Lymphadenopathy Tissue Sampling by EUS-Guided Fine-Needle Biopsy Contributes to Meeting the Conditions for Genomic Profiling.

BACKGROUND AND AIMS: EUS-guided fine-needle biopsy (EUS-FNB) performed with a Franseen needle or Fork-tip needle enables greater tissue acquisition. However, it is unknown whether EUS-FNB could contribute to lymphadenopathy genomic profiling. The aim of this study was to determine the efficacy of EUS-FNB using a Franseen or Fork-tip needle for tissue acquisition and genomic profiling in patients with lymphadenopathy. PATIENTS AND METHODS: Patients with abdominal lymphadenopathy who underwent EUS-guided fine needle aspiration (FNA)/EUS-FNB were included in this study. The amount of acquired tissue and its suitability for genomic profiling were compared between FNA and FNB. Specimen quality was evaluated by a widely used pathologic adequacy scoring system (0: insufficient; 1 to 2: cytologic; 3: limited histologic; 4 to 5: sufficient histologic). The criteria of FoundationOne CDx (F1CDx) and NCC Oncopanel (NOP) were used to assess the suitability for genomic profiling. RESULTS: In total, 72 patients underwent EUS-FNA, and the other 20 patients underwent EUS-FNB. The pathologic adequacy score and suitability for genomic profiling based on the criteria were significantly higher for FNB than for FNA [histologic adequacy score: 5 (4 to 5) versus 3 (0 to 5), P<0.01; F1CDx: 16.7% vs. 0%, P=0.01; NOP: 66.7% vs. 7.5%, P<0.01]. In multivariate analysis, EUS-FNB was identified as the only factor that influenced the suitability for genomic profiling based on the above-mentioned criteria (odds ratio 19.5, 95% CI: 3.74-102, P<0.01). CONCLUSIONS: EUS-FNB performed using Franseen or Fork-tip needles may result in greater lymphadenopathy tissue acquisition and thus enhanced suitability for genomic profiling compared with EUS-FNA.

Factors Associated With Difficult Endoscopic Ultrasonography-guided Biliary Drainage.

BACKGROUND AND AIMS: When endoscopic retrograde cholangiopancreatography-guided biliary drainage is challenging, endoscopic ultrasound-guided biliary drainage (EUS-BD) can be used as an alternate treatment; however, this method requires operator expertise. Therefore, this study aimed to clarify the factors that are associated with a difficult EUS-BD. PATIENTS AND METHODS: Patients who successfully underwent EUS-BD were enrolled in this study. The patients were divided into the easy group and difficult group depending on whether the procedural time was more than 60 minutes, which was the cutoff value elicited from past reports. Patient characteristics and procedural factors were compared between the two groups. The factors associated with difficult procedures were also investigated. RESULTS: The patient characteristics were not significantly different between the easy group (n=22) and the difficult group (n=19). The diameter of the punctured bile duct was significantly different between the two groups. In the multivariate analysis, the diameter of the punctured bile duct was the only factor associated with a difficult EUS-BD (odds ratio 0.65, 95% confidence interval 0.46-0.91, P value=0.012). The cutoff value for the diameter of the punctured bile duct in predicting a difficult EUS-BD was 7.0 mm (area under the curve: 0.83, sensitivity 84.2%, specificity 86.4%). CONCLUSIONS: A nondilated bile duct might be a predictive factor for a difficult EUS-BD. For beginners of EUS-BD, the cutoff value for the punctured bile duct diameter found in this study, 7.0 mm, might become a barometer for puncture point selection.

Prevalence of Cardiac Amyloidosis in Patients Undergoing Carpal Tunnel Release With Amyloid Deposition.

