Pancreatology最新文献

Objective

Serous cystic neoplasms (SCN) are benign pancreatic cystic neoplasms that may require resection based on local complications and rate of growth. We aimed to develop a predictive model for the growth curve of SCNs to aid in the clinical decision making of determining need for surgical resection.

Methods

Utilizing a prospectively maintained pancreatic cyst database from a single institution, patients with SCNs were identified. Diagnosis confirmation included imaging, cyst aspiration, pathology, or expert opinion. Cyst size diameter was measured by radiology or surgery. Patients with interval imaging ≥3 months from diagnosis were included. Flexible restricted cubic splines were utilized for modeling of non-linearities in time and previous measurements. Model fitting and analysis were performed using R (V3.50, Vienna, Austria) with the rms package.

Results

Among 203 eligible patients from 1998 to 2021, the mean initial cyst size was 31 mm (range 5–160 mm), with a mean follow-up of 72 months (range 3–266 months). The model effectively captured the non-linear relationship between cyst size and time, with both time and previous cyst size (not initial cyst size) significantly predicting current cyst growth (p < 0.01). The root mean square error for overall prediction was 10.74. Validation through bootstrapping demonstrated consistent performance, particularly for shorter follow-up intervals.

Conclusion

SCNs typically have a similar growth rate regardless of initial size. An accurate predictive model can be used to identify rapidly growing outliers that may warrant surgical intervention, and this free model (https://riskcalc.org/SerousCystadenomaSize/) can be incorporated in the electronic medical record.

Background

The management of branch-duct type intraductal papillary mucinous neoplasms (BD-IPMN) varies in existing guidelines. This study investigated the optimal surveillance protocol and safe discontinuation of surveillance considering natural history in non-resected IPMN, by systematically reviewing the published literature.

Methods

This review was guided by PRISMA. Research questions were framed in PICO format “CQ1-1: Is size criteria helpful to determine surveillance period? CQ1-2: How often should surveillance be carried out? CQ1-3: When should surveillance be discontinued? CQ1-4: Is nomogram predicting malignancy useful during surveillance?”. PubMed was searched from January–April 2022.

Results

The search generated 2373 citations. After screening, 83 articles were included. Among them, 33 studies were identified for CQ1-1, 19 for CQ1-2, 26 for CQ1-3 and 12 for CQ1-4. Cysts <1.5 or 2 cm without worrisome features (WF) were described as more indolent, and most studies advised an initial period of surveillance. The median growth rate of cysts <2 cm ranged from 0.23 to 0.6 mm/year. Patients with cysts <2 cm showing no morphological changes and no WF after 5-years of surveillance have minimal malignancy risk of 0–2%. Two nomograms created with over 1000 patients had AUCs of around 0.8 and appear to be feasible in a real-world practice.

Conclusions

For patients with suspected BD-IPMN <2 cm and no other WF, less frequent surveillance is recommended. Surveillance may be discontinued for cysts that remain stable during 5-year surveillance, with consideration of patient condition and life expectancy. With this updated surveillance strategy, patients with non-worrisome BD-IPMN should expect more streamlined management and decreased healthcare utilization.

Previously we reported that a novel αvβ6-specific peptide-drug conjugate (SG3299) could eliminate established human pancreatic ductal adenocarcinoma (PDAC) xenografts. However the development of effective therapies for PDAC, which is an essential need, must show efficacy in relevant immunocompetent animals. Previously we reported that the KPC mouse transgenic PDAC model that closely recapitulates most stages of development of human PDAC, unlike in humans, failed to express αvβ6 on their tumours or metastases. In this study we have taken the KPC-derived PDAC line TB32043 and engineered a variant line (TB32043mb6S2) that expresses mouse integrin αvβ6. We report that orthotopic implantation of the αvβ6 over-expressing TB32043mb6S2 cells promotes shorter overall survival and increase in metastases. Moreover, systemic treatment of mice with established TB32043mb6S2 tumours in the pancreas with SG2399 lived significantly longer (p < 0.001; mean OS 48d) compared with PBS or control SG3511 (mean OS 25.5d and 26d, respectively). Thus SG3299 is confirmed as a promising candidate therapeutic for the therapy of PDAC.

Background

Modified FOLFIRINOX (mFOLFIRINOX) is one of the standard first-line therapies in borderline resectable pancreatic cancer (BRPC) and locally advanced unresectable pancreatic cancer (LAPC). However, there is no globally accepted second-line therapy following progression on mFOLFIRINOX.

