Comparison of Hepatic Arterial Infusion Pump Chemotherapy vs Resection for Patients With Multifocal Intrahepatic Cholangiocarcinoma.

Importance: Intrahepatic cholangiocarcinoma (iCCA) is often multifocal (ie, satellites or intrahepatic metastases) at presentation. Objective: To compare the overall survival (OS) of patients with multifocal iCCA after hepatic arterial infusion pump (HAIP) floxuridine chemotherapy vs resection. Design, Setting, and Participants: In this cohort study, patients with histologically confirmed, multifocal iCCA were eligible. The HAIP group consisted of consecutive patients from a single center who underwent HAIP floxuridine chemotherapy for unresectable multifocal iCCA between January 1, 2001, and December 31, 2018. The resection group consisted of consecutive patients from 12 centers who underwent a curative-intent resection for multifocal iCCA between January 1, 1990, and December 31, 2017. Resectable metastatic disease to regional lymph nodes and previous systemic therapy were permitted. Patients with distant metastatic disease (ie, stage IV), those who underwent resection before starting HAIP floxuridine chemotherapy, and those who received a liver transplant were excluded. Data were analyzed on September 1, 2021. Main Outcomes and Measures: Overall survival in the 2 treatment groups was compared using the Kaplan-Meier method and log-rank test. Results: A total of 319 patients with multifocal iCCA were included: 141 in the HAIP group (median [IQR] age, 62 [53-70] years; 79 [56.0%] women) and 178 in the resection group (median [IQR] age, 60 [50-69] years; 91 [51.1%] men). The HAIP group was characterized by a higher percentage of bilobar disease (88.0% [n = 124] vs 34.3% [n = 61]), larger tumors (median, 8.4 cm vs 7.0 cm), and a higher proportion of patients with 4 or more lesions (66.7% [94] vs 24.2% [43]). Postoperative mortality after 30 days was 0.8% (95% CI, 0.0%-2.1%) in the HAIP group vs 6.2% (95% CI, 2.3%-9.7%) in the resection group (P = .01). The median OS for HAIP was 20.3 months vs 18.9 months for resection (P = .32). Five-year OS in patients with 2 or 3 lesions was 23.7% (95% CI, 12.3%-45.7%) in the HAIP group vs 25.7% (95% CI, 17.9%-37.0%) in the resection group. Five-year OS in patients with 4 or more lesions was 5.0% (95% CI, 1.7%-14.3%) in the HAIP group vs 6.8% (95% CI, 1.8%-25.3%) in the resection group. After adjustment for tumor diameter, number of tumors, and lymph node metastases, the hazard ratio of HAIP vs resection was 0.75 (95% CI, 0.55-1.03; P = .07). Conclusions and Relevance: This cohort study found that patients with multifocal iCCA had similar OS after HAIP floxuridine chemotherapy vs resection. Resection of multifocal intrahepatic cholangiocarcinoma needs to be considered carefully given the complication rate of major liver resection; HAIP floxuridine chemotherapy may be an effective alternative option.

Development of a Senior Medical Student Robotic Surgery Training Elective.

As robotic surgery has become more widespread, early exposure to the robotic platform is becoming increasingly important, not only to graduate medical education, but also for medical students pursuing surgical residency. In an effort to orient students to robotic technology and decrease the learning curve for what is likely to become an integral part of residency training, we created a formal, elective robotic surgery curriculum for senior medical students. Throughout this 2-week fourth year rotation, students completed online training modules and assessment; mastered exercises on the simulator system related to the console, camera, energy, dexterity, and suturing skills; attended didactics; utilized the dual console during one-on-one simulation lab sessions with attending robotic surgery experts; and translated new skills to biotissue anastomoses as well as bedside-assisting in the operating room. During cases, students were able to have more meaningful observation experiences, recognizing the significance of various robotic approaches employed and utilization of specific instruments. Future aims of this rotation will assess student experience as it impacts readiness for surgical residency.

Preoperative next-generation sequencing of pancreatic cyst fluid is highly accurate in cyst classification and detection of advanced neoplasia.

OBJECTIVE: DNA-based testing of pancreatic cyst fluid (PCF) is a useful adjunct to the evaluation of pancreatic cysts (PCs). Mutations in KRAS/GNAS are highly specific for intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms (MCNs), while TP53/PIK3CA/PTEN alterations are associated with advanced neoplasia. A prospective study was performed to evaluate preoperative PCF DNA testing. DESIGN: Over 43-months, 626 PCF specimens from 595 patients were obtained by endoscopic ultrasound (EUS)-fine needle aspiration and assessed by targeted next-generation sequencing (NGS). Molecular results were correlated with EUS findings, ancillary studies and follow-up. A separate cohort of 159 PCF specimens was also evaluated for KRAS/GNAS mutations by Sanger sequencing. RESULTS: KRAS/GNAS mutations were identified in 308 (49%) PCs, while alterations in TP53/PIK3CA/PTEN were present in 35 (6%) cases. Based on 102 (17%) patients with surgical follow-up, KRAS/GNAS mutations were detected in 56 (100%) IPMNs and 3 (30%) MCNs, and associated with 89% sensitivity and 100% specificity for a mucinous PC. In comparison, KRAS/GNAS mutations by Sanger sequencing had a 65% sensitivity and 100% specificity. By NGS, the combination of KRAS/GNAS mutations and alterations in TP53/PIK3CA/PTEN had an 89% sensitivity and 100% specificity for advanced neoplasia. Ductal dilatation, a mural nodule and malignant cytopathology had lower sensitivities (42%, 32% and 32%, respectively) and specificities (74%, 94% and 98%, respectively). CONCLUSIONS: In contrast to Sanger sequencing, preoperative NGS of PCF for KRAS/GNAS mutations is highly sensitive for IPMNs and specific for mucinous PCs. In addition, the combination of TP53/PIK3CA/PTEN alterations is a useful preoperative marker for advanced neoplasia.

