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Objective The coronavirus disease (COVID-19) pandemic has altered the delivery of medical care. The present study evaluated the impact of COVID-19 on the outcomes of unresectable pancreatic cancer (PC) patients who received end-of-life care. Methods We retrospectively compared the management of PC patients during the COVID-19 pandemic (from April 2020 to March 2021) to the preceding year, which was unaffected by the pandemic (from April 2019 to March 2020), based on a prospectively maintained institutional database. Results A total of 178 patients were included in the COVID-19-exposed group and 201 patients were included in the COVID-19-unexposed group. The median overall survival was similar between the groups (exposed vs. unexposed: 12.6 vs. 11.9 months, p = 0.174). Treatment regimens and relative dose intensities and the progression-free survival of GnP (gemcitabine in combination with nab-paclitaxel) and mFOLFIRINOX as first- and second-line chemotherapy did not differ significantly between the two groups. Only 9.0% of patients died at home in the COVID-19-unexposed group, compared to 32.0% in the COVID-19-exposed group (p0.001). A multivariate analysis revealed that death during the COVID-19 exposed period was independently associated with home death (odds ratio: 4.536, 95% confidence interval: 2.527-8.140, p0.001). Conclusions While the COVID-19 pandemic did not seem to influence chemotherapeutic treatment for PC patients at our institution, it had a large impact on end-of-life care. These findings may promote discussion about end-of-life care in Japan.

Serial pancreatic-juice aspiration cytologic examination (SPACE) is useful for diagnosis of pancreatic ductal stenosis. This study investigates the utility of adding brush cytology to SPACE during the same procedure.We retrospectively analyzed consecutive patients who underwent SPACE with brush cytology for pancreatic ductal stenosis between February 2014 and July 2020 in our hospital.Thirty-four patients were included. Eleven had lesions in the pancreatic head lesions, and 23 had lesions in the pancreatic body or tail. Malignancies were found in 22 patients. Endoscopic ultrasound, computed tomography, and magnetic resonance imaging showed distal pancreatic duct dilation in 81.8% to 90.6% of cases, with a sensitivity of 63.0% to 65.5%. The sensitivity and diagnostic accuracy of SPACE, brush cytology, and SPACE with brush cytology were 63.6%, 50.0%, and 77.3% (P = 0.19) and 73.5%, 67.6%, and 82.4% (P = 0.42), respectively. No significant differences in diagnostic yield were observed for either pancreatic head lesions or pancreatic body/tail lesions. Post-endoscopic retrograde cholangiopancreatography pancreatitis was observed in 4 cases (11.8%).The utility of adding brush cytology to SPACE was limited.

To evaluate long-term outcomes of endoscopic double stenting using anti-reflux metal stents (ARMS) for combined malignant biliary and duodenal obstruction.Consecutive patients with advanced pancreatic cancer who received endoscopic double stenting with self-expandable metal stents (SEMS) for combined malignant biliary and duodenal obstruction at our institution between July 2014 and March 2021 were evaluated. Patients were divided into the ARMS group, endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) group, and covered metal stent-transpapillary (CMS-transpapillary) group. A Duckbill-type metal stent was used in all ARMS cases.Thirty-eight patients were enrolled: ARMS group (n = 16), EUS-HGS group (n = 13), and CMS-transpapillary group (n = 9). Overall survival among three groups were not significantly different. Recurrent biliary obstruction (RBO) rates of the ARMS, EUS-HGS, and CMS-transpapillary groups were 12.5%, 61.5%, and 88.9% (P .01) and median time to recurrent biliary obstructions (TRBOs) were not reached, 125 days, and 7 days (P .01). Median TRBOs of ARMS-choledochoduodenostomy and ARMS-transpapillary were not statistically different. Major causes of RBO were stent occlusion and symptomatic stent migration in the ARMS group, hyperplasia in the EUS-HGS group, and non-occlusion cholangitis in the CMS-transpapillary group.Endoscopic double stenting with ARMS might be an option for combined malignant biliary and duodenal obstruction.

