Exploring the Clinical Use of Molecular Profiling of Intrahepatic Cholangiocarcinoma in a Comprehensive Multidisciplinary Clinic.

BACKGROUND: Molecular profiling of intrahepatic cholangiocarcinoma (ICC) can detect actionable molecular alterations and guide targeted therapies. We explore the clinical use of molecular profiling of ICC in our comprehensive multidisciplinary clinic. STUDY DESIGN: Patients with a tissue diagnosis of ICC seen between 2019 and 2023 were identified. A retrospective review was performed to identify their molecular profiles and targeted therapy. The association between the detection of actionable molecular alterations and overall survival (OS) from the first clinic visit date was studied. Patients with an OS of less than 2 months were excluded. RESULTS: Among 194 patients with ICC, 125 had molecular profiling. Actionable molecular alterations were detected in 56 (45%) patients, including microsatellite instability (n = 3), high tumor mutational burden (>10 muts/mb; n = 5), isocitrate dehydrogenase 1 and 2 mutations (n = 22 and 6, respectively), BRAF V600E mutations (n = 2), phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha mutations (n = 7), breast cancer 1 and breast cancer 2 mutations (n = 5), mesenchymal epithelial transition amplification (n = 2), fibroblast growth factor receptor 2 and 3 fusions (n = 13), erb-b2 receptor tyrosine kinase 2 overexpression (n = 6), and receptor tyrosine kinase 1 fusion (n = 1). Twenty-one patients received targeted therapies during their treatment course. Survival analysis revealed that for 120 patients with molecular profiling, the detection of an actionable molecular alteration was associated with improved mean OS (34.1 vs 23.6 months, p = 0.008). Among 70 patients with nonmetastatic ICC, the detection of an actionable molecular alteration was associated with improved mean OS (32.1 vs 27.5 months, p = 0.02). CONCLUSIONS: Actionable molecular alterations were frequently observed in patients with ICC. Detection of actionable alterations was associated with improved OS. The role of targeted therapy needs further exploration in prospective multicenter studies.

Robotic Parenchymal-Sparing Pancreatectomy: A Systematic Review.

BACKGROUND: Parenchymal-sparing approaches to pancreatectomy are technically challenging procedures but allow for preserving a normal pancreas and decreasing the rate of postoperative pancreatic insufficiency. The robotic platform is increasingly being used for these procedures. We sought to evaluate robotic parenchymal-sparing pancreatectomy and assess its complication profile and efficacy. METHODS: This systematic review consisted of all studies on robotic parenchymal-sparing pancreatectomy (central pancreatectomy, duodenum-preserving partial pancreatic head resection, enucleation, and uncinate resection) published between January 2001 and December 2022 in PubMed and Embase. RESULTS: A total of 23 studies were included in this review (n = 788). Robotic parenchymal-sparing pancreatectomy is being performed worldwide for benign or indolent pancreatic lesions. When compared to the open approach, robotic parenchymal-sparing pancreatectomies led to a longer average operative time, shorter length of stay, and higher estimated intraoperative blood loss. Postoperative pancreatic fistula is common, but severe complications requiring intervention are exceedingly rare. Long-term complications such as endocrine and exocrine insufficiency are nearly nonexistent. CONCLUSIONS: Robotic parenchymal-sparing pancreatectomy appears to have a higher risk of postoperative pancreatic fistula but is rarely associated with severe or long-term complications. Careful patient selection is required to maximize benefits and minimize morbidity.

Detecting Somatic Mutations for Well-Differentiated Pancreatic Neuroendocrine Tumors in Endoscopic Ultrasound-Guided Fine Needle Aspiration with Next-Generation Sequencing.

