Neoadjuvant-Adjuvant or Adjuvant-Only Pembrolizumab in Advanced Melanoma.

BACKGROUND: Whether pembrolizumab given both before surgery (neoadjuvant therapy) and after surgery (adjuvant therapy), as compared with pembrolizumab given as adjuvant therapy alone, would increase event-free survival among patients with resectable stage III or IV melanoma is unknown. METHODS: In a phase 2 trial, we randomly assigned patients with clinically detectable, measurable stage IIIB to IVC melanoma that was amenable to surgical resection to three doses of neoadjuvant pembrolizumab, surgery, and 15 doses of adjuvant pembrolizumab (neoadjuvant-adjuvant group) or to surgery followed by pembrolizumab (200 mg intravenously every 3 weeks for a total of 18 doses) for approximately 1 year or until disease recurred or unacceptable toxic effects developed (adjuvant-only group). The primary end point was event-free survival in the intention-to-treat population. Events were defined as disease progression or toxic effects that precluded surgery; the inability to resect all gross disease; disease progression, surgical complications, or toxic effects of treatment that precluded the initiation of adjuvant therapy within 84 days after surgery; recurrence of melanoma after surgery; or death from any cause. Safety was also evaluated. RESULTS: At a median follow-up of 14.7 months, the neoadjuvant-adjuvant group (154 patients) had significantly longer event-free survival than the adjuvant-only group (159 patients) (P = 0.004 by the log-rank test). In a landmark analysis, event-free survival at 2 years was 72% (95% confidence interval [CI], 64 to 80) in the neoadjuvant-adjuvant group and 49% (95% CI, 41 to 59) in the adjuvant-only group. The percentage of patients with treatment-related adverse events of grades 3 or higher during therapy was 12% in the neoadjuvant-adjuvant group and 14% in the adjuvant-only group. CONCLUSIONS: Among patients with resectable stage III or IV melanoma, event-free survival was significantly longer among those who received pembrolizumab both before and after surgery than among those who received adjuvant pembrolizumab alone. No new toxic effects were identified. (Funded by the National Cancer Institute and Merck Sharp and Dohme; S1801 ClinicalTrials.gov number, NCT03698019.).

Surgical debulking is associated with improved survival for patients with neuroendocrine liver metastases of unknown primary.

BACKGROUND: Resection of neuroendocrine tumors (NET) with surgical debulking of liver metastasis (NETLM) is associated with improved survival. In patients with an unknown primary (UP-NETLM), the effects of debulking remains unclear. METHODS: The National Cancer Database (2004-2016) was queried for patients with small intestine (SI) and pancreas (P) NETLMs. If the liver was listed as the primary site, the patient's disease was classified as UP-NETLM. RESULTS: Patients with UP-NETLM, SI-NETLM, and P-NETLM who were managed non-operatively demonstrated a significant difference in 5-year overall survival (OS) (21.5% vs. 39.2% vs. 17.1%; p < 0.0001). OS in patients who underwent debulking was higher (63.7% vs. 73.2% vs. 54.2%). Patients with UP-NETLMs who underwent debulking had similar OS to patient with SI-NETLM (p = 0.051), but significantly higher OS, depending on tumor differentiation, compared to patients with P-NETLMs. If well-differentiated, surgery for UP-NETLMs was associated with a higher rate of OS (p = 0.009), while no difference was observed if moderately (p = 0.209) or poorly/undifferentiated (p = 0.633). P-NETLMs were associated with worse OS (p < 0.001) on multivariate analysis. DISCUSSION: Debulking in patients with UP-NETLMs was associated with similar OS compared to patients with SI-NETLMs and better or similar OS compared to patient with P-NETLMs.

Pancreatic Cancer Patient-derived Organoids Can Predict Response to Neoadjuvant Chemotherapy.