Intraductal self-expandable metal stent (SEMS) placement may prolong stent patency by reducing duodenobiliary reflux. This study aimed to evaluate the efficacy and safety of this biliary drainage method in patients with unresectable distal malignant biliary obstruction (MBO). Consecutive patients with unresectable MBO who underwent initial covered SEMS placement between 2015 and 2022 were retrospectively reviewed. We compared the causes of recurrent biliary obstruction (RBO), time to RBO (TRBO), adverse events (AEs), and reintervention rates between two biliary drainage methods (SEMSs placed above and across the papilla). A total of 86 patients were included (above: 38 and across: 48). Overall RBO rates (24% vs. 44%, p = 0.069) and median TRBO (11.6 months vs. 9.8 months, p = 0.189) were not significantly different between the two groups. The frequency of overall AEs was similar between the two groups in the entire cohort, but was significantly lower in patients with non-pancreatic cancer (6% vs. 44%, p = 0.035). Reintervention was successfully performed in the majority of patients in both groups. Intraductal SEMS placement was not associated with a prolonged TRBO in this study. Larger studies are warranted to further evaluate the benefit of intraductal SEMS placement.

This study evaluated the efficacy of adjuvant chemotherapy (AC) for intraductal papillary mucinous carcinoma (IPMC).We retrospectively analyzed patients who underwent pancreatectomy for invasive IPMC from January 2007 to June 2020. We evaluated outcomes of AC in the entire cohort and in patients with known prognostic factors.A total of 51 patients with invasive IPMC underwent surgery, of which 35 received AC. In the entire cohort, there was no significant difference in median overall survival (OS) between the AC and surgery alone (SA) group [hazard ratio (HR)=0.54; p=0.232]. For patients with poorly differentiated adenocarcinoma, median OS was significantly longer in the AC group (HR=0.27; p=0.022). For patients with lymph node metastasis, median OS was significantly higher in the AC group (HR=0.07; p0.001).AC may be effective for selected invasive IPMC patients.

Outcomes and prognostic factors of second-line gemcitabine plus nab-paclitaxel (GnP) after modified FOLFIRINOX (mFFX) for unresectable pancreatic cancer were unclear. We retrospectively analyzed consecutive patients with unresectable pancreatic cancer treated with GnP after first-line mFFX treatment between March 2015 and March 2022 at our hospital. A total of 103 patients were included. Median overall survival (OS) from the start of first-line and second-line treatments was 14.9 months and 7.2 months, respectively. Median progression-free survival (PFS) was 3.6 months. Performance status, modified Glasgow prognostic score, and neutrophil-to-lymphocyte ratio were independently associated with OS. Our prognostic model using these parameters classifies patients into good (n = 70) and poor (n = 33) prognosis groups. Median OS and PFS were longer in the good prognosis group than in the poor prognosis group (OS: 9.3 vs. 3.8 months, p < 0.01; PFS: 4.1 vs. 2.3 months, p < 0.01). Grade 3/4 adverse events were observed in 70.9% of patients, with neutropenia being the most frequent. While GnP as second-line treatment was well-tolerated, efficacy of second-line gemcitabine plus nab-paclitaxel was notably limited, particularly in the poor prognosis group.

Objective Anamorelin, a novel selective ghrelin receptor agonist, was approved in Japan for the treatment of cachexia in pancreatic cancer (PC), albeit with limited evidence. This study evaluated the efficacy and safety of anamorelin in PC and examined the impact of the extent of weight loss on the efficacy of anamorelin. Methods We retrospectively investigated consecutive PC patients with cachexia who received anamorelin at our institution between June 2021 and January 2022. Patients were divided into two groups: moderate-weight-loss group (5%-10%) and severe-weight-loss group (10%). The primary outcome was changes in body weight. The secondary outcomes were changes in appetite and laboratory measures as well as treatment-related severe adverse events. Results A total of 24 patients were included (moderate/severe weight loss: 8/16). The moderate-weight-loss group showed significantly more weight gain than the severe-weight-loss group. Improvements in appetite were consistently observed in each weight-loss group. Changes in laboratory markers were not significantly different between groups. Hyperglycemia (four patients) was the most common cause of severe adverse events, followed by abdominal distension, nausea, elevated liver function tests, and bulimia. Conclusions The efficacy of anamorelin was associated with the extent of weight loss. Although anamorelin improved appetite in each weight-loss group, it increased body weight only in the moderate-weight-loss group. Anamorelin was well-tolerated among advanced PC patients, although caution must be practiced when it is used in patients with concomitant diabetes mellitus.

