Expression of ZKSCAN3 protein suppresses proliferation, migration, and invasion of pancreatic cancer through autophagy.

Elevated autophagy activity enhances the malignancy of pancreatic cancer (PaCa), and autophagy is recognized as a novel therapeutic target. Zinc finger protein with KRAB and SCAN domains 3 (ZKSCAN3) is a transcription factor that suppresses autophagy, but its association with PaCa is unknown. We analyzed the function of ZKSCAN3 in PaCa and investigated whether autophagy regulation through ZKSCAN3 could become a new therapeutic target for PaCa. Using reverse transcription-quantitative polymerase chain reaction and western blotting, we observed that ZKSCAN3 expression was upregulated in several PaCa cell lines compared with normal pancreatic ductal epithelial cells. Additionally, comparing ZKSCAN3 expression with the prognosis of PaCa patients using web databases, we found that higher ZKSCAN3 expression in PaCa was associated with extended overall survival. Knocking down ZKSCAN3 promoted the proliferation of PaCa cells. Moreover, following ZKSCAN3 knockdown, PaCa cells exhibited significantly enhanced migratory and invasive properties. Conversely, overexpression of ZKSCAN3 significantly suppressed the proliferation, migration and invasion of PaCa cells. Additionally, the knockdown of ZKSCAN3 increased the expression of LC3-II, a marker of autophagy, whereas ZKSCAN3 overexpression decreased LC3-II expression. In a xenograft mouse model, tumors formed by MIA PaCa-2 cells in which ZKSCAN3 was knocked down significantly increased in size compared with the control group. In conclusion, ZKSCAN3 expression was upregulated in several pancreatic cancer cells. Additionally, it was revealed that ZKSCAN3 is negatively correlated with the malignancy of PaCa through autophagy. These results suggest that autophagy regulation via ZKSCAN3 may be a new therapeutic target for PaCa.

Impact of Perioperative Immunonutrition on Postoperative Outcomes for Patients Undergoing Head and Neck or Gastrointestinal Cancer Surgeries: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: To clarify whether perioperative immunonutrition is effective in adult patients with or without malnutrition undergoing elective surgery for head and neck (HAN) or gastrointestinal (GI) cancers. BACKGROUND: It is important to avoid postoperative complications in patients with cancer as they can compromise clinical outcomes. There is no consensus on the efficacy of perioperative immunonutrition in patients with or without malnutrition undergoing HAN or GI cancer surgery. MATERIALS AND METHODS: We searched MEDLINE (PubMed), MEDLINE (OVID), EMBASE, Cochrane Central Register of Controlled Trials, Web of Science Core Selection, and Emcare from 1981 to 2022 using search terms related to immunonutrition and HAN or GI cancer. We included randomized controlled trials. Intervention was defined as immunonutritional therapy including arginine, n-3 omega fatty acids, or glutamine during the perioperative period. The control was defined as standard nutritional therapy. The primary outcomes were total postoperative and infectious complications, defined as events with a Clavien-Dindo classification grade ≥ II that occurred within 30 days after surgery. RESULTS: Of the 4825 patients from 48 included studies, 19 had upper GI cancer, 9 had lower, and 8 had mixed cancer, whereas 12 had HAN cancers. Immunonutrition reduced the total postoperative complications (relative risk ratio: 0.78; 95% CI, 0.66-0.93; certainty of evidence: high) and infectious complications (relative risk ratio: 0.71; 95% CI, 0.61-0.82; certainty of evidence: high) compared with standard nutritional therapy. CONCLUSIONS: Nutritional intervention with perioperative immunonutrition in patients with HAN and GI cancers significantly reduced total postoperative complications and infectious complications.

Clinical significance of colonoscopy before laparoscopic bariatric/metabolic surgery in Japanese patients.