Impact of major vascular resection on outcomes and survival in patients with intrahepatic cholangiocarcinoma: A multi-institutional analysis.

BACKGROUND: Major vascular involvement (IVC or portal vein) for intrahepatic cholangiocarcinoma (ICC) has traditionally been considered a contraindication to resection. We sought to define perioperative outcomes and survival of ICC patients undergoing hepatectomy with major vascular resection in a large international multi-institutional database. METHODS: A total of 1087 ICC patients who underwent curative-intent hepatectomy between 1990 and 2016 were identified from 13 institutions. Multivariable logistic and cox regressions were used to determine the impact of major vascular resection on perioperative and survival outcomes. RESULTS: Of 1087 patients who underwent resection, 128 (11.8%) also underwent major vascular resection (21 [16.4%] IVC resections, 98 [76.6%] PV resections, 9 [7.0%] combined resections). Despite more advanced disease, major vascular resection was not associated with the risk of any complication (OR = 0.68, 95%CI 0.32-1.45) or major complications (OR = 0.95, 95%CI 0.49-2.00). Post-operative mortality was also comparable between groups (OR = 1.05, 95%CI 0.32-3.47). In addition, median recurrence-free (14.0 vs 14.7 months, HR = 0.737, 95%CI 0.49-1.10) and overall (33.4 vs 40.2 months, HR = 0.71, 95%CI 0.359-1.40) survival were similar among patients who did and did not undergo major vascular resection (both P > 0.05). CONCLUSION: Among patients with ICC, major vascular resection was not associated with worse perioperative or oncologic outcomes. Concurrent major vascular resection should be considered in appropriately selected patients with ICC undergoing hepatectomy.

Defining when to offer operative treatment for intrahepatic cholangiocarcinoma: A regret-based decision curves analysis.

BACKGROUND: Regret-based decision curve analysis (DCA) is a framework that assesses the medical decision process according to physician attitudes (expected regret) relative to disease-based factors. We sought to apply this methodology to decisions around the operative management of intrahepatic cholangiocarcinoma (ICC). METHODS: Utilizing a multicentric database of 799 patients who underwent liver resection for ICC, we developed a prognostic nomogram. DCA tested 3 strategies: (1) perform an operation on all patients, (2) never perform an operation, and (3) use the nomogram to select patients for an operation. RESULTS: Four preoperative variables were included in the nomogram: major vascular invasion (HR = 1.36), tumor number (multifocal, HR = 1.18), tumor size (>5 cm, HR = 1.45), and suspicious lymph nodes on imaging (HR = 1.47; all P < .05). The regret-DCA was assessed using an online survey of 50 physicians, expert in the treatment of ICC. For a patient with a multifocal ICC, largest lesion measuring >5 cm, one suspicious malignant lymph node, and vascular invasion on imaging, the 1-year predicted survival was 52% according to the nomogram. Based on the therapeutic decision of the regret-DCA, 60% of physicians would advise against an operation for this scenario. Conversely, all physicians recommended an operation to a patient with an early ICC (single nodule measuring 3 cm, no suspicious lymph nodes, and no vascular invasion at imaging). CONCLUSION: By integrating a nomogram based on preoperative variables and a regret-based DCA, we were able to define the elements of how decisions rely on medical knowledge (postoperative survival predicted by a nomogram, severity disease assessment) and physician attitudes (regret of commission and omission).

Does neoadjuvant chemotherapy reveal disease precluding surgical treatment of initially resectable colorectal cancer liver metastases?