Primary pancreatic lymphomas are extremely rare, accounting for 0.1-0.5% of malignant lymphomas and about 0.2% of primary pancreatic tumors. They occur most commonly in the pancreatic head of elderly males, with diffuse large B-cell lymphoma being the most common subtype. Primary pancreatic follicular lymphoma is the most commonly reported primary pancreatic indolent lymphoma, accounting for 9-14% of primary pancreatic lymphomas. We report two cases of primary pancreatic follicular lymphoma treated with obinutuzumab, a second-generation humanized anti-CD20 monoclonal antibody, and bendamustine. One was diagnosed by endoscopic ultrasound-guided fine-needle aspiration, while the other required laparoscopic lymph node sampling to reach a diagnosis. Both achieved complete response with induction therapy and opted for maintenance therapy with obinutuzumab. We also conducted a literature review of primary pancreatic follicular lymphoma cases reported over the last 30 years.

Background Peritoneal metastasis is one of the most important poor prognostic factors in advanced pancreatic cancer (PC). Whether the prognosis of PC with peritoneal metastasis has improved with the advent of gemcitabine plus nab-paclitaxel (GnP) and modified FOLFIRINOX (mFFX) is uncertain. The aim of this study was to evaluate the improvements in treatment outcomes of PC with peritoneal metastasis. Methods We retrospectively investigated consecutive PC patients with peritoneal metastasis treated with chemotherapy at our institution between 2010 and 2019. We compared the clinical characteristics and survival outcomes according to the period of diagnosis (group A, 2010–2014; group B, 2015–2019) and chemotherapy regimen. We also examined the prognostic factors for overall survival (OS). Results Among 180 patients included (GnP 88; mFFX 14; other regimens 78), distant metastasis was confined to the peritoneum in 89 patients. Although group B had a worse performance status compared to group A, median OS was significantly longer in group B. GnP and mFFX showed a significantly higher objective response rate and disease control rate in addition to longer progression free survival and OS compared to other regimens. The administration of GnP or mFFX, performance status, and neutrophil to lymphocyte ratio ≥5 were identified as independent prognostic factors for OS. Furthermore, the amount of ascites and extent of peritoneal metastasis were significantly associated with OS in patients with distant metastasis confined to the peritoneum. Conclusions The prognosis of PC with peritoneal metastasis has significantly improved over time with the advent of GnP and mFFX.

Background: Malignant afferent loop obstruction (ALO) is rare condition and is difficult to manage. Endoscopic transluminal treatment has become easier with the advent of balloon-assisted enteroscopes with a large working channels and self-expandable metal stent (SEMS) with a 9 Fr delivery system. Methods: From July 2016 to March 2022, 22 patients with symptomatic malignant ALO who underwent endoscopic transluminal treatment (Initial cohort), of which 18 patients received endoscopic transluminal SEMS placement (SEMS cohort), were retrospectively evaluated. We evaluated outcomes of endoscopic transluminal treatment and long-term outcomes of SEMS placement for malignant ALO. Results: In the Initial cohort, technical and clinical success rates were both 95.5%. The median procedural time was 28.0 min. One case of guidewire-induced micro-perforation occurred as an early complication (4.5%). In the SEMS cohort, and no early complication was observed. Recurrent obstruction occurred in two cases (11.1%) during the follow-up period (median: 102 days). One was managed by additional SEMS placement and the other was treated conservatively. Conclusions: High technical and clinical success was achieved by endoscopic transluminal treatment with short procedural time for malignant ALO. Endoscopic SEMS placement also appears to be safe and effective, and additional SEMS placement can be considered in cases of re-obstruction.

Objective With the introduction of modified FOLFIRINOX and gemcitabine plus nab-paclitaxel therapy for unresectable pancreatic cancer, erlotinib plus gemcitabine therapy is now occasionally used as late-line therapy. This study investigates outcomes of treatment with erlotinib plus gemcitabine for unresectable pancreatic cancer. Methods We retrospectively analysed consecutive patients with unresectable pancreatic cancer treated with erlotinib plus gemcitabine as the third or later-line chemotherapy between March 2014 and December 2020 in our hospital. Results A total of 56 patients were included (third line/fourth or later line = 42/14). All patients were previously treated with gemcitabine plus nab-paclitaxel and 45 patients were previously treated with modified FOLFIRINOX. The median progression-free survival (PFS) and overall survival (OS) were 1.6 and 4.6 months, respectively. The disease control rate was 21.4%. Performance status, modified Glasgow prognostic score and carcinoembryonic antigen level were independently associated with survival. Our prognostic model using these parameters could classify patients into good (n = 32) and poor (n = 24) prognostic groups. The median PFS and OS were longer in good than in poor prognostic group, but the difference in PFS was very small (PFS: 2.1 vs. 1.4 months, P = 0.01. OS: 6.8 vs. 2.4 months, P < 0.01). Interstitial pneumonia occurred in one patient (1.8%). Conclusions Benefits of erlotinib plus gemcitabine as late-line chemotherapy were limited, particularly with respect to PFS. Development of more effective third-line treatment options is desirable in the future.

