Endoscopic submucosal dissection for superficial esophageal cancer in a diverticulum: A case report with literature review.

Superficial esophageal cancer (SEC) in a diverticulum is rare and has a high risk of perforation during endoscopic resection. Although endoscopic submucosal dissection (ESD) is a standard treatment option, it is challenging to perform. Here, we describe the case of a 79-year-old male patient with a history of ESD for SEC. Surveillance esophagogastroduodenoscopy identified a 20-mm-sized reddish depressed lesion in a diverticulum in the middle esophagus. The lesion was confirmed to be squamous cell carcinoma by biopsy. Magnification endoscopy with narrow-band imaging showed intraepithelial papillary capillary loops of type B1 according to the magnified endoscopic classification of the Japan Esophageal Society. Endoscopic ultrasonography revealed the presence of the muscular layer of the esophagus wall in the diverticulum. Therefore, the lesion was diagnosed as SEC, confined to the epithelium or lamina propria mucosae, in a Rokitansky diverticulum. Based on these findings, ESD was considered technically feasible. Traction-assisted ESD using clip with line was performed, and en bloc resection was achieved without adverse events. The resected specimen pathologically revealed a squamous cell carcinoma confined to the lamina propria mucosae without lymphovascular invasion, suggesting a curative resection. The patient recovered well, and no recurrence has been observed for 5 years after the ESD. Whether ESD is appropriate for the treatment of SEC in a diverticulum remains unclear. However, our case shows that it can be a treatment option in such cases due to its minimal invasiveness and good effectiveness.

Factors Related to Difficulty in Endoscopic Submucosal Dissection for Superficial Esophageal Cancer.

BACKGROUND: Endoscopic submucosal dissection (ESD) for superficial esophageal cancer is technically challenging, and research on predictive factors related to the difficulty in the procedure is limited. This study aimed to investigate the factors predicting the difficulty in esophageal ESD. METHODS: This retrospective study analyzed 303 lesions treated at our institution between April 2005 and June 2021. The following 13 factors were evaluated: sex, age, tumor location, tumor localization, macroscopic type, tumor size, tumor circumference, preoperative diagnosis of histological type, preoperative diagnosis of invasion depth, previous radiotherapy for esophageal cancer, metachronous lesion located close to post-ESD scar, operator's skill, and use of a clip-and-thread traction method. Difficult esophageal ESD cases were defined as those requiring long procedure time (>120 min). RESULTS: Fifty-one lesions (16.8%) met the defined criterion for difficult cases of esophageal ESD. Logistic regression analysis identified tumor size larger than 30 mm (odds ratio: 9.17, 95% confidence interval: 4.27-19.69, p < 0.001) and tumor circumference more than half that of the esophagus (odds ratio 2.53, 95% confidence interval: 1.15-5.54, p = 0.021) as independent predictive factors related to difficulty in esophageal ESD. CONCLUSION: Tumor size larger than 30 mm and tumor circumference more than half that of the esophagus can predict difficulty in performing esophageal ESD. This knowledge can provide useful information for developing ESD strategies and selecting a suitable operator on a case-by-case basis to achieve favorable clinical outcomes.

The usefulness of image-enhanced endoscopy to distinguish gastric carcinoma in tumors initially diagnosed as adenomas by endoscopic biopsy: A retrospective study.