PURPOSE: Obesity is known to be associated with colorectal adenoma (CRA) and colorectal cancer (CRC); yet colonoscopy is not considered an essential preoperative evaluation before bariatric/metabolic surgery. The aim of this study was to clarify the clinical significance of preoperative colonoscopy for obese Japanese patients. METHODS: The subjects of this retrospective study were 114 patients who underwent screening colonoscopy before bariatric/metabolic surgery. Multivariate analyses were performed to evaluate the independent predictors of CRA/CRC among the characteristics identified as significant or nearly significant by univariate analyses. RESULTS: Colonoscopy revealed abnormal findings indicating the need for biopsy or polypectomy in 20 of the 114 patients (17.5%), and CRA was diagnosed in 13 patients (11.4%). Three patients (2.6%), who were all ≥ 56 years old, had a CRA ≥ 10 mm in diameter. The multivariate analysis showed that older age and male sex were significant predictors of CRA/CRC, which was identified in 46.2% of the male patients aged ≥ 46 years. CONCLUSION: Our findings suggest that older age and male sex may be risk factors for CRA/CRC in obese Japanese candidates for bariatric/metabolic surgery; thus, preoperative colonoscopy should be considered for these high-risk patients.

"Role-sharing surgery": a new surgical education system that gives beginner surgeons more chances to operate while ensuring the surgical quality of robotic surgery.

It has been pointed out that robotic surgery is more time-consuming than laparoscopic surgery, and a major challenge for the future is educating young surgeons while maintaining the surgical quality. To solve these problems, we report a role-sharing surgery (RSS) approach in which the surgery is divided into several areas and timetabled, with roles shared by several operators. We performed RSS for 19 standard colorectal cancer surgeries. The surgery was completed within + 28 min of the scheduled operation time, and a beginner robotic surgeon (BRS) was able to perform approximately 66% of the total surgery. There were no statistically significant differences in the short-term outcomes between the RSS and conventional surgery groups. Based on these findings, RSS has the potential to be the best practice for educating BRSs in robotic surgery, the use of which is expected to increase steadily in the future.

[A Case of Transverse Colon Cancer with Gastrointestinal Amyloidosis Prevented from Anastomotic Leakage by Multidimensional Approach].

The patient was a 68-year-old woman who was on hemodialysis due to systemic amyloidosis and nephrotic syndrome. Biopsy revealed amyloid deposition in the stomach, duodenum, and colon. A transverse colon tumor was found on a follow- up CT after the aortic dissection surgery. We performed lower gastrointestinal endoscopy and contrast-enhanced CT and diagnosed transverse colon cancer with gastric wall infiltration(cStage Ⅲc). We considered that transverse colon resection was oncologically sufficient. However, due to concurrent gastrointestinal amyloidosis, which increased the risk of anastomotic leakage we performed laparoscopic extended right hemicolectomy to avoid colon-colon anastomosis with partial gastrectomy. Additionally intraoperative indocyanine green(ICG)fluorescence imaging showed that the fluorescence signal in the small intestinal wall was satisfactory, while it was weak in the colon wall. As a result, we suspected of impaired blood flow of colon wall due to an amyloidosis, so we additionally created a loop ileostomy. It is said that gastrointestinal amyloidosis raises the risk of anastomotic leakage. A case of transverse colon cancer complicated by gastrointestinal amyloidosis in which we successfully prevented anastomotic leakage through a multidimensional evaluation and approach is reported, along with a literature review.

Efficient Establishment of Bile-Derived Organoids From Biliary Cancer Patients.

