Current treatment and recent progress in gastric cancer.

Gastric cancer is not a top-10 malignancy in the United States but represents one of the most common causes of cancer death worldwide. Biological differences between tumors from Eastern and Western countries add to the complexity of identifying standard-of-care therapy based on international trials. Systemic chemotherapy, radiotherapy, surgery, immunotherapy, and targeted therapy all have proven efficacy in gastric adenocarcinoma; therefore, multidisciplinary treatment is paramount to treatment selection. Triplet chemotherapy for resectable gastric cancer is now accepted and could represent a plateau of standard cytotoxic chemotherapy for localized disease. Classification of gastric cancer based on molecular subtypes is providing an opportunity for personalized therapy. Biomarkers, in particular microsatellite instability (MSI), programmed cell death ligand 1 (PD-L1), human epidermal growth factor receptor 2 (HER2), tumor mutation burden, and Epstein-Barr virus, are increasingly driving systemic therapy approaches and allowing for the identification of populations most likely to benefit from immunotherapy and targeted therapy. Significant research opportunities remain for the less differentiated histologic subtypes of gastric adenocarcinoma and those without markers of immunotherapy activity.

Palliative Surgery for Patients with Gastroesophageal Junction or Gastric Cancer: A Report on Clinical Observational Outcomes.

BACKGROUND: Few studies have focused on palliative surgery in patients with advanced gastroesophageal junction (GEJ) or gastric cancer. We sought to evaluate clinical observational outcomes following palliative surgery in this population. PATIENTS AND METHODS: Patients with GEJ or gastric cancer who underwent palliative surgery (1/2010-11/2022) were identified. The primary outcomes were symptom improvement, ability to tolerate an oral diet, discharge to home, 30 "good days" without hospitalization, and receipt of systemic treatment. Postoperative outcomes and survival were secondarily evaluated. RESULTS: Among 93 patients, the median age was 59 (IQR 47-68) years, and the median Eastern Cooperative Oncology Group Performance Status (ECOG-PS) was 1 (range 0-3). The most frequent indication for palliative surgery was primary tumor obstruction [75 (81%) patients]. The most common procedures were feeding tube placement in 60 (65%) and intestinal bypass in 15 (16%) patients. A total of 75 (81%) patients experienced symptom improvement. Of these, 19 (25%) developed recurrent and 49 (65%) developed new symptoms. ECOG-PS was significantly associated with symptom-free time. Among those who underwent a bypass, resection, or ostomy creation for malignant obstruction, 16 (80%) tolerated an oral diet. Postoperatively, 87 (94%) were discharged home, 72 (77%) had 30 good days, and 64 (69%) received systemic treatment. Postoperative complications occurred in 35 (38%) patients, and 7 (8%) died within 30 days. The median survival time was 7.7 (95% CI 6.4-10.40) months. CONCLUSIONS: Patients with incurable GEJ or gastric cancer can benefit from palliative surgery. Prognosis and performance status should inform goals-of-care discussions and patient selection for surgical palliation.

Great Debate: Chemoradiation Should be Added to Chemotherapy as a Neoadjuvant Treatment Strategy for Resectable Gastric Adenocarcinoma.

BACKGROUND: Most patients with resectable gastric cancer present with locally advanced disease and warrant neoadjuvant chemotherapy based on level 1 evidence. However, the incremental benefit of adding radiation to chemotherapy as a neoadjuvant treatment strategy for these patients is less clear. METHODS: While awaiting the results of two ongoing randomized clinical trials attempting to specifically address this question (TOPGEAR and CRITICS-II), this article presents the debate between two gastric cancer surgery experts supporting each side of the argument on the use or omission of neoadjuvant radiation in this setting. RESULTS: On the one hand, neoadjuvant radiation may be better tolerated compared with modern triplet chemotherapy and may be associated with higher rates of major pathologic response. Additionally, there is evidence to suggest that radiation may offer a survival benefit when the tumor is located at the gastroesophageal junction or there is concern for a margin-positive resection. However, in the setting of adequate surgery, no survival benefit has been demonstrated by adding radiation to modern chemotherapy, likely reflecting the fact that death from gastric cancer is a result of distant recurrence, which is not addressed by local treatment such as radiotherapy. CONCLUSION: While awaiting the results of the TOPGEAR and CRITICS-II trials, this discussion of current evidence can facilitate the refinement of an optimal neoadjuvant therapy strategy in patients with resectable gastric cancer.

