Consensus Statement on Safety of Combining Transarterial Radioembolization with Yttrium-90 Microspheres with Systemic Anticancer Agents for the Treatment of Liver Malignancy.

PURPOSE: To provide guidance, via multidisciplinary consensus statements, on the safety interactions between systemic anticancer agents (such as radiosensitizing chemotherapy, immunotherapy, targeted therapy, and peptide receptor radionuclide therapy) and transarterial radioembolization (TARE) with yttrium-90 (90Y)-labeled microspheres in the treatment of primary and metastatic liver malignancies. MATERIALS AND METHODS: A literature search identified 59 references that informed 26 statements on the safety of 90Y TARE combined with systemic therapies. Modified Delphi method was used to develop consensus on statements through online anonymous surveys of the 12 panel members representing the fields of interventional radiology, medical oncology, surgical oncology, hepatology, and pharmacy, focusing on hepatocellular carcinoma (HCC), metastatic colorectal cancer (mCRC), neuroendocrine tumors, metastatic breast cancer, and intrahepatic cholangiocarcinoma. RESULTS: High-level evidence was limited. Level 1 data in patients with mCRC suggest that some radiosensitizing chemotherapies (eg, oxaliplatin) require temporary dose reduction when used concomitantly with 90Y TARE, and some targeted therapies (eg, vascular endothelial growth factor inhibitors and antiangiogenic tyrosine kinase inhibitors) should be avoided for at least 4 weeks before 90Y TARE. In patients with HCC, the feasibility of 90Y TARE and immunotherapy has been demonstrated with Level 4 evidence. Data are more limited for other primary and secondary liver malignancies, and consensus statements were driven by expert opinion (Level 5). CONCLUSIONS: Given the absence of evidence-based guidelines on the safety of 90Y TARE in combination with systemic anticancer therapy, these consensus statements provide expert guidance on the potential risks when considering specific combinations.

Sustained intraoperative allergic reaction to chlorhexidine: A case report.

Physicians should be prepared for the presentation and treatment of an anaphylactic reaction in a patient who has been exposed to chlorhexidine perioperatively and consider a sustained source of allergic exposure when faced with a refractory response to treatment.

How Does the Sequence of the American Board of Surgery Examinations Impact Pass/Fail Outcomes?

OBJECTIVE: Historically, the American Board of Surgery required surgeons to pass the qualifying examination (QE) before taking the certifying examination (CE). However, in the 2020-2021 academic year, with mitigating circumstances related to COVID-19, the ABS removed this sequencing requirement to facilitate the certification process for those candidates who were negatively impacted by a QE delivery failure. This decoupling of the traditional order of exam delivery has provided a natural comparator to the traditional route and an analysis of the impact of examination sequencing on candidate performance. METHODS: All candidates who applied for the canceled July 2020 QE were allowed to take the CE before passing the QE. The sample was then reduced to include only first-time candidates to ensure comparable groups for performance outcomes. Logistic regression was used to analyze the relationship between the order of taking the QE and the CE, controlling for other examination performance, international medical graduate status, and gender. RESULTS: Only first-time candidates who took both examinations were compared (n=947). Examination sequence was not a significant predictor of QE pass/fail outcomes, OR=0.54; 95% CI, 0.19-1.61, P =0.26. However, examination sequence was a significant predictor of CE pass/fail outcomes, OR=2.54; 95% CI, 1.46-4.68, P =0.002. CONCLUSIONS: This important study suggests that preparation for the QE increases the probability of passing the CE and provides evidence that knowledge may be foundational for clinical judgment. The ABS will consider these findings for examination sequencing moving forward.

No Drain, No Problem: Serum-Based Marker Prediction of Clinically Relevant Postoperative Pancreatic Fistula.