OBJECTIVE: To evaluate if patient-derived organoids (PDOs) may predict response to neoadjuvant (NAT) chemotherapy in patients with pancreatic adenocarcinoma. BACKGROUND: PDOs have been explored as a biomarker of therapy response and for personalized therapeutics in patients with pancreatic cancer. METHODS: During 2017-2021, patients were enrolled into an IRB-approved protocol and PDO cultures were established. PDOs of interest were analyzed through a translational pipeline incorporating molecular profiling and drug sensitivity testing. RESULTS: One hundred thirty-six samples, including both surgical resections and fine needle aspiration/biopsy from 117 patients with pancreatic cancer were collected. This biobank included diversity in stage, sex, age, and race, with minority populations representing 1/3 of collected cases (16% Black, 9% Asian, 7% Hispanic/Latino). Among surgical specimens, PDO generation was successful in 71% (15 of 21) of patients who had received NAT prior to sample collection and in 76% (39 of 51) of patients who were untreated with chemotherapy or radiation at the time of collection. Pathological response to NAT correlated with PDO chemotherapy response, particularly oxaliplatin. We demonstrated the feasibility of a rapid PDO drug screen and generated data within 7 days of tissue resection. CONCLUSION: Herein we report a large single-institution organoid biobank, including ethnic minority samples. The ability to establish PDOs from chemotherapy-naive and post-NAT tissue enables longitudinal PDO generation to assess dynamic chemotherapy sensitivity profiling. PDOs can be rapidly screened and further development of rapid screening may aid in the initial stratification of patients to the most active NAT regimen.

The role of resection for melanoma metastases to the pancreas.

BACKGROUND: Among patients with distant metastatic melanoma, the site of metastases is the most significant predictor of survival and visceral-nonpulmonary metastases hold the highest risk of poor outcomes. However, studies demonstrate that a significant percentage of patients may be considered candidates for resection with improved survival over nonsurgical therapeutic modalities. We aimed at analyzing the results of resection in patients with melanoma metastasis to the pancreas by assessing the available evidence. METHODS: The PubMed/MEDLINE, WoS, and Embase electronic databases were systematically searched for articles reporting on the surgical treatment of pancreatic metastases from melanoma. Relevant data from included studies were assessed and analyzed. Overall survival was the primary endpoint of interest. Surgical details and oncological outcomes were also appraised. RESULTS: A total of 109 patients treated surgically for pancreatic metastases were included across 72 articles and considered for data extraction. Overall, patients had a mean age of 51.8 years at diagnosis of pancreatic disease. The cumulative survival was 71%, 38%, and 26% at 1, 3 and 5 years after pancreatectomy, with an estimated median survival of 24 months. Incomplete resection and concomitant extrapancreatic metastasis were the only factors which significantly affected survival. Patients in whom the pancreas was the only metastatic site who received curative resection exhibited significantly longer survival, with a 1-year, 3-year, and 5-year survival rates of 76%, 43%, and 41%, respectively. CONCLUSION: Within the limitations of a review of non-randomized reports, curative surgical resection confers a survival benefit in carefully selected patients with pancreatic dissemination of melanoma.

Ampullary Neuroendocrine Tumors: Insight into a Rare Histology.

BACKGROUND: Ampullary neuroendocrine tumors (NETs) make up < 1% of all gastroenteropancreatic NETs, and information is limited to case series. This study compares patients with ampullary, duodenal, and pancreatic head NETs. METHODS: The National Cancer Database (2004-2016) was queried for patients with ampullary, duodenal, and pancreatic head NETs. Survival was evaluated using Kaplan-Meier analysis and Cox regression. RESULTS: Overall, 872, 9692, and 6561 patients were identified with ampullary, duodenal, and pancreatic head NETs, respectively. Patients with ampullary NETs had more grade 3 tumors (n = 149, 17%) than patients with duodenal (n = 197, 2%) or pancreatic head (n = 740, 11%) NETs. Patients with ampullary NETs had more positive lymph nodes (n = 297, 34%) than patients with duodenal (n = 950, 10%) or pancreatic head (n = 1513, 23%) NETs. On multivariable analysis for patients with ampullary NETs, age (hazard ratio [HR] 1.03, p < 0.0001), Charlson-Deyo score of 2 (HR 2.3, p = 0.001) or ≥3 (HR 2.9, p = 0.013), grade 2 (HR 1.9, p = 0.007) or grade 3 tumors (HR 4.0, p < 0.0001), and metastatic disease (HR 2.0, p = 0.001) were associated with decreased survival. At 5 years, the overall survival (OS) for patients with ampullary, duodenal, and pancreatic head NETs was 59%, 71%, and 50%, respectively (p < 0.0001), whereas the 5-year OS for patients with ampullary, duodenal, and pancreatic head NETs who underwent surgery was 62%, 78%, and 76%, respectively (p < 0.0001). CONCLUSIONS: Ampullary NETs were more likely to present with high-grade tumors and lymph node metastases. Based on the clinicopathologic and survival data, ampullary NETs have a unique underlying biology compared with duodenal and pancreatic head NETs.

