The special suppressive tumor immune microenvironment is a significant factor in the high postoperative recurrence rate and insensitivity to immunotherapy in pancreatic cancer. Tertiary lymphoid structures (TLSs) are pathologic ectopic lymphoid tissues composed of various immune cells, playing a crucial role in regulating adaptive anti-tumor immune responses. The presence of TLSs in pancreatic cancer tissues signifies better prognosis and immune therapy response. Examining the quantity, location, maturity, and cellular components of TLSs in pancreatic cancer specimens helps predict prognosis and screen potential beneficiaries of immunotherapy. Exploring key factors inducing TLSs formation and elucidating the anti-tumor immune mechanisms of TLSs may provide a new theoretical basis for enhancing the efficacy of pancreatic cancer immunotherapy. The authors summarize the clinical status and hot topics of TLSs in pancreatic cancer applications, and look forward to the research directions of TLSs in the field of pancreatic cancer.

Objective:To investigate the application value of nectin-4 targeting radiotracer 68Ga-N188 in the diagnosis of pancreatic cancer. Methods:The prospective study was conducted. The clinicopathologic data of 16 patients diagnosed as pancreatic cancer on enhanced computed tomography (CT) who were admitted to the Peking University First Hospital from August to December 2022 were collected. There were 9 males and 7 females, aged (62±8)years. All patients underwent 18F-flurodeoxyglucose ( 18F-FDG) and 68Ga-N188 positron emission tomography (PET)/CT examination. Observation indicators: (1) distribution of 68Ga-N188 in different tissues and tumor primary lesion of patients; (2) expression of Nectin-4 and uptake of 68Ga-N188 in pancreatic cancer; (3) comparison of examination results between 68Ga-N188 and 18F-FDG PET/CT. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Count data were described as absolute numbers or percentages. Results:(1) Distribution of 68Ga-N188 in different tissues and tumor primary lesion of patients. Results of PET/CT examination showed that in 1 hour after injection, the maximum standard uptake value (SUVmax) and mean standard uptake value (SUVmean) of 68Ga-N188 in fat, muscle, skin, and brain tissues of 16 patients were 0.40±0.16 and 0.25±0.09, 0.68±0.20 and 0.44±0.12, 0.39±0.14 and 0.28±0.11, 0.09±0.04 and 0.05±0.02, respectively. In the tissues of the esophagus, liver, spleen, and pancreas, the above indicators were 1.53±0.48 and 1.16±0.31, 1.49±0.45 and 0.91±0.30, 1.40±0.30 and 1.02±0.24, 1.24±0.31 and 0.96±0.25, respectively. In tumor primary lesion, the above indicators were 3.28±1.02 and 2.14±0.62, respectively, showing significant differences in SUVmax and SUVmean compared with pancreatic tissue ( t=8.03, 6.75, P<0.05). The tumor background ratio in tumor primary lesion based on SUVmax was 1.82±0.58. (2) Expression of Nectin-4 and uptake of 68Ga-N188 in pancreatic cancer. Results of immunohistochemical staining in 16 patients showed that there were 7 patients with high Nectin-4 expression and 9 patients with low Nectin-4 expression. Results of PET/CT examination showed that the SUVmax of 68Ga-N188 in tumor primary lesion of the 7 patients with high Nectin-4 expression and 9 patients with low Nectin-4 expression were 3.77±1.10 and 2.64±0.68, showing a significant difference between them ( t=2.64, P<0.05). The SUVmax of 18F-FDG in tumor primary lesion of the 7 patients with high Nectin-4 expression and 9 patients with low Nectin-4 expression were 6.73±3.24 and 6.43±3.45, showing no significant difference between them ( t=0.17, P>0.05). (3) Comparison of examination results between 68Ga-N188 and 18F-FDG PET/CT. Of the 16 patients, cases with positive results of tumor primary lesion on 68Ga-N188 and 18F-FDG PET/CT were 14 and 11, respectively, for the 14 pancreatic cancer patients diagnosed by postoperative histopathology. Among them, cases with positive results of tumor primary lesion on 68Ga-N188 and 18F-FDG PET/CT were 3 and 1 for the 3 pancreatic cancer patients receiving evaluation for chemotherapy. The SUVmax of 18F-FDG in tumor primary lesion of the 3 patients with chemotherapy and the 11 patients without chemotherapy were 2.80±0.69 and 6.97±2.11, showing a significant difference between them ( t=3.29, P<0.05). The SUVmax of 68Ga-N188 in tumor primary lesion of the 3 patients with chemotherapy and the 11 patients without chemotherapy were 3.38±1.12 and 2.93±0.50, showing no significant difference between them ( t=0.66, P>0.05). Cases with positive results of lymph node metastases in 68Ga-N188 and 18F-FDG PET/CT were 6 and 4, respectively, for the 6 pancreatic cancer patients diagnosed with lymph node metastases by postoperative histopathology, and the SUVmax of 68Ga-N188 and 18F-FDG in lymph node metastases were 2.25±1.12 and 4.02±1.27. Conclusion:68Ga-N188 PET/CT can be used for imaging diagnosis of tumor primary lesion and lymph node metastases of pancreatic cancer.