BACKGROUND: Postoperative day (POD) 1 drain amylase concentration (DAC) is considered the most accurate predictor for the development of a clinically relevant postoperative pancreatic fistula (CR-POPF) after pancreaticoduodenectomy (PD). Recent studies have associated drain placement with negative postoperative outcomes. This study aims to evaluate multiple biochemical markers and their associations with CR-POPF development in order to identify a reliable, non-drain dependent alternative to DAC. METHODS: This is a review of 53 consecutive PD patients between 2021 and 2022. Albumin, C-reactive protein (CRP), C-reactive protein-to-albumin ratio (CAR), DAC, white blood cell count, and procalcitonin values were compared by CR-POPF status. The discriminatory abilities of CAR, CRP, and DAC for CR-POPF were compared using receiver operating characteristic (ROC) curves. RESULTS: Six of 51 included patients developed a CR-POPF. Receiver operating characteristic curve analysis produced an area under the curve of .977 for POD 1 DAC (cut-off 5131.0 IU/L, sensitivity 100%, specificity 95.5%), .858 for POD 1 CRP (cut-off 52.5 mg/L, sensitivity 100%, specificity 72.7%), and 1.000 for POD 3 CAR (cut-off 99.2, sensitivity and specificity 100%). POD 3 CAR produced a positive and negative predictive value of 100%. CONCLUSION: The CAR and CRP provide early and accurate identification of patients with post-PD CR-POPFs. These markers offer a method of safe CR-POPF detection, when the gold standard DAC is unavailable, ultimately allowing for early intervention and patient rescue.

SAGES/AHPBA guidelines for the use of microwave and radiofrequency liver ablation for the surgical treatment of hepatocellular carcinoma or colorectal liver metastases less than 5 cm.

BACKGROUND: Primary hepatocellular carcinoma (HCC) and colorectal liver metastases (CRLM) represent the liver's two most common malignant neoplasms. Liver-directed therapies such as ablation have become part of multidisciplinary therapies despite a paucity of data. Therefore, an expert panel was convened to develop evidence-based recommendations regarding the use of microwave ablation (MWA) and radiofrequency ablation (RFA) for HCC or CRLM less than 5 cm in diameter in patients ineligible for other therapies. METHODS: A systematic review was conducted for six key questions (KQ) regarding MWA or RFA for solitary liver tumors in patients deemed poor candidates for first-line therapy. Subject experts used the GRADE methodology to formulate evidence-based recommendations and future research recommendations. RESULTS: The panel addressed six KQs pertaining to MWA vs. RFA outcomes and laparoscopic vs. percutaneous MWA. The available evidence was poor quality and individual studies included both HCC and CRLM. Therefore, the six KQs were condensed into two, recognizing that these were two disparate tumor groups and this grouping was somewhat arbitrary. With this significant limitation, the panel suggested that in appropriately selected patients, either MWA or RFA can be safe and feasible. However, this recommendation must be implemented cautiously when simultaneously considering patients with two disparate tumor biologies. The limited data suggested that laparoscopic MWA of anatomically more difficult tumors has a compensatory higher morbidity profile compared to percutaneous MWA, while achieving similar overall 1-year survival. Thus, either approach can be appropriate depending on patient-specific factors (very low certainty of evidence). CONCLUSION: Given the weak evidence, these guidelines provide modest guidance regarding liver ablative therapies for HCC and CRLM. Liver ablation is just one component of a multimodal approach and its use is currently limited to a highly selected population. The quality of the existing data is very low and therefore limits the strength of the guidelines.

The impact of virtual interviews on the Fellowship Council application and main match process.

BACKGROUND: The COVID-19 pandemic led the Fellowship Council (FC) to transition rapidly from in-person to virtual interviews. We investigated the impact of this transition on the FC application and main match process. METHODS: Five years (2018-2022) of deidentified FC applicant, program, and match rank data were used to assess differences between in-person (2018-2019) and virtual interview (2021-2022) cycles. Data are expressed as mean ± SD and one-way and two-way MANOVA tests were applied. RESULTS: Trainees applied to an average of 30.4 ± 24.3 programs and ranked an average of 10.7 ± 9.7 programs with a 57% match rate and average rank position of 3.6 ± 3.3. Fellowship programs received an average of 64.9 ± 28.6 applications and ranked an average of 15.4 ± 8.8 applicants with a 95% match rate and average applicant rank position of 3.0 ± 3.4. Applicants who interviewed virtually applied to a greater number of programs (32.7 vs. 27.0; p < 0.001) and ranked a greater number of programs (11.5 vs. 10.0; p = 0.004) with no difference in match rates (58% vs. 55%, p = 0.291). Among matched applicants, there was a significant difference in average rank position (3.20 vs. 4.30, p < 0.001), favoring the in-person cohort. Fellowship programs had more applicants per program (69.2 vs. 57.8; p < 0.001) and ranked more applicants (17.4 vs. 13.3; p < 0.001) during the virtual interview cycles. No difference in either match rates (93% vs. 96%, p = 0.178) or applicant rank position (3.09 vs. 2.93, p = 0.561) was seen between in-person and virtual application cycles. CONCLUSION: Virtual interviews were associated with an increased number of applications for fellowship and applicants ranked by programs but did not impact match rates of either group. Rank match position declined somewhat for applicants but not for fellowship programs. Virtual interviews offer more opportunities for applicants and a greater number of candidates for fellowship programs with only a slight decrement in fellow match rank position.

