the great saphenous vein. METHODS: The study was conducted on 300 volunteers who underwent duplex ultrasound. Volunteers with symptoms and signs of acute or chronic venous disease or known varicose veins, thrombosis, chronic vein insufficiency, and any operation in the lower extremities were excluded. The imaging hallmarks of phlebosclerosis include wall brightness, calcification, and increased wall thickness. Demographics of the volunteers (sex, age, weight, and height), Body Mass Index (BMI) and the presence of smoking, hypertension, diabetes mellitus, and dyslipidemia were recorded. Data obtained were consolidated and statistically evaluated using SPSS Version 16. RESULTS: Of the 300 volunteers who underwent duplex ultrasound, 60.3% were females, and 39.7% were males. The mean age was 60 ± 13, while the mean BMI was 26.01 ± 4.76. Moreover, 66.3% were non-smokers, and 62.3%, 81.3%, and 58.7% did not suffer from hypertension, diabetes mellitus, and dyslipidemia, respectively. The prevalence of phlebosclerosis was found to be 2.3%. Hypertension was a risk factor for the development of phlebosclerosis (p = 0.045). Moreover, there was a link between phlebosclerosis and age, as volunteers with phlebosclerosis were older than volunteers without phlebosclerosis (74.2 vs 59.11 years, p < 0.001). CONCLUSIONS: The prevalence of phlebosclerosis of the great saphenous vein is low, specifically 2.3%. Hypertension and increased age are risk factors for the development of phlebosclerosis. Both sexes are equally affected, while BMI, smoking, diabetes mellitus, and dyslipidemia do not contribute to the development of phlebosclerosis.

Phlebosclerosis in lower extremities veins - a systematic review.

Phlebosclerosis is a venous wall degenerative disease which has gained little popularity in the literature due to its uncertain clinical significance. The objective of this review is to evaluate the epidemiology, etiology and clinical significance of phlebosclerosis in lower extremities veins, particularly the effect of preexisting phlebosclerosis of the great saphenous vein on vein graft patency. Medline was searched from inception until November 1, 2019. Reference lists of included studies were scanned. Only articles published after 1949 were included. Two reviewers independently screened titles/abstracts and full-text papers for any study design in relation to phlebosclerosis in lower extremities veins and abstracted data. A total of 16 Cohort studies and one case-control study (3708 participants, mean age 61.8 years, 59.3 % men, and 40.7 % women) were included after screening 317 titles and abstracts, and 80 full-text articles. The incidence of phlebosclerosis ranged from 1.5-9.7 % depending on the radiological features. On the contrary, the incidence of the phlebosclerotic great saphenous vein prior to its use as a vein graft was 26.9-91 % on histological examination. The small saphenous vein was the most common location of phlebosclerosis followed by the great saphenous vein. There is a link between phlebosclerosis and age, venous insufficiency and haemodialysis. As for the vein graft patency seven studies demonstrated a correlation between preexisting phlebosclerosis and vein graft stenosis, whereas three studies failed to prove any association. In conclusion, the radiological incidence of phlebosclerosis depended on the ultrasound findings. Its presence in the great saphenous vein prior to its use as a vein graft is established on histological examination. The small saphenous vein is mainly affected. Risk factors included age, haemodialysis, and venous insufficiency. Preexisting wall thickness of the great saphenous vein graft seemed to affect negatively its patency in bypass surgery.

Histology of portal vascular changes associated with idiopathic non-cirrhotic portal hypertension: nomenclature and definition.