Venous thromboembolism in patients with cancer undergoing surgical exploration.

Malignancy and surgery are both independent risk factors for venous thromboembolism (VTE) events. The current NCCN guidelines recommend VTE prophylaxis for up to 28 days after major abdominal or pelvic surgery for malignancy. We set out to evaluate the rate and timing of VTEs among patients with gastric, pancreatic, colorectal, and gynecologic malignancies who underwent surgery. We performed a retrospective review of the NSQIP database (2005-2013) focusing on patients with gastric, colorectal, pancreatic, and gynecologic malignancies. Our primary endpoint was a diagnosis of VTE within 30 days of surgery. We analyzed 128,864 patients in this study. On multivariable analysis, patients with pre-operative sepsis (OR 2.36, CI 2.04-2.76, p < 0.001), disseminated cancer (OR 1.73, CI 1.55-1.92, p < 0.001), congestive heart failure (OR 1.69, CI 1.25-2.28, p = 0.001), gastric cancer (OR 1.3, CI 1.09-1.56, p = 0.004), and pancreatic cancer (OR 1.2, CI 1.03-1.30, p = 0.021) were more likely to have a VTE. Of patients who had a VTE event, 34% occurred after discharge from surgery (gastric: 25%, colorectal 34%, pancreatic 31%, gynecologic malignancy 42%). Our study demonstrates that patients who undergo an operation for malignancy with pre-operative sepsis, disseminated cancer, congestive heart failure, gastric cancer, or pancreatic cancer are more likely to develop a VTE within 30 days of their operation. Of those patients who developed a VTE, approximately one-third occurred after discharge during a 30 day post-operative period. This data supports that further studies are needed to determine the appropriate length of post-operative VTE chemoprophylaxis in patients with cancer.

Incorporating surgical quality into the AJCC 7th edition improves staging accuracy in gastric cancer.

BACKGROUND: The staging of gastric cancer has become increasingly complex. With an emerging 15-node quality measure and a revised American Joint Committee on Cancer (AJCC) staging system, we evaluated the need for more intricate staging systems to predict survival outcomes in gastric cancer. METHODS: The Surveillance, Epidemiology and End Results Program (SEER) database was used to identify 124,972 patients with gastric cancer between 2000 and 2010. Primary endpoints were 5-year disease-specific survival (DSS) and overall survival (OS). Analysis was performed on patients with ≥15 nodes evaluated. Multivariable regression with/without the inclusion of lymph node (LN) assessment and LN ratio were compared using the Akaike information criterion. RESULTS: The number of patients included in the final analysis was 12,096. The proportion of patients with an adequate lymphadenectomy increased markedly from 27 % in 2000 to 52 % in 2010. Overall 5-year DSS and OS was 61.9 and 48.8 %, respectively, for patients with ≥15 nodes examined, versus 57.7 and 39.9 %, respectively, for those with <15 sampled nodes (p < 0.0001). In patients with ≥15 nodes evaluated, the addition of LN evaluation and LN ratio to the existing staging model improved its ability to predict 5-year DSS and OS (p < 0.0001). LN evaluation and LN ratio were comparable in their ability to supplement the existing AJCC 7th edition (AJCC7) staging system. CONCLUSION: The inclusion of a minimum 15-LN quality measure improves the prognostic ability of the AJCC7 staging system, without adding significant complexity.

Attitudes and Perceptions of Surgical Oncology Fellows on ACGME Accreditation and the Complex General Surgical Oncology Certification.