BACKGROUND: Pancreatic neuroendocrine tumors (PanNETs) exhibit heterogenous behavior, whereby some small tumors are aggressive with a propensity for metastasis. Detection of somatic mutations associated with aggressive biology may help with patient stratification and surgical decision-making in patients with well-differentiated PanNETs. Using next-generation sequencing (NGS), we investigated the feasibility of detecting somatic mutations in endoscopic ultrasound-guided, fine-needle aspiration (EUS-FNA) specimens and determining the mutational concordance between the EUS-FNA specimens and the primary tumors. METHODS: Thirty-eight patients with well-differentiated, nonfunctioning PanNETs were obtained from two tertiary referral centers. Patient demographic characteristics and tumor, clinicopathologic features were collected. Tissue from both the EUS-FNA specimen and the primary tumor was extracted from archival tissue blocks. NGS using a panel of ten genes was performed on both samples. RESULTS: In our series, the median age was 61.1 years. Tumors were predominantly left-sided (60.5%) and unifocal (94.7%). The median tumor size was 2.2 cm. NGS detected somatic mutations in 29% of primary tumors and 36.8% of EUS-FNA specimens. In primary tumors, DAXX/ATRX mutations were predominantly detected (63.6%). In EUS-FNA specimens, MEN1 mutations were predominantly detected (64.3%). Among non-wild-type specimens, mutational concordance was achieved in 31.6% of cases. In 11 patients with a detectable mutation in the primary tumor, a mutation was detected in the EUS-FNA specimen in 45.5% of cases, with a mutational concordance of 54.5%. CONCLUSIONS: NGS can detect somatic mutations in EUS-FNA specimens of well-differentiated PanNETs. Efforts to improve detection sensitivity and mutational concordance are required to overcome current technical limitations.

Cancer-cell-derived sialylated IgG as a novel biomarker for predicting poor pathological response to neoadjuvant therapy and prognosis in pancreatic cancer.

BACKGROUND: Neoadjuvant therapy (NAT) is increasingly applied in pancreatic ductal adenocarcinoma (PDAC); however, accurate prediction of therapeutic response to NAT remains a pressing clinical challenge. Cancer-cell-derived sialylated immunoglobulin G (SIA-IgG) was previously identified as a prognostic biomarker in PDAC. This study aims to explore whether SIA-IgG expression in treatment-naïve fine needle aspirate (FNA) biopsy specimens could predict the pathological response (PR) to NAT for PDAC. METHODS: Endoscopic ultrasonography-guided FNA biopsy specimens prior to NAT were prospectively obtained from 72 patients with PDAC at the Johns Hopkins Hospital. SIA-IgG expression of PDAC specimens was assessed by immunohistochemistry. Associations between SIA-IgG expression and PR, as well as patient prognosis, were analyzed. A second cohort enrolling surgically resected primary tumor specimens from 79 patients with PDAC was used to validate the prognostic value of SIA-IgG expression. RESULTS: SIA-IgG was expressed in 58.3% of treatment-naïve FNA biopsies. Positive SIA-IgG expression at diagnosis was associated with unfavorable PR and can serve as an independent predictor of PR. The sensitivity and specificity of SIA-IgG expression in FNA specimens in predicting an unfavorable PR were 63.9% and 80.6%, respectively. Both positive SIA-IgG expression in treatment-naïve FNA specimens and high SIA-IgG expression in surgically resected primary tumor specimens were significantly associated with shorter survival. CONCLUSIONS: Assessment of SIA-IgG on FNA specimens prior to NAT may help predict PR for PDAC. Additionally, SIA-IgG expression in treatment-naïve FNA specimens and surgically resected primary tumor specimens were predictive of the prognosis for PDAC.

Robotic Distal Pancreatectomy: A Novel Standard of Care? Benchmark Values for Surgical Outcomes From 16 International Expert Centers.

