Decreased Positive Fecal Occult Blood Tests and Delayed Medical Presentation for Colorectal Cancer during the Initial COVID-19 Pandemic Period: A Single-center Experience.

Objectives: This study aimed to investigate the impact of the COVID-19 pandemic on the examination and treatment of colorectal cancer (CRC) and on the behaviors of patients and practitioners. Methods: This is a retrospective analysis of the CRC patients who presented to our department between April 2019 and March 2021 and underwent surgery. Clinical presentation of CRC and time from symptom onset to medical presentation were compared between the control (April 2019 to March 2020, n=124) and COVID-19 pandemic periods (April 2020 to March 2021, n=111). Results: Two hundred and thirty-five patients were reviewed. The rate of positive fecal occult blood tests was significantly lower during the COVID-19 pandemic period (13.5 vs. 25.0%, P = 0.027). Among the symptomatic patients who had melena and abdominal symptoms, the time from symptom onset to medical presentation was significantly longer during the COVID-19 period (115 vs. 31 days, P < 0.001). In addition, the interval between presenting to a practitioner and being referred to our department was similar between the two periods (19 vs. 13 days, P = 0.092). There were no significant differences in the stage of cancer between the two periods. The rate of preoperative sub-obstruction was significantly higher during the COVID-19 period (41.4 vs 23.4%, P = 0.003). There was no significant difference in overall survival and recurrence-free survival between two periods. Conclusions: Hesitation to seek examination and treatment for CRC was observed in patients but not in practitioners during the COVID-19 pandemic period. The prognosis did not change.

Histological differentiation between sporadic and colitis-associated intestinal cancer in a nationwide study: A propensity-score-matched analysis.

BACKGROUND AND AIM: Colitis-associated intestinal cancer (CAC) can develop in patients with inflammatory bowel disease; however, the malignant grade of CAC may differ from that of sporadic colorectal cancer (CRC). Therefore, we compared histological findings distinct from cancer stage between CAC and sporadic CRC to evaluate the features of CAC. METHODS: We reviewed the clinical and histological data collected from a nationwide database in Japan between 1983 and 2020. Patient characteristics were compared to distinguish ulcerative colitis (UC), Crohn's disease (CD), and sporadic CRC. Comparisons were performed by using all collected data and propensity score-matched data. RESULTS: A total of 1077 patients with UC-CAC, 297 with CD-CAC, and 136 927 with sporadic CRC were included. Although the prevalence of well or moderately differentiated adenocarcinoma (Tub1 and Tub2) decreased according to tumor progression for all diseases (P < 0.01), the prevalence of other histological findings, including signet ring cell carcinoma, mucinous carcinoma, poorly differentiated adenocarcinoma, or squamous cell carcinoma, was significantly higher in CAC than in sporadic CRC. Based on propensity score-matched data for 982 patients with UC and 268 with CD, the prevalence of histological findings other than Tub1 and Tub2 was also significantly higher in those with CAC. At pT4, mucinous carcinoma occurred at a significantly higher rate in patients with CD (45/86 [52.3%]) than in those with sporadic CRC (13/88 [14.8%]) (P < 0.01). CONCLUSION: CAC, including early-stage CAC, has a higher malignant grade than sporadic CRC, and this difference increases in significance with tumor progression.

A proposed new Japanese classification of synchronous peritoneal metastases from colorectal cancer: A multi-institutional, prospective, observational study conducted by the Japanese Society for Cancer of the Colon and Rectum.

Aim: To establish a new Japanese classification of synchronous peritoneal metastases from colorectal cancer. Methods: This multi-institutional, prospective, observational study enrolled patients who underwent surgery for colorectal cancer with synchronous peritoneal metastases. Overall survival rates were compared according to the various models using objective indicators. Each model was evaluated by Akaike's information criterion (AIC). The region of peritoneal metastases was evaluated by the peritoneal cancer index (PCI). Results: Between October 2012 and December 2016, 150 patients were enrolled. The AIC of the present Japanese classification was 1020.7. P1 metastasis was defined as confined to two regions. The minimum AIC was obtained with the cutoff number of 10 or less for P2 metastasis and 11 or more for P3 metastasis. As for size, the best discrimination ability between P2 and P3 metastasis was obtained with a cutoff value of 3 cm. The AIC of the proposed classification was 1014.7. The classification was as follows: P0, no peritoneal metastases; P1, metastases localized to adjacent peritoneum (within two regions of PCI); P2, metastases to distant peritoneum, number ≤10 and size ≤3 cm; P3, metastases to distant peritoneum, number ≥11 or size >3 cm; P3a, metastases to distant peritoneum, number ≥11 and size ≤3 cm, or number ≤10 and size >3 cm; P3b, metastases to distant peritoneum, number ≥11 and size >3 cm. Conclusion: This objective classification could improve the ability to discriminate prognosis in patients with synchronous peritoneal metastases from colorectal cancer.

