Short-term outcomes of endoscopic resection for colorectal neuroendocrine tumors: Japanese multicenter prospective C-NET STUDY.

OBJECTIVES: The incidence of colorectal neuroendocrine tumors (NETs) has increased with colorectal cancer screening programs and increased colonoscopies. The management of colorectal NETs has recently shifted from radical surgery to endoscopic resection. We aimed to evaluate the short-term outcomes of various methods of endoscopic resection for colorectal NETs. METHODS: Among those registered in the C-NET STUDY, patients with colorectal NETs who underwent endoscopic treatment as the initial therapy were included. Short-term outcomes, such as the en bloc resection rate and R0 resection (en bloc resection with tumor-free margin) rate, were analyzed based on treatment modalities. RESULTS: A total of 472 patients with 477 colorectal NETs received endoscopic treatment. Of these, 418 patients with 421 lesions who met the eligibility criteria were included in the analysis. The median age of the patients was 55 years, and 56.9% of them were men. The lower rectum was the most commonly affected site (88.6%), and lesions <10 mm accounted for 87% of the cases. Endoscopic submucosal resection with a ligation device (ESMR-L, 56.5%) was the most common method, followed by endoscopic submucosal dissection (ESD, 31.4%) and endoscopic mucosal resection using a cap (EMR-C, 8.5%). R0 resection rates <10 mm were 95.5%, 94.8%, and 94.3% for ESMR-L, ESD, and EMR-C, respectively. All 16 (3.8%) patients who developed treatment-related complications could be treated conservatively. Overall, 23 (5.5%) patients had incomplete resection without independent clinicopathological risk factors. CONCLUSION: ESMR-L, ESD, and EMR-C were equally effective and safe for colorectal NETs with a diameter <10 mm.

[A case of autopsy-confirmed duodenal perforation due to calcium polystyrene sulfonate].

A 77-year-old male patient was referred to our hospital because of jaundice. He was diagnosed with alcoholic liver cirrhosis and was admitted to our hospital because of liver failure. After admission, we observed conservative liver disease, but the liver damage did not improve and gradually worsened. Renal function deteriorated during liver failure. Hyperkalemia presented due to renal dysfunction. Hence, calcium polystyrene sulfonate (CPS) was initiated. He died because of liver failure although hyperkalemia improved. An autopsy revealed ulcer perforation with CPS crystals in the duodenum. A basic substance considered a crystal of CPS was found by hematoxylin and eosin staining from the ulcer adjacent to the perforation and the exudate attached to the peritoneum. Furthermore, a large amount of CPS crystals were found in the ascites. A final diagnosis of gastrointestinal perforation peritonitis due to CPS was made. Gastrointestinal perforation due to CPS is presumed as a direct mucosal injury due to the drug, most of which is the sigmoid colon of elderly patients. Upper gastrointestinal tract perforation is extremely rare. We experienced a case of autopsy in which duodenal perforation due to CPS was pathologically confirmed. CPS is a widely used drug for renal disorders, but it has a risk of gastrointestinal injury. Therefore, a potential gastrointestinal mucosal injury should be considered when using CPS.

Magnifying Narrow-Band Imaging with Acetic Acid Spray for Superficial Non-Ampullary Duodenal Epithelial Tumors Based on the Mucin Phenotype.

INTRODUCTION: This study aimed to identify the characteristics of superficial non-ampullary duodenal epithelial tumors (SNADETs) based on the mucin phenotype using magnifying narrow-band imaging with acetic acid spray (MA-NBI) and evaluate the efficacy of MA-NBI in differentiating gastric-type (G-type) from intestinal-type (I-type) lesions. METHODS: We retrospectively identified 59 resected SNADETs in 59 patients who underwent MA-NBI. We evaluated surface patterns using MA-NBI to differentiate G-type from I-type lesions. Surface structures were classified into three patterns: tubular, villous, or oval structures. Lesions displaying a single pattern among the three patterns were classified as monotype, whereas those displaying multiple surface patterns were classified as mixed type. In addition, lesions with disorganized and unclear structures with irregular margins were classified as irregular surface structures. RESULTS: In total, 32 (54%), 26 (44%), and 1 (2%) lesions were classified as Vienna category 3, 4, and 5 tumors, respectively, whereas 49 (83%) and 10 (17%) were classified as I- and G-type lesions, respectively. Oval structures were more frequently observed in G-type lesions (70%), whereas tubular structures were more frequently observed in I-type lesions (78%) (p < 0.001). Category 4 and 5 lesions had significantly higher mixed and irregular surface structure rates than category 3 lesions (41 vs. 6%, p = 0.003 and 81 vs. 3%, p < 0.001, respectively). CONCLUSION: MA-NBI can distinguish the mucin phenotypes of SNADETs and may facilitate histological grade diagnosis.