BACKGROUND AND OBJECTIVE: Robotic distal pancreatectomy (DP) is an emerging attractive approach, but its role compared with laparoscopic or open surgery remains unclear. Benchmark values are novel and objective tools for such comparisons. The aim of this study was to identify benchmark cutoffs for many outcome parameters for DP with or without splenectomy beyond the learning curve. METHODS: This study analyzed outcomes from international expert centers from patients undergoing robotic DP for malignant or benign lesions. After excluding the first 10 cases in each center to reduce the effect of the learning curve, consecutive patients were included from the start of robotic DP up to June 2020. Benchmark patients had no significant comorbidities. Benchmark cutoff values were derived from the 75th or the 25th percentile of the median values of all benchmark centers. Benchmark values were compared with a laparoscopic control group from 4 high-volume centers and published open DP landmark series. RESULTS: Sixteen centers contributed 755 cases, whereof 345 benchmark patients (46%) were included the analysis. Benchmark cutoffs included: operation time ≤300 minutes, conversion rate ≤3%, clinically relevant postoperative pancreatic fistula ≤32%, 3 months major complication rate ≤26.7%, and lymph node retrieval ≥9. The comprehensive complication index at 3 months was ≤8.7 without deterioration thereafter. Compared with robotic DP, laparoscopy had significantly higher conversion rates (5×) and overall complications, while open DP was associated with more blood loss and longer hospital stay. CONCLUSION: This first benchmark study demonstrates that robotic DP provides superior postoperative outcomes compared with laparoscopic and open DP. Robotic DP may be expected to become the approach of choice in minimally invasive DP.

Tailoring Adjuvant Chemotherapy to Biologic Response Following Neoadjuvant Chemotherapy Impacts Overall Survival in Pancreatic Cancer.

BACKGROUND: The role of postoperative chemotherapy in patients with resected pancreatic cancer who receive neoadjuvant treatment is unknown. Clinicians use changes in CA19-9 and histopathologic scores to assess treatment response. We sought to investigate if CA19-9 normalization in response to NAT can help guide the need for postoperative treatment. METHODS: Patients with elevated baseline CA19-9 (CA19-9 > 37U/mL) who received NAT followed by surgery between 2011 and 2019 were retrospectively reviewed. Treatment response was determined by CA19-9 normalization following NAT and histopathologic scoring. The role of postoperative chemotherapy was analyzed in light of CA19-9 normalization and histopathologic response. RESULTS: We identified and included 345 patients. Following NAT, CA19-9 normalization was observed in 125 patients (36.2%). CA19-9 normalization was associated with a favorable histopathologic response (41.6% vs 23.2%, p < 0.001) and a lower ypT (p < 0.001) and ypN stage (p = 0.003). Receipt of adjuvant chemotherapy was associated with improved overall survival in patients in whom CA19-9 did not normalize following NAT (26.8 vs 16.4 months, p = 0.008). In patients who received 5FU-based NAT and in whom CA19-9 did not normalize, receipt of 5FU-based adjuvant chemotherapy was associated with improved OS (p = 0.014). CONCLUSION: CA19-9 normalization in response to NAT was associated with favorable outcomes and can serve as a biomarker for treatment response. In patients where CA19-9 did not normalize, receipt of postoperative chemotherapy was associated with improved OS. These patients also benefited from additional 5FU-based postoperative chemotherapy following 5FU-based NAT.

Clinical Trials in Hepatopancreatobiliary Surgery: Assessing Trial Characteristics, Early Discontinuation, Result Reporting, and Publication.

BACKGROUND: Hepatopancreaticobiliary (HPB) diseases carry high morbidity despite efforts aimed at their reduction. An assessment of their trial characteristics is paramount to determine trial design adequacy and highlight areas for improvement. As such, the aim of this study is to assess HPB surgery trial characteristics, summarize logistic, financial, and practical reasons behind early discontinuation, and propose potential interventions to prevent this in the future. METHODS: All clinical trials investigating HPB surgery registered on ClinicalTrials.gov from October 1st, 2007 (inclusive), to April 20th, 2021 (inclusive), were examined. Trial characteristics were collected including, but not limited to, study phase, duration, patient enrollment size, location, and study design. Peer-reviewed publications associated with the selected trials were also assessed to determine outcome reporting. RESULTS: A total of 1776 clinical trials conducted in 43 countries were identified, the majority of which were conducted in the USA. Of these trials, 32% were reported as "completed" whereas 12% were "discontinued." The most common cause of trial discontinuation was low accrual, which was reported in 37% of terminated studies. These resulted in 413 published studies. Most trials had multiple assignment, randomized, or open-label designs. Treatment was the most common study objective (73%) with pharmacological therapy being the most commonly studied intervention. CONCLUSIONS: The main reasons for early discontinuation of clinical trials in HPB surgery are poor patient recruitment and inadequate funding. Improved trial design, recruitment strategies and increased funding are needed to prevent trial discontinuation and increase publication rates of HPB surgery clinical trials.

