Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver malignancy and is increasing in incidence. Long-term outcomes are optimized when patients undergo margin-negative ...resection followed by adjuvant chemotherapy. Unfortunately, a significant proportion of patients present with locally advanced, unresectable disease. Furthermore, recurrence rates are high even among patients who undergo surgical resection. The delivery of systemic and/or liver-directed therapies prior to surgery may increase the proportion of patients who are eligible for surgery and reduce recurrence rates by prioritizing early systemic therapy for this aggressive cancer. Nevertheless, the available evidence for neoadjuvant therapy in ICC is currently limited yet recent advances in liver directed therapies, chemotherapy regimens, and targeted therapies have generated increasing interest its role. In this article, we review the rationale for, current evidence for, and ongoing research efforts in the use of neoadjuvant therapy for ICC.
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy that is best treated in a multidisciplinary fashion using surgery, chemotherapy, and radiation. Adjuvant chemotherapy has shown to ...have a significant survival benefit in patients with resected PDAC. However, up to 50% of patients fail to receive adjuvant chemotherapy due to postoperative complications, poor patient performance status or early disease progression. In order to ensure the delivery of chemotherapy, an alternative strategy is to administer systemic treatment prior to surgery. Precision oncology refers to the application of diverse strategies to target therapies specific to characteristics of a patient’s cancer. While traditionally emphasized in selecting targeted therapies based on molecular, genetic, and radiographic biomarkers for patients with metastatic disease, the neoadjuvant setting is a prime opportunity to utilize personalized approaches. In this article, we describe the current evidence for the use of neoadjuvant therapy (NT) and highlight unique opportunities for personalized care in patients with PDAC undergoing NT.
Introduction
Neoadjuvant therapy (NT) is increasingly recommended for patients with localized pancreatic ductal adenocarcinoma (PDAC). Recent research has highlighted the significant treatment burden ...that patients experience during NT, but caregiver well‐being during NT is poorly understood.
Methods
A cross‐sectional mixed‐methods analysis of primary caregivers of patients with localized PDAC receiving NT was undertaken. All patients completed the Caregiver Quality of Life Index‐Cancer (CQOLC) survey, while semi‐structured interviews were conducted among a convenience sample of participants.
Results
Among 28 caregivers, the mean age was 60.1 years, and most were patient spouses/significant others (71.4%). Patients had resectable (18%), borderline resectable (46%), or locally advanced (36%) PDAC with a mean treatment duration of 2.9 months at the time of their caregiver's enrollment. Most caregivers felt that they received adequate emotional/psychosocial support (80%) and understood the rationale for NT (93%). A majority (60%) reported that caregiving responsibilities impacted their daily lives and required a decrease in their work hours, leading to financial challenges (47%). While overall QOL was moderate (mean 83 ± 21.1, range 0–140), “emotional burden” (47.3 ± 20.9), and “positive adaption” (57.3 ± 13.9) were the lowest ranked CQOLC subsection scores.
Discussion
Caregivers of patients with PDAC undergoing NT experience significant emotional symptoms and impact on their daily lives. Assessing caregiver needs and providing resources during NT should be a priority.