Patient-derived tumor organoids have considerable potential as an in vitro diagnostic tool for drug susceptibility testing. In the present study, we investigated whether bile collected for diagnostic purposes could be a potential source for the establishment of biliary cancer organoids. Among 68 cases of biliary cancer, we successfully generated 60 bile-derived organoids (BDOs) from individual patients. Consistent with previous reports that described biliary cancer organoids from surgical tissues, the BDOs showed diverse morphologies such as simple cysts, multiloculated cysts, thick capsulated cysts, and solid masses. They also harbored mutations in KRAS and TP53 at frequencies of 15% and 55%, respectively. To enrich the cancer organoids by removing contaminated noncancerous components of BDOs, we attempted to verify the effectiveness of 3 different procedures, including repeat passage, xenografting, and selection with an MDM2 inhibitor for TP53 mutation-harboring BDOs. By monitoring the sequence and expression of mutated TP53, we found that all these procedures successfully enriched the cancer organoids. Our data suggest that BDOs can be established with minimal invasiveness from almost all patients with biliary cancers, including inoperable cases. Thus, despite some limitations with respect to the characterization of BDOs and methods for the enrichment of cancer cell-derived organoids, our data suggest that BDOs could have potential applications in personalized medicine.

Epidemiological and clinical characteristics of myelin oligodendrocyte glycoprotein antibody-associated disease in a nationwide survey.

BACKGROUND: To our knowledge, no nationwide epidemiological study of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) has been conducted. OBJECTIVE: We examined the epidemiology and clinical features of MOGAD in Japan. METHODS: We distributed questionnaires on the clinical characteristics of patients with MOGAD to neurology, pediatric-neurology, and neuro-ophthalmology facilities throughout Japan. RESULTS: In total, 887 patients were identified. The estimated number of total and newly diagnosed MOGAD patients was 1,695 [95% confidence interval (CI): 1483-1907] and 487 (95% CI: 414-560), respectively. The estimated prevalence and incidence were 1.34/100,000 (95% CI: 1.18-1.51) and 0.39/100,000 (95% CI: 0.32-0.44), respectively. The median age at onset was 28 years (range: 0-84 years). At onset, optic neuritis was present in approximately 40% of patients, irrespective of the onset age. Acute disseminated encephalomyelitis was more frequent in younger patients, whereas brainstem encephalitis, encephalitis, and myelitis were more frequent in elderly patients. Immunotherapy was highly effective. CONCLUSION: The prevalence and incidence rates of MOGAD in Japan are similar to those in other countries. Notable characteristics such as the preferential occurrence of acute disseminated encephalomyelitis in children exist; however, general characteristics including symptoms and treatment response are common irrespective of the onset age.

Impact of peroral endoscopic myotomy on high-resolution manometry findings and their association with the procedure's outcomes.

BACKGROUND AND AIMS: Peroral endoscopic myotomy (POEM) is conducted for patients with esophageal motility disorders based on high-resolution manometry (HRM) findings. However, the impact of POEM on HRM findings and the associations between post-POEM HRM and outcomes have not been clarified. METHODS: In a multicenter, observational, cohort study, patients with achalasia treated by POEM received follow-up HRM. Associations between patient characteristics, POEM procedures, and post-POEM HRM findings, including integrated relaxation pressure (IRP) and distal contractile integral (DCI), were investigated. Furthermore, POEM procedure outcomes were compared with post-POEM HRM findings. RESULTS: Of 2171 patients, 151 (7.0%) showed residual high post-POEM IRP (≥26 mm Hg; Starlet [Starmedical Ltd, Tokyo, Japan]). In a multivariate analysis, high pre-POEM IRPs (odds ratio [OR], 24.3) and gastric myotomy >2 cm (OR, .22) were found to be positive and negative predictive factors of high post-POEM IRPs, respectively. Peristalsis recovery (DCI ≥500 mm Hg/cm/s, at least 1 swallow; Starlet) was visible in 121 of 618 patients (19.6%) who had type II to III achalasia. High pre-POEM IRP (OR, 2.65) and DCI ≥500 (OR, 2.98) predicted peristalsis recovery, whereas esophageal dilation (OR, .42) predicted a risk of no recovery. Extended myotomy did not reveal a significant impact on peristalsis recovery. High or low post-POEM IRP and DCI did not increase the incidence of clinical failure, reflux esophagitis, or symptomatic GERD. CONCLUSIONS: Extended gastric myotomy decreased IRP values, whereas peristalsis recovery depended on the characteristics of achalasia. A residual high post-POEM IRP does not necessarily mean clinical failure. Routine HRM follow-up is not recommended after POEM.