Endoscopic Lesions of Postoperative Anastomotic Area in Patients With Crohn's Disease in the Biologic Era: A Japanese Multi-Centre Nationwide Cohort Study.

BACKGROUND AND AIMS: Many patients have endoscopic evidence of recurrent Crohn's disease [CD] at 1 year after intestinal resection. These lesions predict future clinical recurrence. We endoscopically evaluated postoperative anastomotic lesions in CD patients from a large cohort of postoperative CD patients. METHODS: We retrospectively enrolled CD patients who underwent surgical resection between 2008 and 2013 at 19 inflammatory bowel disease [IBD]-specialist institutions. The initial analyses included patients who underwent ileocolonoscopy ~1 year after intestinal resection. Follow-up analyses assessed any changes in the endoscopic findings over time. We evaluated the postoperative endoscopic findings, which were classified into four categories [no lesion, mild, intermediate, severe] at the sites of the anastomotic line and peri-anastomosis. RESULTS: In total, 267 CD patients underwent postoperative ileocolonoscopy. Postoperative anastomotic lesions were widely detected in index ileocolonoscopy [61.0%] and were more frequently detected in follow-up ileocolonoscopy [74.9%]. Endoscopic severity also increased. Patients with intermediate or severe peri-anastomotic or anastomotic line lesions at the index ileocolonoscopy required significantly more interventions, including endoscopic dilatation or surgery, than patients with mild lesions or no lesions. CONCLUSIONS: Frequent anastomotic lesions were observed at the postoperative index ileocolonoscopy. These gradually increased for subsequent ileocolonoscopy, even in the biologic era. Regarding lesions on the anastomotic line, intermediate lesions on the anastomotic line [e.g. irregular or deep ulcers] might be considered recurrent disease, and mild lesions [e.g. linear superficial ulcers] might be considered non-recurrent disease. Prospective studies are needed to resolve this issue, including treatment enhancement.

Liver metastases of a neuroendocrine tumor arising from a tailgut cyst treated with interventional locoregional therapies: a case report and review of the literature on recurrent cases.

A tailgut cyst is a rare, developmental cyst occurring in the presacral space. Although primarily benign, malignant transformation is a possible complication. Herein, we report a case of liver metastases after resection of a neuroendocrine tumor (NET) arising from a tailgut cyst. A 53-year-old woman underwent surgery for a presacral cystic lesion with nodules in the cyst wall. The tumor was diagnosed as a Grade 2 NET arising from a tailgut cyst. Thirty-eight months after surgery, multiple liver metastases were identified. The liver metastases were controlled with transcatheter arterial embolization and ablation therapy. The patient has survived for 51 months after the recurrence. Several NETs derived from tailgut cysts have been previously reported. According to our literature review, the proportion of Grade 2 tumors in NETs derived from tailgut cysts was 38.5%, and four of the 5 cases of Grade 2 NETs (80%) relapsed, while all eight cases of Grade 1 NETs did not relapse. Grade 2 NET may be a high-risk group for recurrence in NETs arising from tailgut cysts. The percentage of Grade 2 NETs in tailgut cysts was higher than that of rectal NETs, but lower than that of midgut NETs. To the best of our knowledge, this is the first case of liver metastases of a neuroendocrine tumor arising from a tailgut cyst that was treated with interventional locoregional therapies, and the first report to describe about the degree of malignancy of neuroendocrine tumors originating from tailgut cysts in terms of the percentage of Grade 2 NETs.

Crohn's Disease-Associated Anorectal Cancer Has a Poor Prognosis With High Local Recurrence: A Subanalysis of the Nationwide Japanese Study.