BACKGROUND: With the first qualifying examination administered September 15, 2014, complex general surgical oncology (CGSO) is now a board-certified specialty. We aimed to assess the attitudes and perceptions of current and future surgical oncology fellows regarding the recently instituted Accreditation Council for Graduate Medical Education (ACGME) accreditation. METHODS: A 29-question anonymous survey was distributed to fellows in surgical oncology fellowship programs and applicants interviewing at our fellowship program. RESULTS: There were 110 responses (79 fellows and 31 candidates). The response rate for the first- and second-year fellows was 66 %. Ninety-percent of the respondents were aware that completing an ACGME-accredited fellowship leads to board eligibility in CGSO. However, the majority (80 %) of the respondents stated that their decision to specialize in surgical oncology was not influenced by the ACGME accreditation. The fellows in training were concerned about the cost of the exam (90 %) and expressed anxiety in preparing for another board exam (83 %). However, the majority of the respondents believed that CGSO board certification will be helpful (79 %) in obtaining their future career goals. Interestingly, candidate fellows appeared more focused on a career in general complex surgical oncology (p = 0.004), highlighting the impact that fellowship training may have on organ-specific subspecialization. CONCLUSIONS: The majority of the surveyed surgical oncology fellows and candidates believe that obtaining board certification in CGSO is important and will help them pursue their career goals. However, the decision to specialize in surgical oncology does not appear to be motivated by ACGME accreditation or the new board certification.

Ultrasound-guided placement of midline catheters in the surgical intensive care unit: a cost-effective proposal for timely central line removal.

BACKGROUND: The early removal of central intravenous (IV) catheters, as a means of reducing the incidence of central line-associated blood stream infections (CLABSI), remains a major health care initiative. However, attaining IV access in the surgical intensive care unit (SICU) can be quite difficult. We report the success of a novel, resident-driven program for the placement of ultrasound-guided midline catheters in critically ill patients. MATERIALS AND METHODS: A prospective pilot study of 31 subjects admitted to the SICU from June to December 2011 was performed. Intermediate-length (20 cm) midline catheters were placed by trained housestaff, under ultrasound guidance, into the basilic or cephalic veins. Procedural details including time to cannulation, complications, and costs were recorded. RESULTS: Successful placement was achieved in 96.8% (n = 30), with a mean follow-up of 9.8 ± 5.6 (range 2-21) days. An average of 1.3 ± 0.7 (range 1-4) attempts with a median of 13.0 ± 14.5 (range 0.5-68) minutes was required for successful venous cannulation. The most common site was the basilic vein (n = 23). Only minor complications were encountered; three catheters leaked at the insertion site and one patient developed phlebitis. No CLABSI occurred. The total procedure cost was $87 per catheter for the SICU team compared with $1500 per catheter when performed by an interventional radiologist. During the study period, a total of 283 central line days were avoided with an estimated cost savings of $13,614. CONCLUSIONS: Ultrasound-guided midline catheters placed by the housestaff are a cost-effective alternative for patients in the SICU with difficult IV access. Successful placement can help facilitate early central line removal and thus may reduce CLABSI rates.

NCCN Guideline Concordance Improves Survival in Pediatric and Young Adult Rectal Cancer.

BACKGROUND: Although management guidelines in adult rectal cancer are widely studied, no consensus guidelines exist for the management of pediatric and young adult rectal cancer. METHODS: The National Cancer Database (2004-2018) was queried for pediatric (age 0-21) and young adult (age 22-40) patients with rectal cancer. Patients were analyzed for receipt of National Comprehensive Cancer Network (NCCN) guideline-concordant therapy. Impact on survival was evaluated using Cox regression and Kaplan-Meier analysis. RESULTS: 6655 patients (108 pediatric and 6547 young adult patients) with rectal cancer were included. Similar to previously published NCCN quality measures with overall guideline concordance approaching 90 % in adults, 89.6 % of pediatric and 84.6 % of young adult patients were classified as receiving pre-operative guideline-concordant therapy. However, pediatric patients were significantly less likely to receive post-operative guideline-concordant therapy than young adult patients (65.3 % verse 76.7 %, respectively, p = 0.008). Risk of death was significantly lower for pediatric patients who received post-operative guideline-concordant therapy (HR, 0.313; CI, 0.168-0.581; p < 0.001). In young adult patients, risk of death was significantly lower for those who received pre-operative guideline-concordant therapy (HR, 0.376, CI 0.338-0.417, p < 0.001), and post-operative guideline-concordant therapy (HR, 0.456; CI 0.413-0.505; p < 0.001). DISCUSSION: NCCN-based guidelines may reasonably guide peri-operative management decisions and improve survival in pediatric and young adult rectal cancer. Given the rarity of this cancer in young patients, employment of an experienced surgical and oncologic multidisciplinary team, along with discussion and involvement of the patient and family, are keys for balancing risks and benefits to offering the best therapeutic strategy. TYPE OF STUDY: Retrospective. LEVEL OF EVIDENCE: Level III.