Characteristics of colorectal neuroendocrine tumors in patients prospectively enrolled in a Japanese multicenter study: a first report from the C-NET STUDY.

BACKGROUND: This is the first report from a multicenter prospective cohort study of colorectal neuroendocrine tumor (NET), the C-NET STUDY, conducted to assess the long-term outcomes of the enrolled patients. This report aimed to elucidate the clinicopathological features of the enrolled patients and lesions. METHODS: Colorectal NET patients aged 20-74 years were consecutively enrolled and followed up at 50 institutions. The baseline characteristics and clinicopathological findings at enrollment and treatment were assessed. RESULTS: A total of 495 patients with 500 colorectal NETs were included. The median patient age was 54 years, and 85.3% were asymptomatic. The most frequent lesion location was the lower rectum (88.0%); 99.4% of the lesions were clinically diagnosed to be devoid of metastatic findings, and 95.4% were treated with endoscopic resection. Lesions < 10 mm comprised 87.0% of the total, 96.6% had not invaded the muscularis propria, and 92.6% were classified as WHO NET grade 1. Positive lymphovascular involvement was found in 29.2% of the lesions. Its prevalence was high even in small NETs with immunohistochemical/special staining for pathological assessment (26.4% and 40.9% in lesions sized < 5 mm and 5-9 mm, respectively). Among 70 patients who underwent radical surgery primarily or secondarily, 18 showed positive lymph node metastasis. CONCLUSIONS: The characteristics of real-world colorectal NET patients and lesions are elucidated. The high positivity of lymphovascular involvement in small NETs highlights the necessity of assessing the clinical significance of positive lymphovascular involvement based on long-term outcomes, which will be examined in later stages of the C-NET STUDY. TRIAL REGISTRATION NUMBER: UMIN000025215.

Late recurrence of early gastric cancer 11 years after curative endoscopic submucosal dissection.

A 73-year-old man was initially diagnosed with a 50-mm, depressed-type early gastric cancer on the anterior wall of the angulus, and the lesion was curatively resected en bloc by endoscopic submucosal dissection. Pathology revealed a 54 mm × 43 mm differentiated-type predominant adenocarcinoma with focal undifferentiated-type component that was confined to the mucosa without ulceration. Eleven years after endoscopic submucosal dissection, lymph node metastasis along the lesser curve was incidentally detected on magnetic resonance imaging and diagnosed by endoscopic ultrasound-guided fine-needle aspiration biopsy. The patient received distal gastrectomy with D2 lymph node dissection. A resected lymph node revealed a well-differentiated adenocarcinoma with a poorly differentiated component; thus, the final diagnosis was late recurrence of early gastric cancer originally treated by endoscopic submucosal dissection. This report demonstrates that metastatic recurrence may occur in curative endoscopic submucosal dissection for early gastric cancer and that gastric cancer can recur even after more than 5 years.

Depth of the cutting plane with underwater and conventional endoscopic mucosal resection: Post-hoc analysis of a randomized study.

BACKGROUND AND AIM: A multicenter randomized controlled trial reported a better R0 resection rate for intermediate-sized (10-20 mm) colorectal polyps with underwater endoscopic mucosal resection (UEMR) than conventional endoscopic mucosal resection (CEMR). To clarify whether UEMR removes enough submucosal tissue in the removal of unpredictable invasive cancers, we investigated the cutting plane depth with UEMR versus CEMR. METHODS: This was a post-hoc analysis of a randomized controlled trial in which 210 intermediate-sized colorectal polyps were removed in five Japanese hospitals. One pathologist and two gastroenterologists independently reviewed all resected specimens and measured the cutting plane depth. The cutting plane depth was evaluated as (i) maximum depth of submucosal layer and (ii) mean depth of submucosal layer, calculated using a virtual pathology system. RESULTS: We identified 168 appropriate specimens for the evaluation of the cutting plane depth, resected by UEMR (n = 88) and CEMR (n = 80). The median resection depth was not significantly different between UEMR and CEMR specimens, regardless of the measurement method ([i] 1317 vs 1290 µm, P = 0.52; [ii] 619 vs 545 µm, P = 0.32). All specimens in the UEMR and CEMR groups contained substantial submucosa and no muscularis propria. CONCLUSIONS: The cutting plane depth with UEMR was comparable with that with CEMR. UEMR can be a viable alternative method that adequately resects the submucosal layer for the histopathological assessment of unpredictable submucosal invasive cancers.