Risk scoring system for the preprocedural prediction of the clinical failure of peroral endoscopic myotomy: a multicenter case-control study.

BACKGROUND: Peroral endoscopic myotomy (POEM) is effective for the management of achalasia and its variants; however, it can be ineffective in some patients. We aimed to develop and validate a risk scoring system to predict the clinical failure of POEM preoperatively. METHODS: Consecutive patients who underwent POEM in 14 high volume centers between 2010 and 2020 were enrolled in this study. Clinical failure was defined as an Eckardt score of ≥ 4 or retreatment. A risk scoring system to predict the short-term clinical failure of POEM was developed using multivariable logistic regression and internally validated using bootstrapping and decision curve analysis. RESULTS: Of the 2740 study patients, 112 (4.1 %) experienced clinical failure 6 months after POEM. Risk scores were assigned for three preoperative factors as follows: preoperative Eckardt score (1 point), manometric diagnosis (-4 points for type II achalasia), and a history of prior treatments (1 point for pneumatic dilation or 12 points for surgical/endoscopic myotomy). The discriminative capacity (concordance statistics 0.68, 95 %CI 0.62-0.72) and calibration (slope 1.15, 95 %CI 0.87-1.40) were shown. Decision curve analysis demonstrated its clinical usefulness. Patients were categorized into low (0-8 points; estimated risk of clinical failure < 5 %) and high risk (9-22 points; ≥ 5 %) groups. The proportions of clinical failure for the categories were stratified according to the mid-term outcomes (log-rank test, P < 0.001). CONCLUSIONS: This risk scoring system can predict the clinical failure of POEM preoperatively and provide useful information when making treatment decisions.

Cooperation between artificial intelligence and endoscopists for diagnosing invasion depth of early gastric cancer.

BACKGROUND AND STUDY AIMS: The diagnostic ability of endoscopists to determine invasion depth of early gastric cancer is not favorable. We designed an artificial intelligence (AI) classifier for differentiating intramucosal and submucosal gastric cancers and examined it to establish a diagnostic method based on cooperation between AI and endoscopists. PATIENTS AND METHODS: We prepared 500 training images using cases of mainly depressed-type early gastric cancer from 250 intramucosal cancers and 250 submucosal cancers. We also prepared 200 test images each of 100 cancers from another institution. We designed an AI classifier to differentiate between intramucosal and submucosal cancers by deep learning. We examined the performance of the AI classifier and the majority vote of the endoscopists as high confidence and low confidence diagnostic probability, respectively, and cooperatively combined them to establish a diagnostic method providing high accuracy. RESULTS: Internal evaluation of the training images showed that accuracy, sensitivity, specificity, and F1 measure by the AI classifier were 77%, 76%, 78%, and 0.768, and those of the majority vote of the endoscopists were 72.6%, 53.6%, 91.6%, and 0.662, respectively. A diagnostic method based on cooperation between AI and the endoscopists showed that the respective values were 78.0%, 76.0%, 80.0%, and 0.776 for the test images. The value of F1 measure was especially higher than those by AI or the endoscopists alone. CONCLUSIONS: Cooperation between AI and endoscopists improved the diagnostic ability to determine invasion depth of early gastric cancer.

Clinical characteristics of absent contractility and ineffective esophageal motility: a multicenter study in Japan.