Novel Use of Hypoxia-Inducible Polymerizable Protein to Augment Chemotherapy for Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies and is the fourth leading cause of cancer-related deaths in the United States. Unfortunately, 80-85% of patients are diagnosed with unresectable, advanced stage tumors. These tumors are incurable and result in a median survival less than approximately six months and an overall 5-year survival rate of less than 7%. Whilst chemotherapy is a critical treatment, cure is not possible without surgical resection. The poor clinical outcomes in PDAC can be partially attributed to its dense desmoplastic stroma, taking up roughly 80% of the tumor mass. The stroma surrounding the tumor disrupts the normal architecture of pancreatic tissue leading to poor vascularization, high intratumoral pressure along with hypoxia and an acidic tumor microenvironment. This complicated microenvironment presents a significant challenge for drug delivery. The current manuscript discusses a novel approach to overcome many of these various obstacles. A complex of gemcitabine (GEM) and hemoglobin S (HbS) was formulated, which self-polymerizes under hypoxic and acidic conditions. When polymerized, HbS has the potential to break the tumor stroma, decrease intratumoral pressure, and therefore improve the treatment efficacy of standard therapy. Intratumoral injection of HbS with a fluorescent small molecule surrogate for GEM into a pancreatic tumor xenograft resulted in improved dissemination of the small molecule throughout the pancreatic tumor. The self-polymerization of HbS + GEM was significantly more effective than either agent individually at decreasing tumor size in an in vivo PDAC mouse model. These findings would suggest a clinical benefit from delivering the complex of GEM and HbS via direct injection by endoscopic ultrasound (EUS). With such a treatment option, patients with locally advanced disease would have the potential to become surgical candidates, offering them a chance for cure.

Biologic Keyhole Mesh in Hiatal Hernia Repair.

BACKGROUND AND OBJECTIVES: Laparoscopic paraesophageal hernia repair (LPEHR) is the new standard, but the use of mesh is still debated. Biologic mesh has shown great promise, but only the U-shaped onlay has been extensively studied. Postoperative dysphagia has historically been a concern with the use of synthetic keyhole mesh and subsequently slowed its adoption. The purpose of our study was to identify the incidence of postoperative dysphagia in a series of patients who underwent laparoscopic paraesophageal hernia repair with novel placement of keyhole biologic mesh. METHODS: Thirty consecutive patients who underwent hernia repair with primary suture cruroplasty and human acellular dermal matrix keyhole mesh reinforcement were reviewed over a 2-year period. All procedures were performed at a single institution. Postoperative symptoms were retrospectively identified. Any postoperative hernia on imaging was defined as radiographic recurrence. RESULTS: Of the 30 consecutive patients who underwent hernia repair, 3 (10%) had mild preoperative dysphagia. The number remained unchanged after LPEHR with keyhole mesh. Return of mild reflux symptoms occurred in 6 (20%) patients. Repeat imaging was performed in 11 patients (37%) at an average of 8 months with 2 slight recurrences. All hernias were classified on preoperative imaging as large hiatal hernias. There were no postoperative complications. CONCLUSION: Laparoscopic paraesophageal hernia repair with biologic keyhole mesh reinforcement has a low recurrence rate and no increase in postoperative dysphagia. The traditional belief that keyhole mesh has a higher incidence of dysphagia was not evident in this series.

The Post-SIR-Spheres Surgery Study (P4S): Retrospective Analysis of Safety Following Hepatic Resection or Transplantation in Patients Previously Treated with Selective Internal Radiation Therapy with Yttrium-90 Resin Microspheres.