INTRODUCTION: Colorectal cancer (CRC) is one of the major life-threatening complications in patients with Crohn's disease (CD). Previous studies of CD-associated CRC (CD-CRC) have involved only small numbers of patients, and no large series have been reported from Asia. The aim of this study was to clarify the prognosis and clinicopathological features of CD-CRC compared with sporadic CRC. METHODS: A large nationwide database was used to identify patients with CD-CRC (n = 233) and sporadic CRC (n = 129,783) over a 40-year period, from 1980 to 2020. Five-year overall survival (OS), recurrence-free survival (RFS), and clinicopathological characteristics were investigated. The prognosis of CD-CRC was further evaluated in groups divided by colon cancer and anorectal cancer (RC). Multivariable Cox regression analysis was used to adjust for confounding by unbalanced covariables. RESULTS: Compared with sporadic cases, patients with CD-CRC were younger; more often had RC, multiple lesions, and mucinous adenocarcinoma; and had lower R0 resection rates. Five-year OS was worse for CD-CRC than for sporadic CRC (53.99% vs 71.17%, P < 0.001). Multivariable Cox regression analysis revealed that CD was associated with significantly poorer survival (hazard ratio 2.36, 95% confidence interval: 1.54-3.62, P < 0.0001). Evaluation by tumor location showed significantly worse 5-year OS and RFS of CD-RC compared with sporadic RC. Recurrence was identified in 39.57% of CD-RC cases and was mostly local. DISCUSSION: Poor prognosis of CD-CRC is attributable primarily to RC and high local recurrence. Local control is indispensable to improving prognosis.

Effect of Biologics on the Risk of Advanced-Stage Inflammatory Bowel Disease-Associated Intestinal Cancer: A Nationwide Study.

INTRODUCTION: The aim of this study was to evaluate the effect of biologics on the risk of advanced-stage inflammatory bowel disease (IBD)-associated intestinal cancer from a nationwide multicenter data set. METHODS: The medical records of patients with Crohn's disease (CD) and ulcerative colitis (UC) diagnosed with IBD-associated intestinal neoplasia (dysplasia or cancer) from 1983 to 2020 were included in this study. Therapeutic agents were classified into 3 types: biologics, 5-aminosalicylic acid, and immunomodulators. The pathological cancer stage was compared based on the drug used in both patients with CD and UC. RESULTS: In total, 1,042 patients (214 CD and 828 UC patients) were included. None of the drugs were significantly associated with cancer stage in the patients with CD. In the patients with UC, an advanced cancer stage was significantly associated with less use of biologics (early stage: 7.7% vs advanced stage: 2.0%, P < 0.001), 5-aminosalicylic acid, and immunomodulators. Biologic use was associated with a lower incidence of advanced-stage cancer in patients diagnosed by regular surveillance (biologics [-] 24.5% vs [+] 9.1%, P = 0.043), but this was not the case for the other drugs. Multivariate analysis showed that biologic use was significantly associated with a lower risk of advanced-stage disease (odds ratio = 0.111 [95% confidence interval, 0.034-0.356], P < 0.001). DISCUSSION: Biologic use was associated with a lower risk of advanced IBD-associated cancer in patients with UC but not with CD. The mechanism of cancer progression between UC and CD may be different and needs to be further investigated.

Clinical features and oncological outcomes of intestinal cancers associated with ulcerative colitis and Crohn's disease.

BACKGROUND: Patients with longstanding inflammatory bowel disease are at high risk of developing intestinal cancers. In this study, we aimed to elucidate the differences between intestinal cancers associated with ulcerative colitis and Crohn's disease. METHODS: Intestinal cancers in ulcerative colitis and Crohn's disease patients treated between 1983 and 2020 at 43 Japanese institutions were retrospectively analyzed.. RESULTS: A total of 1505 intestinal cancers in 1189 ulcerative colitis and 316 Crohn's disease patients were studied. Almost all of ulcerative colitis-associated cancers (99%) were in the colon and rectum, whereas half of Crohn's disease-associated cancers (44%) were in the anus, with 11% in the small intestine. Ulcerative colitis-associated cancers were diagnosed more frequently by surveillance (67% vs. 25%, P < 0.0001) and at earlier stages (stages 0-1, 71% vs. 27%, P < 0.0001) compared with Crohn's disease-associated cancers. Colorectal cancers associated with Crohn's disease showed a significantly worse 5-year overall survival rate than those associated with ulcerative colitis (stage 2, 76% vs. 89%, P = 0.01, stage 3, 18% vs. 68%, P = 0.0009, and stage 4, 0% vs. 13%, P = 0.04). Surveillance correlated with earlier diagnoses for ulcerative colitis- and Crohn's disease-associated intestinal cancers, whereas shorter intervals between endoscopic examinations correlated with an earlier cancer diagnosis in ulcerative colitis patients but not in Crohn's disease patients. CONCLUSIONS: The clinical and oncological features of ulcerative colitis- and Crohn's disease-associated cancers were very different. Crohn's disease-associated cancers were diagnosed at more advanced stages and were detected less frequently by surveillance. Additionally, they showed a significantly poorer prognosis.

