Multidisciplinary surgical considerations for en bloc resection of sacral chordoma: review of recent advances and a contemporary single-center series.

OBJECTIVE: Contemporary management of sacral chordomas requires maximizing the potential for recurrence-free and overall survival while minimizing treatment morbidity. En bloc resection can be performed at various levels of the sacrum, with tumor location and volume ultimately dictating the necessary extent of resection and subsequent tissue reconstruction. Because tumor resection involving the upper sacrum may be quite destabilizing, other pertinent considerations relate to instrumentation and subsequent tissue reconstruction. The primary aim of this study was to survey the surgical approaches used for managing primary sacral chordoma according to location of lumbosacral spine involvement, including a narrative review of the literature and examination of the authors' institutional case series. METHODS: The authors performed a narrative review of pertinent literature regarding reconstruction and complication avoidance techniques following en bloc resection of primary sacral tumors, supplemented by a contemporary series of 11 cases from their cohort. Relevant surgical anatomy, advances in instrumentation and reconstruction techniques, intraoperative imaging and navigation, soft-tissue reconstruction, and wound complication avoidance are also discussed. RESULTS: The review of the literature identified several surgical approaches used for management of primary sacral chordoma localized to low sacral levels (mid-S2 and below), high sacral levels (involving upper S2 and above), and high sacral levels with lumbar involvement. In the contemporary case series, the majority of cases (8/11) presented as low sacral tumors that did not require instrumentation. A minority required more extensive instrumentation and reconstruction, with 2 tumors involving upper S2 and/or S1 levels and 1 tumor extending into the lower lumbar spine. En bloc resection was successfully achieved in 10 of 11 cases, with a colostomy required in 2 cases due to rectal involvement. All 11 cases underwent musculocutaneous flap wound closure by plastic surgery, with none experiencing wound complications requiring revision. CONCLUSIONS: The modern management of sacral chordoma involves a multidisciplinary team of surgeons and intraoperative technologies to minimize surgical morbidity while optimizing oncological outcomes through en bloc resection. Most cases present with lower sacral tumors not requiring instrumentation, but stabilizing instrumentation and lumbosacral reconstruction are often required in upper sacral and lumbosacral cases. Among efforts to minimize wound-related complications, musculocutaneous flap closure stands out as an evidence-based measure that may mitigate risk.

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.

Was It Worth It? Critical Evaluation of a Novel Outcomes Measure in Oncologic Palliative Surgery.

BACKGROUND: Patient selection for palliative surgery is complex, and appropriate outcomes measures are incompletely defined. We explored the usefulness of a specific outcomes measure "was it worth it" in patients after palliative-intent operations for advanced malignancy. STUDY DESIGN: A retrospective review of a comprehensive longitudinal palliative surgery database was performed at an academic tertiary care center. All patients who underwent palliative-intent operation for advanced cancer from 2003 to 2022 were included. Patient satisfaction ("was it worth it") was reported within 30 days of operation after palliative-intent surgery. RESULTS: A total of 180 patients were identified, and 81.7% self-reported that their palliative surgery was "worth it." Patients who reported that their surgery was "not worth it" were significantly older and were more likely to have recurrent symptoms and to need reoperation. There was no significant difference in overall, recurrence-free, and reoperation-free survival for patients when comparing "worth it" with "not worth it." Initial symptom improvement was not significantly different between groups. Age older than 65 years (hazard ratio 0.25, 95% CI 0.07 to 0.80, p = 0.03), family engagement (hazard ratio 6.71, 95% CI 1.49 to 31.8, p = 0.01), and need for reoperation (hazard ratio 0.042, 95% CI 0.01 to 0.16, p < 0.0001) were all independently associated with patients reporting that their operation was "worth it." CONCLUSIONS: Here we demonstrate that simply asking a patient "was it worth it" after a palliative-intent operation identifies a distinct cohort of patients that traditional outcomes measures fail to distinguish. Family engagement and durability of an intervention are critical factors in determining patient satisfaction after palliative intervention. These data highlight the need for highly individualized care with special attention paid to patients self-reporting that their operation was "not worth it."

Update on the Financial Well-Being of Surgical Residents in New England.