BACKGROUND: Reports show that selective internal radiation therapy (SIRT) may downsize inoperable liver tumors to resection or transplantation, or enable a bridge-to-transplant. A small-cohort study found that long-term survival in patients undergoing resection following SIRT appears possible but no robust studies on postsurgical safety outcomes exist. The Post-SIR-Spheres Surgery Study was an international, multicenter, retrospective study to assess safety outcomes of liver resection or transplantation following SIRT with yttrium-90 (Y-90) resin microspheres (SIR-Spheres®; Sirtex). METHODS: Data were captured retrospectively at participating SIRT centers, with Y-90 resin microspheres, surgery (resection or transplantation), and follow-up for all eligible patients. Primary endpoints were perioperative and 90-day postoperative morbidity and mortality. Standard statistical methods were used. RESULTS: The study included 100 patients [hepatocellular carcinoma: 49; metastatic colorectal cancer (mCRC): 30; cholangiocarcinoma, metastatic neuroendocrine tumor, other: 7 each]; 36% of patients had one or more lines of chemotherapy pre-SIRT. Sixty-three percent of patients had comorbidities, including hypertension (44%), diabetes (26%), and cardiopathy (16%). Post-SIRT, 71 patients were resected and 29 received a liver transplant. Grade 3+ peri/postoperative complications and any grade of liver failure were experienced by 24 and 7% of patients, respectively. Four patients died <90 days postsurgery; all were trisectionectomies (mCRC: 3; cholangiocarcinoma: 1) and typically had one or more previous chemotherapy lines and presurgical comorbidities. CONCLUSIONS: In 100 patients undergoing liver surgery after receiving SIRT, mortality and complication rates appeared acceptable given the risk profile of the recruited patients.

An unusual case of a coexistent serous cystadenoma and intraductal papillary mucinous neoplasm of pancreas. EUS to the rescue!

CONTEXT: Synchronous cystic neoplasms of pancreas are a highly rare occurrence. CASE REPORT: We report a very rare case of coexistent serous cystadenoma and multi-side branch intraductal papillary mucinous neoplasm (IPMN). CONCLUSION: To our knowledge, there has been only one previous case report in the literature of a synchronous serous cystadenoma and a solitary IPMN lesion. This case report is intended to increase the awareness of this condition while alluding to the need for diligent examination by endosonographers. It also highlights the clinical impact of endosonography on the diagnosis and management of cystic legions in the pancreas.

Covered stents for late postoperative arterial hemorrhage after pancreaticoduodenectomy.

The use of covered stents in treating delayed postoperative hepatic artery hemorrhage after pancreaticoduodenectomy may preserve hepatic arterial flow. The authors report two cases of massive hemorrhage after pancreaticoduodenectomy that were successfully treated with covered stents. Computed tomographic angiography demonstrated postprocedure patency of the hepatic arteries at 13 and 15 months, respectively. When technically feasible, percutaneous placement of stent-grafts may be used as a first-line intervention in delayed hemorrhage after pancreaticoduodenectomy.

The relationship between hepatic immunoglobulin production and CD154 expression in chronic liver diseases.

BACKGROUND: CD40-CD154 is a receptor-ligand pair that provides key communication signals between cells of the adaptive immune system in states of inflammation and autoimmunity. The CD40 receptor is expressed constitutively on B lymphocytes, for which it provides important signals regulating clonal expansion and antibody production. CD154 is a member of the tumor necrosis factor superfamily, which is primarily expressed by activated T cells. METHODS: Because many chronic liver diseases are characterized by lymphocytic infiltration of the liver and several have increased immunoglobulin (Ig) production, the role of CD40-CD154 in hepatic Ig production was investigated in patients with primary biliary cirrhosis (PBC), primary sclerosing cholangitis, autoimmune hepatitis (AIH), hepatitis C, hepatitis B, alcoholic and non-alcoholic steatohepatitis, as well as normal controls. RESULTS: Soluble CD154 levels in the serum were found to be no different in chronic liver diseases vs normal controls. Likewise, CD154 mRNA levels in peripheral blood mononuclear cells did not differ. However, mRNA for CD154 was significantly increased in the liver of individuals with PBC and AIH as compared with the other groups. The quantity of CD154 mRNA in the liver correlated positively with the quantity of mRNA for secretory Ig. CONCLUSION: These findings suggest that CD40-CD154 signals may be involved in Ig production within the liver of autoimmune liver diseases.