BACKGROUND: Carpal tunnel syndrome (CTS) is considered an early sign of cardiac amyloidosis (CA) because amyloid deposition is often confirmed in the tenosynovium removed during carpal tunnel release (CTR); however, the prevalence of concomitant CA is unclear.Methods and Results: We prospectively examined 700 patients who underwent CTR and evaluated amyloid deposition after tenosynovium removal. Amyloid deposition was observed in 261 (37%) patients, who were significantly older and predominantly male (P<0.05). Of them, 120 agreed to cardiac screening. We performed 99 mTc-labeled pyrophosphate (99 mTc-PYP) scintigraphy in 12 patients who met either of the following criteria: (1) interventricular septal diameter (IVSd) ≥14 mm or (2) 12 mm ≤ IVSd < 14 mm with above-normal limits in high-sensitivity cardiac troponin T (hs-cTnT). Six patients (50%) had positive findings on 99 mTc-PYP scintigraphy and were diagnosed with wild-type transthyretin CA. Concomitant CA was observed in 6/120 (5%) CTR patients with amyloid deposition and 50% (6/12) in patients with left ventricular hypertrophy (≥12 mm) with increased hs-cTnT levels. CONCLUSIONS: Amyloid deposition was frequently observed in the removed tenosynovium of elderly men with CTS. Cardiac screening may be useful for early diagnosis of CA in patients undergoing CTR with amyloid deposition.

Novel Photodynamic Therapy for Esophageal Squamous Cell Carcinoma following Radiotherapy.

Radiotherapy (RT) or chemoradiotherapy (CRT) are frequently selected as treatments for esophageal squamous cell carcinoma (ESCC). However, salvage treatment remains challenging when endoscopic resection is not indicated for residual or recurrent ESCC following RT or CRT. Recently, owing to the emergence of second-generation photodynamic therapy (PDT) using talaporfin sodium, PDT can be performed with less phototoxicity and therefore has regained popularity in the treatment of ESCC. In this study, the effectiveness and safety of second-generation PDT in patients with residual or recurrent ESCC following RT or CRT were examined. Local complete response (L-CR) rates, procedure-related adverse events, and prognosis were evaluated. In 12 patients with 20 ESCC lesions, the L-CR rates were 95.0%. Perforation, postoperative bleeding, and photosensitivity were not observed. Esophageal stricture following PDT developed in one patient, but this could be addressed using balloon dilation. During a median follow-up period of 12 (range, 3-42) months, the 3-year cause-specific survival rate was 85.7%. Even in patients with a Charlson comorbidity index score ≥ 3, the 2-year overall survival rates were 100%. In conclusion, PDT was an efficacious and a safe salvage treatment in patients with local residual or recurrent ESCC following RT or CRT.

Comparison of time to recurrent biliary obstruction between plastic stents and metallic stents for endoscopic ultrasound­guided biliary drainage.

Endoscopic ultrasound-guided biliary drainage (EUS-BD) may prevent stent placement at the bile duct stricture. Therefore, whether a plastic stent (PS) or metallic stent (MS) should be used for EUS-BD remains to be undetermined. The present study aimed to clarify whether a PS or MS was more efficient for EUS-BD. Patients with malignant biliary obstruction who were successfully treated with EUS-BD were enrolled in the present study. The clinical characteristics, procedural outcomes and time to recurrent biliary obstruction (TRBO) were compared between patients treated with a PS (PS group) and patients treated with an MS (MS group). Consequently, 28 patients underwent PS placement and 11 patients underwent MS placement. In the PS group, 12 patients also underwent EUS-antegrade stenting (AGS) using an MS. The TRBO was not significantly different between the two groups (P=0.25). When the patients with AGS were excluded, the TRBO was significantly longer in the MS group than in the PS group (P=0.036). However, the TRBO was not significantly different between the patients in the MS group and those in the PS group who underwent AGS (P=0.61). In EUS-BD, MS is expected to be associated with a longer TRBO than PS. However, combining EUS-BD with AGS may help overcome the shorter TRBO associated with the use of PS.

Clinical benefit of subsequent chemotherapy after drug-induced interstitial lung disease in pancreatic cancer patients: a multicenter retrospective study from Japan.