Objectives To compare the treatment outcomes of gemcitabine with nab-paclitaxel (GnP) and modified FOLFIRINOX (mFFX; a combination of fluorouracil, leucovorin, irinotecan, and oxaliplatin) for metastatic pancreatic cancer. Methods We retrospectively analyzed consecutive patients with metastatic or recurrent pancreatic cancer treated with GnP or mFFX as the first-line chemotherapy between March 2014 and December 2019 in our hospital. Treatment outcomes were compared using propensity score matching to adjust for age, sex, performance status, carcinoembryonic antigen levels, carbohydrate antigen 19-9 levels, and disease status (metastatic or recurrent). Results Five hundred sixty-eight patients were included (GnP/mFFX, 456/112). After propensity score matching, 218 patients were extracted. The median age was around 61 years, and the proportion of performance status 0 was approximately 90%. The median overall survival values were 14.6 and 15.5 months (P = 0.45), and the median progression-free survival was 7.4 months (P = 0.53) for GnP and mFFX, respectively. The disease control rates were higher in the GnP group (82.6% vs 67.9%, P = 0.02). In nonhematologic adverse events, grade 3/4 anorexia and diarrhea occurred significantly more frequently in the mFFX group. Conclusions Gemcitabine with nab-paclitaxel had a higher disease control rate and lower rates of severe anorexia and diarrhea in our propensity-matched population.

Elderly pancreatic cancer (PC) patients are often considered vulnerable to treatment and standard treatment strategy for this subpopulation is uncertain. Cachexia and sarcopenia are reported to be associated with reduced physical performance, reduced anti-tumor response, increased chemotherapy toxicity, and poor prognosis in several malignancies. The aim of this study was to evaluate the impact of cachexia and sarcopenia on the clinical course of elderly PC patients receiving chemotherapy. We retrospectively investigated consecutive elderly metastatic PC patients (≥ 75 years) treated with chemotherapy at our institution between January 2015 and April 2020. Skeletal muscle index was calculated at the third lumbar vertebra using pretreatment computed tomography. We evaluated time to treatment failure (TTF), progression-free survival (PFS), overall survival (OS), early treatment discontinuation, relative dose intensity (RDI), and severe adverse events (AEs). Among 80 patients included (gemcitabine plus nab-paclitaxel [GnP] 52; gemcitabine 21; S1 6; modified FOLFIRINOX 1), cachexia and sarcopenia were present in 48 (60%) and 61 (76%) patients, respectively. Cachexia was associated with older age, worse performance status, higher level of neutrophil to lymphocyte ratio, worse nutritional status, and shorter TTF and PFS. Furthermore, it was also associated with early treatment discontinuation, reduced RDI of nab-paclitaxel, and increased incidence of grade 4 neutropenia in patients receiving GnP. On the other hand, sarcopenia had less impact on the clinical course of elderly PC patients. In our experience, cachexia was considered an effective tool in the management of elderly PC patients receiving palliative chemotherapy.

Biliary tract cancer (BTC) arises from biliary epithelial cells (BECs) and includes intrahepatic cholangiocarcinoma (IHCC), gallbladder cancer (GC), and extrahepatic cholangiocarcinoma (EHCC). Although frequent KRAS mutations and epigenetic changes at the INK4A/ARF locus have been identified, the molecular pathogenesis of BTC is unclear and the development of corresponding anticancer agents remains inadequate. We isolated epithelial cell adhesion molecule (EpCAM)–positive BECs from the mouse intrahepatic bile duct, gallbladder, and extrahepatic bile duct, and established organoids derived from these cells. Introduction of activated KRAS and homozygous deletion of Ink4a/Arf in the cells of each organoid type conferred the ability to form lethal metastatic adenocarcinoma with differentiated components and a pronounced desmoplastic reaction on cell transplantation into syngeneic mice, indicating that the manipulated cells correspond to BTC–initiating cells. The syngeneic mouse models recapitulate the pathological features of human IHCC, GC, and EHCC, and they should therefore prove useful for the investigation of BTC carcinogenesis and the development of new therapeutic strategies. Tumor cells isolated from primary tumors formed organoids in three‐dimensional culture, and serial syngeneic transplantation of these cells revealed that their cancer stem cell properties were supported by organoid culture, but not by adherent culture. Adherent culture thus attenuated tumorigenic activity as well as the expression of both epithelial and stem cell markers, whereas the expression of epithelial‐mesenchymal transition (EMT)–related transcription factor genes and mesenchymal cell markers was induced. Our data show that organoid culture is important for maintenance of epithelial cell characteristics, stemness, and tumorigenic activity of BTC–initiating cells., New models of biliary tract cancer (intrahepatic cholangiocarcinoma, gallbladder cancer, and extrahepatic cholangiocarcinoma) were generated through a combination of three‐dimensional organoid culture and transplantation of cancer‐initiating cells with epithelial stem cell properties into syngeneic mice.