Methods

Patients with BRPC and LAPC (n = 647) treated with first-line mFOLFIRINOX between January 2017 and December 2020 were included in this retrospective analysis. The details of the treatment outcomes and patterns of subsequent therapy after mFOLFIRINOX were reviewed.

Results

With a median follow-up duration of 44.2 months (95% confidence interval [CI], 42.3–47.6), 322 patients exhibited disease progression on mFOLFIRINOX—locoregional progression only in 177 patients (55.0%) and distant metastasis in 145 patients (45.0%). The locoregional progression group demonstrated significantly longer post-progression survival (PPS) than that of the distant metastasis group (10.1 vs. 7.3 months, p = 0.002). In the locoregional progression group, survival outcomes did not differ between second-line chemoradiation/radiotherapy and systemic chemotherapy (progression-free survival with second-line therapy [PFS-2], 3.2 vs. 4.3 months; p = 0.649; PPS, 10.7 vs. 10.2 months; p = 0.791). In patients who received second-line systemic chemotherapy following progression on mFOLFIRINOX (n = 211), gemcitabine plus nab-paclitaxel was associated with better disease control rates (69.2% vs. 42.3%, p = 0.005) and PFS-2 (3.8 vs. 1.7 months, p = 0.035) than gemcitabine monotherapy.

Conclusions

The current study showed the real-world practice pattern of subsequent therapy and clinical outcomes following progression on first-line mFOLFIRINOX in BRPC and LAPC. Further investigation is necessary to establish the optimal therapy after failure of mFOLFIRINOX.

Background

Acute pancreatitis (AP) often presents with varying severity, with a small fraction evolving into severe AP, and is associated with high mortality. Complications such as intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) are intricately associated with AP.

Objective

To assess the clinical implications and predictors of ACS in AP patients.

Methods

We conducted a retrospective study using the National Inpatient Sample (NIS) database on adult AP patients, further stratified by the presence of concurrent ACS. The data extraction included demographics, underlying comorbidities, and clinical outcomes. Multivariate linear and logistic regression analyses were performed using STATA (v.14.2).

Results

Of the 1,099,175 adult AP patients, only 1,090 (0.001%) exhibited ACS. AP patients with ACS had elevated inpatient mortality and all major complications, including septic shock, acute respiratory distress syndrome (ARDS), requirement for total parenteral nutrition (TPN), and intensive care unit (ICU) admission (P < 0.01). These patients also exhibited increased odds of requiring pancreatic drainage and necrosectomy (P < 0.01). Predictor analysis identified blood transfusion, obesity (BMI ≥30), and admission to large teaching hospitals as factors associated with the development of ACS in AP patients. Conversely, age, female gender, biliary etiology of AP, and smoking were found less frequently in patients with ACS.

Conclusion

Our study highlights the significant morbidity, mortality, and healthcare resource utilization associated with the concurrence of ACS in AP patients. We identified potential factors associated with ACS in AP patients. Significantly worse outcomes in ACS necessitate the need for early diagnosis, meticulous monitoring, and targeted therapeutic interventions for AP patients at risk of developing ACS.

Background

Psychiatric comorbidity measured by screening instruments is common in patients with chronic pancreatitis (CP) but whether this accurately reflects clinical diagnosis of psychiatric comorbidity is unknown and the prevalence of psychotropic medication prescription in CP remains largely unexplored.

Methods

Adult patients (≥18 years) with definite CP were enrolled and completed the Hospital Anxiety and Depression Scale (HADS). Demographics, clinical characteristics and medications were retrieved from case report forms and the electronic health record (EHR). Clinical diagnosis of depression or anxiety was determined by presence of ICD-10 code or inclusion in the patient's EHR problem list or treatment plan. Comparisons were made between patients with and without clinical psychiatric comorbidity.

Results

Total of 81 patients (48, 59.3% male; mean age 57.6 ± 14.3 years) were included. Clinical diagnoses of anxiety and depression were each noted in 47 (58%) patients, with overlap in 42 (51.9%). Compared to clinical diagnoses, the sensitivity and specificity of a positive screen for anxiety (HADS >7) were 76.6% and 91.2%; for depression 55.3% and 88.2%. Patients with anxiety and/or depression were more frequently female (51.9% v 20.7%), younger (53.6 v 64.9 years), and had alcohol etiology (51.9% v 27.6%) (all p < 0.01). In those with psychiatric comorbidity, 42 (80.8%) were prescribed psychotropic medication, most commonly gabapentinoid (24, 57.1%), selective serotonin reuptake inhibitor (n = 22, 52.4%) or benzodiazepine (n = 20, 47.6%).