PURPOSE: Drug-induced interstitial lung disease (ILD) is not a rare adverse event in the current chemotherapy strategy for pancreatic ductal adenocarcinoma (PDAC). Thus, we aimed to find the optimal management for PDAC patients with a history of ILD induced by a gemcitabine-based regimen. METHODS: We conducted a multicenter retrospective study. The primary endpoint was the overall survival (OS) of patients who underwent either S-1 monotherapy or FOLFOX after the onset of ILD. Toxicity data was also analyzed in the 2 groups. RESULTS: Twenty-four patients were diagnosed with ILD and 17 patients who received subsequent chemotherapy were enrolled in the study. Among 17 patients who were managed with subsequent chemotherapy after recovering from ILD, we did not observe significant difference in OS between S-1 and FOLFOX (290.0 days vs. undefined, p = 0.39). Relapse of drug-induced ILD was not observed in all cases during the course. Overall, severe adverse events (CTCAE Grade 3 or 4) were observed in 3 patients (23.1%) in S-1 treatment group and 1 patient (25.0%) in FOLFOX treatment group (p = 0.93). CONCLUSIONS: S-1 monotherapy and FOLFOX are comparable as the subsequent chemotherapy after gemcitabine-based chemotherapy-induced ILD in unresectable PDAC.

A neonate with multiple hand flexor tendon ruptures due to methicillin-susceptible Staphylococcus aureus sepsis: a case report.

BACKGROUND: Neonatal pyogenic tenosynovitis is a highly emergent soft tissue infection. We report a case of a neonate with pyogenic tendinopathy and tendon rupture diagnosed by ultrasonography (US). He subsequently developed pyogenic arthritis and osteomyelitis during antimicrobial therapy. CASE PRESENTATION: A 7-day-old boy was admitted to our hospital with redness and swelling of the right index finger. US on admission showed rupture of the flexor tendon of the right index finger with inactivity. The day after admission, he developed pyogenic arthritis of the right elbow and, subsequently, pyogenic osteomyelitis. Staphylococcus aureus was identified through bacterial culture, and the patient was treated with intravenous antibiotics for 6 weeks. However, after discharge from our hospital, rupture of the flexor tendon of the left thumb was confirmed. A two-stage flexor tendinoplasty was completed at the age of 2 years and 1 month for the flexor tendon rupture on his right index finger. CONCLUSIONS: In addition to blood culture, ultrasonographic evaluation should be performed in neonates with erythematous and swollen joints to identify the focus of infection as soon as possible. Moreover, repeated regular US examination is important in the follow-up of bone and soft tissue infections.

A multicenter comparative study of endoscopic ultrasound-guided fine-needle biopsy using a Franseen needle versus conventional endoscopic ultrasound-guided fine-needle aspiration to evaluate microsatellite instability in patients with unresectable pancreatic cancer.

BACKGROUND/AIMS: Immune checkpoint blockade has recently been reported to be effective in treating microsatellite instability (MSI)-high tumors. Therefore, sufficient sampling of histological specimens is necessary in cases of unresectable pancreatic cancer (UR-PC). This multicenter study investigated the efficacy of endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) using a Franseen needle for MSI evaluation in patients with UR-PC. METHODS: A total of 89 patients with UR-PC who underwent endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) or EUS-FNB using 22-G needles at three hospitals in Japan (2018-2021) were enrolled. Fifty-six of these patients (FNB 23 and FNA 33) were followed up or evaluated for MSI. Patient characteristics, UR-PC data, and procedural outcomes were compared between patients who underwent EUS-FNB and those who underwent EUS-FNA. RESULTS: No significant difference in terms of sufficient tissue acquisition for histology was observed between patients who underwent EUS-FNB and those who underwent EUS-FNA. MSI evaluation was possible significantly more with tissue samples obtained using EUS-FNB than with tissue samples obtained using EUS-FNA (82.6% [19/23] vs. 45.5% [15/33], respectively; p<0.01). In the multivariate analysis, EUS-FNB was the only significant factor influencing the possibility of MSI evaluation. CONCLUSION: EUS-FNB using a Franseen needle is desirable for ensuring sufficient tissue acquisition for MSI evaluation.

Endoscopic submucosal dissection for superficial esophageal squamous cell carcinoma in patients with cirrhosis and esophageal varices.