Prevalence of and Factors Associated with Financial Toxicity After Pancreatectomy and Gastrectomy.

BACKGROUND: Financial toxicity (FT) refers to the adverse impact of cancer treatment costs on patients' experiences, potentially leading to poor adherence to treatment and outcomes. However, the prevalence of FT among patients undergoing major upper gastrointestinal cancer operations, as well as factors associated with FT, remain unclear. METHODS: We conducted a cross-sectional study by sending the Comprehensive Score for financial Toxicity (COST) survey and Surgery-Q (a survey specifically developed for this study) to patients who underwent gastrectomy or pancreatectomy for malignant disease at our institution in 2019-2021. RESULTS: We sent the surveys to 627 patients and received responses from 101 (16%) patients. The FT prevalence (COST score <26) was 48 (48%). Patients likely to experience FT were younger than 50 years of age, of non-White race, earned an annual income <$75,000, and had credit scores <740 (all p < 0.05). Additionally, longer hospital stay (p = 0.041), extended time off work for surgery (p = 0.011), and extended time off work for caregivers (p = 0.005) were associated with FT. Procedure type was not associated with FT; however, patients who underwent minimally invasive surgery (MIS) had a lower FT probability (p = 0.042). In a multivariable analysis, age <50 years (p = 0.031) and credit score <740 (p < 0.001) were associated with high FT risk, while MIS was associated with low FT risk (p = 0.024). CONCLUSIONS: Patients with upper gastrointestinal cancer have a major risk of FT. In addition to predicting the FT risk before surgery, facilitating quicker functional recovery with the appropriate use of MIS is considered important to reducing the FT risk.

High symptom burden in patients undergoing gastrectomy for cancer.

BACKGROUND: There is little data describing symptom burden before or after gastrectomy for patients with cancer. We aimed to examine the perioperative patterns of symptom severity in patients undergoing gastrectomy. METHODS: In this single-institution prospective cohort study, patients scheduled to undergo gastrectomy for cancer completed serial symptom measurement questionnaires preoperatively, at postoperative day (POD) 1-3, and POD 4-7. The percent of patients with moderate to severe scores was calculated at each time point. RESULTS: Thirty-nine patients completed 94 surveys. Preoperatively, 46% reported at least one moderate/severe symptom. This increased to 88% during POD 1-3 and 79% during POD 4-7. During the preoperative period, 25% of patients reported moderate to severe interference in at least one aspect of daily life. This increased to 73% of patients at both POD 1-3 and POD 4-7. CONCLUSIONS: Patients undergoing gastrectomy for cancer frequently experience symptoms that interfere with daily life. A better understanding of these symptoms may improve patients' experiences with, and recovery from, gastrectomy.

Patient-reported outcome measures in surgical patients with upper gastrointestinal cancers: A qualitative interview study.

BACKGROUND AND OBJECTIVES: Patients with pancreatic and gastroesophageal (PGE) cancers experience high symptom burden, but patient experience throughout multimodality treatment remains unclear. We aimed to delineate the experience and symptom burden of patients throughout their perioperative course. METHODS: Qualitative interviews were performed with 17 surgical patients with PGE cancer. Interview transcripts were analyzed and symptoms were ranked by frequency. An expert panel assessed the relevance of these symptom inventory items. RESULTS: Of the 17 patients included, 35% (n = 6) underwent gastrectomy, 30% (n = 5) underwent esophagectomy, and 35% (n = 6) underwent pancreatectomy; 76% (n = 13) received neoadjuvant systemic chemotherapy and/or chemoradiation. Overall, 32 symptoms were reported, and 19 were reported by over 20% of patients. An expert panel rated nine symptoms to be relevant or very relevant to PGE surgical patients. These symptoms (difficulty swallowing, heartburn/reflux, diarrhea, constipation, flushing/sweating, stomach feeling full, malaise, dizziness, or feeling cold) were added to the core MD Anderson Symptom Inventory (MDASI) if they were commonly reported or reached a threshold relevancy score. CONCLUSIONS: In this qualitative study, we developed a provisional symptom inventory for patients undergoing surgery for PGE cancer. This symptom inventory module of the MDASI for PGE surgical patients will be psychometrically tested for validity and reliability.

Palliative and Supportive Care Consultation for Patients With Malignant Gastrointestinal Obstruction is Associated With Broad Interdisciplinary Management.