BACKGROUNDNeoadjuvant therapy (NT) has increasingly been utilized for patients with localized pancreatic ductal adenocarcinoma (PDAC). It is the recommended approach for borderline resectable (BR) ...and locally advanced (LA) cancers and an increasingly utilized option for potentially resectable (PR) disease. Despite its increased use, little research has focused on patient-centered metrics among patients undergoing NT, including patient experiences, preferences, and recommendations. A better understanding of all aspects of the patient experience during NT may identify opportunities to design interventions aimed at improving quality of life; it may also facilitate the completion of NT and receipt of surgery, ultimately optimizing long-term outcomes. AIMTo understand the experience of patients initiating and receiving NT to identify opportunities to improve neoadjuvant cancer care delivery. METHODSSemi-structured interviews of patients with localized PDAC during NT were conducted to explore their experience initiating and receiving NT. Interviews took place between August 2020 and October 2021. Due to the descriptive nature of the research, questions were open ended. Interviews were conducted over the phone, audio recorded and then transcribed. All interviews were coded by two independent researchers using NVivo 12, iteratively identifying themes until thematic saturation was achieved. An integrative approach to qualitative analysis was used, utilizing both inductive and deductive methods. RESULTSA total of 12 patients with localized PDAC were interviewed. Patients with BR (n = 7), PR (n = 2), and LA (n = 3) cancers participated in the study. All patients indicated that choosing NT was the doctor's recommendation, while most reported not being familiar with the concept of NT (n = 11) and that NT was presented as the only option (n = 8). Five themes describing the patient experience emerged: physical symptoms, emotional symptoms, coping mechanisms, access to care, and life factors. The most commonly cited recommendation for improving the experience of NT was improved education before and during NT (n = 7). Patients highlighted the need for more information on the rationale behind choosing NT prior to surgery, the anticipated surgery and its likelihood of surgery occurring after NT, as well as general information prior to starting NT treatment. The need for seeing different members of the healthcare team, including ancillary services was also frequently cited as a recommendation for improving the experience of NT (n = 5). CONCLUSIONThis study provides a framework to allow for a better understanding of the PDAC patient experience during NT and highlights opportunities to improve quality and quantity of life outcomes.
Although surgical resection is associated with the best long-term outcomes for neuroendocrine liver metastases (NELM), the current indications for and outcomes of surgery for NELM from a population ...perspective are not well understood.
To determine the current indications for and outcomes of liver resection (LR) for NELM using a population-based cohort.
A retrospective review of the 2014-2017 American College of Surgeons National Surgical Quality Improvement Program and targeted hepatectomy databases was performed to identify patients who underwent LR for NELM. Perioperative characteristics and 30-d morbidity and mortality were analyzed.
Among 669 patients who underwent LR for NELM, the median age was 60 (interquartile range: 51-67) and 51% were male. While the number of metastases resected ranged from 1 to 9, the most common (45%) number of tumors resected was one. The majority (68%) of patients had a largest tumor size of < 5 cm. Most patients underwent partial hepatectomy (71%) while fewer underwent a right or left hepatectomy or trisectionectomy. The majority of operations were open (82%) versus laparoscopic (17%) or robotic (1%). In addition, 30% of patients underwent intraoperative ablation while 45% had another concomitant operation including cholecystectomy (28.8%), bowel resection (20.2%), or partial pancreatectomy (3.4%). Overall 30-d morbidity and mortality was 29% and 1.3%, respectively. On multivariate analysis, American Society of Anesthesiologists class ≥ 3 odds ratios (OR), OR = 2.089, 95% confidence intervals (CI): 1.197-3.645, open approach (OR = 1.867, 95%CI: 1.148-3.036), right hepatectomy (OR = 1.618, 95%CI: 1.014-2.582), and prolonged operative time of > 230 min (OR = 1.731, 95%CI: 1.168-2.565) were associated with higher 30-d morbidity while intraoperative ablation and concomitant procedures were not.
LR for NELM was performed with relatively low postoperative morbidity and mortality. Concomitant procedures performed at the time of LR did not increase morbidity.