Endoscopic submucosal dissection (ESD) has become the standard treatment for superficial esophageal squamous cell carcinoma (SESCC). However, the treatment strategy for SESCC complicated by esophageal varices (EVs) has not been established. We report two cases of SESCC in patients with alcoholic cirrhosis complicated by EVs who underwent ESD. Case 1 presented with EVs on the anal side of the SESCC, and endoscopic variceal ligation (EVL) was performed before ESD. After EVL, the SESCC was successfully treated by ESD without any adverse events. Case 2 presented EVs from the anal side of the SESCC to the submucosa just below the SESCC. Then, EVL and endoscopic injection sclerotherapy with polidocanol were performed before ESD. However, ESD was not completed because of severe bleeding by uncontrolled blood flow below and around the SESCC. Bleeding during ESD was controlled in case 1, but not in case 2.

Intracellular C3 Modulates EMT via the Akt/Smad Pathway in Pancreatic Cancer Cells.

BACKGROUND/AIM: We aimed to explore the role of intracellular C3 in pancreatic ductal adenocarcinoma (PDAC). MATERIALS AND METHODS: We evaluated C3 expression in PDAC using a gene expression database and tissue microarray. To clarify the role of C3 expression in PDAC, we conducted knockdown experiments using C3 short hairpin RNA (shRNA) in BxPC-3 cells. Differences in protein expression and cell behaviours were analysed. RESULTS: C3 was highly expressed in PDAC and correlated with cancer metastasis. In vitro experiments using BxPX-3 cells showed that C3 and its active form, C3a, were expressed in tumour cells. C3 knockdown reduced cell migration and invasion by inhibiting Akt/Smad pathway activation. TNF-α, not IL-6, enhanced C3 expression in this PDAC cell line. CONCLUSION: Intracellular C3 may regulate epithelial-mesenchymal transition in pancreatic cancer.

Association between Submucosal Fibrosis and Endoscopic Submucosal Dissection of Recurrent Esophageal Squamous Cell Cancers after Chemoradiotherapy.

Endoscopic resection is a treatment of choice for a metachronous early-stage esophageal squamous cell carcinoma (ESCC) appearing after a radical cure of esophageal cancer by chemoradiotherapy (CRT). However, non-curative resection, and procedural complications including perforation due to radiation-induced submucosal fibrosis, are a concern. This study aimed to evaluate the association between submucosal fibrosis and the usefulness and safety of endoscopic submucosal dissection (ESD) in ESCC after CRT. This study retrospectively analyzed 13 lesions in 11 patients in our institute. Submucosal fibrosis under the lesion (F score) was classified into three levels (F0: none or mild, F1: moderate, and F2: severe) based on endoscopic and histopathologic findings. All lesions were F1 or greater (F1: 8 lesions and F2: 5 lesions). En bloc and R0 resection rates were both 100%. The procedural speed was slower in F2 than in F1 (F1 vs. F2; 15.1 mm2/min vs. 7.1 mm2/min, p = 0.019), without procedure-related adverse events. At a median follow-up of 42 months (range: 14-117 months) after ESD, 7 of 11 (63.6%) patients were alive without recurrence, and without ESCC-related death. ESCC after CRT reliably and safely resected en bloc by ESD but was more difficult in lesions with strong submucosal fibrosis.

Endoscopic Submucosal Dissection in Patients with Early Gastric Cancer in the Remnant Stomach.

Endoscopic submucosal dissection (ESD) in patients with early gastric cancers (EGCs) in the remnant stomach is technically difficult, owing to the limited space and fibrosis under the suture lines and anastomoses. Conversely, ESD for patients with EGCs in the remnant stomach is less invasive and provides better quality of life than completion total gastrectomy. To clarify the effectiveness and safety of ESD, we reviewed the medical records of patients with EGCs in the remnant stomach who underwent ESD between July 2006 and October 2020 at our institution. All identified patients were included in the analysis. Of 25 patients with 27 lesions, the en bloc and R0 resection rates were 88.9% and 85.2%, respectively. Neither perforation nor postoperative bleeding was observed. During a median follow-up period of 48 (range, 5-162) months, the 5-year overall survival rate was 71.0%, whereas the 5-year cause-specific survival rate was 100%. No obvious differences in the outcomes of procedures with suture line involvement and without suture line or anastomosis involvement were noted. In conclusion, ESD was effective and safe in patients with EGCs in the remnant stomach despite the suture line involvement.