Impact of postoperative pancreatic fistula on outcomes in pancreatoduodenectomy: a comprehensive analysis of American College of Surgeons National Surgical Quality Improvement Program data.

BACKGROUND: Pancreatoduodenectomy (PD) is a major surgical procedure associated with significant risks, particularly postoperative pancreatic fistula (POPF). Studies have highlighted the importance of certain risk factors for POPF, which are crucial for surgical decision-making and the management of high-risk patients undergoing PD. This study aimed to assess the surgical outcomes of patients undergoing PD who met the International Study Group of Pancreatic Surgery - Class D (ISGPS-D) criteria. METHODS: This study analyzed American College of Surgeons National Surgical Quality Improvement Program data (2014-2021) for patients undergoing ISGPS-D PD, classified as having a soft pancreatic texture and a pancreatic duct of ≤3 mm. This study focused on mortality rates and the correlation between several factors and POPF (ISGPS grade B/C). RESULTS: From 5964 patients who underwent PD and met the ISGPS-D criteria, the 30-day mortality rate was 1.98%. Males had a higher incidence of POPF than females (57.42% vs 47.35%, respectively; P < .001). Patients with POPF experienced significantly higher rates of major postoperative complications (Clavien-Dindo grade ≥ IIIa), including thrombosis, pneumonia, sepsis, delayed gastric emptying, wound disruption, infections, and acute renal failure. There was a marked increase in the 30-day readmission and mortality rates in patients with POPF (30.0% vs 17.6% and 3.2% vs 1.4%, respectively; all P < .001). Multivariate analysis highlighted female sex as a protective factor against mortality (odds ratio [OR], 0.47; P < .001) and extended hospital stay (>10 days) as a predictor of increased mortality risk (OR, 2.37; P < .001). CONCLUSION: This study underscored the significant association between POPF and increased postoperative morbidity and mortality rates. Future efforts should concentrate on refining surgical techniques and improving preoperative assessments to mitigate the risks associated with POPF in patients undergoing PD.

Early, precise, and safe clinical evaluation of the pharmacodynamic effects of novel agents in the intact human tumor microenvironment.

Introduction: Drug development is systemically inefficient. Research and development costs for novel therapeutics average hundreds of millions to billions of dollars, with the overall likelihood of approval estimated to be as low as 6.7% for oncology drugs. Over half of these failures are due to a lack of drug efficacy. This pervasive and repeated low rate of success exemplifies how preclinical models fail to adequately replicate the complexity and heterogeneity of human cancer. Therefore, new methods of evaluation, early in the development trajectory, are essential both to rule-in and rule-out novel agents with more rigor and speed, but also to spare clinical trial patients from the potentially toxic sequelae (high risk) of testing investigational agents that have a low likelihood of producing a response (low benefit). Methods: The clinical in vivo oncology (CIVO®) platform was designed to change this drug development paradigm. CIVO precisely delivers microdose quantities of up to 8 drugs or combinations directly into patient tumors 4-96 h prior to planned surgical resection. Resected tissue is then analyzed for responses at each site of intratumoral drug exposure. Results: To date, CIVO has been used safely in 6 clinical trials, including 68 subjects, with 5 investigational and 17 approved agents. Resected tissues were analyzed initially using immunohistochemistry and in situ hybridization assays (115 biomarkers). As technology advanced, the platform was paired with spatial biology analysis platforms, to successfully track anti-neoplastic and immune-modulating activity of the injected agents in the intact tumor microenvironment. Discussion: Herein we provide a report of the use of CIVO technology in patients, a depiction of the robust analysis methods enabled by this platform, and a description of the operational and regulatory mechanisms used to deploy this approach in synergistic partnership with pharmaceutical partners. We further detail how use of the CIVO platform is a clinically safe and scientifically precise alternative or complement to preclinical efficacy modeling, with outputs that inform, streamline, and de-risk drug development.