BACKGROUND AND AIM: Absent contractility (AC) and ineffective esophageal motility (IEM) are esophageal hypomotility disorders diagnosed using high-resolution manometry (HRM). Patient characteristics and disease course of these conditions and differential diagnosis between AC and achalasia are yet to be elucidated. METHODS: A multicenter study involving 10 high-volume hospitals was conducted. Starlet HRM findings were compared between AC and achalasia. Patient characteristics including underlying disorders and disease courses were analyzed in AC and IEM. RESULTS: Fifty-three patients with AC and 92 with IEM were diagnosed, while achalasia was diagnosed in 1784 patients using the Chicago classification v3.0 (CCv3.0). The cut-off integrated relaxation pressure (IRP) value at 15.7 mmHg showed maximum sensitivity (0.80) and specificity (0.87) for differential diagnosis of AC from type I achalasia. While most ACs were based on systemic disorders such as scleroderma (34%) and neuromuscular diseases (8%), 23% were sporadic cases. The symptom severity of AC was not higher than that of IEM. Regarding the diagnosis of IEM, the more stringent CCv4.0 excluded 14.1% of IEM patients than the CCv3.0, although patient characteristics did not change. In patients with the hypomotile esophagus, concomitance of reflux esophagitis was associated with low distal contractile integral and IRP values. AC and IEM transferred between each other, paralleling with the underlying disease course, although no transition to achalasia was observed. CONCLUSION: A successful determination of the optimal cut-off IRP value was achieved using the starlet HRM system to differentiate AC and achalasia. Follow-up HRM is also useful for differentiating AC from achalasia. Symptom severity may depend on underlying diseases instead of hypomotility severity.

Neurodevelopment and physical measurements in infants with birthweight of 500 grams or less.

BACKGROUND: In infants born weighing ≤500 g, little has been studied about the association between neurodevelopmental prognosis and growth. This study aimed to evaluate the association between neurodevelopmental impairment (NDI) and z-scores of physical measurements in infants born weighing ≤500 g. METHODS: A single-center, retrospective cohort study in a level IV neonatal intensive care unit in Japan. Infants born weighing ≤500 g between 2010 and 2019 were eligible. Z-scores in weight, length/height, and head circumference at birth, due date (or discharge), 6 and 18 months of corrected age, and 3 years of age were compared between infants with and without NDI at 3 years of age. Three infants with severe intraventricular hemorrhage or periventricular leukomalacia were excluded from the comparison analyses. NDI was defined as having a developmental quotient of ≤70, cerebral palsy, visual impairment, or hearing impairment. RESULTS: Of 22 eligible infants, the incidence of NDI at 3 years of age was 54.5%. The z-score was significantly smaller in the NDI group (n = 10) than that in the non-NDI group (n = 9) in head circumference at birth (median, -1.94 vs. -0.75; Z = 0.54; p = 0.020), and in height at 18 months of corrected age (median, -2.84 vs. -1.79; Z = 0.58; p = 0.013) and 3 years of age (median, -2.02 vs. -1.21; Z = 0.47; p = 0.046). CONCLUSIONS: NDI at 3 years of age was associated with a small head circumference z-score at birth, height at 18 months of corrected age, and height at 3 years of age in infants born weighing ≤500 g.

Prospective cohort study for postnatal cytomegalovirus infection in preterm infants.

AIM: Cytomegalovirus (CMV) is a virus that can cause congenital and postnatal infections. Postnatal CMV is mainly transmitted via breast milk and blood transfusions. Frozen-thawed breast milk is used to prevent postnatal CMV infection. A prospective cohort study was conducted to determine the infection rate, risk, and clinical findings of postnatal CMV infection. METHODS: This prospective cohort study included infants born at 32 weeks or earlier than the gestational age (GA). Participants were prospectively screened for infection in the urine by performing urine CMV DNA tests twice, that is, once within the first 3 weeks of life and again after 35 weeks postmenstrual age (PMA). Postnatal CMV infection was defined as a case of CMV negative tests within 3 weeks of birth and CMV positive tests after 35 weeks PMA. CMV-negative blood products were used for transfusions in all cases. RESULTS: A total of 139 patients were subjected to two urine CMV DNA tests. The prevalence of postnatal CMV infection was 5.0%. One patient died of sepsis-like syndrome. The risk factors of postnatal CMV infection were younger GA and older age of the mother. The characteristic clinical findings of postnatal CMV infection were pneumonia. CONCLUSIONS: Frozen-thawed breast milk feeding is not fully effective in preventing postnatal CMV infection. The prevention of postnatal CMV infection is important to further improve the survival rate of preterm infants. Development of guidelines on breast milk feeding for the prevention of postnatal CMV infection is necessary in Japan.