Conclusions

Psychiatric comorbidities are common among CP patients and many receive psychotropic medications. Further studies are needed to evaluate the impact of these medications on CP symptoms.

Background

/Objective: Preoperative treatment of resectable pancreatic ductal adenocarcinoma (PDAC) is gaining popularity worldwide. However, the characteristics of tumors located in the pancreatic head (Ph), or those in the body or tail (Pbt), after surgery following neoadjuvant chemoradiotherapy (NACRT) remain unclear. This study aimed to evaluate and compare the clinicopathological features, perioperative outcomes, and prognosis of patients with resectable PDAC who underwent NACRT followed by curative pancreatic resection, focusing on distinguishing between Ph and Pbt PDACs.

Methods

We included 107 patients with resectable PDAC who underwent curative resection following NACRT between 2009 and 2023. Clinicopathological features, perioperative and prognostic outcomes, recurrence patterns, and prognoses were compared between Ph and Pbt PDAC groups.

Results

Tumors were found in the Ph and Pbt in 64 and 43 patients, respectively. Albumin levels and lymphocyte-to-monocyte ratios after NACRT were significantly lower in the Ph group than in the Pbt group. The Pbt group showed significantly higher rates of positive peritoneal lavage cytology and serosal, arterial, and portal vein invasion than the Ph group did. Overall and recurrence-free survival were similar between the two groups. The most common site of initial postoperative recurrence was the lung only in both groups; however, the rate of peritoneal dissemination only was significantly higher in the Pbt group than in the Ph group.

Conclusions

The prognoses based on tumor locations in the Ph and Pbt after surgery following NACRT are similar. Following the resection of resectable Pbt PDAC, the possibility of peritoneal dissemination recurrence should be considered.

Objective

Hemin, a heme oxygenase 1 activator has shown efficacy in the prevention and treatment of acute pancreatitis in mouse models. We conducted a randomized controlled trial (RCT) to assess the protective effect of Hemin administration to prevent post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) in patients at risk.

Methods

In this multicenter, multinational, placebo-controlled, double-blind RCT, we assigned patients at risk for PEP to receive a single intravenous dose of Hemin (4 mg/kg) or placebo immediately after ERCP. Patients were considered to be at risk on the basis of validated patient- and/or procedure-related risk factors. Neither rectal NSAIDs nor pancreatic stent insertion were allowed in randomized patients. The primary outcome was the incidence of PEP. Secondary outcomes included lipase elevation, mortality, safety, and length of stay.

Results

A total of 282 of the 294 randomized patients had complete follow-up. Groups were similar in terms of clinical, laboratory, and technical risk factors for PEP. PEP occurred in 16 of 142 patients (11.3%) in the Hemin group and in 20 of 140 patients (14.3%) in the placebo group (p = 0.48). Incidence of severe PEP reached 0.7% and 4.3% in the Hemin and placebo groups, respectively (p = 0.07). Significant lipase elevation after ERCP did not differ between groups. Length of hospital stay, mortality and severe adverse events rates were similar between groups.

Conclusion

We failed to detect large improvements in PEP rate among participants at risk for PEP who received IV hemin immediately after the procedure compared to placebo.

Trial registration number

ClinicalTrials.gov number, NCT01855841).

Background/objectives

The outcomes of patients with intraepithelial neoplasia at the pancreatic transection margin after pancreatic cancer surgery remain unclear. We evaluated the clinical impact of pancreatic transection margin status.

Methods

This retrospective observational study included 171 patients who underwent surgery for pancreatic ductal adenocarcinoma between January 2008 and December 2019. Patients were classified into three groups: negative pancreatic transection margin (group N), positive low-grade (group L), and positive high-grade (group H) intraepithelial neoplasia. The clinicopathological findings and prognoses were analyzed for each group.

Results

There were 140, 14, and 9 patients in groups N, L, and H, respectively. The median age was significantly higher in group H (p = 0.035). There were no significant differences in male ratio, preoperative chemotherapy administration rate, pretreatment tumor markers, operative procedure, operative time, or blood loss. Overall survival and recurrence-free survival were not significantly different; however, the cumulative risk of recurrence in the remnant pancreas was significantly higher in group H (p = 0.018).

Conclusions

Intraepithelial neoplasia at the pancreatic transection margin did not affect overall/recurrence-free survival. As patients with high-grade intraepithelial neoplasia at the pancreatic transection margin have an increased risk of recurrence in the remnant pancreas, careful postoperative follow-up is required.