Efficacy and Safety of Upadacitinib Plus Intensive Granulocyte and Monocyte Adsorptive Apheresis as Induction for Intractable Ulcerative Colitis.

Monotherapy with a selective Janus kinase (JAK) inhibitor or intensive granulocyte and monocyte adsorptive apheresis (GMA) has been limited to patients with intractable ulcerative colitis (UC). No previous reports have described the efficacy including histopathological evaluations and the safety of combination therapy with upadacitinib (UPA) plus intensive GMA (two sessions per week) for intractable UC showing resistance to conventional agents and adalimumab. This retrospective study evaluated the 10-week clinical and histopathological efficacy of induction combination therapy with UPA plus intensive GMA in patients with intractable UC. Among eight patients (moderate UC, n = 1; severe UC, n = 7) who received combination therapy with UPA plus intensive GMA, 50.0% had achieved clinical remission by 10 weeks. Percentages of patients with histological-endoscopic mucosal improvement and mucosal healing at 10 weeks were 62.5% and 12.5%, respectively. After excluding one patient who discontinued treatment by week 10 because of intolerance for UPA, mean full Mayo score, endoscopic subscore and C-reactive protein concentration at baseline were 11.43 ± 0.37, 3 ± 0 and 1.29 ± 0.70 mg/dL, respectively. Corresponding values at 10 weeks were 2.28 ± 0.77 (P < 0.03), 1.14 ± 0.34 (P < 0.03) and 0.03 ± 0.008 mg/dL (P < 0.05), respectively. Adverse events of herpes zoster, temporary increase in creatinine phosphokinase and anemia were observed in one patient each. One patient discontinued combination therapy at week 4 because of temporary taste abnormality due to UPA. Combination comprising UPA plus intensive GMA appears likely to achieve satisfactory induction of clinical remission and histopathological improvement for patients with intractable UC for whom conventional agents and anti-tumor necrosis factor-α antibody have failed.

Late-onset Rupture of the Intrahepatic Pseudoaneurysm Developed by Endoscopic Ultrasonography-guided Hepaticogastrostomy: A Case Report and Literature Review.

Endoscopic ultrasonography-guided hepaticogastrostomy (EUS-HGS) has emerged as an alternative drainage technique for patients with malignant biliary obstruction. However, few reports have discussed the occurrence of late-onset rupture of hepatic artery pseudoaneurysms following EUS-HGS. A recently available drill dilator equipped with a long screw segment was used in the dilation step of EUS-HGS. We highlight the potential concern that this long screw segment may increase the risk of damage to the hepatic artery, leading to late-onset life-threatening rupture of a pseudoaneurysm.

Impact of a Time-Related Benchmark on the Adenoma Detection Rate in Surveillance Colonoscopy: A STROBE Statement-Oriented Cross-Sectional Cohort Study.

BACKGROUND/AIMS: Colorectal adenomas are precursor lesions of globally increasing colorectal cancer. Hence, a high adenoma detection rate in colonoscopy is pivotal. We investigated the clinical impact of stratified colonoscopy observation time combined with observation time/intubation time ratio on the detection of colorectal adenomas. MATERIALS AND METHODS: We conducted a single-center retrospective study including 369 consecutive patients who underwent colonoscopy following fecal immunochemical tests between May 2021 and April 2022. The primary outcome measure was the impact of the stratified observation time and observation time/ intubation time ratio (category 1: <6.0 minutes and <1.0, category 2: <6.0 minutes and ≥1.0, category 3: ≥6.0 minutes and <1.0, and category 4: ≥6.0 minutes and ≥1.0) on adenoma detection rate. RESULTS: Cecum intubation was obtained in 367 patients (99.5%). Adenomas were detected in 226 patients (61.2%). From the univariate analysis, age ≥53 years, habitual alcohol intake, colonoscopy attachment (+), and observation time with observation time/intubation time ratio categories 3 and 4 were determined as significant factors for adenoma detection rate. From the logistic regression analysis, age ≥ 53 years (odds ratio: 4.86, 95% CI: 2.25-10.52), habitual alcohol intake (odds ratio: 2.26, 95% CI: 1.33-3.82), category 3 (odds ratio: 3.66, 95% CI: 1.81-7.45), and category 4 (odds ratio: 5.60, 95% CI: 2.92-10.73) were significant factors for adenoma detection rate. CONCLUSION: We propose the observation time with observation time/intubation time ratio combined benchmark (with categories' thresholds based on observation time >6 minutes and scope withdrawal time exceeding intubation time [observation time/intubation time ratio > 1]) as a novel colonoscopy quality indicator. These findings represent an important educational message for endoscopists.