BACKGROUND: Poor personal financial health has been linked to key components of health including burnout, substance abuse, and worsening personal relationships. Understanding the state of resident financial health is key to improving their overall well-being. STUDY DESIGN: A secondary analysis of a survey of New England general surgery residents was performed to understand their financial well-being. Questions from the National Financial Capability Study were used to compare to an age-matched and regionally matched cohort. RESULTS: Overall, 44% (250 of 570) of surveyed residents responded. Residents more frequently reported spending less than their income each year compared to the control cohort (54% vs 34%, p < 0.01). However, 17% (39 of 234) of residents reported spending more than their income each year. A total of 65% of residents (152 of 234), found it "not at all difficult" to pay monthly bills vs 17% (76 of 445) of the control cohort (p < 0.01). However, 32% (75 of 234) of residents reported it was "somewhat" or "very" difficult to pay monthly bills. Residents more frequently reported they "certainly" or "probably" could "come up with" $2,000 in a month compared to the control cohort (85% vs 62% p < 0.01), but 16% (37 of 234) of residents reported they could not. In this survey, 21% (50 of 234) of residents reported having a personal life insurance policy, 25% (59 of 234) had disability insurance, 6% (15 of 234) had a will, and 27% (63 of 234) had >$300,000 worth of student loans. CONCLUSIONS: Surgical residents have better financial well-being than an age-matched and regionally matched cohort, but there is still a large proportion who suffer from financial difficulties.

ONC201/TIC10 plus TLY012 anti-cancer effects via apoptosis inhibitor downregulation, stimulation of integrated stress response and death receptor DR5 in gastric adenocarcinoma.

Gastric adenocarcinoma typically presents with advanced stage when inoperable. Chemotherapy options include non-targeted and toxic agents, leading to poor 5-year patient survival outcomes. Small molecule ONC201/TIC10 (TRAIL-Inducing Compound #10) induces cancer cell death via ClpP-dependent activation of the integrated stress response (ISR) and up-regulation of the TRAIL pathway. We previously found in breast cancer, pancreatic cancer and endometrial cancer that ONC201 primes tumor cells for TRAIL-mediated cell death through ISR-dependent upregulation of ATF4, CHOP and TRAIL death receptor DR5. We investigated the ability of ONC201 to induce apoptosis in gastric adenocarcinoma cells in combination with recombinant human TRAIL (rhTRAIL) or PEGylated trimeric TRAIL (TLY012). AGS (caspase 8-, KRAS-, PIK3CA-mutant, HER2-amplified), SNU-1 (KRAS-, MLH1-mutant, microsatellite unstable), SNU-5 (p53-mutant) and SNU-16 (p53-mutant) gastric adenocarcinoma cells were treated with ONC201 and TRAIL both in cell culture and in vivo. Gastric cancer cells showed synergy following dual therapy with ONC201 and rhTRAIL/TLY012 (combination indices < 0.6 at doses that were non-toxic towards normal fibroblasts). Synergy was observed with increased cells in the sub-G1 phase of the cell cycle with dual ONC201 plus TRAIL therapy. Increased PARP, caspase 8 and caspase 3 cleavage after ONC201 plus TRAIL further documented apoptosis. Increased cell surface expression of DR5 with ONC201 therapy was observed by flow cytometry, and immunoblotting revealed ONC201 upregulation of the ISR, ATF4, and CHOP. We observed downregulation of anti-apoptotic cIAP-1 and XIAP in all cells except AGS, and cFLIP in all cells except SNU-16. We tested the regimen in an organoid model of human gastric cancer, and in murine sub-cutaneous xenografts using AGS and SNU-1 cells. Our results suggest that ONC201 in combination with TRAIL may be an effective and non-toxic option for the treatment of gastric adenocarcinoma by inducing apoptosis via activation of the ISR, increased cell surface expression of DR5 and down-regulation of inhibitors of apoptosis. Our results demonstrate in vivo anti-tumor effects of ONC201 plus TLY012 against gastric cancer that could be further investigated in clinical trials.

Update on the Personal and Professional Well-Being of Surgical Residents in New England.

BACKGROUND: Surgical culture has shifted to recognize the importance of resident well-being. This is the first study to longitudinally track regional surgical resident well-being over 5 years. STUDY DESIGN: An anonymous cross-sectional, multi-institutional survey of New England general surgery residents using novel and published instruments to create three domains: health maintenance, burnout, and work environment. RESULTS: Overall, 75% (15 of 20) of programs participated. The response rate was 44% (250 of 570), and 53% (133 of 250) were women, 94% (234 of 250) were 25 to 34 years old, and 71% (178 of 250) were in a relationship. For health maintenance, 57% (143 of 250) reported having a primary care provider, 26% (64 of 250) had not seen a primary care provider in 2 years, and 59% (147 of 250) endorsed being up to date with age-appropriate health screening, but only 44% (109 of 250) were found to actually be up to date. Only 14% (35 of 250) reported exercising more than 150 minutes/week. The burnout rate was 19% (47 of 250), with 32% (81 of 250) and 25% (63 of 250) reporting high levels of emotional exhaustion and depersonalization, respectively. For program directors and attendings, 90% of residents reported that they cared about resident well-being. Eighty-seven percent of residents believed that it was acceptable to take time off during the workday for a personal appointment, but only 49% reported that they would personally take the time. CONCLUSIONS: The personal health maintenance of general surgery residents has changed little over the past five years, despite an overwhelming majority of residents reporting that attendings and program directors care about their well-being. Further study is needed to understand the barriers to improvement of resident wellbeing.