OBJECTIVE: The aim of this study was to assess rates of palliative care (PC) involvement in the care of patients with malignant gastrointestinal obstruction (GIO) and its influence on interdisciplinary team involvement. BACKGROUND: Malignant GIO is an advanced oncologic diagnosis with associated poor prognosis. Data regarding PC and interdisciplinary team involvement in these patients is lacking. METHODS: We identified consecutive surgical consultations for GIO in cancer patients at a single institution from August 2017 to July 2019. Clinical characteristics were collected. Rates of PC consultation, ACP discussion, code status change to do not resuscitate, and interdisciplinary service consultation were evaluated. RESULTS: We identified 200 patients with consultations for GIO, of whom 114 (57%) had malignant GIO and were included in our study. Of these patients, 95 (83%) had stage IV disease; 68 (60%) had peritoneal metastasis, and 70 (61%) had other intra-abdominal recurrence or metastasis. PC consultation was obtained in 69 patients (61%). PC consultation was associated with higher rates of ACP discussion (64% vs 29%; P < 0.001), code status change to do not resuscitate (30% vs 2%; P < 0.001), nonsurgical procedure (46% vs 11%; P < 0.001), discharge to hospice (30% vs 7%; P < 0.001), and involvement of spiritual care (48% vs 22%; P = 0.01), social work (77% vs 42%, P < 0.001), psychology/psychiatry (42% vs 4%, P < 0.001), nutrition (86% vs 62%, P = 0.006), physical therapy (54% vs 31%, P = 0.02), and occupational therapy (42% vs 16%, P = 0.004). CONCLUSIONS: PC consultation benefits patients with malignant GIO by facilitating comprehensive interdisciplinary care, ACP discussions, and transition to hospice care, where appropriate. Diagnosis of malignant GIO should be a trigger for PC consultation or, in facilities with limited PC resources, consideration of deliberately broad interdisciplinary consultation.

Communication Frameworks for Palliative Surgical Consultations: A Randomized Study of Advanced Cancer Patients.

OBJECTIVE: To evaluate whether patients with advanced cancer prefer surgeons to use the best case/worst case (BC/WC) communication framework over the traditional risk/benefit (R/B) framework in the context of palliative surgical scenarios. BACKGROUND: Identifying the patient's preferred communication frameworks may improve satisfaction and outcome measures during difficult clinical decision-making. METHODS: In a video-vignette-based randomized, double-blinded study from November 2020 to May 2021, patients with advanced cancer viewed 2 videos depicting a physician-patient encounter in a palliative surgical scenario, in which the surgeon uses either the BC/WC or the R/B framework to discuss treatment options. The primary outcome was the patients' preferred video surgeon. RESULTS: One hundred fifty-five patients were approached to participate; 66 were randomized and 58 completed the study (mean age 55.8 ± 13.8 years, 60.3% males). 22 patients (37.9%, 95% CI: 25.4%-50.4%) preferred the surgeon using the BC/WC framework, 21 (36.2%, 95% CI: 23.8%-48.6%) preferred the surgeon using the R/B framework, and 15 (25.9%, 95% CI: 14.6%-37.2%) indicated no preference. High trust in the medical profession was inversely associated with a preference for the surgeon using BC/WC framework (odds ratio: 0.83, 95% CI: 0.70-0.98, P = 0.03). The BC/WC framework rated higher for perceived surgeon's listening (4.6 ± 0.7 vs 4.3±0.9, P = 0.03) and confidence in the surgeon's trustworthiness (4.3 ± 0.8 vs 4.0 ± 0.9, P = 0.04). CONCLUSIONS: Surgeon use of the BC/WC communication framework was not universally preferred but was as acceptable to patients as the traditional R/B framework and rated higher in certain aspects of communication. A preference for a surgeon using BC/WC was associated with lower trust in the medical profession. Surgeons should consider the BC/WC framework to individualize their approach to challenging clinical discussions.

Evidence-Based Surgical Approach to Gastroesophageal Junction Cancer: How We Do Robotic Transhiatal Lower Mediastinal Dissection and Esophagojejunostomy.