Potential Risk of Misjudgment in the Decision-making Process Based on the 2018 Tokyo Guidelines in Older Patients with Acute Cholecystitis.

Objective The 2018 Tokyo Guidelines (TG18) were published to facilitate the decision-making processes (DMP), including the diagnosis and operation of acute cholecystitis (AC). However, only a few guidelines consider older adults. This study evaluated the DMP based on the TG18, focusing on older patients with AC. Methods This was a single-armed, single-center retrospective study. The primary outcome measure was the "undiagnosable" AC rate, and the secondary outcome measure was the degree of concordance of "unfit for surgery" decisions. Patients Two hundred and nine patients with AC. Results Sixty (28.7%) of 209 patients with AC were "undiagnosable" on admission based on the TG18 criteria. The numbers and rate of "undiagnosable" AC in patients ≤59, 60-79, and ≥80 years old were 4 (10.0%), 20 (24.4%), and 36 (41.4%), respectively (p<0.001). The multiple logistic regression analysis following the univariate analysis revealed that age >73 years old was the most significant risk factor for undiagnosable AC [p=0.006, odds ratio (OR): 3.06, 95% confidence interval (CI): 1.38-6.81]. Female sex (p=0.033, OR: 2.09, 95% CI: 1.06-4.09) and severe AC (p=0.049, OR: 2.97, 95% CI: 1.01-8.76) were also significant risk factors for undiagnosable AC. The number of cases unfit for surgery based on the Charlson Comorbidity Index and American Society of Anesthesiologists physical status was 90 (43.1%) and 75 (35.9%), respectively. The κ value between these 2 indicators revealed a minimal concordance of 0.33 (95% CI: 0.20-0.47). Conclusion The DMP based on the TG18 potentially harbors a misjudgment risk, especially in older patients with AC (UMIN000047715).

A Transanal Endoscopic Ultrasound-guided Fine-needle Aspiration Biopsy for an Intrapelvic Tumor Diagnosed as Recurrence of a Smooth Muscle Tumor of Uncertain Malignant Potential Following Uterine Morcellation.

A transoral endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNAB) is a well-established tissue-sampling method. However, performing a transanal EUS-FNAB remains challenging. Uterine morcellation has emerged as a minimally invasive approach for benign tumor treatment. However, uterine myomas are heterogeneous and include malignant and indeterminate malignant cells. We herein report a rare case of intrapelvic tumor diagnosed by a transanal EUS-FNAB as a recurrence of smooth muscle tumors of uncertain malignant potential following uterine morcellation. Physicians should be aware that a previous uterine myoma resected under morcellation has the possibility of intra-abdominal recurrence. A transanal EUS-FNAB is a practical option for making a pathological diagnosis.

Soehendra stent retriever as a useful delivery device of drainage stent for passing an impacted cystic duct stone in a patient with acute cholecystitis.

Endoscopic transpapillary gallbladder drainage is an alternative procedure for patients with acute cholecystitis. However, this procedure is technically challenging because the drainage stent is sometimes obstructed by an impacted cystic duct stone, even if the guidewire is advanced into the gallbladder. In this report, the front end of a standard endoscopic retrograde cholangiopancreatography catheter was cut to an appropriate length as a drainage stent for transpapillary gallbladder drainage. However, this modified stent became stuck because of an impacted cystic duct stone. The Soehendra stent retriever was used as a stent delivery device in this setting. A Soehendra stent retriever with clockwise rotation was coupled with the drainage stent. Integrated devices provide a stent tip for pushability and torqueability. The stuck drainage stent at the impacted cystic duct stone resumed advancement into the gallbladder. After stent indwelling, decoupling was easy under counterclockwise rotation of the Soehendra stent retriever.

Unusual Gastrointestinal Hemorrhaging Mimicking a Rupture of Solitary Gastric Varices Due to a Gastric Gastrointestinal Stromal Tumor with Exogenous Growth.

Gastric gastrointestinal stromal tumors can lead to upper gastrointestinal hemorrhaging, which is usually caused by dimpling or ulceration on the tumor surface. While rare, pedunculated gastric gastrointestinal stromal tumors outside the stomach can present as a huge mass with delayed complaints. We herein report an unusual hemorrhaging mimicking a rupture of solitary gastric varices due to a pedunculated gastric gastrointestinal stromal tumor. In this case, contrast-enhanced computed tomography (CECT) was essential for tumor detection. An endoscopic investigation revealed dilated, aberrant veins and arteries in the submucosa of this tumor, recognized as solitary gastric varices.