Background Reports on recurrence and outcomes of US patients with gastric cancer are scarce. The aim of this study was to determine incidence and pattern of recurrence after curative intent surgery ...for gastric cancer. Study Design Using the multi-institutional US Gastric Cancer Collaborative database, we identified 817 patients undergoing curative intent resection for gastric cancer between 2000 and 2012. Patterns and rates of recurrence along with associated risk factors were identified using adjusted regression analysis. Recurrences were classified as locoregional, peritoneal, or hematogenous. Results Median patient age was 65.8 years (interquartile range IQR 56.4, 74.7); the majority of patients were male (n = 462, 56.6%) and white (n = 511, 62.5%). At the time of surgery, the majority of patients underwent a partial gastrectomy (n = 481, 59.2%) with a complete R0 resection achieved in 91.6% (n = 748) of patients. At the time of last follow-up, 244 (29.9%) of 817 patients developed a recurrence; 163 (66.8%) patients had recurrence at only a single site; the remaining 81 (33.2%) had multiple sites of initial recurrence. Among patients who recurred at a single site, recurrence was most common at a distant location and included hematogenous (n = 57, 23.4%) or peritoneal (n = 47, 19.3%) only metastasis. Tumors at the gastroesophageal junction (odds ratio OR 3.18, 95% CI 1.08 to 9.40; p = 0.04) were associated with higher risk of locoregional recurrence, while the presence of multiple lesions (OR 10.82, 95% CI 3.56 to 32.85; p < 0.001) remained associated with an increased risk of distant hematogenous recurrence after adjusted analysis. Recurrence was associated with worse survival, with a median recurrence-free survival of 10.8 months (IQR 8.9, 12.8) among those who experienced a recurrence. Conclusions Nearly one-third of patients experienced recurrence after gastric cancer surgery. The most common site of recurrence was distant.
Abstract Background Surgical site infections (SSIs) are a common source of postoperative morbidity and a marker of surgical quality. The ability to predict the incidence of SSIs is limited and most ...models have poor predictive value. We sought to identify risk factors associated with SSIs and develop a prediction model for SSIs after major abdominal surgery. Methods A total of 1744 patients undergoing pancreatic, hepatobiliary, and colorectal resections between January 1, 2010 and August 31, 2013 at Johns Hopkins Hospital were identified. Risk factors for any inpatient SSI (superficial and deep) were evaluated using multivariable logistic regression. Results Median patient age was 58 y (interquartile range 47, 68); surgical procedures included colorectal (59.0%), liver (26.2%), and pancreas (14.8%) resections. SSI occurred in 7.6% ( n = 132) of patients. Factors associated with SSI included preoperative weight loss >4.5 kg (odds ratio OR, 2.12; 95% confidence interval CI, 1.06-4.25), emergency operations (OR, 2.05; 95% CI, 1.32-3.17), and colorectal resections (OR, 1.65; 95% CI, 1.13-2.43) (all P ≤ 0.003). Intraoperative and postoperative risk factors included estimated blood loss (EBL) >600 mL (OR, 2.23; 95% CI, 1.54-3.25), maximum respiratory rate (tachypnea) >20 breaths/min (OR, 1.74; 95% CI, 1.19-2.54), and perioperative transfusion (OR, 2.01; 95% CI, 1.33-3.04) (all P = 0.001). Intraoperative hypothermia, hyperthermia, bradycardia, tachycardia, hypotension, and hypertension were not associated with SSIs (all P > 0.05). After controlling competing risk factors, transfusion, EBL >600 mL, tachypnea, and colorectal resection were independently associated with SSIs (all P < 0.003). On the basis of the beta-coefficients in the multivariable model, an SSI scoring system was created by assigning 2 points for EBL >600 mL, 2 points for a colorectal resection, 3 points for tachypnea, and 3 points for a transfusion. The model showed good discriminatory ability to predict SSI (c-statistic = 0.7232; Akaike information criterion 875.37). Conclusions A novel, simple 10-point SSI scoring system that incorporated perioperative risk factors such as blood transfusion, EBL, tachypnea, and the type of surgical procedure accurately stratifies patients according to SSI risk.