Reducing the risk of developing walled-off necrosis in patients with acute necrotic collection using recombinant human soluble thrombomodulin.

BACKGROUND/PURPOSE: The purpose of the present study was to investigate the possibility of reducing clinical impacts of acute necrotic collection (ANC) on patients with acute pancreatitis (AP) using recombinant human soluble thrombomodulin (rTM). METHODS: In this retrospective multicenter study, 233 consecutive AP patients with ANC and acute peripancreatic fluid collection (APFC) from 2012 to 2016 were enrolled. To assess clinical impacts of ANC, severity on admission (JPN score, JPN CT grade, and Modified CT severity index), development of walled-off necrosis (WON), imaging costs for follow-up, and mortality were recorded. Finally, we investigated whether rTM could reduce the clinical impacts, adjusting the severity using propensity analysis with Inverse probability of treatment weighting. RESULTS: Patients with ANC developed WON with higher ratio than APFC (58/98 [59.2%] vs 20/135 [14.8%], OR = 8.3, P < .01]. Severity on admission and imaging costs for follow-up in ANC patients were significantly higher than those in APFC (P < .01). However, regarding mortality, there was no significant difference between patients with ANC and APFC (P = .41). Adjusting severity, it was revealed that rTM administration significantly reduced the risk of ANC developed WON (OR = 0.23, P = .01). CONCLUSIONS: While ANC had a higher clinical impact than that of APFC, we found that early administration of rTM may reduce the impact.

Gastric Cancer with Multiple Lymph Node Enlargement at the Time of the Sarcoidosis Diagnosis.

An 80-year-old woman was found to have a 40-mm depressed-type gastric cancer. Computed tomography showed multiple lymph node enlargement, including paraaortic lymph nodes. The extent of lymph node enlargement was significant compared with the depth of the primary lesion. We conducted distal gastrectomy, D2 lymph node dissection, and a paraaortic lymph node biopsy. Microscopically, the tumor was diagnosed as mucosal cancer. In the dissected lymph nodes, noncaseating granuloma was found without metastasis of adenocarcinoma. Immunohistochemical staining using Propionibacterium acnes-specific antibodies showed a large number of P. acnes-positive cells in the granulomas. Finally, the tumor was diagnosed as early-stage gastric cancer and sarcoidosis.

Efficacy of Magnifying Narrow Band Imaging with Acetic Acid Spray in Diagnosing Superficial Non-Ampullary Duodenal Epithelial Tumors.

BACKGROUND/AIMS: The aim of the present study was to evaluate the efficacy of magnifying narrow band imaging with acetic acid spray (MA-NBI) in differentiating category 4/5 lesions from category 3 lesions of superficial non-ampullary duodenal epithelial tumors (SNADETs) as per Vienna Classification and to compare the diagnostic performances of both MA-NBI and magnifying narrow band imaging (M-NBI). METHODS: We retrospectively identified 60 resected SNADETs (31 category 3 lesions and 29 category 4/5 lesions) in 60 patients who underwent M-NBI and MA-NBI preoperatively. We evaluated vascular and surface patterns using M-NBI and MA-NBI for characterizing category 3 and 4/5 lesions. The surface pattern was classified as tubular, villous, or mix structure using MA-NBI. In addition, lesions with disorganized and unclear structures with irregular margins that can be clearly recognized by MA-NBI were defined as irregular surface structures. RESULTS: For MA-NBI, category 4/5 lesions had a significantly higher mix structure rate and higher irregular surface structure rate than category 3 lesions (62 vs. 16%, p < 0.001, and 86 vs. 19%, p < 0.001, respectively). The diagnostic accuracy of MA-NBI using mix and irregular surface structures for identifying category 4/5 lesions was as follows: sensitivity, 62/86%; specificity, 84/77%; positive predictive value, 78/78%; negative predictive value, 70/86%; and accuracy, 73/82%. The diagnostic accuracy of MA-NBI using irregular surface structure was significantly higher than that of M-NBI (p < 0.05). CONCLUSION: MA-NBI may be useful in differentiating between category 3 and category 4/5 lesions of SNADETs.