The cisplatin-induced acute kidney injury is a novel risk factor for postoperative complications in patients with esophageal cancer: a retrospective cohort study.

BACKGROUND: Cisplatin-induced acute kidney injury (AKI) is common during preoperative chemotherapy for esophageal cancer. The purpose of this study was to investigate the association between AKI after preoperative chemotherapy and postoperative complications in patients with esophageal cancer. METHODS: In this retrospective cohort study, we included patients who had received preoperative chemotherapy with cisplatin and underwent surgical resection for esophageal cancer under general anesthesia from January 2017 to February 2022 at an education hospital. A predictor was stage 2 or higher cisplatin-induced AKI (c-AKI) defined by the KDIGO criteria within 10 days after chemotherapy. Outcomes were postoperative complications and length of hospital stays. Associations between c-AKI and outcomes including postoperative complications and length of hospital stays were examined with logistic regression models. RESULTS: Among 101 subjects, 22 developed c-AKI with full recovery of the estimated glomerular filtration (eGFR) before surgery. Demographics were not significantly different between patients with and without c-AKI. Patients with c-AKI had significantly longer hospital stays than those without c-AKI [mean (95% confidence interval (95%CI)) 27.6 days (23.3-31.9) and 43.8 days (26.5-61.2), respectively, mean difference (95%CI) 16.2 days (4.4-28.1)]. Those with c-AKI had higher C-reactive protein (CRP) levels and prolonged weight gain after surgery and before the events of interest despite having comparable eGFR trajectories after surgery. c-AKI was significantly associated with anastomotic leakage and postoperative pneumonia [odds ratios (95%CI) 4.14 (1.30-13.18) and 3.87 (1.35-11.0), respectively]. Propensity score adjustment and inverse probability weighing yielded similar results. Mediation analysis showed that a higher incidence of anastomotic leakage in patients with c-AKI was primarily mediated by CRP levels (mediation percentage 48%). CONCLUSION: c-AKI after preoperative chemotherapy in esophageal cancer patients was significantly associated with the development of postoperative complications and led to a resultant longer hospital stay. Increased vascular permeability and tissue edema due to prolonged inflammation might explain the mechanisms for the higher incidence of postoperative complications.

Achalasia phenotypes and prediction of peroral endoscopic myotomy outcomes using machine learning.

OBJECTIVES: High-resolution manometry (HRM) and esophagography are used for achalasia diagnosis; however, achalasia phenotypes combining esophageal motility and morphology are unknown. Moreover, predicting treatment outcomes of peroral endoscopic myotomy (POEM) in treatment-naïve patients remains an unmet need. METHODS: In this multicenter cohort study, we included 1824 treatment-naïve patients diagnosed with achalasia. In total, 1778 patients underwent POEM. Clustering by machine learning was conducted to identify achalasia phenotypes using patients' demographic data, including age, sex, disease duration, body mass index, and HRM/esophagography findings. Machine learning models were developed to predict persistent symptoms (Eckardt score ≥3) and reflux esophagitis (RE) (Los Angeles grades A-D) after POEM. RESULTS: Machine learning identified three achalasia phenotypes: phenotype 1, type I achalasia with a dilated esophagus (n = 676; 37.0%); phenotype 2, type II achalasia with a dilated esophagus (n = 203; 11.1%); and phenotype 3, late-onset type I-III achalasia with a nondilated esophagus (n = 619, 33.9%). Types I and II achalasia in phenotypes 1 and 2 exhibited different clinical characteristics from those in phenotype 3, implying different pathophysiologies within the same HRM diagnosis. A predictive model for persistent symptoms exhibited an area under the curve of 0.70. Pre-POEM Eckardt score ≥6 was the greatest contributing factor for persistent symptoms. The area under the curve for post-POEM RE was 0.61. CONCLUSION: Achalasia phenotypes combining esophageal motility and morphology indicated multiple disease pathophysiologies. Machine learning helped develop an optimal risk stratification model for persistent symptoms with novel insights into treatment resistance factors.