A case of Cronkhite-Canada syndrome with repeated linked color imaging observation of the subepithelial capillary network in the colon.

Cronkhite-Canada syndrome (CCS) is a non-hereditary disorder characterized by non-neoplastic gastrointestinal polyposis and ectodermal changes. While corticosteroids are considered effective, some cases are refractory. A 48-year-old woman presented with diarrhea, anorexia, and epigastralgia lasting for 3 months. She suffered from alopecia and nail dystrophy. Gastrointestinal endoscopy with histological examination confirmed non-neoplastic polyposis from the stomach to the rectum, confirming the diagnosis of CCS. Linked color imaging (LCI) with magnified endoscopy revealed a ribbon-like proliferation of capillaries surrounding the pits in the colonic mucosa. Histologically, the polyps had dilated glands, edematous stroma with inflammatory cell infiltrates and increased capillaries just beneath the epithelium. Immunohistochemical examination confirmed the expression of vascular endothelial growth factor (VEGF), mainly in the superficial epithelial and crypt cells. Steroid therapy was ineffective, and concomitant infliximab therapy provided symptomatic relief. Although symptoms rapidly improved with combination therapy, capillary hyperplasia and slight inflammation persisted in the colon mucosa after polyp resolution. Withdrawal of steroid treatment resulted in flare-ups of symptoms and polyps. Repeated magnified observations at LCI during post-relapse retreatment clearly captured the resolution process of both neovascularization and inflammation. Once the capillary hyperplasia and inflammation subsided, the steroid could be tapered off without relapse. To our knowledge, this is the first report describing the involvement of VEGF-induced angiogenesis and LCI findings in CCS; LCI observations are useful not only in the active phase of CCS, but also in determining subtle capillary hyperplasia and residual inflammation in remission, which may be an indicator of continued treatment.

Serrated polyposis syndrome with multiple inverted lesions in the colon: Case report and elucidation of morphogenetic mechanism.

A 70-year-old man underwent surveillance colonoscopy following surgery for occlusive sigmoid colon cancer. The procedure revealed nine sessile serrated lesions (SSLs), including three inverted lesions. Endoscopic and surgical resections were performed. All nine lesions were confirmed pathologically as SSL, and the patient was diagnosed with serrated polyposis syndrome (SPS). Three inverted SSLs (iSSLs) showed endophytic growth without epithelial misplacement. Crypt analysis revealed that iSSL crypts were wider at the bottom than the opening, roughly resembling a frustoconical shape. Our results suggest that a horizontal arrangement of frustoconical crypts leads to hemispherical deformation of the muscularis mucosa, forming an inverted shape. This is the first report to reveal the morphogenesis of iSSLs from the shape of the crypt.

Acute superior mesenteric artery occlusion associated with COVID-19 pneumonia: a case report.