Currently available data suggest that gastroesophageal junction (GEJ) cancers with an esophageal extension less than 2 cm can be removed using gastrectomy with a limited esophagectomy via a transhiatal approach and selective lower mediastinal dissection.1 In this multimedia article, we demonstrate our approach to robotic total gastrectomy with data-driven mediastinal lymph node (LN) dissection and sutured esophagojejunostomy for GEJ cancer.The video shows the case of a 63-year-old man with Siewert type 2 GEJ adenocarcinoma. The size of the tumor was 3 cm, and its esophageal extension was 2 cm. The man underwent preoperative chemoradiotherapy (5-FU/oxaliplatin, 45 Gy) with excellent treatment effect. After dissection of the esophagus from the bilateral diaphragmatic crus, surrounding lymph node (LN) tissue (#110) was identified and dissected. In this case, intraoperative findings showed the posterior lower mediastinal LNs (#112) to be swollen, and they were sampled. Surgeons should take care to avoid penetration of the pleura and thoracic duct injury if pleura penetration is oncologically unnecessary. Because the esophagus often is thickened and prone to ischemia after preoperative chemoradiotherapy,2 the authors perform the anastomosis with hand-suturing techniques regardless whether a robotic or open approach is used. The patient recovered well and was discharged on postoperative day 4 in good condition. Pathology reported a ypT1bN0 tumor with negative margins.

Cytoreduction and HIPEC for Gastric Carcinomatosis: Multi-institutional Analysis of Two Phase II Clinical Trials.

INTRODUCTION: There are no approved locoregional therapies for peritoneal carcinomatosis from gastric adenocarcinoma (GA). Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) represents a potential treatment for advanced GA with isolated peritoneal metastasis. PATIENTS AND METHODS: Two separate single-institution phase II, single-arm studies evaluating CRS-HIPEC using cisplatin with mitomycin C (NIH: NCT03092518, MDACC: NCT02891447) in patients with GA and confirmed peritoneal metastasis were analyzed. The primary endpoint of each trial was overall survival (OS). Clinical, pathologic, and treatment variables were analyzed for association with outcomes. RESULTS: Over 4 years, 41 patients with peritoneal carcinomatosis from GA underwent CRS-HIPEC. All patients had synchronous peritoneal metastasis and received systemic chemotherapy as front-line therapy. A total of 23 patients also received laparoscopic HIPEC prior to open CRS-HIPEC. The majority (63%, n = 26) were male, and median PCI score at CRS-HIPEC was 2. Median OS was 24.9 months from diagnosis and 14.4 months from CRS-HIPEC. Three-year OS was 25% from diagnosis and 22% from CRS-HIPEC. Median RFS was 7.4 months. The rate of 30-day Clavien-Dindo grade ≥ 3 complications was 32%; specifically, the rate of anastomotic leak was 22%. Multivariable analysis identified the number of pathologically positive lymph nodes as an independent predictor of postoperative OS. CONCLUSIONS: In patients with gastric adenocarcinoma and isolated peritoneal metastasis treated with CRS-HIPEC, 3-year OS was 22% from CRS-HIPEC, and complications were common. The number of pathologic lymph node metastases was inversely correlated with overall survival. Further investigation of CRS-HIPEC for GA should include patient selection based on response to systemic chemotherapy or incorporate novel intraperitoneal treatment strategies.

Clinical Impact of Positive Surgical Margins in Gastric Adenocarcinoma in the Era of Preoperative Therapy.

BACKGROUND: Microscopically positive (R1) surgical margins after gastrectomy increase gastric cancer recurrence risk, but optimal management after R1 gastrectomy is controversial. We sought to identify the impact of R1 margins on recurrence patterns and survival in the era of preoperative therapy for gastric cancer. METHODS: Patients who underwent gastrectomy for adenocarcinoma during 1998-2017 at a major cancer center were enrolled. Clinicopathologic factors associated with positive margins were examined, and incidence, sites, and timing of recurrence and survival outcomes were compared between patients with positive and negative margins. RESULTS: Of 688 patients, 432 (63%) received preoperative therapy. Thirty-four patients (5%) had R1 margins. Compared with patients with negative margins, patients with R1 margins more frequently had aggressive clinicopathologic features, such as linitis plastica (odds ratio [OR] 7.79, p < 0.001) and failure to achieve cT downstaging with preoperative treatment (OR 5.20, p = 0.005). The 5 year overall survival (OS) rate was lower in patients with R1 margins (6% vs 60%; p < 0.001), and R1 margins independently predicted worse OS (hazard ratio 2.37, 95% CI 1.51-3.75, p < 0.001). Most patients with R1 margins (58%) experienced peritoneal recurrence, and locoregional recurrence was relatively rare in this group (14%). Median time to recurrence was 8.5 months for peritoneal dissemination and 15.7 months for locoregional recurrence. CONCLUSION: R1 margins after gastrectomy were associated with aggressive tumor biology, high incidence of peritoneal recurrence after a short interval, and poor OS. In patients with R1 margins, re-resection to achieve microscopically negative margins has to be considered with caution.