Pancreatic cancer (PC) is a malignant digestive tract tumor with poor prognosis. Most of patients with PC are insensitive to traditional strategies of chemotherapy, targeted therapy and immunotherapy. PC with microsatellite instability-high/deficient mismatch repair (MSI-H/dMMR) is rare in clinic, which has distinctive clinicopathological characteristics and better prognosis from conventional PC. Reasonable acquisition of pancreatic tumor biopsy and accurate assessment of MSI-H/dMMR status are helpful for accurate diagnosis of such patients. Individualized treatment strategy based on immunotherapy can significantly improve the prognosis of patients with MSI-H/dMMR PC. Based on relevant literatures of domestic and foreign, the authors discuss the current status and research hotspots of diagnosis and treatment for MSI-H/dMMR PC.

Objective:To explore the indications and effect of surgical treatment of autoimmune pancreatitis.Methods:Clinical data of these 15 patients with autoimmune pancreatitis diagnosed and treated at the Department of General Surgery, the First Hospital of Peking University from 2010 to 2021 were retrospectively analyzed.Results:The main clinical symptoms were obstructive jaundice, abdominal pain, distension and weight loss. The diagnosis of AIP was confirmed by EUS-FNA in 6 patients,among them, 4 did not relapse after oral hormone treatment, 2 did not receive relevant treatment, and 1 developed gastric cancer one year later. Under a suspicion of malignancy, 9 patients underwent surgical laparotomy ,and the diagnosis was established by pathology. There was no recurrence after oral hormone therapy in 1 patient who underwent laparotomy and pancreatic biopsy. One out of the 3 patients with choledochojejunostomy relapsed after 3 years. Of the 5 patients who underwent pancreatectomy, 4 had no obvious recurrence, and 1 had recurrence after 3 years.Conclusions:Untypical autoimmune pancreatitis is likely to be misdiagnosed as pancreatic cancer. For patients with suspicious malignancy, operational management and biopsy may benefit.

Pancreatic cancer is the fourth leading cause of cancer-related death in the world.Most patients are diagnosed as locally advanced or metastatic disease at initial visit,losing the opportunity of surgery.Conversion therapy aims to give unresectable tumors the opportunity to receive radical surgery through comprehensive treatment.For unresectable pancreatic cancer,chemotherapy based on AG(abraxane+gemcitabine)or FOLFIRINOX(5-fluorouracil+leucovorin+irinotecan+oxaliplatin),radiotherapy combined with chemotherapy as well as other regimens have shown conversion potential.Targeted therapy and immunotherapy have also become new frontiers of conversion therapy for pancreatic cancer.Focusing on new drugs and new regimens,this review has summarized the latest research progress of conversion therapy for pancreatic cancer.