Palliative surgery and the surgeon's role in the palliative care team: a review.

This review focuses on the role of palliative surgery in the care of the palliative care patient, and the appropriate role of the surgeon. The surgeon has much to bring to the palliative care team. The surgeon's role goes beyond the technical requirements of the palliative procedure, which itself must be strictly defined, and has recognized utility for improving quality of life in selected patients. These benefits may be substantial, but come at significant risk; requiring careful balancing of risks and benefits that is most completely understood by the surgeon. The surgeon's judgement can help determine which procedure best meets a patient's goals. The complex dialogue involved in the decision to undergo a palliative operation requires excellent communication between the palliative care team, the patient, and their family. Integrating the surgeon into the palliative care team could help with earlier initiation of those palliative discussions, and assist deliberation of palliative surgery. Surgeons also understand the importance of communication around palliative surgical interventions and have adapted several teaching models to the specifics of this crucial communication. A palliative team combining both surgeons and palliative care physicians may promote goal-concordant decision-making and remove barriers to communication and team engagement. The future of palliative surgery research will involve measures of success that go beyond physiology or mortality, to include more evaluations of communication and patient goals.

Who Should Decide When Palliative Surgery Is Justifiable?

No one person has the right or ability to make decisions about to whom or according to which criteria palliative surgery should be offered. Instead, patient and surgeon together must consider symptom severity, goals of care, and the value palliative surgery could add to the patient's health experience or quality of life.

Selecting Patients for Palliative Procedures in Oncology.

Surgical palliation in oncology can be defined as "procedures employed with non-curative intent with the primary goal of improving symptoms caused by an advanced malignancy," and is an important aspect of the end-of-life care of patients with incurable malignancies. Palliative interventions may provide great benefit, but they also carry high risk for morbidity and mortality, which may be minimized with careful patient selection. This can be done by consideration of the patient and his or her indication for the given intervention via open communication, as well as prediction of benefits and risks to define the therapeutic index of the operation or procedure.

Lymphopenia following pancreaticoduodenectomy is associated with pancreatic fistula formation.

BACKGROUNDS/AIMS: Post-operative pancreatic fistulas (POPF) are a major source of morbidity following pancreaticoduodenectomy (PD). This study aims to investigate if persistent lymphopenia, a known marker of sepsis, can act as an additional marker of POPF with clinical implications that could help direct drain management. METHODS: A retrospective chart review of all patients who underwent PD in a single hospital network from 2008 to 2018. Persistent lymphopenia was defined as lymphopenia beyond post-operative day #3. RESULTS: Of the 201 patients who underwent PD during the study period 161 patients had relevant laboratory data, 81 of whom had persistent lymphopenia. 17 patients with persistent lymphopenia went on to develop a POPF, compared to 7 patients without. Persistent lymphopenia had a negative predictive value of 91.3%. Multivariate analysis revealed only persistent lymphopenia as being independently associated with POPF (HR 2.57, 95% CI 1.07-6.643, p=0.039). Patients with persistent lymphopenia were more likely to have a complication requiring intervention (56.8% vs 35.0%, p<0.001). CONCLUSIONS: Persistent lymphopenia is a readily available early marker of POPF that holds the potential to identify clinically relevant POPF in patients where no surgical drain is present, and to act as an adjunct of drain amylase helping to guide drain management.

Providing Appropriate Pancreatic Cancer Care for People Experiencing Homelessness: A Surgical Perspective.