[Endoscopic ultrasound-guided fine-needle biopsy for diagnosis of pancreatic metastases producing parathyroid hormone-related protein].

A 66-year-old man was admitted to our department with hypercalcemia, pancreatic and liver tumors, and periportal lymph node enlargement. Contrast-enhanced computed tomography revealed a tumor in the pancreatic tail and the right hepatic lobe along with periportal lymphadenopathy. Laboratory data revealed hypercalcemia and high serum parathyroid hormone-related protein (PTHrP) levels. Using a 22-gauge Franseen needle, we performed endoscopic ultrasonography-guided fine-needle biopsy of the pancreatic mass and an enlarged lymph node. Histopathological examination of the biopsy specimen revealed moderately to well-differentiated pancreatic adenocarcinoma with poorly differentiated squamous cell elements, as well as squamous cell carcinoma of the lymph node. Immunohistochemical examination showed that the pancreatic tissue was weakly immunopositive and the lymph node was strongly immunopositive for anti-PTHrP antibody. We diagnosed the patient with pancreatic adenosquamous carcinoma with liver and lymph node metastasis, associated with hypercalcemia of malignancy secondary to PTHrP secretion. We administered systemic chemotherapy comprising gemcitabine and nab-paclitaxel. Unfortunately, the patient died 8 months after being diagnosed with this malignancy. PTHrP-producing adenosquamous carcinoma of the pancreas is rare;only 14 cases are reported in the literature. Based on immunohistochemical evaluation, this case report suggests that metastatic lymph nodes may lead to the overproduction of PTHrP in such cases.

Clinical characteristics of adult T-cell leukemia/lymphoma infiltration in the gastrointestinal tract.

BACKGROUND: Adult T-cell leukemia/lymphoma (ATLL) is a peripheral T-cell malignancy caused by human T-cell leukemia virus type 1. The clinical course of ATLL is very heterogeneous, and many organs, including the gastrointestinal (GI) tract, can be involved. However, there are few detailed reports on ATLL infiltration in the GI tract. We investigated the clinical characteristics of ATLL infiltration in the GI tract. METHODS: This retrospective observational single-center study included 40 consecutive ATLL patients who underwent GI endoscopy. The patients' demographic and clinical characteristics and endoscopic findings were analyzed retrospectively. Patients with ATLL who were diagnosed by histological examination were divided into two groups based on GI tract infiltration. RESULTS: Multivariate analysis revealed that the absence of skin lesions was significantly associated with GI infiltration (P < 0.05). Furthermore, the infiltration group tended to have similar macroscopic lesions in the upper and lower GI tracts, such as diffuse type, tumor-forming type, and giant-fold type. CONCLUSIONS: GI endoscopy may be considered for ATLL patients without skin lesions.

Planned limited resection of the extrahepatic bile duct in a case of intraductal papillary neoplasm of the bile duct based on preoperative examinations.

Intraductal papillary neoplasm of the bile duct (IPNB) is defined as a non-invasive malignancy; however, since there are disparities in its histological diagnosis, the operative strategy for typical IPNB has not yet been established. A 69-year-old male was diagnosed with a bile duct mass lesion at the confluence of the cystic duct by ultrasonography without clinical symptoms. Liver functional parameters and tumor markers were within normal ranges. Computed tomography showed an enhanced tumor with no findings of ductal invasion or node metastasis. The tumor was exposed in the hepatic duct lumen and biopsy via SpyGlass DS cholangiography revealed that it was a low-grade papillary lesion, indicating type 1 IPNB. Under preoperative diagnostic modalities, limited resection of the extrahepatic bile duct with D2 lymphadenectomy was planned and R0 resection was achieved. The postoperative histological diagnosis was type 1 IPNB without node metastasis. The postoperative course was uneventful and a good prognosis is expected at this stage. In the field of biliary surgery, although extended resection is generally performed for bile duct carcinomas, satisfactory limited surgical resection is possible for type 1 IPNB with lower malignant behavior.

Single Rectal Neuroendocrine Tumor Associated with Multiple Endocrine Cell Micronests.