Screening for hilar biliary invasion in ampullary cancer patients.

BACKGROUND: The treatment for ampullary cancer is pancreatoduodenectomy or local ampullectomy. However, effective methods for the preoperative investigation of hilar biliary invasion in ampullary cancer patients have not yet been identified. AIM: To determine the necessity of and an appropriate method for investigating hilar biliary invasion of ampullary cancer. METHODS: Among 43 ampullary cancer patients, 34 underwent endoscopic treatment (n = 9) or surgery (n = 25). The use of imaging findings (thickening and enhancement of the bile duct wall on contrast-enhanced computed tomography, irregularity on endoscopic retrograde cholangiography, thickening of the entire bile duct wall on intraductal ultrasonography (IDUS), and partial thickening of the bile duct wall on IDUS) and biliary biopsy results for diagnosing hilar biliary invasion of ampullary cancer was compared. RESULTS: Hilar invasion was not observed in every patient. Among the patients who did not undergo biliary stent insertion, the combination of partial thickening of the bile duct wall on IDUS and biliary biopsy results showed the highest accuracy (100%) for diagnosing hilar biliary invasion. However, each imaging method and biliary biopsy yielded some false-positive results. CONCLUSION: Although some false-positive results were obtained with each method, the combination of partial thickening of the bile duct wall on IDUS and biliary biopsy results was useful for diagnosing hilar biliary invasion of ampullary cancer. However, hilar invasion of ampullary cancer is rare; therefore, the investigation of hilar biliary invasion of ampullary cancer might be unnecessary.

Clinical usefulness and acceleratory effect of macrophage inhibitory cytokine-1 on biliary tract cancer: an experimental biomarker analysis.

BACKGROUND: Biliary tract cancer (BTC) has a poor prognosis; therefore, useful biomarkers and treatments are needed. Serum levels of macrophage inhibitory cytokine-1 (MIC-1), a member of the TGF-ß superfamily, are elevated in patients with pancreaticobiliary cancers. However, the effect of MIC-1 on BTC is unknown. Therefore, we investigated the effect of MIC-1 on BTC and assessed whether MIC-1 is a biomarker of or therapeutic target for BTC. METHODS: MIC-1 expression in BTC cells was determined by performing histological immunostaining, tissue microarray (TMA), western blotting, and reverse transcription PCR (RT-PCR). Cell culture experiments were performed to investigate the effect of MIC-1 on BTC cell lines (HuCCT-1 and TFK-1). The relationships between serum MIC-1 levels and either the disease state or the serum level of the apoptosis marker M30 were retrospectively verified in 118 patients with pancreaticobiliary disease (individuals with benign disease served as a control group, n = 62; BTC, n = 56). The most efficient diagnostic marker for BTC was also investigated. RESULTS: MIC-1 expression was confirmed in BTC tissue specimens and was higher in BTC cells than in normal bile duct epithelial cells, as determined using TMA, western blotting and RT-PCR. In cell culture experiments, MIC-1 increased BTC cell proliferation and invasion by preventing apoptosis and inhibited the effect of gemcitabine. In serum analyses, serum MIC-1 levels showed a positive correlation with BTC progression and serum M30 levels. The ability to diagnose BTC at an early stage or at all stages was improved using the combination of MIC-1 and M30. The overall survival was significantly longer in BTC patients with serum MIC-1 < the median than in BTC patients with serum MIC-1 ≥ the median. CONCLUSIONS: MIC-1 is a useful diagnostic and prognostic biomarker and might be a potential therapeutic target for BTC.

Transjejunal endoscopic ultrasound-guided pancreatic drainage for pancreatic jejunostomy stricture using a forward-viewing echoendoscope in a patient with altered anatomy.