Localized Gastroesophageal Adenocarcinoma in the Elderly: Is Age a Factor Associated with Suboptimal Treatment?

INTRODUCTION: Gastroesophageal adenocarcinoma is relatively common in elderly patients as the incidence increases with age. However, the optimal treatment approach is not well established in this group of patients. The aim of this study is to review our experience for localized gastroesophageal adenocarcinoma in patients aged ≥80 years and to assess association between patient characteristics, clinical factors, and overall survival (OS) in order to optimize the therapeutic approaches for this population. METHODS: Patients ≥80 years old treated for localized gastroesophageal adenocarcinoma were retrospectively analyzed. Survival curves were estimated using the Kaplan-Meier method. Univariate and multivariate Cox proportional hazards regression models were applied to assess the association between patient characteristics and OS. Factors that were significant in the multivariate model were included in the final reduced model. RESULTS: 127 patients ≥80 years old, were included in this study with median age of 83 years. The median follow-up time was 3.2 years, and median OS was 2.5 years (95% CI: 2.0-3.1 years). Independent prognostic factors for OS were Eastern Cooperative Oncology Group (ECOG) performance status (PS) (p = 0.003), baseline clinical stage (p = 0.01), and surgery (p = 0.001). ECOG PS, tumor location, baseline stage, tumor grade, and surgery were included in the final reduced model. CONCLUSION: Surgical treatment can improve survival in elderly patients. Therapeutic decisions should be based on the patients' general condition rather that age alone.

Laparoscopic transverse abdominis plane block: how I do it and a cost efficiency analysis.

PURPOSE: To determine the efficacy and efficiency of laparoscopic transverse abdominis plane block (Lap-TAP) in patients undergoing pancreatoduodenectomy and gastrectomy compared to those of ultrasound-guided TAP (US-TAP). METHODS: We retrospectively analyzed the records of patients who underwent open or minimally invasive (MIS) pancreatoduodenectomy and major gastrectomy with the use of Lap-TAP or US-TAP at our institution between November 1, 2018, and September 30, 2021. We compared the estimated time and cost associated with Lap-TAP and US-TAP. We also compared postoperative opioid use and pain scores between patients who underwent open laparotomy with these TAPs. RESULTS: A total of 194 patients were included. Overall, 114 patients (59%) underwent pancreatectomy, and 80 patients (41%) underwent gastrectomy. Additionally, 138 patients (71%) underwent an open procedure, and 56 patients (29%) underwent MIS. A total of 102 patients (53%) underwent US-TAP, and 92 (47%) underwent Lap-TAP. The median time to skin incision was significantly shorter in the Lap-TAP group (US-TAP, 59 min vs. Lap-TAP, 45 min; P < 0.001), resulting in an estimated reduction in operation cost by $602. Pain scores and postoperative opioid use were similar between Lap-TAP and US-TAP among open surgery patients, indicating equivalent pain control between Lap-TAP and US-TAP. CONCLUSION: Lap-TAP was equally effective in pain control as US-TAP after pancreatectomy and gastrectomy, and Lap-TAP can reduce operation time and cost. Lap-TAP is considered the preferred approach for MIS pancreatectomy and gastrectomy, which occasionally needs conversion to laparotomy.

Trans-pacific multicenter collaborative study of minimally invasive proximal versus total gastrectomy for proximal gastric and gastroesophageal junction cancers.