Superficial epithelial gastric neoplasms can be divided into adenomas and early carcinomas. Histological diagnosis by endoscopic forceps biopsy is crucial for the diagnosis and management of gastric neoplasms. It is difficult to distinguish features of gastric neoplasms in small biopsy specimens; hence, gastric carcinomas can be underdiagnosed as adenomas. Recent developments in image-enhanced endoscopy have improved the ability to differentiate between carcinomatous and non-carcinomatous lesions. To investigate the prevalence of gastric carcinoma in lesions initially diagnosed as adenomas by forceps biopsy and assess the usefulness of image-enhanced endoscopy in distinguishing carcinomas. A total of 142 lesions of gastric adenomas, diagnosed by biopsy and resected endoscopically between January 2010 and May 2020, were retrospectively evaluated. Images were captured by white-light endoscopy (WLE), magnifying endoscopy with narrow-band imaging (M-NBI), and magnifying endoscopy with acetic acid and narrow-band imaging (M-AANBI); they were analyzed and compared with histopathological results. The diagnostic performance of M-AANBI was compared with that of M-NBI. Of the 142 lesions, 58 (40.8%) were pathologically diagnosed as adenocarcinomas. On WLE images, a depressed macroscopic type and size ≥20 mm were significant predictors of carcinoma (P < .001); however, they displayed low sensitivities (32.8% and 41.4%, respectively). M-AANBI displayed significantly higher sensitivity, specificity, and accuracy for distinguishing carcinomas than M-NBI (94.8% vs 74.1%, 81.0% vs 72.6%, and 86.6% vs 73.2%, P < .05). In conclusion, carcinoma was prevalent in 40.8% of gastric lesions initially diagnosed as adenomas by forceps biopsy. M-AANBI may be more useful than M-NBI and WLE in distinguishing gastric carcinomas from adenomas.

Obscure Gastrointestinal Bleeding Caused by a Small Intestinal Lymphatic-venous Malformation: A Case Report with a Literature Review.

A 44-year-old woman presented with severe anemia. We strongly suspected gastrointestinal bleeding; however, esophagogastroduodenoscopy, colonoscopy, and computed tomography showed no bleeding sources. Video capsule endoscopy revealed an actively bleeding submucosal lesion within the jejunum. Double-balloon enteroscopy revealed a 20-mm continuously bleeding submucosal lesion in the distal jejunum. We suspected small intestinal vascular malformation and performed surgical resection. The resected specimen pathologically comprised dilated, thin-walled lymphatic channels and blood vessels involving the small intestinal submucosa. Therefore, the patient was diagnosed with small intestinal lymphatic-venous malformation. Postoperatively, the patient recovered well, and recurrence was not observed.

Autoimmune Pancreatitis with Massive Ascites and Multiple Pancreatic Cysts Successfully Treated with Prednisolone.

A 64-year-old man with a history of diabetes and gallstones was admitted to our institution with suspected pancreatic malignancy. Computed tomography (CT) revealed multiple pancreatic cysts and massive ascites, and endoscopic ultrasonography (EUS) revealed a 28×27-mm hypoechoic mass in the pancreatic head. An EUS-guided fine-needle aspiration biopsy was performed, and there were no malignant findings. Based on the test results and imaging findings, type 1 autoimmune pancreatitis was suspected. The patient was administered 30 mg of prednisolone daily. After 11 days, CT revealed that the pancreatic cysts and ascites had reduced in size.

Long-term outcomes after endoscopic submucosal dissection for colorectal epithelial neoplasms in patients with severe comorbidities.

Background and Aim: Long-term outcomes after endoscopic submucosal dissection (ESD) for colorectal epithelial neoplasms (CENs) in patients with severe comorbidities have not been clarified; the current study aimed to examine these long-term outcomes and compared them with those in patients with non-severe comorbidities. Methods: We included 231 patients with CENs who underwent ESD between April 2005 and March 2023. Patients with comorbidities were categorized according to the American Society of Anesthesiologists Physical Status (ASA-PS). We conducted a propensity score-matched analysis and compared long-term outcomes of the two groups after ESD for CENs. Results: Of the 156 patients enrolled in the study, 43 and 113 had severe (ASA-PS III) and non-severe (ASA-PS I/II) comorbidities, respectively. The 1:1 propensity score analysis matched 36 patients with severe comorbidities to 36 patients with non-severe comorbidities. After matching, there was no difference in the procedural outcomes of ESD between both groups. Regarding long-term outcomes, the 5-year overall survival rates after matching in the ASA-PS I/II and III groups were 100% and 73.5%, respectively, and patients in the ASA-PS III group exhibited significantly shorter overall survival than those in the ASA-PS I/II group (hazard ratio 7.209; 95% confidence interval 1.592-32.646; P = 0.010). No colorectal cancer-related deaths were noted in either group. Conclusion: Overall survival after ESD for CENs was shorter in patients with severe comorbidities than in those with non-severe comorbidities. Clinicians should carefully determine whether the benefits of CEN resection with ESD outweigh the procedural risks in patients with severe comorbidities.