Background The prognostic effect of perioperative blood transfusion on recurrence and survival in patients undergoing resection of gastric adenocarcinoma (GAC) remains controversial. Study Design All ...patients who underwent resection for GAC from 2000 to 2012 at the 7 institutions of the US Gastric Cancer Collaborative were identified. The effect of transfusion on recurrence-free (RFS) and overall survival (OS) in the context of adverse clinicopathologic variables was examined by univariate and multivariate regression analyses. Results Of 965 patients, 765 underwent curative intent R0 resection. Median follow-up was 44 months; 30-day mortalities were excluded. Median estimated blood loss (EBL) was 200 mL, and 168 patients (22%) received perioperative allogeneic blood transfusions. Transfused patients were less likely to receive adjuvant therapy (44% vs 56%; p = 0.01). Transfusion was associated with significantly decreased median RFS (13.5 vs 37.2 months, p < 0.001). Median OS was similarly decreased in patients receiving transfusions (18.6 vs 49.8 months, p < 0.001). On multivariate analysis, transfusion remained an independent risk factor for decreased RFS (hazard ratio HR 1.63; 95% CI 1.13 to 2.37; p = 0.010) and decreased OS (HR 1.79; 95% CI 1.21 to 2.67; p = 0.004), regardless of EBL or need for splenectomy. Timing (intraoperative vs postoperative) and volume of transfusion did not alter the negative prognostic effect of transfusion on survival. Conclusions Perioperative allogeneic blood transfusion is associated with decreased RFS and OS after resection of gastric cancer, independent of adverse clinicopathologic factors. This supports the judicious use of perioperative transfusion during resection of gastric cancer.
Abstract Background Among patients undergoing resection for gastric cancer, the impact of body mass index (BMI) on outcomes is not well understood. We sought to define the impact of non-normal BMI on ...short- and long-term outcomes after gastric cancer resection. Methods We identified 775 patients who underwent gastrectomy for adenocarcinoma between 2000 and 2012 from the multi-institutional US Gastric Cancer Collaborative. Clinicopathologic characteristics, operative details, and oncologic outcomes were collected, and patients were stratified according to BMI. Results Most patients in the cohort were classified as having normal BMI ( n = 338, 43.6%), followed by overweight ( n = 229, 29.6%), obese ( n = 153, 19.7%), and underweight ( n = 55, 7.1%). After stratifying by BMI, there were no significant differences in the incidence of postoperative blood transfusions, perioperative morbidity, postoperative infectious complications, length of stay, perioperative 30-d in-hospital death, or readmission across groups (all P > 0.05). BMI did not impact overall or recurrence-free survival after stratifying by stage (all P > 0.05). However, underweight patients with low preoperative albumin levels had worse overall survival (OS) compared with that of patients of normal BMI. Conclusions BMI did not impact perioperative morbidity, recurrence-free, or OS in patients undergoing gastric resection for adenocarcinoma. Underweight patients with BMI <18.5 kg/m2 and low preoperative albumin levels, however, had a significantly decreased OS after gastrectomy for cancer. These high-risk patients should have their nutritional status optimized both before and after gastrectomy in an attempt to modify this risk factor and, in turn, achieve better outcomes.
Background Resident participation during hepatic and pancreatic resections varies. The impact of resident participation on surgical outcomes in hepatic and pancreatic operations is poorly defined. ...Methods We identified 25,511 patients undergoing a hepatic or pancreatic resection between 2006 and 2012 using the American College of Surgeons National Surgical Quality Improvement Program database. Multivariate regression models were constructed to determine any association between resident participation and surgical outcomes. Results Pancreatic resections ( n = 16,045; 62.9%) were more common than liver resections ( n = 9,466; 37%). Residents participated in the majority of cases ( n = 21,857; 86%), with most involvement at the senior level (postgraduate year ≥ 3, n = 21,147; 97%). Resident participation resulted in slightly longer mean operative times (hepatic, 9 minutes; pancreatic, 22 minutes; both P < .01). Need for perioperative transfusion, hospital duration of stay, and reoperation rates were unaffected by resident participation (all P > .05). Resident participation resulted in a higher risk of overall morbidity (odds ratio OR, 1.14; 95% CI, 1.05–1.24; P = .001), but not major morbidity (OR, 1.05; 95% CI, 0.93–1.20; P = .40) after liver and pancreas resection. Resident participation resulted in lower odds of 30-day mortality after liver and pancreas resections (OR, 0.75; 95% CI, 0.60–0.94; P = .01). Conclusion Although resident participation resulted in slightly longer operative times and a modest increase in overall complications after liver and pancreatic resection, other metrics such as duration of stay, major morbidity, and mortality were unaffected. These data have important implications for educating patients regarding resident participation in these complex cases.
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