Objectives The aim of this multicenter retrospective study was to identify the optimal chemotherapeutic regimen for advanced pancreatic acinar cell carcinoma (PACC). Methods Fifty-eight patients with histopathologically confirmed advanced PACC who had received chemotherapy between 1996 and 2013 were enrolled. The clinical characteristics of the patients and the treatment efficacy data were collected from the medical records at 16 Japanese institutions, using standardized data collection instrument. Results The most commonly selected treatment regimens were gemcitabine-, fluoropyrimidine-, platinum-, and irinotecan-containing regimens. The overall response rate in the patients who received first-line chemotherapy were 7% and 38%, respectively, and the median overall survival was 13.2 months. When the data for all the treatment lines were aggregated, the response rates to gemcitabine-, fluoropyrimidine-, platinum-, and irinotecan-containing regimens were 7%, 18%, 40%, and 29%, respectively. The overall survival tended to be better in patients who had received a platinum-containing regimen (hazard ratio, 0.50; 95% confidence interval, 0.23-1.11; P = 0.08) or irinotecan-containing regimen (hazard ratio, 0.42; 95% confidence interval, 0.15-1.19; P = 0.09) at least once in the treatment course as compared with those who had not. Conclusions Our findings suggested that platinum- and irinotecan-containing regimens exhibited some potential efficacy in patients with advanced PACC.

Single-balloon enteroscopy-assisted endoscopic retrograde cholangiopancreatography (SBE-ERCP) has been increasingly performed for the treatment of malignant biliary obstruction (MBO) in patients with surgically altered anatomy (SAA), however evidence is scarce. Therefore, we conducted this study to evaluate the efficacy and safety of self-expandable metallic stent (SEMS) placement using a short type SBE.We retrospectively examined consecutive patients with SAA who received initial SEMS for MBO at our institution between February 2016 and February 2019. We evaluated patient characteristics, technical and functional success rates, time to recurrent biliary obstruction (TRBO) and complications according to the location of the biliary stricture.A total of 26 patients were included in this study. The primary tumor was gastric cancer in 12, pancreatic cancer in 6, cholangiocarcinoma in 6 and gallbladder cancer in 2. The biliary stricture site was distal bile duct in 14, hilar bile duct in 3 and hepaticojejunostomy (HJ) anastomosis in 9. Technical and functional success rates were 92 and 88%, respectively. TRBO, median survival time, overall rate of RBO and early complications were not different according to the stricture site (SEMS placement

Drug-induced interstitial lung disease (ILD) is one of the most serious adverse events with a high mortality rate and represents a serious clinical problem. However, gemcitabine plus nab-paclitaxel (GnP)-induced ILD in pancreatic cancer (PC) patients has not been thoroughly investigated. Therefore, we conducted this study to examine the clinical characteristics of GnP-induced ILD and identify risk factors for developing ILD. We retrospectively investigated consecutive patients with PC who received GnP between January 2015 and April 2020. We compared the clinical characteristics and overall survival (OS) according to ILD occurrence and explored risk factors including ABO blood type for developing ILD. Of the 910 patients included in this study, ILD occurred in 20 patients (2.2%). PC patients who developed ILD had a significantly higher frequency of blood type B compared to those without ILD (42% vs. 22%, p ˂ 0.05). Other baseline characteristics including smoking history and current/previous lung disease were not different between the two groups. Median time from initiation of GnP to onset of ILD was 80 days. All patients recovered from ILD and OS was not significantly different according to ILD occurrence. Multivariate analysis revealed that blood type B was an independent risk factor for developing ILD. We demonstrated that GnP-induced ILD occurred in 2.2% of PC patients with no mortality and OS did not differ according to ILD occurrence. Furthermore, we clarified that ABO blood type B was an independent risk factor for developing ILD in PC patients receiving GnP.