People experiencing homelessness are particularly vulnerable when diagnosed with pancreatic cancer. Patients with lower socioeconomic status have worse outcomes from pancreatic cancer as the result of disparities in access to treatment and barriers to navigation of the health care system. Patients with lower socioeconomic status, or who are vulnerably housed, are less likely to receive surgical treatment even when it is recommended by National Comprehensive Cancer Network guidelines. This disparity in access to surgical care explains much of the gap in pancreatic cancer outcomes. There are many factors that contribute to this disparity in surgical management of pancreatic cancer in people experiencing homelessness. These include a lack of reliable transportation, feeling unwelcome in the medical setting, a lack of primary care and health insurance, and implicit biases of health care providers, including racial bias. Solutions that focus on rectifying these problems include utilizing patient navigators, addressing implicit biases of all health care providers and staff, creating an environment that caters to the needs of patients experiencing homelessness, and improving their access to insurance and regional support networks. Implementing these potential solutions all the way from the individual provider to national safety nets could improve outcomes for patients with pancreatic cancer who are experiencing homelessness.

A Pilot Study of Short-course Nivolumab and Low-dose Ipilimumab for Adjuvant Treatment of Melanoma: Brown University Oncology Research Group Trial, BrUOG 324.

BACKGROUND: Combined cytotoxic T-lymphocyte-associated antigen 4 and programmed death 1 inhibitor blockade is a promising strategy in advanced melanoma and other solid tumors. This pilot study assessed the safety and toxicity of nivolumab plus low-dose ipilimumab in patients with high-risk completely resected melanoma. PATIENTS AND METHODS: Patients received ipilimumab, 1 mg/kg every 6 weeks, and nivolumab, 3 mg/kg every 2 weeks, for a total of 24 weeks (4 cycles). The primary objective was to assess the toxicity of the combined regimen. RESULTS: Twenty-one patients with resected melanoma were enrolled. One patient was stage IIC, 16 patients were stage III and 4 patients had resected stage 4 disease. Ten of 21 (48%) had grade 3 treatment-related toxicities but there was no grade 4 or grade 5 toxicities. The rate of grade 3 nonhematologic toxicities exceeded the toxicity limits defined by the study. Fifteen of 21 patients (71%) completed all 4 cycles of therapy. The median follow-up is 41 months. The 2-year recurrence-free survival is 85.7% and the 2-year overall survival is 90.5%. CONCLUSION: A 6-month course of nivolumab and low-dose ipilimumab may be a promising adjuvant treatment for patients with resected melanoma. Further studies of this regimen are indicated.

Improving the value of palliative surgery by optimizing patient selection: The role of long-term survival on high impact palliative intent operations.

BACKGROUND: In order to better characterize outcomes of palliative surgery (PS), we evaluated patients that experienced top quartile survival to elucidate predictors of high impact PS. METHODS: All PS performed on advanced cancer patients from 2003 to 2017 were identified from a PS database. RESULTS: 167 patients were identified. Multivariate analysis demonstrated the ability to rise from a chair was independently associated with top quartile survival (HR 7.61, 95% CI 2.12-48.82, p=0.008) as was the need for re-operation (HR 2.81, 95% CI 1.26-6.30, p=0.0012). Patients who were able to rise from a chair had significantly prolonged overall survival (320 vs 87 days, p < 0.001). CONCLUSIONS: Although not the primary goal, long-term survival can be achieved following PS and is associated with re-operation and the ability to rise from a chair. These patients experience the benefits of PS for a longer period of time, which in turn maximizes value and positive impact. SUMMARY: Long-term survival and symptom control can be achieved in highly selected advanced cancer patients following palliative surgery. The ability of the patient to independently rise from a chair and the provider to offer a re-operation when indicated are associated with long-term survival following a palliative operation.

Malignant Bowel Obstruction in the Time of the COVID-19 Pandemic.

Regardless of the anatomic site of malignant bowel obstruction leading to the need for palliative intervention, decisions must consider the natural history of the disease, the availability and success of nonsurgical treatments, the individual patient's symptom severity, goals, preferences, quality, and expectancy of life. Therapy for symptoms must remain flexible and individualized because the specific needs of the patient will change as disease progresses. Because strangulation is uncommon, malignant bowel obstruction is usually not a surgical emergency. There is usually time to proceed with deliberate and thoughtful decisions on how best to meet the needs and expectations of the individual patient and family. Providers must be well versed in both surgical and nonsurgical therapeutic options, the natural history of disease, and be active and compassionate providers to foster meaningful ongoing dialogue focused on excellent care even after cure is no longer possible. The palliative triangle not only allows patient, family, and surgeon to effectively utilize the full continuum of care that can be delivered, but also it supports end-of-life decisions when continuity in care matters most. Due to social distancing requirements, the dynamics of communication between patient, family, and surgeon have changed. Zoom, Skype, and FaceTime have become tools in our communication armamentarium.