BACKGROUND: The novel 2019 coronavirus disease (COVID-19), which is caused by infection with the severe acute respiratory syndrome coronavirus 2, has spread rapidly around the world and has caused many deaths. COVID-19 involves a systemic hypercoagulable state and arterial/venous thrombosis which induces unfavorable prognosis. Herein, we present a first case in East Asia where an acute superior mesenteric artery (SMA) occlusion associated with COVID-19 pneumonia was successfully treated by surgical intervention. CASE PRESENTATION: A 70-year-old man presented to his local physician with a 3-day history of cough and diarrhea. A real-time reverse transcriptase-polymerase chain reaction test showed positive for COVID-19, and he was admitted to the source hospital with the diagnosis of moderate COVID-19 pneumonia. Eight days later, acute onset of severe abdominal pain appeared with worsening respiratory condition. Contrast CT showed that bilateral lower lobe/middle lobe and lingula ground glass opacification with distribution suggestive of COVID-19 pneumonia and right renal infarction. In addition, it demonstrated SMA occlusion with intestinal ischemia suggesting extensive necrosis from the jejunum to the transverse colon. The patient underwent an emergency exploratory laparotomy with implementing institutional COVID-19 precaution guideline. Upon exploration, the intestine from jejunum at 100 cm from Treitz ligament to middle of transverse colon appeared necrotic. Necrotic bowel resection was performed with constructing jejunostomy and transverse colon mucous fistula. We performed second surgery to close the jejunostomy and transverse colon mucous fistula with end-to-end anastomosis on postoperative day 22. The postoperative course was uneventful and he moved to another hospital for rehabilitation to improve activities of daily living (ADLs) on postoperative day 45. As of 6 months after the surgery, his ADLs have completely improved and he has returned to social life without any intravenous nutritional supports. CONCLUSIONS: Intensive treatment including surgical procedures allowed the patient with SMA occlusion in COVID-19 pneumonia to return to social life with completely independent ADLs. Although treatment for COVID-19 involves many challenges, including securing medical resources and controlling the spread of infection, when severe abdominal pain occurs in patients with COVID-19, physicians should consider SMA occlusion and treat promptly for life-saving from this deadly combination.

In vitro analysis of exfoliated tumor cells in intraluminal lavage samples after colorectal endoscopic submucosal dissection.

PURPOSE: Colorectal endoscopic submucosal dissection (ESD) produces exfoliated tumor cells that occasionally cause local recurrence. However, the biological characteristics of these tumor cells have not been clarified. The aim of this study was to clarify the genetic background and viability of exfoliated tumor cells in colorectal ESDs, as well as possible method for their elimination. METHODS: Post-ESD intraluminal lavage samples from 19 patients who underwent colorectal ESDs were collected. In four patients with adenocarcinoma, gene mutations in the primary tumors and exfoliated cells in lavage samples were analyzed using a next-generation sequencer (NGS). In 15 patients with adenoma or adenocarcinoma, the viability of exfoliated cells and the cell-killing effect of povidone-iodine on exfoliated cells were evaluated. RESULTS: The analysis using a NGS demonstrated that tumors targeted for ESD had already acquired mutations in many genes involved in cell proliferation, angiogenesis, and invasions. Furthermore, gene mutations between the exfoliated tumor cells and tumors resected by ESDs showed a 92 to 100% concordance. The median viable cell counts and the median viability of exfoliated cells in intraluminal lavage samples after ESDs were 4.9 × 105 cells/mL and 24%, respectively. The viability of the exfoliated cells did not decrease even 12 h after ESD. However, contact with 2.0% povidone-iodine solution reduced both viable cell counts and viability, significantly. CONCLUSION: A large number of tumor cells exfoliated during colorectal ESDs had acquired survival-favorable gene mutations and could survive for some time. Therefore, a lavage using a solution of 2.0% povidone-iodine may be effective against such cells. TRIAL REGISTRATION: The prospective study registered 1317, and the retrospective study registered 2729. The prospective study approved on June 20, 2016, and the retrospective study approved on October 6, 2020.

Effect of preoperative asymptomatic renal dysfunction on the clinical course after colectomy for colon cancer.

PURPOSE: To evaluate the effect of mild renal dysfunction on the clinical course after colectomy in patients with colon cancer. METHODS: The subjects of this retrospective study were 263 patients who underwent surgical resection for colon cancer at our hospital between 2011 and 2015. Renal function was assessed based on preoperative estimated glomerular filtration rate (eGFR) values. Patients were divided into groups based on their eGFR value of 55 ml/min/1.73 m2. The Mann-Whitney U test, chi-square or Fisher exact test, and log-rank test were used in the data analysis. RESULTS: There were 59 patients (22.4%) in the low eGFR group and 204 patients in the normal eGFR group. There were differences between the groups in age, comorbidities, and the levels of hemoglobin, albumin, and serum creatinine. The overall postoperative complication rate, frequency of severe complications, and length of stay were significantly higher in the low eGFR group than in the normal eGFR group. Multivariate analysis revealed that low eGFR was the only independent risk factor for severe complications (Clavien-Dindo classification III/IV). There were no differences in survival between the groups. CONCLUSION: Preoperative asymptomatic renal dysfunction may be correlated with the development of postoperative complications and a possible significant risk factor for severe complications after colon cancer surgery.