Liver oligometastatic pancreatic cancer (PC) may have favorable outcomes. This study aims to evaluate outcomes and factors associated with overall survival (OS) of these patients.We retrospectively investigated consecutive PC patients with liver metastasis treated at our institution between 2013 and 2020. Clinical characteristics and outcomes were compared and analyzed according to the extent of liver metastasis. Cox proportional hazards model was used to identify prognostic factors for OS.A total of 417 patients were included (multi-organ metastasis/polymetastasis/oligometastasis 174/158/85). Oligometastasis showed a longer OS compared to other types of metastases (7.7 vs 8.2 vs 13.1 months). Age70 years, performance status of 0, modified Glasgow prognostic score of 0, carbohydrate antigen 19-91000 U/mL were identified as significant prognostic factors for OS. A prognostic index consisting of these four factors successfully stratified the prognosis of these patients (prognostic index; high vs low, 19.9 vs 8.3 months). Highly selected patients who underwent surgical resection showed a median OS of 54.6 months.Oligometastasis presented a relatively favorable outcome. Our new prognostic index was useful in stratifying the prognosis of these patients. Multimodal treatment including surgery may have additional survival benefits for highly selected patients.

A 67-year-old woman underwent distal pancreatectomy for pancreatic cancer. Recurrence in the form of lung metastasis was discovered eight months after surgery, and chemotherapy was initiated. Two years after the surgery, she was admitted for the evaluation of melena. Esophagogastroduodenoscopy revealed multiple subepithelial lesions with ulceration from the gastric body to the fornix. The histopathology of biopsy specimens was consistent with ductal adenocarcinoma, which appeared similar to the resected pancreatic cancer. The patient was diagnosed with multiple gastric metastases of pancreatic cancer. We herein report a case of pancreatic cancer with multiple gastric metastases that occurred after surgery for pancreatic tail cancer.

Background and study aims Self-expandable metallic stents (SEMS) are now widely used even for patients with borderline resectable (BR) pancreatic cancer (PC), as neoadjuvant therapy has become common. Therefore, we conducted this study to evaluate safety of SEMS placement in the population including BR PC and to explore risk factors for recurrent biliary obstruction (RBO), pancreatitis, and cholecystitis. Patients and methods We retrospectively investigated consecutive patients with PC who received initial SEMS between January 2015 and March 2019. We compared time to RBO (TRBO), causes of RBO, and stent-related adverse events (AEs) according to resectability status. Univariate and multivariate analyses were performed to explore risk factors for TRBO, pancreatitis, and cholecystitis. Results A total of 135 patients were included (BR 31 and unresectable [UR] 104). Stent-related AEs occurred in 39 patients: pancreatitis 14 (mild/moderate/severe 1/6/7), cholecystitis 12, and non-occluding cholangitis 13. TRBO, causes of RBO, and stent-related AEs were not significantly different according to resectability status. Overall rate of RBO was higher in UR PC due to the longer follow-up period. Sharp common bile duct (CBD) angulation was an independent risk factor for short duration of TRBO. High pancreatic volume index and SEMS of high axial force were independent risk factors for pancreatitis, whereas tumor involvement to orifice of cystic duct was the only risk factor for cholecystitis. Conclusions We demonstrated that SEMS can be safely deployed even in patients with BR PC. Sharp CBD angulation and high pancreatic volume index were identified as novel risk factors for RBO and pancreatitis, respectively, after SEMS placement.

Background and study aims Endoscopic ultrasound (EUS)-guided tissue acquisition is sometimes required to diagnose small solid pancreatic lesions. The aim of this study was to evaluate the diagnostic yield of EUS-guided tissue acquisition for small solid pancreatic lesions and the differences in diagnostic yield among different needles. Patients and method We retrospectively analyzed consecutive patients who had undergone EUS-guided tissue acquisition for solid pancreatic lesions less than 2 cm between November 2012 and June 2019. Three types of needles were evaluated in this study: a 22-gauge fine-needle aspiration (FNA) Lancet needle, a 20-gauge fine-needle biopsy (FNB) Menghini needle with a lateral forward bevel, and a 22-gauge FNB Franseen needle. We evaluated the diagnostic yield and safety of the procedure using these needles. Results We analyzed 160 patients with 163 lesions. The overall sensitivity, specificity, and accuracy were 92.0 %, 100 %, and 92.6 %, respectively. In the histological plus cytological diagnosis, accuracies of the Lancet, Menghini, and Franseen needles were 92.7 %, 97.0 %, and 85.7 %, respectively (P = 0.10). In the histological diagnosis alone, the negative predictive values (NPVs) of the Lancet, Menghini, and Franseen needles were 13.3 %, 53.3 %, and 27.3 %, respectively (P = 0.08). Adverse events occurred in four cases (2.5 %): one postprocedural bleeding, two cases of pancreatitis, and one pancreatic abscess. Conclusions EUS-guided tissue acquisition for small solid pancreatic lesions has a high diagnostic yield and safety. This study suggested a difference in the diagnostic yield of each needle for small solid pancreatic lesions.