Is the neutrophil-to-lymphocyte ratio a useful prognostic indicator in melanoma patients?

The neutrophil-to-lymphocyte ratio (NLR) is gaining traction as a biomarker with utility in a variety of malignancies including melanoma. Intact lymphocyte function is necessary for tumor surveillance and destruction, and neutrophils play a role in suppressing lymphocyte proliferation and in the induction of lymphocyte apoptosis. Early research in melanoma indicates that in high-risk localized melanoma, a high NLR is correlated with worse overall and disease-free survival. Similarly, in metastatic melanoma treated with both metastasectomy and immunotherapies, an elevated NLR is predictive of shortened overall survival and progression-free survival. Future studies incorporating NLR into more traditional melanoma prognostic markers while employing more granular outcomes, are needed to realize the full potential of NLR.

Prognosis and Management of Thick and Ultrathick Melanoma.

OBJECTIVES: Thick melanomas, defined as ≥4 mm in thickness, represent ~5% of new melanoma diagnoses and have been associated with poor overall survival (OS). Ultrathick melanomas, those lesions ≥8 mm in thickness, have been associated with worse survival. We sought to compare prognostic factors for thick and ultrathick melanoma. METHODS: Retrospective analysis of a prospective database of all patients receiving an operation for melanoma, June 2005 to December 2016 was performed. Multivariate Cox proportional hazards regression analyses were performed to identify predictors of progression-free survival (PFS) and OS. RESULTS: Of 95 patients with thick melanoma, 37 (39%) had ultrathick tumors (≥8 mm thick). Thick and ultrathick lesions were not significantly different on the basis of tumor location, ulceration, mitotic rate, lymphovascular invasion, or performance or positivity of sentinel node biopsy or therapeutic lymphadenectomy. Disease recurrence was identified in 38 patients overall (40%), more commonly in ultrathick disease (55% vs. 29%, P=0.008). Serum neutrophil to lymphocyte ratio (NLR) was available for 36 patients, of whom 23 (64%) had high NLR (>3.0). Decreased PFS was independently associated with ultrathick tumors (HR, 2.9; P=0.003), head/neck location (HR, 2.6; P=0.023), and positive lymph nodes (HR, 3.3; P=0.004). Decreased OS was independently associated with high NLR (HR, 5.0; P=0.042). CONCLUSIONS: Disease progression was higher in the ultrathick melanoma group. Thicker tumors, head/neck location, and positive lymph nodes were associated with decreased PFS. High NLR was associated with decreased OS. Ultrathick melanomas represent advanced malignancy; however, patients may derive benefit from surgical treatment to achieve locoregional control.

The Resident Outcome Project: Increased Academic Productivity Associated with a Formal Clinical Research Curriculum.

PURPOSE: A formal 2-year clinical research project in conjunction with a system-based practice and practice-based learning and improvement curriculum was initiated for all residents in our program. Within the structure of this formal clinical research curriculum, residents are required to develop a research hypothesis, develop an appropriate study design, collect and analyze data, and present a completed project. METHODS: At the end of the PGY1 year, residents select a project with an emphasis on quality improvement or clinical outcomes. The first 6 months of the 2-year program are dedicated to the identification of a faculty mentor and submission of a formal proposal to both the departmental education committee and to the institutional IRB. Over the following 12 months, residents meet monthly for required group research meetings. The final 6 months are focused on data analysis and project completion. RESULTS: Seventy-five residents have successfully completed the clinical research program since it was initiated in 2002. Completed projects led to abstracts accepted at 33 national or regional meetings and 11 peer reviewed publications to date. In addition, 3 major hospital wide quality improvement measures were initiated based on project findings. Following the first peer reviewed publication associated with these research projects in 2006, there have been significant increases in not only the number of accepted abstracts from these resident projects (3/18 [17%] vs 30/57 [53%], p = 0.008) but also the total number of all accepted resident clinical research (mean accepted abstracts per year 7.9 vs 1.0, p = 0.009 and mean peer reviewed publications per year 6.8 vs 2.0, p = 0.003.) DISCUSSION: Increased academic productivity was observed after a formal resident clinical research program was initiated in our program. Resident research efforts extended beyond the specific initial outcome projects as skills gained allowed for future independent clinical research.

Patient selection in palliative surgery: Defining value.

Proper patient selection for palliative surgery requires a challenging and often complex decision-making process. Optimally, proposed palliative procedures must be undertaken with an intent to provide the greatest possible value to patients at the end of life. This review describes the process of patient selection and identifies psychosocial, biochemical, and functional markers that can complement sound surgical judgment.