Effect of adding acetic acid when performing magnifying endoscopy with narrow band imaging for diagnosis of Barrett's esophageal adenocarcinoma.

Background and study aims Magnifying endoscopy with narrow band imaging (M-NBI) was developed to diagnose Barrett's esophageal adenocarcinoma (BEA); however, this method remains challenging for inexperienced endoscopists. We aimed to evaluate a modified M-NBI technique that included spraying acetic acid (M-AANBI). Patients and methods Eight endoscopists retrospectively examined 456 endoscopic images obtained from 28 patients with 29 endoscopically resected BEA lesions using three validation schemes: Validation 1 (260 images), wherein the diagnostic performances of M-NBI and M-AANBI were compared - the dataset included 65 images each of BEA and non-neoplastic Barrett's esophagus (NNBE) obtained using each modality; validation 2 (112 images), wherein 56 pairs of M-NBI and M-AANBI images were prepared from the same BEA and NNBE lesions, and diagnoses derived using M-NBI alone were compared to those obtained using both M-NBI and M-AANBI; and validation 3 (84 images), wherein the ease of identifying the BEA demarcation line (DL) was scored via a visual analog scale in 28 patients using magnifying endoscopy with white-light imaging (M-WLI), M-NBI, and M-AANBI. Results For validation 1, M-AANBI was superior to M-NBI in terms of sensitivity (90.8 % vs. 64.6 %), specificity (98.5 % vs. 76.9 %), and accuracy (94.6 % vs. 70.4 %) (all P  < 0.05). For validation 2, the accuracy of M-NBI alone was significantly improved when combined with M-AANBI (from 70.5 % to 89.3 %; P  < 0.05). For validation 3, M-AANBI had the highest mean score for ease of DL recognition (8.75) compared to M-WLI (3.63) and M-NBI (6.25) (all P <  0.001). Conclusions Using M-AANBI might improve the accuracy of BEA diagnosis.

Propensity-score matched analysis to evaluate efficacy of endoscopic submucosal dissection for superficial esophageal cancer in gastrectomized patients.

Endoscopic submucosal dissection (ESD) is a minimally invasive treatment option for superficial esophageal cancer (SEC) with high rates of complete resection. However, limited research exists on the efficacy of ESD for SEC in gastrectomized patients. This study aimed to evaluate the efficacy of ESD for SEC in gastrectomized patients. We included 318 patients of SEC treated at our institution between April 2005 and October 2021. To minimize bias between the gastrectomized and non-gastrectomized groups, we conducted a propensity-score matched analysis and compared the ESD outcomes for SEC of the two groups. Of the 318 patients included in the study, 48 and 270 patients were in the gastrectomized and non-gastrectomized groups, respectively. After 1:2 propensity-score matching, we matched 44 patients in the gastrectomized group to 88 patients in the non-gastrectomized group, and found no significant differences in the baseline clinicopathological characteristics. Regarding the ESD outcomes, there were no significant differences in the complete resection rate, procedure time, hospitalized period, and recurrence rates between the two groups. Multivariate analysis also cofirmed that the history of gastrectomy was not a risk factor of the difficult case of esophageal ESD. In conclusion, history of gastrectomy might not negatively affect the ESD outcomes of SECs.

Usefulness of magnifying endoscopy with acetic acid and narrow-band imaging for the diagnosis of duodenal neoplasms: proposal of a diagnostic algorithm.