Idiopathic non-cirrhotic portal hypertension (INCPH) is a rare vascular liver disease that has attracted new interest in recent years. It is characterised by clinical signs of portal hypertension in the absence of cirrhosis or severe fibrosis and any known cause of portal hypertension. As much uncertainty exists about INCPH pathophysiology, and no definite diagnostic tests are available, liver biopsy is an essential tool for achieving a definite diagnosis. Unfortunately, the histological diagnosis of INCPH is not always straightforward, as the characteristic lesions are unevenly distributed, vary greatly in their severity, are often very subtle, and are not all necessarily present in a single case. Furthermore, specifically for the characteristic portal vessel changes observed in INCPH, the terminology and definition are ambiguous, which adds complexity to the already complex clinicopathological scenario. An international study group of liver pathologists and hepatologists pursued a consensus on nomenclature for the portal vascular lesions of INCPH. Such standardisation may assist pathologists in the recognition of such lesions, and will possibly facilitate further advancement in this field.

Histopathological and proteomic analyses identify integrin-ß1 as a potential mediator of phlebosclerosis in uremic patients.

BACKGROUND: Patients with uremia have an excessive mortality from cardiovascular disease (CVD). Arterial remodeling is mainly responsible for uremia-induced CVD and has been well studied, yet venous remodeling is poorly understood. Here we investigate the histopathology and proteomic profiles of venous remodeling in uremic patients. METHODS: Forearm cephalic veins were isolated from nine uremic patients during surgeries for arteriovenous fistula, and from nine healthy controls when applying surgical debridement. Hematoxylin-eosin, Masson's trichrome, von Kossa, and immunohistochemistry (IHC) against proliferating cell nuclear antigen were stained for histopathology. Isobaric tags for relative and absolute quantitation (iTRAQ) proteomic analysis was executed to explore the proteome of the veins. The core regulatory protein was validated by western blot, IHC, and immunofluorescence. RESULTS: Phlebosclerosis, characterized by intimal rarefaction and medial thickening with disordered proliferation of vascular smooth muscle cells (VSMCs), was the prominent pathological manifestation of peripheral veins in uremic patients, while inflammatory cell infiltration, atherosclerosis or calcification were not obviously detected. iTRAQ analysis showed that 350 proteins were significantly changed in phlebosclerosis of uremic patients compared with healthy controls, of which integrin-ß1 (ITGß1) exhibited the strongest regulatory ability by intermolecular interaction network analysis. The enhanced ITGß1 expression was mainly co-expressed with the disordered proliferation of VSMCs while a little with vascular endothelial cells in the forearm cephalic veins of uremic patients. CONCLUSIONS: Phlebosclerosis is the prominent pathological manifestation in peripheral veins of uremic patients. This pathological alteration mainly attributes to the disordered proliferation of VSMCs, which is potentially mediated by ITGß1.

Total dosage of gardenia fruit used by patients with mesenteric phlebosclerosis.

BACKGROUND: Mesenteric phlebosclerosis (MP) is a disease characterized by fibrotic change or calcification of the mesenteric vein. Recently, there has been an increase in case reports of MP related to herbal medicine usage. Long-term intake of gardenia fruit (GF) is suspected as a possible cause. However, many GF users do not develop this disease and the association between GF and MP remains unclear. In this study, we investigated for the first time the dosage of GF used by patients with and without MP. METHODS: We used a medical chart review study design to assess the association between GF and MP. We reviewed patients with a history of intake of herbal medicines containing GF. Among these patients, we selected patients who were examined by colonoscopy and abdominal plain computed tomography (CT). We investigated the findings of colonoscopy, CT scan and histological examination. We assessed the total dosages of GF alongside the duration of ambulatory visit, the administration period of herbal medicine containing GF and pre-existing disease in order to compare MP cases and non-MP patients. RESULTS: Ten MP cases and 42 non-MP patients were analyzed. We summarized clinical findings of MP cases. All MP cases used more GF than non-MP patients and were administered more than approximately 5,000 grams of GF in cumulative dosage. CONCLUSIONS: This study indicated that excessive intake of GF contributes to and/or accelerates the development of MP suggesting that long-term usage of GF in excessive amounts increases the risk of MP.

Phlebosclerotic colitis that was difficult to distinguish from collagenous colitis.