Although a few reports of neuroendocrine tumor (NET) in the stomach or appendix with surrounding micronests have been published, cases of rectal NET are rare. We herein report a unique case of a patient with single rectal NET treated endoscopically. A pathological examination revealed multiple endocrine cell micronests (ECMs) in the submucosal layer around the main NET lesion. Neither lymph node metastasis nor distant metastasis in computed tomography was observed six years after the treatment. Because case reports of multiple ECM are very rare, the significance of malignancy is unclear. It therefore appears to be necessary to accumulate similar cases.

Two cases of bile duct carcinoma patients who underwent the photodynamic therapy using talaporfin sodium (Laserphyrin®).

The efficacy of adjuvant photodynamic therapy (PDT) using the new photosensitizer, talaporfin sodium (TPS) has been clinically examined in some patients with bile duct carcinoma (BDC). Based on our previous cohorts, a prospective clinical trial was attempted; however, only two cases were ultimately enrolled in 27 months. A 664-nm semiconductor laser (100 J/cm2) was applied through an endoscope to the tumor lesion within 6 h of an intravenous injection of 40 mg/m2 TPS according to the protocol for lung cancer. Case 1 was an 82-y.o. female patient with BDC at the left hepatic duct with biliary obstruction, percutaneous transhepatic biliary drainage (PTBD) was achieved, and the patient did not consent to surgery. She was followed up for 15 months to search for non-surgical treatments and eventually received PDT. Although mild photosensitivity occurred, she was discharged without severe adverse events. Biliary stenosis markedly extended and a PTBD tube was scheduled at 1 month. However, cancer immediately metastasized to the liver and she died 155 days after PDT. Case 2 was a 70-y.o. female with perihilar BDC and multiple biliary stenoses. Multiple biliary stenting was considered to be difficult. She received PDT and no adverse events were observed. Biliary stenoses markedly improved and multiple stenting was successfully performed. On day 132, she died of cancer progression. These two cases demonstrated the safety and efficacy of biliary malignant stenosis soon after PDT; however, long-term survival and a sufficient quality of life were not achieved. The combination of the PDT protocol and system chemotherapy or brachytherapy needs to be examined in clinical trials for advanced stage BDC.

Verification of the effectiveness of fucosylated haptoglobin as a pancreatic cancer marker in clinical diagnosis.

BACKGROUND: Fucosylated haptoglobin detected by Pholiota squarrosa lectin (PhoSL) that had specificity for fucose α1-6 was reported as an effective biomarker for several gastrointestinal diseases. The aim of this study was to verify Fucosylated haptoglobin detected by Pholiota squarrosa lectin (PhoSL-HP) as a pancreatic cancer (PC) marker using a new method of PhoSL-ELISA. METHODS: PhoSL-HP in sera from 98 PC patients and 158 non-PC samples including 32 intraductal papillary mucinous neoplasm (IPMN) patients, 21 chronic pancreatitis (CP) patients and 105 non-pancreatic disease controls (NPDC) were measured. We compared sensitivities, specificities and areas under the curves (AUC) of PhoSL-HP, CA19-9 and CEA as single markers. We also evaluated PhoSL-HP as combination marker by comparing AUC of CA19-9 combined with PhoSL-HP or CEA. RESULTS: The sensitivities of PhoSL-HP, CA19-9 and CEA for PC were 58%, 76% and 42%, respectively. Although the specificity of PhoSL-HP for NPDC was inferior to both of CA19-9 and CEA, that for pancreatic diseases was higher than both of CA19-9 and CEA. Combined CA19-9 with PhoSL-HP, the AUC was significantly higher at 0.880 than single use of CA19-9 at 0.825 in case of distinguishing PC from other pancreatic diseases. In contrast, the AUC of CA19-9 was not elevated significantly when combined with CEA. CONCLUSION: PhoSL-HP would be a useful marker for PC and have sufficient complementarity for CA19-9.

The Development of Gastric Outlet Obstruction due to a Lumen-occupying Protruding Duodenal Ulcer Mimicking a Submucosal Tumor.

Even in the era of Helicobacter pylori eradication and proton pump inhibitors, peptic ulcer remains an important disease. Stricture due to a duodenal ulcer in the healing stage is a well-known etiology of benign gastric outlet obstruction. However, a duodenal ulcer-induced submucosal tumor-like change with gastric outlet obstruction is a very rare manifestation. We herein present a rare case of a patient with deteriorating symptoms of gastric outlet obstruction caused by an unusual manifestation of a lumen-occupying protruding duodenal ulcer mimicking a submucosal tumor.