A Ventral Hernia-repair-related Mycobacterium mageritense Mesh Infection Treated with NPWT without Mesh Removal.

Abdominal hernias are often repaired using prosthetic mesh, which is susceptible to infections. Normally, it is necessary to remove the mesh. However, successful mesh salvation with negative-pressure wound therapy (NPWT) has recently been reported. We encountered Mycobacterium(M) mageritense infection after hernia repair using the mesh. M. mageritense is classified as a fast-growing nontuberculous mycobacterium, but few cases have been reported. Nontuberculous mycobacterium can cause rare chronic infections. Skin and soft-tissue infections by nontuberculous mycobacterium involving localized abscess formation and chronic abscesses under various situations have been reported. We report an 85-year-old woman in whom a ventral hernia repair-related M. mageritense mesh infection was treated with NPWT without mesh removal. The hernia was repaired using Bard Ventralex mesh. Pus discharge was seen on the seventh postoperative day, and there was a small area of necrosis under the mesh. From the 13th postoperative day, NPWT was performed for 4 weeks. On the 29th postoperative day, a M. mageritense infection was diagnosed, which was resistant to multiple drugs. After the NPWT, most of the wound showed good granulation tissue formation. In conclusion, the mesh used to repair a hernia became infected with M. mageritense, but NPWT was able to salvage it. In cases of mesh infection involving small necrotic areas, performing NPWT under the guidance of an infectious disease expert may make it possible to preserve the mesh.

Immunohistochemistry and RNA-sequencing have been useful in evaluating the pathological significance of a non-consensus site intronic variant in suspected cases of Lynch syndrome.

Immunohistochemistry of mismatch repair proteins is a universal strategy for Lynch syndrome screening. In this case, Lynch syndrome was suspected, because MLH1 and PMS2 expression was negative by IHC. However, mismatch repair genetic analysis revealed a variant of unknown significance of c.454-13A > G in MLH1. Therefore, we performed reverse transcription-PCR using mRNA extracted from the patient's lymphocytes and detected a heterozygous gene allele indicating splicing abnormalities that complex splicing, with exon 5 followed by only the first codon (ACG) of exon 6 and leading to exon 7 of the MLH1. Two years later, this mutation was corrected to "likely pathogenic". For Lynch syndrome in which mismatch repair protein expression is undetectable by immunohistochemistry, reverse transcription-PCR may be useful to identify an intronic variant of unknown significance as the likely pathogenic variant.

Endoscopic Features of Postoperative Anastomotic Lesions in Patients with Crohn's Disease Compared with Right-side Colon Cancer: Are Anastomotic Linear Superficial Ulcers Recurrent in Crohn's Disease?

OBJECTIVES: Many patients have endoscopic evidence of recurrent Crohn's disease (CD) 1 year after intestinal resection, and endoscopic lesions predict future clinical recurrence. The aim of this study was to describe some anastomotic lesions including changes in endoscopic features in CD patients and to discuss recurrence. We also compared anastomotic lesions in CD patients and in right-side colon cancer (rt-CC) patients. METHODS: We enrolled patients with CD and rt-CC who underwent surgical resection between 2008 and 2014. Eleven CD patients underwent postoperative endoscopy at least twice, with the first time being from 6 months to 1 year after surgery and the second time being from 2 to 3 years after surgery. Eighty-six patients with rt-CC underwent postoperative endoscopy after approximately one year. RESULTS: A total of 90.9% of CD patients had postoperative lesions around the anastomosis at the first postoperative ileocolonoscopy, which was markedly higher than that in rt-CC patients (3.5%, p<0.001). Many of these lesions in CD required enhanced treatment. However, linear superficial ulcers at the anastomotic line at the first ileocolonoscopy did not worsen with the same treatment (18.1%). CONCLUSIONS: Postoperative anastomotic lesions were detected at a higher rate in CD cases than that in rt-CC cases. Many anastomotic lesions were recognized as recurrent disease and required enhanced treatment, whereas linear superficial ulcers did not require treatment changes. Therefore, linear superficial ulcers might not be recurrent disease. As this issue is related to recurrence, it should be further explored with the accumulation of more cases in a multicenter analysis.