Objective:To investigate the risk factors and treatment of postpancreatico-duodenectomy hemorrhage(PPH).Methods:The retrospective case-control study was conducted. The clinical data of 712 patients who underwent pancreaticoduodenectomy in Peking University First Hospital from January 2012 to November 2021 were collected. There were 392 males and 320 females, aged from 16 to 89 years, with a median age of 62 years. Observation indicators: (1) diagnosis of PPH; (2) analysis of influencing factors for PPH; (3) treatment of PPH. Measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers or percentages. Univariate analysis was performed using the chi-square test or Fisher exact probability, and multivariate analysis was performed using the Logistic regression model. Results:(1) Diagnosis of PPH. Of the 712 patients, 72 cases had PPH and 7 cases died. The incidence of PPH was 10.11%(72/712), and PPH related mortality was 9.72%(7/72). There were 7 cases of early PPH and 65 cases of delayed PPH. There were 23 cases of mild PPH and 49 cases of severe PPH. (2) Analysis of influencing factors for PPH. Results of univariate analysis showed that preoperative serum total bilirubin (TBil), extended surgery, postoperative pancreatic fistula, postoperative biliary fistula, postoperative abdominal infection were related factors for delayed PPH ( χ2=13.17, 3.93, 87.89, 22.77, 36.13, P<0.05). Results of multivariate analysis showed that preoperative serum TBil ≥171 μmol/L, postoperative grade B or C pancreatic fistula, postoperative biliary fistula, postoperative abdominal infection were independent risk factors for delayed PPH ( odds ratio=1.91, 8.10, 2.11, 2.42, 95% confidence interval as 1.09-3.33, 4.62-14.20, 1.06-4.23,1.35-4.31, P<0.05). (3) Treatment of PPH. ① Treatment of early PPH. Of the 7 cases with early PPH, 4 cases had mild PPH and 3 cases had severe PPH. The 4 cases with mild PPH were stanched by conservative treatment. The bleeding location of the 3 cases with severe PPH were the posterior wall of pancreatoenteric anastomosis, the pancreatic uncinate stump and the unintentional puncture of the jejunostomy tube of the left upper abdominal wall vessels and the 3 cases were stanched by reoperation. All the 7 cases were discharged without other complications. ② Treatment of delayed PPH. Of the 65 cases with delayed PPH, 19 cases had mild PPH and 46 cases had severe PPH. Of the 19 cases with mild PPH, 18 cases were stanched by conservative treatment including 2 cases died of pancreatic fistula and abdominal infection, 1 case were stanched by endoscope therapy. Of the 46 cases with severe PPH, 18 cases with stable vital signs and slow bleeding were stanched by conservative treatment including 1 case died of infectious toxic shock and the other 28 cases underwent invasive treatment, including 2 cases undergoing gastroscopy, 20 cases undergoing interventional treatment and 6 cases under-going reoperation as the initial treatment. Of the 22 cases taking endoscope or interventional treatment as the initial treatment, 5 cases underwent rebleeding and 2 cases died, with the reblee-ding rate and mortality as 22.7%(5/22) and 9.1%(2/22), respectively. Of the 6 cases taking reopera-tion as the initial treatment, 3 cases underwent rebleeding and 2 cases died, with the rebleeding rate and mortality as 3/6 and 2/6, respectively. There was no significant difference in the rebleeding rate and mortality in patients taking endoscope or interventional treatment as the initial treatment and patients taking reoperation as the initial treatment ( P>0.05). Of the 28 cases undergoing invasive treatment, 10 cases underwent secondary surgical treatment, including 6 cases taking reoperation and 4 cases taking interventional treatment as the initial treatment for hemorrhage, and 4 cases died with the mortality as 4/10, and the other 18 cases who did not receive secondary surgical treatment survived. There was a significant difference in the mortality between patients with or without secondary surgical treatment ( P<0.05). Conclusions:Preoperative serum TBil ≥171 μmol/L, post-operative grade B or C pancreatic fistula, postoperative biliary fistula, postoperative abdominal infection are independent risk factors for delayed PPH. Surgical treatment should be performed decisively for early severe PPH. For delayed severe PPH patients who undergoing conservative treat-ment without effect, endoscope therapy and interventional treatment should be the first choice, and surgical treatment should be performed if those above procedures not working.