Surgical versus non-surgical management for patients with malignant bowel obstruction (S1316): a pragmatic comparative effectiveness trial.

BACKGROUND: Malignant small bowel obstruction has a poor prognosis and is associated with multiple related symptoms. The optimal treatment approach is often unclear. We aimed to compare surgical versus non-surgical management with the aim to determine the optimal approach for managing malignant bowel obstruction. METHODS: S1316 was a pragmatic comparative effectiveness trial done within the National Cancer Trials Network at 30 hospital and cancer research centres in the USA, Mexico, Peru, and Colombia. Participants had an intra-abdominal or retroperitoneal primary cancer confirmed via pathological report and malignant bowel disease; were aged 18 years or older with a Zubrod performance status 0-2 within 1 week before admission; had a surgical indication; and treatment equipoise. Participants were randomly assigned (1:1) to surgical or non-surgical treatment using a dynamic balancing algorithm, balancing on primary tumour type. Patients who declined consent for random assignment were offered a prospective observational patient choice pathway. The primary outcome was the number of days alive and out of the hospital (good days) at 91 days. Analyses were based on intention-to-treat linear, logistic, and Cox regression models combining data from both pathways and adjusting for potential confounders. Treatment complications were assessed in all analysed patients in the study. This completed study is registered with ClinicalTrials.gov, NCT02270450. FINDINGS: From May 11, 2015, to April 27, 2020, 221 patients were enrolled (143 [65%] were female and 78 [35%] were male). There were 199 evaluable participants: 49 in the randomised pathway (24 surgery and 25 non-surgery) and 150 in the patient choice pathway (58 surgery and 92 non-surgery). No difference was seen between surgery and non-surgery for the primary outcome of good days: mean 42·6 days (SD 32·2) in the randomised surgery group, 43·9 days (29·5) in the randomised non-surgery group, 54·8 days (27·0) in the patient choice surgery group, and 52·7 days (30·7) in the patient choice non-surgery group (adjusted mean difference 2·9 additional good days in surgical versus non-surgical treatment [95% CI -5·5 to 11·3]; p=0·50). During their initial hospital stay, six participants died, five due to cancer progression (four patients from the randomised pathway, two in each treatment group, and one from the patient choice pathway, in the surgery group) and one due to malignant bowel obstruction treatment complications (patient choice pathway, non-surgery). The most common grade 3-4 malignant bowel obstruction treatment complication was anaemia (three [6%] patients in the randomised pathway, all in the surgical group, and five [3%] patients in the patient choice pathway, four in the surgical group and one in the non-surgical group). INTERPRETATION: In our study, whether patients received a surgical or non-surgical treatment approach did not influence good days during the first 91 days after registration. These findings should inform treatment decisions for patients hospitalised with malignant bowel obstruction. FUNDING: Agency for Healthcare Research and Quality and the National Cancer Institute. TRANSLATION: For the Spanish translation of the abstract see Supplementary Materials section.

Bleeding risk secondary to deep vein thrombosis prophylaxis in patients with lower gastrointestinal bleeding.

INTRODUCTION: Deep vein thrombosis (DVT) and pulmonary embolism (PE) continue to pose a major burden on the health care system in the United States. The precise timing of anticoagulation initiation in critically ill patients with recent or active lower gastrointestinal bleeding (LGIB) is not well defined. We set out to study the safety and efficacy of early heparin administration for DVT prophylaxis in these patients. METHODS: A review of all patients admitted to the ICU with a diagnosis of LGIB over a 13-year period was performed. A total of 60 patients received subcutaneous heparin along with mechanical prophylaxis, whereas 59 patients had intermittent pneumatic compression devices alone. RESULTS: There was no difference in morbidity or mortality between the groups who received heparin and the nonheparin cohort. Neither of the groups developed a DVT or PE during the study period. Patients who received heparin had a median ICU LOS of 3 days, when compared with 2 days for patients who did not receive heparin (P < .0118). There was a significant association between units of blood received during the first 24 hours in the ICU and heparin usage (P < .0229). Those administered heparin received more units (median 3) than those who did not receive heparin (median 2). CONCLUSIONS: Administration of subcutaneous heparin increases the transfusion requirements and LOS in ICU patients with LGIB. After 24 hours, however, the blood transfusion requirements are equivalent. DVT prophylaxis in patients with a diagnosis of LGIB should be initiated after 24 hours of ICU admission.