Pancreatic jejunostomy stricture (PJS) is one of the major late complications after pancreaticoduodenectomy. Endoscopic ultrasound-guided pancreatic drainage (EUS-PD) is considered a salvage treatment for symptomatic PJS after endoscopic retrograde pancreatography failure; however, the technical success rate of the endoscopic treatment of PJS remains unsatisfactory, mainly due to surgically altered anatomy. Herein, we describe a case of PJS successfully treated with transjejunal EUS-PD using a forward-viewing echoendoscope. A 62-year-old man who suffered from repetitive severe back pain due to PJS was referred to our hospital. Since transgastric EUS-PD was difficult, we attempted transjejunal EUS-PD using a forward-viewing echoendoscope. To facilitate scope insertion, we first straightened the afferent jejunal loop and placed a stiff guidewire. With this scheme, we successfully performed transjejunal EUS-PD and placed a 5-Fr plastic stent. In conclusion, this technique is useful for treating patients with PJS when transgastric EUS-PD is difficult.

Biliary metal stents should be placed near the hilar duct in distal malignant biliary stricture patients.

BACKGROUND: Endoscopic biliary drainage using a self-expandable metallic stent (SEMS) has been widely performed to treat distal malignant biliary obstruction (DMBO). However, the optimal position of the stent remains unclear. AIM: To determine the ideal position for SEMS placement. METHODS: In total, 135 DMBO patients underwent SEMS (uncovered or covered) placement over a ten-year period. A total of 127 patients with biliary obstruction between the junction of the cystic duct and Vater's papilla were enrolled. An SEMS was placed through the upper common bile duct 2 cm from the biliary hilar duct in 83 patients (Hilar group) or near the top of the biliary obstruction in 44 patients (Lower group). Technical and functional success, adverse events, and risk factors for SEMS dysfunction were evaluated. RESULTS: The stent patency period was significantly longer in the Hilar group than in the Lower group (P value < 0.01). In multivariate analysis, the only statistically significant risk factor for SEMS dysfunction was being in the Lower group (hazard ratio: 9.94, 95% confidence interval: 2.25-44.0, P < 0.01). CONCLUSION: A longer patency period was achieved by positioning the SEMS near the biliary hilar duct.

Efficacy of a novel large-cell Niti-S stent with a slim delivery system for hilar biliary obstruction: a preliminary study.

OBJECTIVES: The large-cell Niti-S stent is useful for multiple stenting in patients with malignant hilar biliary obstruction (MHBO). Recently, a novel uncovered self-expandable metallic stent (USEMS) (a Niti-S large-cell SR slim delivery system) was developed. In this study, we aimed to evaluate the efficacy of this USEMS slim delivery system in MHBO patients. MATERIALS AND METHODS: Outcomes related to USEMS placement, the clinical course, and the period to recurrent biliary obstruction (RBO) were evaluated in MHBO patients who received multiple USEMSs with the Niti-S large-cell SR slim delivery system. RESULTS: Twenty-two MHBO patients underwent the placement of multiple USEMSs, including the novel slim-delivery stent. Six patients had a past history of upper gastrointestinal reconstruction (Billroth I: 1, Billroth II: 4, Roux-en-Y: 1). The number of USEMSs placed in each patient was 2-6. Three procedures were reinterventions. The new slim delivery system was placed as the first stent in ten patients and as an additional stent in the remaining patients. Seven patients were drained using only Niti-S large-cell SR slim delivery stents. The technical and clinical success rates were both 100%. CONCLUSIONS: Placing multiple USEMSs in patients with a past history of abdominal surgery or in reintervention is difficult. Although difficult cases were included in this study, stent-in-stent placement with the novel Niti-S large-cell SR slim delivery system was useful in treating MHBO patients. In addition, this novel stent might be the first choice for MHBO patients.KEY MESSAGESEndoscopic multistenting for MHBO is challenging. In addition, reintervention or multistenting for MHBO patients with a past history of abdominal surgery becomes more difficult.The novel Niti-S large-cell SR slim delivery USEMS is useful as an additional stent because the delivery system is thin and suitable for a 0.025 guidewire. In addition, the novel stent is of the braided type and has a large mesh. Therefore, the novel stent is expected to have strong radial force and can be used as the first SEMS.The Niti-S large-cell SR slim delivery stent is long enough to be used in patients with upper gastrointestinal reconstruction. Although this study included patients with reintervention or a past history of upper gastrointestinal reconstruction, the technical success rate of multiple stenting for MHBO patients was 100%. The slim-delivery stent might overcome several difficulties of endoscopic multistenting.