Incidence and Contemporary Management of Delayed Bleeding Following Pancreaticoduodenectomy.

BACKGROUND: Delayed bleeding after pancreaticoduodenectomy (PD) is a life-threatening complication. However, the optimal management remains unclear. We summarize our experience of the management of delayed bleeding after PD and define the outcomes associated with different types of management. METHODS: All patients who underwent a PD between January 1987 and June 2020 at Johns Hopkins University were retrospectively reviewed. Delayed bleeding was defined as bleeding on or after postoperative day 5 following PD. Incidence, outcomes, and trends were reported. RESULTS: Among the 6201 patients that underwent PD, delayed bleeding occurred in 130 (2.1%) at a median of 12 days (IQR: 9, 24) postoperation. The pattern of bleeding was classified as intraluminal (51.5%), extraluminal (40.8%), and mixed (7.7%). A clinically relevant postoperative pancreatic fistula and an intraabdominal abscess preceded the delayed bleeding in 43.1% and 31.5% of cases, respectively. Arterial pseudoaneurysm or bleeding from peripancreatic vessels was the most common reason (54.6%) with the gastroduodenal artery being the most common source (18.5%). Endoscopy, angiography, and reoperation were performed as a first-line approach in 35.4%, 52.3%, and 6.2% of patients, respectively. The overall mortality was 16.2% and decreased over the study period (p < 0.01). CONCLUSIONS: Delayed bleeding following PD remains a life-threatening complication. The most common location of delayed bleeding is from the gastroduodenal artery. Angiography with embolization should be the initial approach for urgent bleeding with surgical re-exploration reserved for unstable patients or failed control of bleeding after interventional angiography or endoscopy.

COVID-19 transmission in surgical smoke during laparoscopy and open surgery: a systematic review.

AIM: To evaluate the risk of SARS-CoV-2 transmission in surgical smoke and aerosols during laparoscopy and open surgery. MATERIAL AND METHODS: A systematic review (PROSPERO ID: CRD42021268366) was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Articles were selected based on the title and abstract as well as the type of publication. Primary objectives of the study were to assess potential risk of contamination as well as comparing laparoscopic and open procedures in terms of danger of SARS-COV-2 transmission. RESULTS: Fifty-three articles were identified and included in the review. No case of SARS-CoV-2 transmission to operating room personnel during open or minimally invasive surgery was identified at the time the review was conducted. Furthermore, no significant difference was observed between smoke and aerosols generated from open surgery and those generated from minimally invasive surgery. CONCLUSION: COVID-19 transmission in surgical smoke and aerosols has yet to be observed. However, given the potential risk of viral transmission, caution should be exercised when performing surgery to ensure the safety of the operating room personnel. When clinically indicated and when protective measures can be implemented, minimally invasive surgery should be performed instead of open surgery to ensure optimal patient outcomes.

Impact of the COVID-19 Pandemic on Liver Cancer Staging at a Multidisciplinary Liver Cancer Clinic.

