Management of Acute Cholecystitis during Neoadjuvant Therapy in Patients with Pancreatic Adenocarcinoma

Jariwalla, Neil R.; Khan, Abdul Hye; Dua, Kulwinder S.; Christians, Kathleen K.; Clarke, Callisia N.; Aldakkak, Mohammed; George, Ben; Tutton, Sean; Rilling, William S.; Erickson, Beth; Evans, Douglas B.; Tsai, Susan

doi:10.1245/s10434-019-07906-7

Cited by 7 publications

(6 citation statements)

References 17 publications

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“…In particular, the incidence of acute cholecystitis after stenting has been reported to be 6%. 21 Similarly, the percentage of patients undergoing ERCP with stenting for biliary obstruction during neoadjuvant therapy ranges from 6% to 10%. 23,24 These interventions did not disrupt neoadjuvant therapy or proceeding to surgery.…”

Section: Discussionmentioning

confidence: 99%

“…For those who were managed with cholecystostomy drainage, this did not impact completion of neoadjuvant therapy and surgical resection whereas a very small minority who had cholecystectomies did not progress on to surgical resection of their pancreatic cancer. 21 We aimed to quantify the incidence and clinical significance of biliary complications that occur during neoadjuvant therapy in a cohort of borderline resectable patients with adenocarcinoma of the pancreatic head. We hypothesized that biliary interventions interfere with neoadjuvant therapy and negatively impact overall survival.…”

Section: Introductionmentioning

confidence: 99%

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Biliary intervention rates during neoadjuvant therapy for adenocarcinoma of the pancreatic head

Kirkpatrick

Gillies

Underwood

et al. 2021

HPB

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Biliary intervention rates during neoadjuvant therapy for adenocarcinoma of the pancreatic head

Kirkpatrick

Gillies

Underwood

et al. 2021

HPB

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“…We emphasized the importance of managing acute cholecystitis with a cholecystostomy tube rather than cholecystectomy; placement of a cholecystostomy tube did not delay the delivery of NAT and subsequent surgery. 21 In this expanded study, the rate of biliary-stent-associated acute cholecystitis remained the same. The relatively low rate of stent-associated cholecystitis is likely due to the routine placement of uncovered stents when the gallbladder is in situ.…”

Section: Discussionmentioning

confidence: 82%

Biliary Adverse Events during Neoadjuvant Therapy for Pancreatic Cancer

Thalji¹,

Fernando²,

Dua³

et al. 2023

Annals of Surgery

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Objective: To describe a high-volume experience with biliary drainage before neoadjuvant therapy (NAT) for patients with operable pancreatic cancer (PC) and characterize the association between biliary adverse events (BAEs) and patient outcome. Background: Patients with PC presenting with biliary obstruction require durable decompression before NAT. Methods: Patients with operable PC and tumor-associated biliary obstruction were examined and grouped by the presence or absence of a BAE during NAT. The incidence, timing, and management of BAEs are described, and outcomes, including the completion of all treatment and overall survival (OS), were compared. Results: Of 426 patients who received pretreatment biliary decompression, 92 (22%) experienced at least 1 BAE during NAT, and 56 (13%) required repeat intervention on their biliary stent. The median duration of NAT was 161 days for all patients and was not different in the group that experienced BAEs. The median time from initial stent placement to BAE was 64 days. An interruption in the delivery of NAT (median 7 days) occurred in 25 (6%) of 426 patients. Among 426 patients, 290 (68%) completed all NAT, including surgery: 60 (65%) of 92 patients with BAE and 230 (69%) of 334 patients without BAE (P = 0.51). Among 290 patients who completed NAT and surgery, the median OS was 39 months, 26 months for the 60 patients with BAE, and 43 months for the 230 patients without BAE (P = 0.02). Conclusions: During extended multimodal NAT for PC, 22% of patients experienced a BAE. Although BAEs were not associated with a significant interruption of treatment, patients who experienced a BAE had worse OS.

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“…Using a prospectively maintained pancreatic cancer database at MCW, we reviewed consecutive patients with biopsy-proven PDAC from 2009 to 2017. Statistics were performed as previously described ( 55 , 56 ). Briefly, categorical variables were compared using Chi-squared test or Fischer’s Exact test.…”

Section: Methodsmentioning

confidence: 99%

Interpreting Sequence Variation in PDAC-Predisposing Genes Using a Multi-Tier Annotation Approach Performed at the Gene, Patient, and Cohort Level

Zimmermann¹,

Mathison²,

Stodola³

et al. 2021

Front. Oncol.

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We investigated germline variation in pancreatic ductal adenocarcinoma (PDAC) predisposition genes in 535 patients, using a custom-built panel and a new complementary bioinformatic approach. Our panel assessed genes belonging to DNA repair, cell cycle checkpoints, migration, and preneoplastic pancreatic conditions. Our bioinformatics approach integrated annotations of variants by using data derived from both germline and somatic references. This integrated approach with expanded evidence enabled us to consider patterns even among private mutations, supporting a functional role for certain alleles, which we believe enhances individualized medicine beyond classic gene-centric approaches. Concurrent evaluation of three levels of evidence, at the gene, sample, and cohort level, has not been previously done. Overall, we identified in PDAC patient germline samples, 12% with mutations previously observed in pancreatic cancers, 23% with mutations previously discovered by sequencing other human tumors, and 46% with mutations with germline associations to cancer. Non-polymorphic protein-coding pathogenic variants were found in 18.4% of patient samples. Moreover, among patients with metastatic PDAC, 16% carried at least one pathogenic variant, and this subgroup was found to have an improved overall survival (22.0 months versus 9.8; p=0.008) despite a higher pre-treatment CA19-9 level (p=0.02). Genetic alterations in DNA damage repair genes were associated with longer overall survival among patients who underwent resection surgery (92 months vs. 46; p=0.06). ATM alterations were associated with more frequent metastatic stage (p = 0.04) while patients with BRCA1 or BRCA2 alterations had improved overall survival (79 months vs. 39; p=0.05). We found that mutations in genes associated with chronic pancreatitis were more common in non-white patients (p<0.001) and associated with longer overall survival (52 months vs. 26; p=0.004), indicating the need for greater study of the relationship among these factors. More than 90% of patients were found to have variants of uncertain significance, which is higher than previously reported. Furthermore, we generated 3D models for selected mutant proteins, which suggested distinct mechanisms underlying their dysfunction, likely caused by genetic alterations. Notably, this type of information is not predictable from sequence alone, underscoring the value of structural bioinformatics to improve genomic interpretation. In conclusion, the variation in PDAC predisposition genes appears to be more extensive than anticipated. This information adds to the growing body of literature on the genomic landscape of PDAC and brings us closer to a more widespread use of precision medicine for this challenging disease.

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Management of Acute Cholecystitis during Neoadjuvant Therapy in Patients with Pancreatic Adenocarcinoma

Cited by 7 publications

References 17 publications

Biliary intervention rates during neoadjuvant therapy for adenocarcinoma of the pancreatic head

Biliary intervention rates during neoadjuvant therapy for adenocarcinoma of the pancreatic head

Biliary Adverse Events during Neoadjuvant Therapy for Pancreatic Cancer

Interpreting Sequence Variation in PDAC-Predisposing Genes Using a Multi-Tier Annotation Approach Performed at the Gene, Patient, and Cohort Level

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