BACKGROUND: This study aimed to clarify the features of superficial non-ampullary duodenal epithelial tumors (SNADETs) on magnifying endoscopy with narrow-band imaging (M-NBI) and magnifying endoscopy with acetic acid and narrow-band imaging (M-AANBI), and evaluate the efficacy of M-NBI/M-AANBI to distinguish high-grade adenomas or adenocarcinomas (HGA/AC) from low-grade adenomas (LGA). METHODS: Clinicopathological data on 62 SNADETs in 58 patients who underwent preoperative M-NBI/M-AANBI and endoscopic resection were retrospectively reviewed. The pathological results were classified into two categories, LGA and HGA/AC. We evaluated microvascular patterns (MVPs) and microsurface patterns (MSPs) observed by M-NBI and MSPs observed by M-AANBI for characterizing LGA and HGA/AC. The kappa value was calculated to assess the interobserver and intraobserver agreements of evaluation of M-AANBI images. RESULTS: Pathologically, 38 lesions (61.3%) were LGA and 24 lesions (38.7%) were HGA/AC. HGA/AC tended to have irregular MVP and/or MSP on M-NBI. M-NBI diagnostic performance to distinguish HGA/AC from LGA showed 62.5% sensitivity, 68.4% specificity, and 66.1% accuracy. SNADETs had irregular MSP on M-AANBI. Three irregularity grades (iG) of MSP were observed by M-AANBI as follows: iG1, mild; iG2, moderate; iG3, significant. HGA/AC lesions had a significantly higher rate of iG3 than LGA lesions (p < 0.001). The iG2 was associated with HGA/AC in elevated lesions and LGA in depressed lesions. The diagnostic performance of M-AANBI was as follows: 95.8% sensitivity, 97.4% specificity, and 96.8% accuracy. The diagnostic accuracy of M-AANBI was significantly higher than that of M-NBI (p < 0.001). The kappa value for interobserver agreement on the diagnosis and irregularity grading of M-AANBI images was 0.742 and 0.719, respectively. These data indicate substantial interobserver agreement. Based on the above-mentioned results, we developed a M-AANBI diagnostic algorithm for SNADETs. CONCLUSION: The diagnostic algorithm for SNADETs using M-AANBI may be useful for differentiating between LGA and HGA/AC.

Clinical utility of endoscopic submucosal dissection using the pocket-creation method with a HookKnife and preoperative evaluation by endoscopic ultrasonography for the treatment of rectal neuroendocrine tumors.

BACKGROUND: Various endoscopic methods have been developed to remove small rectal neuroendocrine tumors (NETs). This study aimed to evaluate the clinical utility of endoscopic submucosal dissection using the pocket-creation method (ESD-PCM) with a HookKnife, following preoperative evaluation by endoscopic ultrasonography (EUS), for the treatment of rectal NETs. METHODS: We analyzed retrospectively consecutive patients who underwent ESD-PCM with a HookKnife for the removal of rectal NETs, with a size less than 10 mm, at Mie University Hospital between June 2015 and December 2019. All the rectal NETs were resected by ESD-PCM with a HookKnife. The R0 resection rate, procedure time, adverse event rate, diagnostic accuracy of tumor size and invasion depth evaluated by preoperative EUS, and follow-up outcome were evaluated retrospectively. RESULTS: The study group comprised 12 patients with 12 resected lesions. The median tumor size of the resected specimens was 5 mm and the size and invasion depth of each tumor was approximately equal to that predicted by preoperative EUS. R0 resection was achieved in all cases, without adverse events. The median procedure time was 50.5 min, which did not differ from previous studies. No recurrence was observed during the median follow-up period of 34.4 months (range, 5.2-60.0 months). CONCLUSIONS: ESD-PCM with a HookKnife provides a favorable clinical utility for removing rectal NETs, with high R0 resection rate and good follow-up outcome. In addition, EUS is useful for evaluating preoperatively the size and invasion depth of rectal NETs.