Phlebosclerotic colitis is a rare and recently known disease entity and its etiology is still to be elucidated. Some phlebosclerotic colitis cases are difficult to distinguish from collagenous colitis because of the similarity of pathological findings. In all Japanese case reports of phlebosclerotic colitis in which an association with the use of Chinese herbal medicine is suspected, sansisi (gardenia fruit) was included, suggesting pathogenesis of this disease. We report a case of phlebosclerotic colitis that wasdifficult to be distinguished from collagenous colitis, and an association with the use of Chinese herbal medicine was suspected as the cause of the disease.

Drug-related: A case of idiopathic mesenteric phlebosclerosis combined with calcification of the esophageal veins.

Idiopathic mesenteric phlebosclerosis (IMP) is characterized by mesenteric vein calcification and ischemic bowel disease. We describe a unique clinical case of IMP in a patient with a history of oral administration of various drugs, including traditional Chinese medicines (mainly selfheal), vitamin D, and calcium supplements. The disease was not diagnosed in its early stages and was later detected because of the initial symptoms of chest tightness and difficulties in swallowing. During medical examination, esophageal venous sinuses were found through gastroscopy, and CT revealed thickening and widespread calcification of the colonic wall (esophageal wall calcification). Moreover, typical purple-brown changes in the colonic mucosa were found during colonoscopy. Microscopic examination showed more foam phagocyte, focal lymphocyte aggregation, small-vessel proliferation, and surrounding collagen-like deposition which is a typical finding of IMP. More specifically, the patient's mesenteric veins and colon veins were calcified, and the calcification extended to the esophageal veins. These findings were related to long-term use of traditional Chinese medicines (mainly selfheal). It is possible that excessive intake vitamin D and calcium supplementation may have played a role in the occurrence of vascular calcification, which might have exacerbated the progression of IMP disease.

Hangeshashinto-Associated Mesenteric Phlebosclerosis and Highly Atypical Adenoma Requiring Laparoscopic Right Hemicolectomy.

Mesenteric phlebosclerosis is a rare ischemic colonic disorder caused by impaired venous drainage. Its prevalence is higher in East Asia, where herbal medicine is widely used. Treatment remains controversial. A 76-year-old woman who had taken Hangeshashinto, an herbal medicine, for 11 years was admitted for endoscopic treatment of high-grade dysplasia in the ascending colon. She had diarrhea and mesenteric phlebosclerosis diagnosed by abdominal computed tomography at age 71. At age 75, small polyps were detected in the ascending colon. A subsequent study revealed an increase in polyp size to 15 mm. Endoscopic mucosal resection failed to remove the lesion. A biopsy showed high-grade dysplasia with possible colon cancer risk. Conservative therapy did not improve mesenteric phlebosclerosis-related diarrhea; therefore, a laparoscopic right hemicolectomy was performed. Intraoperatively, the cecum was adherent to the abdominal wall and the right ovary. The specimen showed high-grade dysplasia in the mucosa and severe submucosal fibrosis. No metastasis was observed. This case shows the link between mesenteric phlebosclerosis and high-grade dysplasia in the ascending colon. Endoscopic mucosal resection was unsuccessful in removing the tumor. Endoscopic submucosal dissection was an alternative, but its safety in mesenteric phlebosclerosis-affected colonic segments remains uncertain. A laparoscopic right hemicolectomy was performed.

Case report and literature review: Laparoscopic extended right hemicolectomy for a 55-year-old patient with idiopathic mesenteric phlebosclerosis.