BACKGROUND: The objective of this study is to determine whether neoadjuvant chemotherapy reveals occult disease precluding surgical extirpation of initially resectable colorectal cancer liver metastases (CRCLM). METHODS: Demographics, clinicopathologic tumor characteristics, treatments, and post-operative outcomes of patients aged 18-80 years, with one to four initially resectable CRCLM, and without concurrent extra-hepatic (EHMD) or previous metastatic disease were reviewed. RESULTS: Two hundred and two patients evaluated from 2000 to 2010 met study criteria; 88 (43.6%) were given neoadjuvant chemotherapy. Patients treated with neoadjuvant chemotherapy were younger (median 58 years vs. 65 years, P = 0.0096), had shorter disease free interval from resection of primary tumor to CRCLM diagnosis (median 0 months vs. 12 months, P < 0.0001), and had more CRCLM (median 1 [1-3] vs. 1 [1-2], P = 0.0096) compared to untreated counterparts. There were no differences in rates of concurrent EHMD noted intra-operatively and not on pre-operative imaging (4.5% vs. 3.5%, P = 0.7290), greater intra-operatively observed CRCLM compared to pre-operative imaging (25.3% vs. 17.5%, P = 0.2449), hepatic resection and/or ablation (97.7% vs. 100.0%, P = 0.9853), or 6-month disease recurrence after surgical treatment (25.6% vs. 14.9%, P = 0.0882). Only two (2.3%) patients treated with neoadjuvant chemotherapy had disease progression precluding surgical extirpation. CONCLUSIONS: Neoadjuvant chemotherapy for initially resectable CRCLM does not reveal occult disease precluding surgical treatment.

External validation of a pre-operative nomogram predicting peri-operative mortality risk after liver resections for malignancy.

AIM: A pre-operative nomogram using a population-based database to predict peri-operative mortality risk after liver resections for malignancy has recently been developed. The aim of the present study was to perform an external validation of the nomogram using data from a high volume institution. METHODS: The National Inpatient Sample (NIS) database (2000-2004) was used initially to construct the nomogram. The dataset for external validation was obtained from a high volume centre specializing in hepatobiliary surgery. Validation was performed using calibration plots and concordance index. RESULTS: A total of 794 patients who underwent liver resection from the years 2000-2010 at the external institute were included in the validation set with an observed mortality rate of 1.6%. The mean total points for this sample of patients was 124.9 [standard error (SE) 1.8, range 0-383] which translates to a nomogram predicted mortality rate of 1.5%, similar to the actual observed overall mortality rate. The nomogram concordance index was 0.65 [95% confidence interval (CI) 0.46-0.82] and calibration plots stratified by quartiles revealed good agreement between the predicted and observed mortality rates. CONCLUSIONS: The present study provides an external validation of the pre-operative nomogram to predict the risk of peri-operative mortality after liver resection for malignancy.

Analysis of surgical and perioperative complications in seventy-five right hepatectomies for living donor liver transplantation.

AIM: To present an analysis of the surgical and perioperative complications in a series of seventy-five right hepatectomies for living-donation (RHLD) performed in our center. METHODS: From January 2002 to September 2007, we performed 75 RHLD, defined as removal of a portion of the liver corresponding to Couinaud segments 5-8, in order to obtain a graft for adult to adult living-related liver transplantation (ALRLT). Surgical complications were stratified according to the most recent version of the Clavien classification of postoperative surgical complications. The perioperative period was defined as within 90 d of surgery. RESULTS: No living donor mortality was present in this series, no donor operation was aborted and no donors received any blood transfusion. Twenty-three (30.6%) living donors presented one or more episodes of complication in the perioperative period. Seven patients (9.33%) out of 75 developed biliary complications, which were the most common complications in our series. CONCLUSION: The need to define, categorize and record complications when healthy individuals, such as living donors, undergo a major surgical procedure, such as a right hepatectomy, reflects the need for prompt and detailed reports of complications arising in this particular category of patient. Perioperative complications and post resection liver regeneration are not influenced by anatomic variations or patient demographic.

Assessment of transcutaneous bilirubinometry in hospitalized adults.

BACKGROUND: Transcutaneous techniques to measure serum bilirubin have been validated in neonates but not in adult patients. We evaluated transcutaneous bilirubinometry (TcB) in adults at risk for or diagnosed with hepatic dysfunction to determine if this technology has clinical use in quantifying the presence and magnitude of hyperbilirubinemia. DESIGN: Unblinded, consecutive hospitalized adult patients (n = 80) from the general surgery, trauma surgery, and liver resection/transplantation services of a tertiary care, university-affiliated medical center, who were having serum bilirubin measurements performed, underwent transcutaneous bilirubin measurement from the forehead, sternum, forearm, and deltoid. Transcutaneous bilirubin measurements were repeated each time serum bilirubin measurements were performed. RESULTS: Transcutaneous bilirubin measurements from the forehead correlated with serum bilirubin better (r, 0.963) than measurements from the forearm (r, 0.792), deltoid (r, 0.922), or sternum (r, 0.928). Forehead TcB detected hepatic dysfunction (serum bilirubin > or = 2 mg/dL) by receiver operator curves (area under the curve = 0.971) and sternum (area under the curve = 0.970) and better than deltoid and forearm measurements (area under the curve = 0.935 and 0.893, respectively). A Bland-Altman plot demonstrated that forehead measurements became less accurate as the magnitude of hyperbilirubinemia increased. CONCLUSIONS: Forehead TcB correlated best with serum bilirubin levels but became less accurate at higher values. Refinements in the technology will be required before this technique, although promising, can be considered for routine clinical application in adults being evaluated for hyperbilirubinemia.