A novel CDK-independent function of p27Kip1 in preciliary vesicle trafficking during ciliogenesis.

p27Kip1, a member of the Cip/Kip family of cyclin-dependent kinase (CDK) inhibitors, is now known as a multifunctional protein that plays crucial roles in cell architecture and migration by regulating rearrangements of the actin cytoskeleton and microtubules. The intracellular level of p27Kip1 is increased by anti-proliferative stimuli, such as mitogen deprivation and contact inhibition, which also induce formation of primary cilia, microtubule-based membranous organelles that protrude from the cell surface. However, it remains unknown whether p27Kip1 is associated with ciliogenesis. Here, we have generated p27Kip1-knockout hTERT-immortalized human retinal pigment epithelial cells, and found that ciliogenesis is almost completely disrupted in p27Kip1-knockout cells. The defect of ciliogenesis is rescued by the exogenous expression of wild-type p27Kip1 and, surprisingly, its 86-140 amino acid region, which is neither responsible for CDK inhibition nor remodeling of the actin cytoskeleton and microtubules. Moreover, transmission electron microscopy and immunofluorescence analyses reveal that p27Kip1 abrogation impairs one of the earliest events of ciliogenesis, docking of the Ehd1-associated preciliary vesicles to the distal appendages of the basal body. Our findings identify a novel CDK-independent function of p27Kip1 in primary cilia formation.

Needle tract seeding following endoscopic ultrasound-guided fine-needle aspiration for pancreatic cancer: a report of two cases.

BACKGROUND: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is a useful tool in pancreatic cancer diagnosis. However, the procedure itself may cause peritoneal dissemination and needle tract seeding at the puncture site. We herein report two cases of gastric wall metastasis due to needle tract seeding after EUS-FNA. CASE PRESENTATION: Case 1: A 68-year-old woman was admitted to our hospital for persistent cough. Computed tomography (CT) scan revealed inflammatory changes in the left lung field, and incidentally, a 15-mm hypovascular mass was detected in the pancreatic body. She underwent EUS-FNA and was diagnosed as pancreatic adenocarcinoma. She underwent distal pancreatectomy with splenectomy; however, a small hard mass was observed in the posterior gastric wall during surgery. We performed partial gastrectomy, and the resected specimen was diagnosed as a needle tract seeding following EUS-FNA. She then underwent adjuvant chemotherapy with TS-1, but the pancreatic cancer showed recurrence 6 months after surgery. She died due to peritoneal dissemination 18 months after surgery. Case 2: A 70-year-old man was incidentally detected with a pancreatic body mass on a CT scan as part of his follow-up for recurrence of basal cell carcinoma. He underwent EUS-FNA and was diagnosed as pancreatic adenocarcinoma. He had nodules in both lungs, and it was difficult to differentiate them from lung metastasis of pancreatic cancer. Therefore, he underwent neoadjuvant chemoradiotherapy, and thereafter, the lung nodules showed no changes; hence, he underwent distal pancreatectomy with splenectomy. During surgery, we observed a hard mass in the posterior gastric wall. We performed partial gastrectomy, and the resected specimen was diagnosed as needle tract seeding due to EUS-FNA. He underwent chemotherapy with TS-1, and he is still alive 18 months after surgery at the time of writing. CONCLUSION: For resectable pancreatic body or tail tumors, EUS-FNA should be carefully performed to prevent needle tract seeding and intraoperative as well as postoperative assessment for gastric wall metastasis is mandatory.

A case report of adenosquamous cell carcinoma of the duodenal papilla.