The Complement C3a-C3a Receptor Axis Regulates Epithelial-to-Mesenchymal Transition by Activating the ERK Pathway in Pancreatic Ductal Adenocarcinoma.

BACKGROUND: We aimed to clarify the role of complement C3a and its receptor C3aR in progression of pancreatic ductal adenocarcinoma (PDAC). MATERIALS AND METHODS: We evaluated the serum levels of C3 and C3a in patients with PDAC. C3aR expression in tissue was assessed using a tissue microarray. To confirm the protumoral effects of C3a in PDAC, we conducted in vitro experiments using PDAC cell lines (Panc-1 and MiaPaca-2) that exhibit high C3aR expression. RESULTS: Serum levels of both C3 and C3a were higher in 26 patients with PDAC than in 28 nontumor-bearing controls. In the tissue microarray, we observed increased expression of C3aR in PDAC cells, especially in cases with metastatic lesions. In vitro experiments showed that C3a facilitated tumor cell proliferation, migration and invasion by activating the extracellular-regulated kinase signaling pathway and inducing epithelial-to-mesenchymal transition. Inhibition of the C3a-C3aR axis by pharmacological blockade and short-hairpin RNA-mediated knockdown of C3aR alleviated its protumoral effect. CONCLUSION: These findings provide a new approach for the development of treatments targeting the C3a-C3aR axis.

Drug treatment for chemotherapy-induced peripheral neuropathy in patients with pancreatic cancer.

Pancreatic cancer (PC) is a lethal disease where most tumors are too advanced at diagnosis for resection, leaving chemotherapy as the mainstay of treatment. Although the prognosis of unresectable PC is poor, it has been dramatically improved by new chemotherapy treatments, such as the combination of 5-fluorouracil, oxaliplatin, irinotecan, and leucovorin (FOLFIRINOX) or gemcitabine plus nab-paclitaxel. However, as oxaliplatin and paclitaxel are common neurotoxic drugs, chemotherapy-induced peripheral neuropathy (CIPN) is a common and severe adverse effect of both treatments. As there are no agents recommended in the ASCO guidelines, we review the methods used to treat CIPN caused by PC treatment. The efficacy of duloxetine was observed in a large randomized controlled trial (RCT). In addition, pregabalin was more effective than duloxetine for CIPN in two RCTs. Although duloxetine and pregabalin can be effective for CIPN, they have several side effects. Therefore, the choice between the two drugs should be determined according to effect and tolerability. Mirogabalin is also used in patients with PC and there is hope it will yield positive outcomes when treating CIPN in the future.

Esophageal achalasia with severe malnutrition and liver enzyme elevation.

A 70-year-old woman presented dysphagia and postprandial vomiting, and weight loss of about 15 kg in one year. She was markedly emaciated with a body mass index of 12.4 kg/m2 and had difficulty in movement. Esophagogastroduodenoscopy and computed tomography revealed stenosis of the esophagogastric junction (EGJ) with no malignant findings. Additionally, based on the findings of the esophagogram and high-resolution manometry, the patient was diagnosed with esophageal achalasia. The patient also had an elevation in liver enzymes but was ruled out alcoholic, drug-induced, viral, or other hepatitis. It was considered that malnutrition caused by esophageal achalasia led to a rise in liver enzymes. After the onset of nutritional therapy, the liver enzyme elevation deteriorated, electrolyte abnormalities and hypoglycemic attacks occurred frequently. She had developed the refeeding syndrome, thus feeding was reduced, but the condition deteriorated further and the liver enzymes reached a peak. These findings were assumed to be due to persistent malnutrition, and normalized with gradually increased nutrition. After improving the general condition, per-oral endoscopic myotomy (POEM) was performed. After POEM, her dysphagia disappeared and nutritional state completely improved. Careful nutritional therapy improved her general condition, and POEM improved gastrointestinal symptoms and prevented the recurrence of malnutrition.