Robotic vs. laparoscopic colorectal surgery: an institutional experience.

BACKGROUND: Robotic colorectal surgery is gaining interest in general and colorectal surgery. The use of the da Vinci(®) Robotic system has been postulated to improve outcomes, primarily by increasing the dexterity and facility with which complex dissections can be performed. We report a large, single institution, comparative study of laparoscopic and robotic colectomies, attempting to better elucidate the benefits of robotic surgery in patients with colorectal disease. METHODS: We conducted a retrospective review of 171 patients who underwent robotic and laparoscopic colectomies (79 and 92, respectively) at our institution between November 2004 and November 2009. Patients in both groups had well-matched preoperative parameters. All cases were further subdivided by their anatomical location into right-sided and left-sided colectomy, and analysis was performed within these two subgroups. Perioperative outcomes reported include operative time, operative blood loss, time to return of bowel function, time to discontinuation of patient controlled analgesia, length of stay, and intraoperative or postoperative complications. RESULTS: Our results indicate that there is no statistical difference in length of stay, time to return of bowel function, and time to discontinuation of patient-controlled analgesia between robotic and laparoscopic left and right colectomies. Interestingly, the total procedure time difference between the laparoscopic and robotic colectomies was much smaller than previously published accounts (mean 140 min vs. 135 min for right colectomy; mean 168 min vs. 203 min for left colectomy). CONCLUSIONS: Our study is one of the largest reviews of robotic colorectal surgery to date. We believe that our results further demonstrate the equivalence of robotic surgery to laparoscopic surgery in colorectal procedures. Future research should focus on surgeon-specific variables, such as comfort, ergonomics, distractibility, and ease of use, as other ways to potentially distinguish robotic from laparoscopic colorectal surgery.

Advance care planning in patients undergoing surgery to resect pancreatic adenocarcinoma: Underlying tension between balancing hope and realism.

BACKGROUND: The timing and the dose of Advanced Care Planning in patients with pancreatic ductal adenocarcinoma undergoing curative-intent resection are generally dictated by the surgeon performing the operation. METHODS: A qualitative investigation using 1:1 interviews with 40 open-ended questions was conducted with a convenience sample of 10 high-volume pancreatic surgeons from across the country. The grounded theory approach was used for data analysis. RESULTS: A total of 10 interviews were conducted with expert pancreatic surgeons-6 males and 4 females. During preoperative counseling, all surgeons attempt to motivate patients by emphasizing hope, optimism, and the fact that surgery offers the only opportunity for cure. All surgeons discuss the possibility of recurrence as well as postoperative complications; however, a majority perceived that patients do not fully appreciate the likelihood of recurrence or postoperative complications. All surgeons acknowledged the importance of end-of-life conversations when death is imminent. Seventy percent of surgeons had mixed opinions regarding benefits of preoperative Advanced Care Planning in the preoperative setting, while 20% felt it was definitely beneficial, particularly that delivery of care aligned with patient goals. All surgeons emphasized that Advanced Care Planning should be led by a physician who both knows the patient well and understands the nuances of pancreatic ductal adenocarcinoma management. Most common barriers to in-depth Advanced Care Planning discussion reported by surgeons include taking away hope, lack of time, and concern for sending "mixed messages." CONCLUSION: We identified that surgeons experience a fundamental tension between promoting realistic long-term goals and expectations versus focusing on hope and enabling an overly optimistic perception of prognosis.

Enhanced postoperative recovery with minimally invasive cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal surface malignancies of gastrointestinal origin.

BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are the treatment of choice for select patients with peritoneal surface malignancies; however, the traditional open approach may be associated with significant morbidity. We evaluated postoperative outcomes with minimally invasive (MI) CRS and HIPEC. METHODS: Review of our institutional database identified 47 patients who underwent optimal cytoreduction (CC0 or CC1). Those with a PCI ≤ 15 and primary malignancy of gastrointestinal origin were then selected for subgroup analysis. Multivariable regression was performed to identify factors impacting postoperative outcomes. RESULTS: Demographic data did not significantly differ between open (n = 24) and minimally invasive (n = 9) groups. The MI group had a mean age of 57.34 ± 14.92, BMI of 27.03 ± 4.27, Charlson comorbidity score of 1.78 ± 1.72, and PCI of 5.56 ± 5.08. Mean time to flatus (days) was 2.78 in the MI group and 5.04 in the open group (p < 0.001), and mean length of IV analgesic use (days) was 3.11 in the MI group compared to 6.00 in the open group (p = 0.006). Mean length of stay (days) was 5.11 in the MI group and 8.67 in the open group (p = 0.033). Surgical approach (p = 0.037) and BMI (p = 0.039) were the only factors impacting length of stay. CONCLUSIONS: Minimally invasive CRS and HIPEC is an excellent option for low volume peritoneal disease of gastrointestinal origin. A minimally invasive approach yields faster return of bowel function, reduced postoperative analgesia requirements, and shorter hospital stay.

Intellectual Equipoise and Challenges: Accruing Patients With Advanced Cancer to a Trial Randomizing to Surgical or Nonsurgical Management (SWOG S1316).

BACKGROUND: Prospective, randomized trials are needed to determine optimal treatment approaches for palliative care problems such as malignant bowel obstruction (MBO). Randomization poses unique issues for such studies, especially with divergent treatment approaches and varying levels of equipoise. We report our experience accruing randomized patients to the Prospective Comparative Effectiveness Trial for Malignant Bowel Obstruction (SWOG S1316) study, comparing surgical and nonsurgical management of MBO. METHODS: Patients with MBO who were surgical candidates and had treatment equipoise were accrued and offered randomization to surgical or nonsurgical management. Patients choosing nonrandomization were offered prospective observation. Trial details are listed on www.clinicaltrials.gov (NCT #02270450). An accrual algorithm was developed to enhance enrollment. RESULTS: Accrual is ongoing with 176 patients enrolled. Most (89%) patients chose nonrandomization, opting for nonsurgical management. Of 25 sites that have accrued to this study, 6 enrolled patients on the randomization arm. Approximately 59% (20/34) of the randomization accrual goal has been achieved. Patient-related factors and clinician bias have been the most prevalent reasons for lack of randomization. An algorithm was developed from clinician experience to aid randomization. Using principles in this tool, repeated physician conversations discussing treatment options and goals of care, and a supportive team-approach has helped increase accrual. CONCLUSIONS: Experience gained from the S1316 study can aid future palliative care trials. Although difficult, it is possible to randomize patients to palliative studies by giving clinicians clear recommendations utilizing an algorithm of conversation, allotment of necessary time to discuss the trial, and encouragement to overcome internal bias.

Multiplexed Evaluation of Microdosed Antineoplastic Agents In Situ in the Tumor Microenvironment of Patients with Soft Tissue Sarcoma.

PURPOSE: A persistent issue in cancer drug development is the discordance between robust antitumor drug activity observed in laboratory models and the limited benefit frequently observed when patients are treated with the same agents in clinical trials. Difficulties in accurately modeling the complexities of human tumors may underlie this problem. To address this issue, we developed Comparative In Vivo Oncology (CIVO), which enables in situ investigation of multiple microdosed drugs simultaneously in a patient's tumor. This study was designed to test CIVO's safety and feasibility in patients with soft tissue sarcoma (STS). PATIENTS AND METHODS: We conducted a single arm, prospective, 13-patient pilot study. Patients scheduled for incisional biopsy or tumor resection were CIVO-injected 1 to 3 days prior to surgery. Saline or microdoses of anticancer agents were percutaneously injected into the tumor in a columnar fashion through each of eight needles. Following excision, drug responses were evaluated in the injected tissue. RESULTS: The primary objective was met, establishing CIVO's feasibility and safety. Device-related adverse events were limited to transient grade 1 nonserious events. In addition, biomarker evaluation of localized tumor response to CIVO microinjected drugs by IHC or with NanoString GeoMx Digital Spatial Profiler demonstrated consistency with known mechanisms of action of each drug, impact on the tumor microenvironment, and historic clinical activity. CONCLUSIONS: These results are an advance toward use of CIVO as a translational research tool for early evaluation of investigational agents and drug combinations in a novel approach to phase 0 trials.See related commentary by Sleijfer and Lolkema, p. 3897.