BACKGROUND: The current standard operation for proximal gastric and gastroesophageal junction (P/GEJ) cancers with limited esophageal extension is total gastrectomy (TG). TG is associated with impaired appetite and weight loss due to the loss of gastric functions such as production of ghrelin and with anemia due to intrinsic factor loss and vitamin B12 malabsorption. Theoretically, proximal gastrectomy (PG) can mitigate these problems by preserving gastric function. However, PG with direct esophagogastric reconstruction is associated with severe postoperative reflux, delayed gastric emptying, and poor quality of life (QoL). Minimally invasive PG (MIPG) with antireflux techniques has been increasingly performed by experts but is technically demanding owing to its complexity. Moreover, the actual advantages of MIPG over minimally invasive TG (MITG) with regards to postoperative QoL are unknown. Our overall objective of this study is to determine the short-term QoL benefits of MIPG. Our central hypotheses are that MIPG is safe and that patients have improved appetite after MIPG with effective antireflux techniques, which leads to an overall QoL improvement when compared with MITG. METHODS: Enrollment of a total of 60 patients in this prospective survey-collection study is expected. Procedures (MITG versus MIPG, antireflux techniques for MIPG [double-tract reconstruction versus the double-flap technique]) will be chosen based on surgeon and/or patient preference. Randomization is not considered feasible because patients often have strong preferences regarding MITG and MIPG. The primary outcome is appetite level (reported on a 0-10 scale) at 3 months after surgery. With an expected 30 patients per cohort (MITG versus MIPG), this study will have 80% power to detect a one-point difference in appetite level. Patient-reported outcomes will be longitudinally collected (including questions about appetite and reflux), and specific QoL items, body weight, body mass index and ghrelin, albumin, and hemoglobin levels will be compared. DISCUSSION: Surgeons from the US, Japan, and South Korea formed this collaboration with the agreement that the surgical approach to P/GEJ cancers is an internationally important but controversial topic that requires immediate action. At the completion of the proposed research, our expected outcome is the establishment of the benefit and safety of MIPG. TRIAL REGISTRATION: This trial was registered with Clinical Trials Reporting Program Registration under the registration number NCI-2022-00267 on January 11, 2022, as well as with ClinicalTrials.gov under the registration number NCT05205343 on January 11, 2022.

Analysis of Opioid Use in Patients Undergoing Open Versus Robotic Gastrectomy.

BACKGROUND: Minimally invasive, robotic gastrectomy is associated with better short-term outcomes and quicker functional recovery. However, the degree to which the robotic approach influences postoperative pain and opioid use after gastrectomy is unknown. Our primary aim was to determine whether the robotic approach to gastrectomy reduces postoperative opioid use compared with the open approach. METHODS: Patients who underwent gastrectomy (November 2018 to September 2021) were identified retrospectively. Clinical characteristics, short-term surgical outcomes, oral morphine equivalent (OME) use, and pain scores were collected. Both groups were managed through an enhanced recovery program in the perioperative period. RESULTS: Of 81 patients, 50 underwent open and 31 underwent robotic gastrectomy. Compared with open gastrectomy patients, robotic gastrectomy patients had longer surgery time (360 vs. 288 min), less blood loss (50 vs. 138 mL), and shorter hospital stay (4 vs. 6 days) (all medians, P < 0.001). Robotic gastrectomy patients used lower OMEs on postoperative days 0-4 (all P < 0.05) and in total for days 0-4 (total mean dose 65.0 vs. 169.5 mg; P < 0.001) than did open gastrectomy patients. The robotic gastrectomy patients were prescribed a lower mean OME dose than the open gastrectomy patients (19.0 vs. 29.0 mg, respectively; P = 0.001). Multivariable analysis showed that robotic approach was associated with lower opioid use (odds ratio 3.70; 95% CI 1.01-14.3; P = 0.049). CONCLUSIONS: Compared with open gastrectomy, robotic gastrectomy reduces opioid use in the early postoperative period and is associated with fewer OME discharge prescriptions and shorter hospital stay.

Early Experience of a Robotic Foregut Surgery Program at a Cancer Center: Video of Shared Steps in Robotic Pancreatoduodenectomy and Gastrectomy.