Background The prognosis of borderline resectable (BR) pancreatic cancer (PC) has improved by multidisciplinary therapy. However, the differences in clinical course between pancreatic head (Ph) and pancreatic body and tail (Pbt) cancer has not been fully elucidated. Therefore, we conducted this study to compare the clinical course of BR PC patients according to tumor location. Methods We retrospectively investigated consecutive patients with BR PC who initiated neoadjuvant chemotherapy (NAC) between March 2015 and April 2019. We compared clinicopathological characteristics, treatment, recurrence pattern and post recurrence treatment between Ph and Pbt cancer patients. We also compared recurrence free survival (RFS) and overall survival (OS) according to tumor location. Results A total of 108 patients with BR PC were included. Tumor location was Ph 74 and Pbt 34, respectively. Initial regimen of NAC was nab-paclitaxel/gemcitabine in 106 and gemcitabine in 2, respectively. Although Pbt location was associated with more advanced T stage, it showed similar N stage, pathological stage, RFS, OS, and details of adjuvant chemotherapy compared to Ph location. The most common site of postoperative recurrence was liver-only recurrence in Ph tumor (32% vs. 6%, p = 0.04) and peritoneal dissemination-only recurrence in Pbt tumor (35% vs. 11%, p = 0.06). Furthermore, Ph cancer patients received a higher rate of monotherapy compared to Pbt cancer patients (19% vs. 0%, p = 0.08). Conclusions In our experience tumor location was not a prognostic factor for OS in BR PC. Postoperative recurrence pattern and treatment after recurrence were different according to tumor location.

Early-onset pancreatic cancer (≤50 years, EOPC) is uncommon. This study aims to characterize the clinical and survival characteristics of EOPC in comparison to late-onset pancreatic cancer (50 years, LOPC).We retrospectively investigated consecutive PC patients treated at our institution between 2010 and 2019. We analyzed and compared clinicopathological characteristics, treatments, and outcomes of EOPC and LOPC.Of 1646 PC patients identified (768 resectable/borderline resectable; 248 locally advanced; 630 metastatic), 127 (8%) had EOPC. Current smoking and heavy drinking were associated with EOPC. EOPC presented at a more advanced stage and had higher neutrophil-to-lymphocyte ratios than LOPC. Survival outcomes were similar between the two groups, both in the entire cohort and in each resectability group. In patients undergoing resection, EOPC tended to have a higher N stage (p = 0.099) and had a higher pathological stage (stage IV, 20% vs. 7%, p = 0.005) and a lower rate of macroscopically curative resection (80% vs. 93%, p = 0.006). Liver recurrence was more commonly observed in EOPC (42% vs. 23%, p = 0.015). In the metastatic cohort, combination chemotherapy regimens were more frequently administered in EOPC as first-line treatment (79% vs. 64%, p = 0.028). Both median PFS (4.4 vs. 5.3 months, p = 0.647) and OS (11.5 vs. 9.5 months, p = 0.183) were not significantly different between the two groups.EOPC presented with a more aggressive tumor biology. Survival outcomes were similar to LOPC due to more intensive treatment.

Pancreatic cancer is the fourth leading cause of cancer-related death in Japan. Pancreatic cancer is categorized as resectable, borderline resectable, or unresectable based on the degree of adjacent vascular invasion and the presence of distant metastases. Neoadjuvant chemotherapy with gemcitabine and S-1 (NAC-GS) has recently become a standard option for resectable pancreatic cancer in Japanese patients. According to previous reports, GS is considered to be relatively safe and feasible treatment for Japanese patients, including the elderly. However, NAC-GS is occasionally associated with severe adverse events which may ultimately render the patient unfit for surgery. A 60-year-old man with resectable pancreatic cancer suffered from severe necrotic enteritis during NAC-GS, which required surgical resection. Considering the time course and histological findings of the resected bowel, S-1 was believed to be the causative agent. The low urinary dihydrouracil to uracil ratio also suggested possible dihydropyrimidine dehydrogenase deficiency, which may have hindered the metabolism of S-1 and contributed to the development of necrotic enteritis. Life-threatening enteritis occurs in approximately 0.3% of all patients who receive S-1. As initial symptoms are non-specific, patients should be instructed to lower the hurdle for contacting the hospital during NAC-GS.