To compare liver cancer resectability rates before and during the COVID-19 pandemic. Background: Liver cancers usually present with nonspecific symptoms or are diagnosed through screening programs for at-risk patients, and early detection can improve patient outcomes. In 2020, the COVID-19 pandemic upended medical care across all specialties, but whether the pandemic was associated with delays in liver cancer diagnosis is not known. Methods: We performed a retrospective review of all patients evaluated at the Johns Hopkins Multidisciplinary Liver Cancer Clinic from January 2019 to June 2021 with a new diagnosis of suspected or confirmed hepatocellular carcinoma (HCC) or biliary tract cancer (BTC). Results: There were 456 liver cancer patients (258 HCC and 198 BTC). From January 2019 to March 2020 (pre-pandemic), the surgical resectability rate was 20%. The subsequent 6 months (early pandemic), the resectability rate decreased to 11%. Afterward from October 2020 to June 2021 (late pandemic), the resectability rate increased to 27%. The resectability rate early pandemic was significantly lower than that for pre-pandemic and later pandemic combined (11% lower; 95% confidence interval [CI], 2%-20%). There was no significant difference in resectability rates pre-pandemic and later pandemic (7% difference; 95% CI, -3% to 16%). In subgroup analyses, the early pandemic was associated with a larger impact in BTC resectability rates than HCC resectability rates. Time from BTC symptom onset until Multidisciplinary Liver Clinic evaluation increased by over 6 weeks early pandemic versus pre-pandemic (Hazard Ratio, 0.63; 95% CI, 0.44-0.91). Conclusions: During the early COVID-19 pandemic, we observed a drop in the percentage of patients presenting with curable liver cancers. This may reflect delays in liver cancer diagnosis and contribute to excess mortality related to the COVID-19 pandemic.

Management of a Gastrobronchial Fistula Presenting 5 Years After a One-Loop Gastric Bypass.

Anastomotic leaks and gastric fistulas are recognized complications after sleeve gastrectomy and Roux-en-Y gastric bypass. They are, however, almost unheard of following a one-anastomosis gastric bypass. A gastrobronchial fistula, an exceedingly rare complication after bariatric surgery, has to date never been described following a one-anastomosis gastric bypass. Furthermore, there is no consensus regarding the management of this challenging complication. In our case, we present a patient who was discovered to have a gastrobronchial fistula 5 years after a one anastomosis gastric bypass. After 2 failed attempts at endoscopic stent placement, the patient was successfully managed with a laparoscopic Roux-en-Y gastrojejunostomy over the fistula.

Establishing a sorting protocol for healthcare databases.

BACKGROUND: Health information records in many countries, especially developing countries, are still paper based. Compared to electronic systems, paper-based systems are disadvantageous in terms of data storage and data extraction. Given the importance of health records for epidemiological studies, guidelines for effective data cleaning and sorting are essential. They are, however, largely absent from the literature. The following paper discusses the process by which an algorithm was developed for the cleaning and sorting of a database generated from emergency department records in Lebanon. DESIGN AND METHODS: Demographic and health related information were extracted from the emergency department records of three hospitals in Beirut. Appropriate categories were selected for data categorization. For health information, disease categories and codes were selected according to the International Classification of Disease 10th Edition. RESULTS: A total of 16,537 entries were collected. Demographic information was categorized into groups for future epidemiological studies. Analysis of the health information led to the creation of a sorting algorithm which was then used to categorize and code the health data. Several counts were then performed to represent and visualize the data numerically and graphically. CONCLUSIONS: The article describes the current state of health information records in Lebanon and the associated disadvantages of a paper-based system in terms of storage and data extraction. Furthermore, the article describes the algorithm by which health information was sorted and categorized to allow for future data analysis using paper records.

A Conservative Approach to Inflammatory Myofibroblastic Tumor of the Bladder: A Case Report and Review of Literature.

