LAUSR

To the Editor: Idiopathic mesenteric phlebosclerosis (IMP) is a rare chronic disease that usually develops in the proximal colon. Since Koyama et al. reported the first patient with IMP in 1991, there have been less than 100 cases reported. Most cases have occurred in Asian countries. IMP is characterized by venous calcifications extending from the colon wall to the mesentery, thus causing chronic colonic ischemia due to venous return impairment. However, it has been reported that no definite calcification has been observed during the very early stage of IMP. The pathogenesis of IMP remains unclear; however, the long-term oral intake of herbal medicine, especially sanshishi, has been suggested to contribute to IMP onset. We report two cases of earlystage IMP incidentally combined with adenocarcinoma of the ascending colon. Both patients had a history of herbal medicine intake for several years. Case 1 was a 63-year-old woman who presented to Saku Central Hospital Advanced Care Center for investigation of fecal occult blood (FOB). She had a medical history of climacteric disorder. She did not report any abdominal symptoms. Computed tomography (CT) revealed a mass in the ascending colon. No lymph node or distal metastasis was observed. No definite calcification was found. Colon endoscopy revealed an ulcerative tumor in the ascending colon. No erosive or ulcerative lesion, discoloration, or edematous changes in the background colonic mucosa were observed. Therefore, colonic cancer was diagnosed and laparoscopic right hemicolectomy was performed. Case 2 was a 77-year-old woman who presented to Nagano Red Cross Hospital for investigation of melena, abdominal pain, and anemia (hemoglobin, 7.8 g/dL). CT revealed a mass in the ascending colon, and swelling of the regional lymph nodes was observed. No distal metastasis was detected. Scattered calcifications were found in the middle colic artery; however, characteristic calcification patterns such as serpentine calcification next to the colonic and mesenteric veins on CT scan and thread-like calcifications on abdominal radiography were not identified. Colon endoscopy revealed an ulcerative tumor in the ascending colon. No erosive or ulcerative lesion, discoloration, or edematous changes in the background colonic mucosa were observed. Therefore, she was diagnosed with colonic cancer and right hemicolectomy was performed. Histopathologically, in both cases, adenocarcinoma invading the subserosa was observed. In addition, marked fibrous thickening of the vascular wall and mild fibrosis were observed in the submucosa (Fig. 1a). Also, eosinophilic deposition was observed in the subepithelium and perivascular region (Fig. 1c). These findings were observed from the near part of the Bauhin valve to the anal side margin of the ascending colon in Case 1, and from the near part of the Bauhin valve to the anal side margin of the ascending colon but not in the appendix (Case 2). These lesions were negative for Congo red staining and stained green by Elastica-Goldner staining (Fig. 1b, d); therefore, we judged these lesions as collagen deposits. Furthermore, some small calcifications (approximately 1mm in diameter) of the vessel wall were observed in the mesenteric vein, therefore, adenocarcinoma (pT3N0M0) and IMP were diagnosed. After the histopathological diagnosis, we confirmed their medical history and found that the Case 1 patient was prescribed kamisyoyosan and kamikihito, which are herbal medicines containing sanshishi, for climacteric disorder for more than 10 years (detailed term was unknown), and the Case 2 patient was prescribed kamisyoyosan for approximately 32 years. Both patients stopped using these herbal medicines and have been followed-up without treatment for 1 year. Radiological diagnosis of early-stage IMP is quite difficult because it lacks definite calcification. IMP causes abdominal symptoms; however, IMP is often asymptomatic. Furthermore, the severity of mesenteric venous calcification is associated with the number of active symptoms (i.e., fever, abdominal pain, severe constipation, bowel obstruction, vomiting, or diarrhea). Therefore, patients may experience only mild clinical symptoms or may be asymptomatic, especially during the early stage, and they may not have visited the hospital. Thus, it is difficult to detect early-stage IMP using clinical findings, as was the case for our patients. Eleven combined cases of IMP and colonic cancer have been reported in the English and Japanese literature with an English summary. Summaries of these 11 cases and our two cases are shown in the Supporting Information (Supporting Table S1). Patients were predominantly female (10; 77%) and had a mean age of 72.7 years (range, 57–82). Of these, 12 had abdominal imaging findings. Six cases (50%) lacked the characteristic calcifications found during preoperative examination. All these patients