Objective:To investigate the clinicopathological characteristics and treatment strategies of undifferentiated carcinoma with osteoclast-like giant cells of pancreas (UCOGCP).Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 5 patients with UCOGCP who were admitted to Peking University First Hospital from January 2004 to January 2019 were collected. There were 1 male and 4 females, aged from 33 to 71 years, with a median age of 56 years. Patients underwent preoperative laboratory test, imaging and histopatho-logical examinations. Patients with pancreatic head tumors underwent pancreaticoduodenectomy, and those with tumors in the body or tail of pancreas underwent distal pancreatectomy combined with splenectomy. All patients underwent standard lymph node dissection. Postoperative adjuvant therapy was individually decided by a multidisciplinary team. Observation indicators: (1) preopera-tive examination and treatment; (2) postoperative histopathological situations; (3) follow-up. Follow-up using outpatient examination and telephone interview was performed to detect tumor recurrence of patients up to January 2020. Measurement data with normal distribution were represented as Mean± SD. Measurement data with skewed distribution were described as M (range). Count data were described as absolute numbers. Results:(1) Preoperative examination and treatment: of the 5 UCOGCP patients, CA19-9 was elevated as 65.43 U/mL in only 1 patient preoperatively, while the CA19-9 was normal in other 4 patients. Four patients showed a solid cystic mass on preoperative contrast-enhanced computed tomography (CT) scan, and 1 patient showed a delayed peripheral enhancement of the solid tumor with central necrosis. The magnetic resonance imaging (MRI) scan showed hypointense signals on T1, T2 and weighted diffusion sequences in all 5 patients. Three of the 5 patients were resectable according to imaging data, 1 patient had locally advanced tumor, infiltrating the transverse colon, stomach, and partial small intestine, with the portal vein thrombus, and 1 patient had pancreatic head tumor with a liver metastatic lesion of 0.4 cm diameter which was detected on position emission tomography CT and was diagnosed as UCOGCP by endoscopic ultrasound-guided fine-needle aspiration biopsy. All patients underwent radical resection. Of the 3 patients with resectable tumors, 2 patients underwent pancreaticoduo-denectomy and 1 patient underwent distal pancreatectomy combined with splenectomy. One patient with locally advanced tumor in the body and tail of pancreas underwent distal pancreatectomy + transverse colostomy + partial gastrectomy + portal vein thrombectomy, and 1 patient with pancreatic head tumor and liver metastasis underwent pancreatoduodenectomy combined with left lateral hepatectomy. Of the 5 patients, 2 received postoperative adjuvant chemotherapy with single-agent gemcitabine, 1 received albumin-paclitaxel+gemcitabine combination chemotherapy, 1 received S1 as single agent chemotherapy, and 1 did not receive adjuvant chemotherapy. (2) Postoperative histopathological situations: of the 5 patients, 4 cases showed a cystic solid appearance of gross specimens, and 1 case had a solid appearance with central hemorrhagic necrosis. The tumor diameter was 5.2 cm(range, 2.0?14.0 cm). All the 5 patients achieved negative margins. Of the 5 patients, there was 1 case with portal vein invasion, 2 cases with vascular invasion, 3 cases with perineural invasion, and 2 cases with regional lymph node metastasis. One patient may had multiple tumor invasion and metastasis. Four of 5 patients had paraffin specimens available for immuno-histochemical staining. Four patients were positive for both CD68 and vimentin stains, while 3 patients were positive for programmed death ligand-1 (PD-L1), including 2 samples with 5% positive cells and 1 sample with 25% positive cells. Postoperative pathological examination showed a large number of spindle histiocytoid sarcoma cells scattered with osteoclast like giant cells and pleomorphic carcinoma giant cells. The tumor mutation burden in the 4 patients was 3.23 Muts/Mb(range, 2.61?21.77 Muts/Mb). Microsatellite status was stable in 4 patients. The next generation sequencing of 4 patients showed that all patients had KRAS mutation which was the most frequently mutation in pancreatic ductal adenocarcinoma. Of the 4 patients, 1 case had germline pathogenic mutation in TP53, 1case had somatic mutation in TP53, 1 case had somatic mutation in TP53, BLM, CDKN2A, and 1 case had somatic mutation in ARID1A. (3) Follow-up: 5 patients were followed up for 14?173 months, with a median follow-up time of 46 months. During the follow-up, 4 patients achieved disease-free survival and 1 patient had local recurrence at postoperative 11 months.Conclusions:UCOGCP is a rare variant of pancreatic tumor that exhibits a cystic solid mass in imaging examinations. High expression of PD-L1 is common in UCOGCP. The prognosis for UCOGCP is favorable following radical surgery. Patients may benefit from extended radical surgery even if the tumor has locally progression or distant metastasis.

Circulating tumor cells (CTC) disseminate from primary tumors by undergoing epithelial mesenchymal transition that allow their entry into the circulation to drive metastatic formation in pancreatic cancer patients.Technological advances in detection and characterization of CTC are conducive to the early diagnosis, differential diagnosis, monitoring disease progression and predicating the probability of canceration or the chemotherapeutic efficacy. Nowadays, detection methods of CTC can be based on immunomagnetic beads technique, cell filtration or microfluidic chips technology, but there are great differences in the sample throughput, CTC recovery rate, purity, and CTC viability among them.Owing to the dilemma in detection methods, the intrinsic relevance between the biological characteristics of CTC and clinical manifestations is still not exactly elucidated. By the improved methodology, next generation sequencing technology and exploring the technique for culturing CTC in vitro and establishing xenotransplanted tumor model in nude mice, more and more biological information will be revealed, and finally, individualized treatment is achieved.

Objective To explore the impact of abdominal situs inversus on the diagnosis and treatment of abdominal diseases.Methods Clinical data and course of 13 abdominal situs inversus cases from January 2012 to December 2016 were retrospectively analyzed.Results A total of 13 cases accounting for 1.5/10 000 of all cases who had abdominal CT were diagnosed situs inversus.6 of them were diagnosed for routine physical examination,4 of them for urinary tract symptoms,and the other 3 for digestive complaints.Conservative treatment or follow-up was prescribed for 8 patients who were asymptomatic and healthy;Five patients received operation,including 2 nephrecctomy,1 pancreatico duodenectomy,1 laparoscopic cholecystectomy,and 1 endoscopic retrograde cholangiopancreatography.All the cases recovered uneventfully.Conclusions Abdominal situs inversus is rare,non-disease entity,usually an incidental finding during clinical examination.It does not affect the therapeutic principle of concurrent primary disease.