Inflammatory myofibroblastic tumors (IMTs) are particularly rare tumors that have been described in various anatomic locations, of which the urinary bladder is the most common. These benign tumors are amendable to conservative therapy but are notoriously difficult to diagnose given their mimicry of malignant sarcomas and sarcomatoid carcinomas, making an accurate diagnosis paramount to spare a patient radical and unnecessary treatment. We hereby present the case of a 37-year-old female patient who was diagnosed with an IMT of the urinary bladder during workup for painless gross hematuria. Patient was successfully managed with a laparoscopic partial cystectomy and is free of recurrence 5 years after surgery. IMTs are rare benign tumors that share the same clinical presentation as malignant bladder tumors. Deep biopsy and experienced pathologist are crucial in establishing diagnosis and avoiding patient radical treatment. This case is a classical demonstration of a remarkably rare tumor that was adequately managed with conservative therapy, achieving excellent clinical outcomes.

Platelet-to-lymphocyte ratio is correlated with a delay in feeding resumption following a transhiatal esophagectomy with cervical anastomosis.

INTRODUCTION: The lymphocytic population, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) are prognostic tools predictive of adverse outcomes for several solid tumors and oncologic surgeries, one of which is esophageal adenocarcinoma. Furthermore, delayed resumption of oral feeding postoperatively is associated with significant morbidity. Given the controversies regarding post-op nutritional support in these patients, this study investigates the prognostic role of the lymphocytic percentage, the NLR, and the PLR in predicting prolonged length of hospital stay (LOHS) and ICU stay (LOICUS) as well as delayed oral feeding following transhiatal esophagectomy (THE) for adenocarcinoma of the esophagogastric junction (AEG). METHODS: Forty consecutive patients who underwent transhiatal esophagectomy performed by a single surgeon for Siewert type II and type III adenocarcinoma of the esophagogastric junction at a tertiary referral center were selected. Retrospective data collection was performed from the patients' medical records, and statistical analysis was performed using Pearson correlation and Student's t test and Chi-square testing. RESULTS: An increased LOHS was correlated with a lower preoperative lymphocyte percentage (p = 0.043), higher NLR (p = 0.010) and PLR (p = 0.015), and an increased number of packed red blood cell (PRBC) transfusions perioperatively (p = 0.030). An increased LOICUS was correlated with a lower preoperative lymphocyte percentage (p = 0.033), higher NLR (p = 0.018) and PLR (p = 0.044), an increased number of PRBC transfusions (p = 0.001), and patients' comorbidities (p < 0.05). A delay in feeding resumption was correlated with a lower preoperative lymphocyte percentage (p = 0.022), higher NLR (p = 0.004) and PLR (p = 0.001), an increased PRBC transfusions (p = 0.001), and diabetes mellitus (p = 0.033). Multivariate analysis with automatic linear modeling showed that only the preoperative PLR was a powerful predictor for the delay of feeding resumption (p < 0.01). CONCLUSION: The lymphocyte percentage, PLR, and NLR are found to be associated with prolonged hospitalization and ICU stay and delayed oral feeding following THE for Siewert types II and III AEG. We hope by this series, to have set, at least one preliminary cornerstone, in the creation of a prognostic model, capable of assessing the need for an intraoperative jejunostomy placement, in patients undergoing esophagectomy for distal esophageal carcinoma.

Epididymal polar dissociation: A rare entity.

Epididymal fusional anomalies have been found to be associated with conditions of testicular maldescent with the several studies investigating this association reporting several variations in epididymal anatomy and epididymal-testicular fusion. To our knowledge, a single case of an isolated lower epididymal pole with a normal vas deferens, dubbed "Epididymal Polar Dissociation", has been reported in the literature. In this report, we report the second case of epididymal polar dissociation discovered in a 17-year-old during surgical management of left testicular torsion.

Perinephric Hematoma with Active Arterial Hemorrhage following Extracorporeal Shockwave Lithotripsy.

Subcapsular hematoma is an exceedingly rare complication of extracorporeal shockwave lithotripsy (ESWL) for renal stones with cases demonstrating evidence of active arterial bleeding even more so. A 49-year-old male presented with acute onset right flank pain two hours following ESWL. CT scan with contrast revealed active contrast extravasation consistent with arterial bleeding. The patient was managed with arterial embolization and recovered uneventfully following a 4-day hospitalization.