[A Case Report of Hepatic Angiosarcoma Developed against the Background of Hepatic Hemochromatosis].

A 35-year-old man who had fever and stomachache was referred to our hospital. He underwent surgery and chemoradiotherapy for neuroblastoma as a child and subsequently developed leukemia. Frequent blood transfusions and bone marrow transplants were performed due to anemia. Abdominal contrast CT scan and contrast MRI showed tumorous lesions with a diameter of 60×42 mm in liver S6, and a tendency to increase in a short term. There was also hemochromatosis in the liver. We considered it a malignant tumor and performed a right lobectomy. Pathological examination diagnosed the tumor hepatic angiosarcoma. The postoperative course was fine and he was discharged without complications. But multiple liver metastases appeared 6 months after surgery. We performed chemotherapy but he passed away 10 months after surgery. Hepatic angiosarcoma is a rare disease among liver malignancies and has a very poor prognosis. As for the cause of hepatic angiosarcoma, many of them are unknown, but chronic exposures such as vinyl monomers have been reported in some cases. Hemochromatosis has been reported as a background factor for malignant tumors such as hepatocellular carcinoma. In this case it is possible that it contributed to the development of hepatic angiosarcoma.

[A Case of Surgical Resection of Advanced Gallbladder Cancer with Adult Annular Pancreas].

An-81-year-old man presented to another doctor complaining of epigastric pain. He was referred to us after the laboratory data revealed a high serum CEA and abdominal ultrasonography showed the space occupying lesion in the left liver. Abdominal CT revealed advanced gallbladder cancer infiltrating the liver and colon and found annular pancreas surrounding the descending portion of duodenum. We chose partial hepatectomy(S4a+S5), extrahepatic bile duct resection with hepaticojejunostomy and partial colectomy. Pathological diagnosis of the tumor was pT3N1M0, gallbladder cancer. The patient was discharged on the 21 days after operation. The frequency of malignant tumors in adult annular pancreas are not revealed. But some cases present with adult annular pancreas complicating the biliary tract tumor. We experienced a case of advanced gallbladder cancer with adult annular pancreas and report our case and review the pertinent literature.

[An Intraductal Papillary Mucinous Neoplasm of the Pancreas with Metachronous Quadruple Cancers].

The patient described herein was diagnosed with left breast, endometrial, and early gastric cancers at 49, 53, and 57 years of age, respectively. Magnetic resonance cholangiopancreatography performed when she was undergoing treatment for cholecystitis at 50 years of age showed local pancreatic duct dilatation in the pancreatic head. She was followed in the Department of Gastroenterology at our hospital for an intraductal papillary mucinous neoplasm(IPMN). An abdominal computed tomography scan obtained at 59 years of age revealed dilation of the main pancreatic duct in the pancreas body and tail, therefore an endoscopic ultrasound-guided fine needle aspiration was performed. She was diagnosed with pancreatic cancer and underwent a laparoscopic distal pancreatectomy. The postoperative course was uneventful; however, the pancreatic cancer recurred and she died approximately 14 months postoperatively. Reports of multiple cancers associated with IPMNs are rare, yet we managed a patient with a pancreatic head IPMN complicated by metachronous quadruple carcinomas( breast, endometrial, gastric, and pancreatic cancers).

Risks of refractory chest pain after peroral endoscopic myotomy in achalasia-related esophageal motility disorders: short-term results from a multicenter study in Japan.