Idiopathic mesenteric phlebosclerosis (IMP) is an extremely rare disease with an unclear pathogenesis and risk factors. The clinical manifestations of IMP are mostly non-specific, mainly consisting of digestive symptoms such as abdominal pain, bloating and diarrhea. The diagnosis of IMP mainly relies on abdominal computed tomography (CT) and colonoscopy. Pathological changes associated with IMP often involve fibrous degeneration of the venous wall, which results in the thickening of the colonic wall and longitudinal calcification of the mesenteric arteries. Currently, there is no standard treatment protocol for IMP, and nonsurgical treatment is the mainstay of most medical centers. In this study, we reported a case of a 55-year-old female patient with IMP whose main clinical presentation was recurrent abdominal pain. The patient's initial diagnosis was considered an incomplete intestinal obstruction and received non-surgical treatments; however, the efficacy of the treatment was unsatisfactory. After completing abdominal CT and colonoscopy, we excluded common diseases of the digestive system (e.g., tumors, Crohn's disease), and finally considered that this patient had a high likelihood of IMP. This patient eventually underwent laparoscopic enlarged right hemicolectomy due to recurrent symptoms and poor outcomes of non-surgical treatment. Postoperative pathological results confirmed the diagnosis of IMP. During the follow-up period, the patient recovered well without recurrence of IMP. Furthermore, we have reviewed the literature related to IMP and summarized the etiology, risk factors, diagnostic methods, treatment options and prognosis of IMP.

Idiopathic mesenteric phlebosclerosis missed by a radiologist at initial diagnosis: A case report.

BACKGROUND: Idiopathic mesenteric phlebosclerosis (IMP) is a rare type of ischemic colitis characterized by thickening of the wall of the right hemicolon and calcification, sclerosis, and fibrosis of mesenteric veins. The diagnosis of IMP is based on typical clinical features and imaging findings. We report a case of IMP that was initially missed by the radiologist. CASE SUMMARY: A 77-year-old woman was admitted to the hospital due to chronic diarrhea for over 2 months. She had been consuming Chinese patent medicines (CPM) containing fructus gardeniae for more than 15 years. Colonoscopy revealed an edematous mucosa, bluish-purple discoloration, erosions, and ulcerations throughout the colorectal area. Abdominal computed tomography (CT) showed diffuse mural thickening of the entire colorectum, with tortuous thread-like calcifications in the right hemicolon, left hemicolon, and rectum. Most of the calcifications were located in the mesenteric vein. The diagnosis of IMP was established based on medical history, colonoscopy, CT findings, and histopathological examination. The patient was treated conservatively with papaverine and rifaximin, and CPM was stopped. Her diarrhea symptoms improved, indicating the effectiveness of the treatment. Over the next several years, she took opium alkaloids for an extended period and did not require hospitalization for the aforementioned gastrointestinal disorder. CONCLUSION: IMP is a rare gastrointestinal disease affecting Asian populations, possibly related to long-term herbal medicine intake. Accurate imaging analysis is crucial for diagnosis, but insufficient understanding of the disease can lead to misdiagnosis or missed diagnosis. Treatment strategies should be personalized.

Release of 6-nitrodopamine from human popliteal artery and vein.

6-Nitrodopamine (6-ND) is a novel catecholamine that is released from human umbilical cord vessels, and it causes vascular relaxation by acting as a dopamine D2-receptor antagonist. Here it was investigated whether human peripheral vessels obtained from patients who have undergone surgery for leg amputation release 6-ND, and its action in these tissues. Popliteal artery and vein strips present basal release of 6-ND, as measured by liquid chromatography coupled to tandem mass spectrometry. The release was significantly reduced when the tissues were pre-treated with the nitric oxide synthase inhibitor L-NAME (100 µM), or when the endothelium was mechanically removed. In U-46619 (3 nM) pre-contracted rings, 6-ND induced concentration-dependent relaxations (pEC50 8.18 ± 0.05 and 8.40 ± 0.08, in artery and vein rings, respectively). The concentration-dependent relaxations induced by 6-ND were unaffected in tissues pre-treated with L-NAME, but significantly reduced in tissues where the endothelium has been mechanically removed. In U-46619 (3 nM) pre-contracted rings, the selective dopamine D2 receptor antagonist L-741,626 also caused concentration-dependent relaxations (pEC50 8.92 ± 0.22 and 8.79 ± 0.19, in artery and vein rings, respectively). The concentration-dependent relaxations induced by L-741,626 were unaffected in tissues pre-treated with L-NAME, but significantly reduced in tissues where the endothelium has been mechanically removed. This is the first demonstration that 6-nitrodopamine is released from human peripheral artery and vein rings. The results also indicate that endothelium-derived dopamine is a major contractile agent in the popliteal artery and vein, and that selective dopamine D2-receptor antagonists such as 6-ND, may have therapeutic potential in the treatment of human peripheral vascular diseases.