Over the past few decades, robotic surgery techniques required to resect gastric and pancreatic malignancies have evolved remarkably; however, the safety and generalizability of robotic pancreatoduodenectomy remain unknown. At our cancer center, gastrectomies and pancreatectomies are performed in a combined foregut minimally-invasive surgery program; this effectively increases the composite case volume and shortens the learning curve for any individual surgeon. In this video, we demonstrate the shared steps in pancreatoduodenectomy and gastrectomy and explain how the skills gained through robotic gastrectomy can be used during robotic pancreatoduodenectomy. During the initial 2-year period of our robotic foregut surgery program, we performed 120 pancreatic and gastric operations, including 22 pancreatoduodenectomies and 37 gastrectomies. Our first robotic pancreatoduodenectomy was performed following successful completion of 45 other robotic foregut operations. Of those 22 patients who underwent robotic pancreatoduodenectomy, the median hospital stay was 4 days (range 3-17 days) and the readmission rate was 14% (3/22). The rate of grade B/C pancreatic fistula was 9% (2/22) and there was no 90-day mortality. In conclusion, the presented video showing the shared steps in robotic pancreatoduodenectomy and gastrectomy demonstrates the potential for a combined robotic surgery program to increase composite case volumes and to shorten the learning curve. At our cancer center, implementation of this approach has been helpful in accelerating the development of our new robotic pancreatectomy program, especially in honing the skills necessary to perform robotic pancreatoduodenectomy.

YAP1 mediates gastric adenocarcinoma peritoneal metastases that are attenuated by YAP1 inhibition.

OBJECTIVE: Peritoneal carcinomatosis (PC; malignant ascites or implants) occurs in approximately 45% of advanced gastric adenocarcinoma (GAC) patients and associated with a poor survival. The molecular events leading to PC are unknown. The yes-associated protein 1 (YAP1) oncogene has emerged in many tumour types, but its clinical significance in PC is unclear. Here, we investigated the role of YAP1 in PC and its potential as a therapeutic target. METHODS: Patient-derived PC cells, patient-derived xenograft (PDX) and patient-derived orthotopic (PDO) models were used to study the function of YAP1 in vitro and in vivo. Immunofluorescence and immunohistochemical staining, RNA sequencing (RNA-Seq) and single-cell RNA-Seq (sc-RNA-Seq) were used to elucidate the expression of YAP1 and PC cell heterogeneity. LentiCRISPR/Cas9 knockout of YAP1 and a YAP1 inhibitor were used to dissect its role in PC metastases. RESULTS: YAP1 was highly upregulated in PC tumour cells, conferred cancer stem cell (CSC) properties and appeared to be a metastatic driver. Dual staining of YAP1/EpCAM and sc-RNA-Seq revealed that PC tumour cells were highly heterogeneous, YAP1high PC cells had CSC-like properties and easily formed PDX/PDO tumours but also formed PC in mice, while genetic knockout YAP1 significantly slowed tumour growth and eliminated PC in PDO model. Additionally, pharmacologic inhibition of YAP1 specifically reduced CSC-like properties and suppressed tumour growth in YAP1high PC cells especially in combination with cytotoxics in vivo PDX model. CONCLUSIONS: YAP1 is essential for PC that is attenuated by YAP1 inhibition. Our data provide a strong rationale to target YAP1 in clinic for GAC patients with PC.

Frequency and Implications of Paratracheal Lymph Node Metastases in Resectable Esophageal or Gastroesophageal Junction Adenocarcinoma.

OBJECTIVE: We aimed to evaluate the frequency of paratracheal lymph nodes (LN) metastases and their prognostic influence. SUMMARY BACKGROUND DATA: Paratracheal LNs are considered regional nodes in the esophageal cancer classification, but their metastatic rate and influence on survival remain unclear. METHODS: One thousand one hundred ninety-nine patients with resectable esophageal or gastroesophageal junction adenocarcinoma (EAC) (January 2002 and December 2016) in our Gastrointestinal Medical Oncology Database were analyzed. Paratracheal LNs were defined as1R, 1L, 2R, 2L, 4R, and 4L, according to the 8th American Joint Committee on Cancer classification. RESULTS: Of 1199 patients, 73 (6.1%) had positive paratracheal LNs at diagnosis. The median overall survival (OS) of 73 patients with initial paratracheal LN involvement was 2.10 years (range 0.01-10.1, 5-yrs OS 24.2%). Of 1071 patients who were eligible for recurrence evaluation, 70 patients (6.5%) developed paratracheal LN metastases as the first recurrence. The median time to recurrence was 1.28 years (range 0.28-5.96 yrs) and the median OS following recurrence was only 0.95 year (range 0.03-7.88). OS in 35 patients who had only paratracheal LN recurrence was significantly longer than in patients who had other recurrences (median OS 2.26 vs 0.51 yrs, 5-yrs OS; 26.8% vs 0%, P < 0.0001). Higher T stage (T3/T4) was an independently risk factor for paratracheal LN recurrence (odds ratio 5.10, 95% confidence interval 1.46-17.89). We segregated patients in 3 groups based on the distance of tumor's proximal edge to esophagogastric junction (low; ≤2 cm, medium; 2.0-7.0 cm, and high; >7.0 cm). Paratracheal LN metastases were more frequent with the proximal tumors (low, 4.2%; medium, 12.0%; high, 30.3%; Cochran-Armitage Trend test, P < 0.001). CONCLUSION: Paratracheal LN metastases were associated with a shorter survival in resectable EAC patients. Alternate approaches to prolong survival of this group of patients are warranted.