Background: In the absence of a current standard of care, precision oncology with next-generation sequencing provides an important therapeutic option for patients with rare malignancy. Here, we sought to establish the clinical relevancy of comprehensive genomic profiling (CGP) for patients with rare malignancy. Methods: We reviewed 341 patients who underwent CGP (FoundationOne CDx; OncoGuide NCC OncoPanel System)in our institution between 2019 and 2021. Cases were classified as common or rare malignancy based on the Rare Cancers in Europe (RARECARE) definition (incidence of Results: With the exception of 7 unclassifiable cases, rare malignancy accounted for 149 of the 334 cases (45%), with the most common being female genital cancers (32%), followed by digestive cancers (24%), sarcoma (16%), and others (28%). Many (83%) of the patients with rare malignancy harbored at least one pathogenic/likely-pathogenic variant. The commonly mutated genes were TP53 (41%), PIK3CA (20%), ARID1A (14%), and KRAS (13%). ERBB2amplification was detected in 6% of patients (median copy number, 8). Gene fusion in EWSR1 was found in 4% of patients (sarcoma) and in FGFR2 in 1% (cholangiocarcinoma and salivary duct carcinoma). TMB-high (≥10 mut/Mb) and MSI-high cases were found in 8% and 2% of cases, respectively. Druggable alterations were detected in 36 patients; this percentage was not significantly different to that of common malignancy (24% vs. 17%, P=0.10). The common druggable alterations were BRAF V600E (n=10), ERBB2 amplification (n=9), PIK3CA E542K (n=6), and BRCA1/2 variant (n=6). There was no significant difference in OS between the rare and common malignancy groups (1-year OS rate: 62% vs. 46%, P=0.24). Conclusion: In this study, the ratio of rare malignancy was higher than that typically found in previous epidemiological studies (about 20%-25%). We observed no adverse impact for OS, which might be due to the high number of patients (n=48) with intractable pancreatic cancer. Remarkably, >20% of patients harbored a potential druggable alteration. Our results suggest the clinical relevance of CGP for patients with rare malignancy, and its potential utility to provide clues for future clinical development. Citation Format: Akihiro Ohmoto, Naomi Hayashi, Ippei Fukada, Masumi Yamazaki, Mayu Yunokawa, Akiyoshi Kasuga, Eiji Shinozaki, Arisa Ueki, Akiko Tonooka, Kengo Takeuchi, Seiichi Mori, Kazuma Kiyotani, Shunji Takahashi. Druggable gene alterations in Japanese patients with rare malignancy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5735.

BACKGROUND Stenting against recurrent biliary obstruction (RBO) after placement of covered metal stent (CMS) for distal malignant biliary obstruction (MBO) is still challenging. This study investigated the feasibility of a novel laser-cut fully CMS with anti-reflux valve in patients with distal MBO refractory to conventional CMS. METHODS Patients who underwent Duckbill-type metal stent (DMS) placement between June 2019 and May 2020 were included. Early complications, causes of RBO including non-occlusion cholangitis, and time to RBO (TRBO) were evaluated. TRBO of DMS was also compared with that of previous CMS. RESULTS Thirty patients were included: pancreatic cancer/metastatic lymph nodes in 29 patients/one patient; duodenal stenosis in 13 patients. Technical and functional success were achieved in all patients. Mild cholangitis and mild pancreatitis developed in each one. Median follow-up period was 167 days (range, 23-527 days). RBO occurred in nine patients (30%): sludge formation in four patients, hemobilia in one patient, symptomatic distal stent migration in three patients, and non-occlusion cholangitis in one patient. TRBO of DMS was significantly longer than that of previous CMS (median 224 days vs median 120 days, P = .0025). DMS was successfully removed in all of six patients when re-intervention was needed. CONCLUSIONS Duckbill-type metal stent might be safe and effective in patients with distal MBO refractory to conventional CMS.