Phlebosclerosis: An overlooked complication of varicose veins that affects clinical outcome: A case report.

BACKGROUND: Phlebosclerosis is a common age-related fibrotic degeneration of the venous wall. It is a disorder rather than a disease, which may cause venous dysfunction and even venous thrombosis. It is rarely reported in patients with varicose veins. CASE SUMMARY: The present report describes the case of a 70-year-old man with varicose veins, vitiligo, and phlebosclerosis. Venous angiography revealed blood reflux in the superficial and deep veins. The patient underwent surgery to remove the saphenous veins. During the operation, a calcified vein resembling a wooden stick was found, which was surprisingly extracted from the thickened venous wall. A cross-section of this wooden stick-like vein revealed venous fibrosis and calcification, obvious thickening of the venous wall, extensive collagen deposition on the venous wall, hyaline degeneration, and venous sclerosis causing closure of the venous lumen. CONCLUSION: This is probably the first report of a wooden stick-like structure being found in the venous wall in patients with varicose veins and venous ulcers. Phlebosclerosis can be observed in the late stage of varicose veins complicated by frequent infections and worse clinical outcomes. Therefore, it is important to be aware of this condition and address it rather than overlook it.

An unusual colonic mass in a phlebosclerosis patient.

A 47-year-old man with idiopathic mesenteric phlebosclerosis presented to our hospital because of a 2-month history of diarrhea and edema of both lower limbs. Contrastenhanced abdominal computed tomography (CT) showed a 2-cm mass of mixed density in the ascending colon. On coloscopy, a solid, ulcerated, semi-pedunculated, lobulated protruding mass of 3.5×3.5×1.5 cm was observed and removed with hot snare polypectomy. Histologic examination demonstrated a hamartomatous polyp with normal epithelium and an inflammatory infiltrate with dilated, mucus-filled cystic glands in the lamina propria, indicating a juvenile polyp.

Widespread mesenteric phlebosclerosis presenting as intestinal obstruction due to stenosis of the right-sided colon.

Mesenteric phlebosclerosis is a rare form of intestinal ischemia characterized by thickening of the right-sided colon and calcification of the mesenteric vein. We describe the case of a 58-year-old woman admitted to our hospital because of abdominal pain and distension. An abdominal computed tomography study revealed remarkable dilatation and fluid collection of the small intestine compatible with intestinal obstruction, which was considered to be the result of stenosis of the ascending colon. The thickened wall of the cecum and ascending colon was associated with calcification of the colonic wall and mesenteric veins. Colonoscopy showed dark purple discoloration of the edematous mucosa from the splenic flexure through the hepatic flexure, at which point the colonoscope could not be advanced further because of stenosis of the ascending colon. Over 10 years previously, the patient had taken an herbal medicine containing gardenia fruit, which can cause mesenteric phlebosclerosis. An extensive colonic resection was performed after intestinal decompression. This case highlights extensive mesenteric phlebosclerosis causing intestinal obstruction from the cecum through the proximal portion of the sigmoid colon, which was treated with extensive colonic resection.

Phlebosclerotic colitis: an analysis of clinical and CT findings in 29 patients with long-term follow-up.