Upper Gastrointestinal Langerhans Cell Histiocytosis: A Report of 2 Adult Cases and a Literature Review.

Langerhans cell histiocytosis (LCH) with primary involvement of the upper gastrointestinal (GI) tract is rare. We report 2 adult cases of localized LCH in the upper-GI tract, including the second reported adult case of esophageal LCH and review 11 previously reported cases. Case 1 involved the esophagus of a 61-year-old man; histiocytosis was detected when endoscopy was performed for an examination of epigastric pain. Case 2 involved the stomach of a 56-year-old woman wherein the lesion was detected during a follow-up endoscopy after Helicobacter pylori infection. Both biopsy specimens exhibited diffuse proliferation of mononuclear cells with nuclear convolution and a background of eosinophilic infiltrate. The cells were immunohistochemically positive for CD1a and langerin, and BRAF V600E mutation was detected in Case 2. Follow-up endoscopy for both cases revealed that the lesions disappeared without any treatment. It is important to avoid misdiagnosing LCH of the upper-GI tract as a malignant neoplasm.

[A case of concomitant pancreatic neuroendocrine neoplasm and intraductal papillary mucinous neoplasm in which preoperative diagnosis was difficult].

A 75-year-old male patient has been followed-up for mixed-type intraductal papillary mucinous neoplasm (IPMN) in the tail of the pancreas for about 20 years. Upon close examination, he was diagnosed of high-risk stigmata due to a nodule having a contrast effect of 5mm or more in the tumor. Based on this, a distal pancreatectomy was performed. Histopathological analysis revealed concomitant IPMN (low-grade) and pancreatic neuroendocrine neoplasm (PNEN) (G1). This prompted us to report a very rare case of coexisting PNEN and IPMN with an interesting pathological finding that might suggest its pathogenic mechanism.

[Prediction of pancreatitis following endoscopic retrograde cholangiopancreatography].

OBJECTIVE: The aim of this study was to determine if the difference in serum amylase levels prior to, and two hours following, an endoscopic retrograde cholangiopancreatography (ERCP), or the ratio of the two-hour post-ERCP amylase level to the pre-ERCP amylase level was a better predictor of post-ERCP pancreatitis (PEP). METHODS: This was a retrospective, single-center study of consecutive patients, who underwent ERCP between April 2015 and August 2018. Serum amylase was measured before and two hours following ERCP. We compared the difference and the ratio of the two levels in predicting PEP using a receiver operating characteristic (ROC) curve analysis. RESULTS: A total of 1029 patients underwent ERCP, with PEP occurring in 118 (11.5%). Multivariate analysis revealed that an elevated two-hour post-ERCP serum amylase level was a significant predictor of PEP. ROC analysis of the difference and the ratio of the two levels found good performance for both parameters, with an area under the curve (AUC) of 0.861 (95% confidence interval [CI], 0.823-0.900) and 0.847 (95% CI, 0.809-0.886), respectively. The difference between the values was a significantly more effective predictor of PEP, based on the AUC analysis (P = 0.011). CONCLUSION: The difference between pre and two-hour post-ERCP amylase levels is a better predictor of PEP than the ratio of the two.

Gastric MiNEN Arising from the Heterotopic Gastric Glands.

An 80-year-old woman presented with a 30-mm protruding lesion-like submucosal tumor with a central depression located at the anterior wall of the upper gastric body. The depressed area had a well-demarcated margin, while the other area was covered by a non-neoplastic mucosa. A biopsy specimen revealed neuroendocrine carcinoma. Endoscopic ultrasonography revealed a heterogeneous mass with a clearly distinguished border in the submucosal layer. The mass had two distinct areas adjacent to each other. In addition, a hypoechoic zone was observed on the margin of the mass. Distal gastrectomy was performed. The final diagnosis was a mixed neuroendocrine-non-neuroendocrine neoplasm arising from the heterotopic gastric gland.