Adenosquamous carcinoma of the duodenal papilla is rare. A 73-year-old man was referred to the Saiseikai-Matsusaka General Hospital with upper abdominal pain and liver dysfunction. Computed tomography (CT) revealed dilatation of the common bile duct (CBD) and intrahepatic bile duct along with a tumor in the distal CBD. The tumor showed enhancement in the arterial phase on contrast-enhanced CT. We performed endoscopic retrograde cholangiopancreatography and noted a red, erosive, bleeding mass in the duodenal papilla with obstruction of the distal CBD, and dilatation of the CBD. Histopathological inspection of a biopsy of the duodenal papilla showed a mixture of adenocarcinoma and squamous cell carcinoma, suggesting the presence of adenosquamous cell carcinoma in the duodenal papilla. Abdominal examinations including positron emission tomography/CT showed no metastasis or lymph node swelling. The clinical stage was determined to be cT2N0M0 Stage IB. We performed subtotal stomach-preserving pancreaticoduodenectomy. Histopathological inspection of the specimen showed a mixture of adenocarcinoma and squamous cell carcinoma, and squamous cell carcinoma accounted for 40% of the tumor. The tumor was defined as pathological Stage IIA, AcbBd, mixed type, med, pT3b, sci, INFb, ly2, v1, ne2, pN1, HM0, PM0, EM0, PV0, A0, R0, pT3N0M0. We suggested adjuvant chemotherapy, but the patient declined adjuvant chemotherapy and wished to be discharged. Abdominal ultrasonography revealed multiple liver metastases 3 months postoperatively. The patient opted for best supportive care and died 9 months postoperatively. Examination of 23 reports of adenosquamous cell carcinoma of the duodenal papilla in Japan suggested that adenosquamous cell carcinoma of the duodenal papilla has a poorer prognosis compared with adenocarcinoma of the duodenal papilla. Some reports have stated that the growth rate is faster for squamous cell carcinoma than for adenocarcinoma. In our case, the tumor was enhanced in the arterial phase and this represents a feature of adenosquamous cell carcinoma of the duodenal papilla. Chemotherapy has not been established for adenosquamous cell carcinoma of the duodenal papilla. We are confident that we can establish effective chemotherapies in the future.

Ly6C(+) monocytes are extrahepatic precursors of hepatic stellate cells in the injured liver of mice.

OBJECTIVE: We previously reported that hepatic stellate cells (HpSCs) are of hematopoietic origin in liver injury. However, the immediate precursors of HpSCs remain unknown. This study was conducted to elucidate whether terminally differentiated blood cells can differentiate into HpSCs. MATERIALS AND METHODS: We adoptively transferred a variety of cells isolated from enhanced green fluorescent protein (EGFP)-transgenic mice into carbon tetrachloride (CCl(4))-treated nontransgenic mice twice weekly for 2 weeks. We examined the presence of EGFP(+) HpSCs in the injured liver using immunofluorescence analysis. RESULTS: Monocytes, neutrophils, eosinophils, B cells, or T cells from EGFP mice were transferred into CCl(4)-treated mice. Thirty percent of EGFP(+) cells in the livers of mice given Ly6C(high)c-kit(-) monocytes were negative for CD45, but were positive for glial fibrillary acidic protein, desmin, CD146, ADAMTS13, and α-smooth muscle actin, well-known markers of HpSCs. EGFP(+)CD45(-) cells were predominantly positive for glial fibrillary acidic protein. Although 48% of EGFP(+) cells were positive for procollagen type I, half of them were CD45(-). In the livers of mice given neutrophils, eosinophils, B cells, or T cells, all of the EGFP(+) cells were CD45(+). The majority of EGFP(+) cells in the nonparenchymal cell fraction purified from the livers of mice given Ly6C(high)c-kit(-) monocytes contained lipid droplets and were positive for glial fibrillary acidic protein, desmin, ADAMTS13, and procollagen type I. When Ly6C(+) monocyte-depleted peripheral blood total nucleated cells were adoptively transferred into CCl(4)-treated mice, we found no EGFP(+)CD45(-) cells in the liver. CONCLUSIONS: These results suggest that Ly6C(+) monocytes can become HpSCs in the injured liver.