Chemotherapy Versus Chemotherapy Plus Chemoradiation as Neoadjuvant Therapy for Resectable Gastric Adenocarcinoma: A Multi-institutional Analysis.

OBJECTIVE: We compare neoadjuvant chemotherapy (CT) to neoadjuvant chemotherapy plus chemoradiation (CRT) for patients with gastric adenocarcinoma (GA). SUMMARY OF BACKGROUND DATA: The optimal neoadjuvant therapy regimen for resectable GA is not defined. METHODS: Utilizing data from 2 high-volume cancer centers, we analyzed patients who underwent surgery for localized GA from 1/1/2000-12/31/2017. Standard CT regimens were used according to treatment period. We compared propensity matched cohorts based on age, sex, race, histology, and clinical stage. RESULTS: Four-hundred five patients (age 62 ± 12 year, 58% male, 56% White) were analyzed. 231 (57%) received CRT and 174 (43%) received CT. Groups differed based on histopathologic characteristics including preoperative stage (p = 0.013). To control for these differences, propensity matched cohorts of 113 CT and 113 CRT patients were compared. CRT had similar frequencies of microscopically negative resections to CT (93% vs 91%, p = 0.81), but higher rates of complete pathologic response (15% vs 4%, p = 0.003) and lower pathologic stage (p = 0.002). Completion of intended perioperative therapy occurred in 63% of CT and 91% of CRT patients (p < 0.001). Median DFS was 45mo (95%CI: 20-70) in the CT group and 113mo (95%CI: 75-151) in the CRT group (p = 0.018). Median OS was 53mo (95%CI: 30-77) versus 120mo (95%CI: 101-138); p = 0.015. CONCLUSIONS: In this multi-institutional comparison of neoadjuvant CT and CRT for resectable GA, CRT is associated with higher rates of completed perioperative therapy, higher rates of complete pathologic response, lower pathologic stage, and improved survival.Level of Evidence: Level III.

Determinants of Survival for Patients with Neoadjuvant-Treated Node-Negative Gastric Cancer.

BACKGROUND: This study sought to determine prognostic markers for disease recurrence and survival in a cohort of neoadjuvant-treated, node-negative gastric cancer patients (ypT0-4N0M0). METHODS: Clinicopathologic data from patients treated with neoadjuvant therapy followed by curative-intent gastrectomy at the University of Texas MD Anderson Cancer Center from 1995 to 2017 were evaluated. Patients with AJCC TNM stage ypT0-4N0M0 were considered for analysis. RESULTS: The inclusion criteria were met by 212 patients with a mean age of 58.3 years. Of these patients, 60 % were male, 53 % were Caucasian, 87 % received chemoradiation, and 13 % received chemotherapy. The findings showed a median overall survival (OS) rate of 11.3 years, a 5-year survival rate of 72 %, and a 10-year survival rate of 57 %. During a median follow-up period of 5.5 years, 38.2 % of the patients died. In the multivariable analysis, ypT4-stage and nodal yield fewer than 16 were significantly associated with reduced OS. Cancer classified as ypT4 had more aggressive biologic traits, including lymphovascular and perineural invasion, and was treated more aggressively with total gastrectomy and additional organ resection despite frequent positive margins. Depth of invasion remained significantly associated with worse outcome after the analysis controlled for nodal yield and possible stage migration. Compared with ypT0-3 tumors, ypT4 cancers were associated with significantly more recurrences (13 % vs. 45 %; p < 0.05), and the primary modes of failure for ypT4 lesions were local recurrence and peritoneal metastases (88 % of recurrences). CONCLUSIONS: Depth of primary tumor invasion and nodal yield were significantly associated with OS among the patients with ypT0-4N0M0 gastric cancer. Serosal invasion (ypT4) was associated with a high rate of peritoneal recurrence, and trials of intraperitoneal therapy targeting these patients should be considered.