[Vitamin K deficiency caused by nutritional malabsorption accompanying afferent loop obstruction:a case report].

This case involves a 73-year-old man who visited a clinic because he was experiencing dyspnea on exertion and acid reflux. He was diagnosed with anemia and referred for a medical check-up and treatment by his primary care physician. Iron deficiency anemia and prolonged prothrombin time were confirmed with a blood test and an abdominal enhanced CT revealed marked expansion of the afferent loop after a gastrectomy. The medical check-up revealed abnormal blood coagulation due to afferent loop obstruction, which resulted in vitamin K deficiency. He was supplemented with vitamin K, and surgery was performed for the afferent loop obstruction. Postoperatively, his anemia, nutritional status, serum vitamin K levels, and prothrombin time improved steadily. In conclusion, nutrient malabsorption may occur in cases of afferent loop obstruction and abnormal blood coagulation due to vitamin K deficiency.

Comparison of Underwater vs Conventional Endoscopic Mucosal Resection of Intermediate-Size Colorectal Polyps.

BACKGROUND & AIMS: Endoscopic mucosal resection (EMR) with submucosal injection is an established method for removing colorectal polyps, although the en bloc resection rate decreases when polyp size exceeds 10 mm. Piecemeal resection increases local recurrence. Underwater EMR (UEMR) is an effective technique for removal of sessile colorectal polyps and we investigated whether it is superior to conventional EMR (CEMR). METHODS: We conducted a multicenter randomized controlled trial at 5 institutions in Japan. Patients with endoscopically diagnosed, intermediate-size (10-20 mm) sessile colorectal lesions were randomly assigned to undergo UEMR or CEMR. Only the most proximal lesion was registered. The UEMR procedure included immersion of the entire lumen in water and snare resection of the lesion without submucosal injection of normal saline. We analyzed outcomes of 108 colorectal lesions in the UEMR group and 102 lesions in the CEMR group. R0 resection was defined as en bloc resection with a histologically confirmed negative resection margin. The primary endpoint was the difference in the R0 resection rates between groups. RESULTS: The proportions of R0 resections were 69% (95% confidence interval [CI] 59%-77%) in the UEMR group vs 50% (95% CI 40%-60%) in the CEMR group (P = .011). The proportions of en bloc resections were 89% (95% CI 81%-94%) in the UEMR group vs 75% (95% CI 65%-83%) in the CEMR group (P = .007). There was no significant difference in median procedure time (165 vs 175 seconds) or proportions of patients with adverse events (2.8% in the UEMR group vs 2.0% in the CEMR group). CONCLUSIONS: In a multicenter randomized controlled trial, we found that UEMR significantly increased the proportions of R0 resections for 10- to 20-mm sessile colorectal lesions without increasing adverse events or procedure time. Use of this procedure should be encouraged. Trials registry number: UMIN000018989.

Early-stage Neuroendocrine Carcinoma of the Esophagus Observed with Annual Endoscopy for Three Years.

An 80-year-old man was found to have a reddish depressed lesion on the middle thoracic esophagus. The morphology of the lesion had been almost unchanged for 3 years, but it transformed to a 2-cm depressed lesion with elevated margins and an irregular nodular surface. The lesion was resected endoscopically and ultimately diagnosed as a combined neuroendocrine carcinoma and squamous cell carcinoma with submucosal invasion. The patient was additionally treated with chemoradiotherapy but died of the primary disease eight months after the initial treatment. It is important to elucidate the natural history of this disease at an early stage.

[A case of relapsed hemosuccus pancreaticus successfully treated with interventional radiology].

A 67-year-old male with chronic pancreatitis presented with upper abdominal pain and melena. Abdominal dynamic computed tomography revealed a splenic artery aneurysm in the main pancreatic duct. Esophagogastroduodenoscopy showed active bleeding from Vater's papilla. The patient was diagnosed with hemosuccus pancreaticus (HP) due to rupture of the aneurysm and treated with interventional radiology (IVR). The patient's poor lung function did not allow for a radical operation and a follow-up examination was recommended. The HP relapsed 7 months later and was successfully retreated with IVR. Although IVR is associated with a high recurrence rate, it is less invasive and therefore effective for treating relapsing HP in patients with a poor general condition.