BACKGROUND AND AIMS: The etiology of chest pain in achalasia-related esophageal motility disorders and the frequency and risk factors of persistent chest pain after peroral endoscopic myotomy (POEM) remain unclear. METHODS: A multicenter cohort study including 14 hospitals was conducted to elucidate the characteristics of patients with chest pain and the efficacy of POEM. RESULTS: Consecutive cases of achalasia-related esophageal motility disorders included 2294 (64.2%) and 1280 (35.8%) patients with and without chest pain, respectively. Among the 2107 patients with chest pain who underwent POEM, we observed complete remission in 1464 patients (69.5%) and nonremission in 643 patients (30.5%), including a partial response in 619 patients (29.4%) and resistance in 24 patients (1.1%). Multivariate analysis revealed that advanced age (odds ratio [OR], .28), male sex (OR, .70), prior treatment (OR, 1.39), and sigmoid type (OR, .65) were related to the prevalence of chest pain. Long disease duration (OR, .69) and esophageal dilation (OR, .79) were related to decreased severity. POEM improved patients' quality of life that was hindered by chest pain. Early onset (OR, 1.45), advanced age (OR, .58), male sex (OR, .79), prior treatment (OR, 1.37), and posterior myotomy (OR, 1.42) were associated with nonremission after POEM; high-resolution manometry (HRM) findings and myotomy length showed no statistical significance on pain etiology and persistence after POEM. CONCLUSIONS: The prevalence and severity of chest pain were dependent on age, sex, disease duration, prior treatment, and esophageal morphology rather than HRM findings. The efficacy of POEM is satisfactory; however, residual pain was often observed. Excessively long myotomy can be avoided, and anterior myotomy may be recommended.

Risk factors and long-term course of gastroesophageal reflux disease after peroral endoscopic myotomy: A large-scale multicenter cohort study in Japan.

BACKGROUND : Gastroesophageal reflux disease (GERD) and reflux esophagitis remain problems after peroral endoscopic myotomy (POEM). This study aimed to elucidate the risk factors and long-term course of reflux esophagitis and symptomatic GERD after POEM. METHODS : This multicenter cohort study involved 14 high volume centers. Overall, 2905 patients with achalasia-related esophageal motility disorders treated with POEM were analyzed for reflux esophagitis, severe reflux esophagitis (Los Angeles classification C or D), and symptomatic GERD. RESULTS : Reflux esophagitis was diagnosed in 1886 patients (64.9 %). Age ≥ 65 years (risk ratio [RR] 0.85), male sex (RR 1.11), posterior myotomy (RR 1.12), esophageal myotomy > 10 cm (RR 1.12), and gastric myotomy > 2 cm (RR 1.17) were independently associated with reflux esophagitis. Severe reflux esophagitis was diagnosed in 219 patients (7.5 %). Age ≥ 65 years (RR 1.72), previous treatments (RR 2.21), Eckardt score ≥ 7 (RR 0.68), sigmoid-type achalasia (RR 1.40), and esophageal myotomy > 10 cm (RR 1.59) were factors associated with severe reflux esophagitis. Proton pump inhibitors (PPIs) were more effective for reflux esophagitis at 5-year follow-up (P = 0.03) than after 1 year (P = 0.08). Symptomatic GERD was present in 458 patients (15.9 %). Symptom duration ≥ 10 years (RR 1.28), achalasia diagnosis (RR 0.68), integrated relaxation pressure ≥ 26 (RR 0.60), and posterior myotomy (RR 0.80) were associated with symptomatic GERD. The incidence of symptomatic GERD was lower at 5-year follow-up compared with that after 1 year (P = 0.04), particularly in PPI users (P < 0.001). CONCLUSIONS : The incidence of severe reflux esophagitis was low after POEM, but excessive myotomy for older patients with previous treatments should be avoided. Early phase symptomatic GERD is non-acid reflux dependent and the natural course is favorable, basically supporting conservative treatment.