BACKGROUND: Phlebosclerotic colitis (PC) is a rare form of nonthrombotic colonic ischemia. This retrospective study analyzed the clinical findings and temporal CT changes in 29 PC patients with long-term follow-up. METHODS: Twenty-nine patients with characteristic CT features of PC collected between 1997 and 2020 were stratified into the acute abdomen group (AA-group) (n = 10), chronic-progressive group (CP-group) (n = 14) and chronic-stable group (CS-group) (n = 5). Clinical and CT changes during follow-up, comorbidities and final outcomes were compared. RESULTS: The AA-group exhibited a significantly thicker colonic wall and more involved segments and pericolic inflammation than the CP-group and CS-group on initial CT (p = < 0.001-0.031). Seven patients in the AA-group who underwent right hemicolectomy had no recurrence during follow-up (mean ± SD, 7.1 ± 3.3 years), and the remaining three patients with renal or hepatic comorbidities who underwent conservative treatment died within 14 days. The CP-group showed significantly higher frequencies of chronic renal failure, urinary tract malignancies and liver cirrhosis than the AA-group (p = 0.005-0.008). In addition, CT follow-up (7.9 ± 4.3 years) showed significant increases in mesenteric venous calcifications, colonic wall thickening and involved colonic segments (p = 0.001-0.008) but conservative treatments were effective. The CS-group remained unchanged for years (8.2 ± 3.9 years). CONCLUSIONS: Early surgery offered excellent prognosis in PC-related acute abdomen denoted by marked right colonic wall thickening and pericolic inflammation on CT. Conservative treatments with a wait-and-watch strategy were appropriate for CP-PC and CS-PC, albeit CP-PC harbored significant increases in calcifications, colonic wall thickening and affected segments in long-term CT follow-up.

Phlebosclerotic colitis with long-term herbal medicine use.

Phlebosclerotic colitis (PC), also known as idiopathic mesenteric phlebosclerosis, is a rare disease resulting in ischemic colon due to venous sclerosis and calcifications that can be identified by characteristic imaging features on computed tomography and colonoscopy. Clinical examination reveals nonspecific symptoms with slow progression in the majority of cases. Patients with PC often require late-stage hospitalization and colectomy. We report a 79-year-old man with long-term clinical symptoms who used herbal medicines. Computed tomography and colonoscopy studies revealed several classical PC characteristics, and the patient subsequently underwent emergency total colectomy.

Adverse Effects of Kampo Medicines.

This review summarizes the adverse effects of Kampo medicines. These adverse effects in terms of immunoallergic reactions include interstitial pneumonia, liver injury, allergic cystitis, and drug eruption. Many cases of interstitial pneumonia, liver injury, and allergic cystitis associated with Kampo formulas have been reported to be caused by formulas containing Scutellariae Radix (Scutellaria root, ogon). The known adverse effects linked to overdose of Kampo formulas include pseudoaldosteronism [caused by Glycyrrhizae Radix (licorice, kanzo)], sympathomimetic symptoms [caused by Ephedrae Herba (ephedra, mao)], aconite poisoning [caused by Aconiti Tuber (processed aconite root, bushi and uzu)], and diarrhea [caused by Rhei Rhizoma (rhubarb, daio)]. In recent years, mesenteric phlebosclerosis caused by the long-term administration of Gardeniae Fructus (gardenia fruit, sanshishi) has also been reported. It is necessary to consider these potential adverse effects when prescribing Kampo medicines in clinical practice.

Intestinal obstruction due to idiopathic mesenteric phlebosclerosis colitis: A case report.

Introduction: Idiopathic mesenteric phlebosclerosis colitis (IMP) is a rare condition that impairs colonic venous blood return owing to mesenteric venous sclerosis and fibrosis. At present, many studies have suggested that long-term intake of Chinese herbal medicines is associated with its pathogenesis. IMP has no characteristic clinical manifestations, and most patients with IMP present with acute intestinal obstruction. As a rare disease, the etiology, pathogenesis, pathophysiology, and treatment of IMP are being explored and studied. Case Description: A 60-year-old Chinese male patient with IMP was admitted to our hospital for acute intestinal obstruction, received subtotal colectomy and ileostomy after 10 days of ineffective conservative treatment, and was discharged after postoperative supportive treatment for 1 month. Conclusion: There are many causes of intestinal obstruction, and we report a relatively rare one. After failure of conservative treatment, it is necessary to surgically resect part of the diseased bowel.