The Landmark Series: Appendiceal Primary Peritoneal Surface Malignancy

Appendiceal primary peritoneal surface malignancies are rare and include a broad spectrum of pathologies ranging from indolent disease to aggressive disease. As such, the data that drive the management of appendiceal peritoneal surface malignancies is generally not based on prospective clinical trial data, but rather consists of level 1 data based on retrospective studies and high-volume institutional experiences. Complete surgical debulking typically offers the best chance for long-term survival. This review highlights the landmark articles on which management of primary appendiceal peritoneal surface malignancies are based

Pancreatic lymphoepithelial cyst with concurrent HIV infection: A case report and review of the literature

Pancreatic lymphoepithelial cysts are rare, benign, non-neoplastic unilocular or multilocular cystic lesions. These circumscribed pancreatic lesions are filled with keratinous material grossly and exhibit distinct microscopic features. Pancreatic lymphoepithelial cysts are like the more common lymphoepithelial cysts of the parotid glands, which have been associated with the diffuse infiltrative lymphocytosis syndrome often seen in patients with HIV infection. However, pancreatic lymphoepithelial cysts are rare and their association with HIV infection has not been established. The presence of secondary changes in non-neoplastic cysts such as goblet cell metaplasia that was present in our case is an important feature to be included in the differential diagnosis and not to be interpreted as a mucinous neoplasm, particularly on fine-needle aspiration specimen microscopic evaluation that would impact further management. Here we describe the diagnosis and treatment of lymphoepithelial cysts in a patient who was on highly active antiretroviral therapy for HIV infection and we provide a brief literature review. Defining the clinical characteristics of lymphoepithelial cysts in patients with HIV and determining accurate preoperative diagnostic procedures will be critical for establishing effective surgical and medical approaches to treating these cysts, which differ substantially from other more serious pancreatic cystic lesions

Evaluation of Practice Patterns and Outcomes after Implementing SMART for Pancreatic Cancer

Purpose/Objective(s): Stereotactic MRI-guided adaptive radiation therapy (SMART) enables safe dose escalation for locally advanced, borderline resectable, and medically inoperable pancreatic cancer and has shown favorable toxicity and survival outcomes. In late 2018, our institution commissioned SMART for these patients, making it available to all patient referrals. We wanted to review changes in our patient population and differences in clinical outcomes for patients before and after the implementation of SMART. Materials/Methods: In this IRB approved analysis, we retrospectively reviewed 167 consecutive patients from 2015-2021 with locally advanced, borderline resectable, or medically unresectable pancreatic cancer who were treated with radiation therapy. Chemoradiation (chemoRT) was defined as any 28-30 fraction radiation regimen that included concurrent chemotherapy. SMART was defined as 50 Gy over 5 consecutive daily fractions without concurrent chemotherapy. Baseline patient characteristics were compared between groups. Overall survival (OS) was evaluated by Kaplan-Meier (KM) and log-rank test. Univariate (UVA) and multivariate analysis (MVA) were also performed on multiple treatment variables. Results: Of the patients included, 58 received chemoRT (2015-2018) and 109 received SMART (2018-2021). Median follow up from time of diagnosis for the chemoRT and SMART cohorts were 53.7 months and 29.2 months respectively. Cohorts did not have significant differences in age, gender, race, T or N staging, rates of surgery or surgical margin status. Patients receiving SMART had overall worse performance (p = 0.011) including a lower percentage of PS 0 patients (22.9% vs 44.8%) and a higher percentage of PS 2+ patients (34% vs 15.5%). Similarly, the SMART patients did numerically more often have locally advanced (50% vs 43%) and medically inoperable (26% vs 21%) disease (p = 0.294). The SMART cohort did have longer neoadjuvant chemotherapy with mean of 3.5 months vs 2.3 months in the chemoRT cohort (p = 0.002). There was no OS difference between each group when measured from diagnosis (p=0.79) or from first day of radiation (p=0.2). Median survival in the chemoRT and SMART groups was 18.7 vs 17.4 months from diagnosis. When including only PS 0-1 patients, the median survival in the chemoRT and SMART groups was 18.8 vs 22.3 months (p=0.37). There was also no difference in locoregional control, distant control, or progression free survival using KM. On MVA positive prognostic factors for OS from diagnosis included ECOG \u3c2 (HR 0.54, p=0.015), increasing months of neoadjuvant chemo (HR 0.88, p=0.004) and pancreatectomy (HR 0.14, p \u3c0.001). Conclusion: Despite the fact that the patient cohort receiving radiation therapy per the SMART approach had poorer performance status compared with chemoRT, OS was not significantly different. The multidisciplinary team was highly supportive of SMART with increased patients being treated

Stereotactic MRI-guided Adaptive Radiation Therapy for Non-metastatic Pancreatic Cancer; Outcomes and Toxicity Analysis for Patients Treated in an Underserved Urban Center

Background: Stereotactic MRI-guided Adaptive Radiation Therapy (SMART) is an emerging technology for treatment of pancreatic cancer patients. Initial results show favorable survival and toxicity. However, data is still sparse overall, and especially in underserved patient populations. The purpose of this study is to review SMART outcomes at our underserved urban academic cancer. Objectives: Stereotactic MRI-guided Adaptive Radiation Therapy (SMART) is an emerging technology for treatment of pancreatic cancer patients. Initial results show favorable survival and toxicity. However, data is still sparse overall, and especially in underserved patient populations. The purpose of this study is to review SMART outcomes at our underserved urban academic cancer. Methods: In this IRB approved retrospective chart review we reviewed 98 patients with non-metastatic pancreatic cancer, who completed SMART between November 2018-January 2021. All 98 patients were treated with 50 Gy in 5 daily fractions with adaptive technique as deemed appropriate by treating radiation oncologist. The primary endpoints were overall survival (OS), progression free survival (PFS), and both acute and late grade 3+ GI toxicity. OS, PFS, locoregional control and distant control were estimated by Kaplan-Meier method and compared using log-rank test. The effect of clinical features on OS was assessed using univariate and multivariate Cox proportional hazard models. OS and PFS were calculated from completion of radiation. Grade 3+ GI toxicity probably or definitively related to radiation was recorded. All incidences of GI bleeding, regardless of attribution, were also recorded. Results: Median follow up was 20.9 months from time of diagnosis and 14 months from radiation. 21 (21%) patients were borderline resectable, 42 (43%) locally advanced, 22 (22%) medically inoperable and 13 (13%) resectable. Neoadjuvant chemotherapy was given to 86 (88%) patients with a median of 3.5 months of chemotherapy (range 1-12), leaving 11 (12%) patients who did not have systemic chemotherapy. Median overall survival from radiation for the whole group was 15.7 months, and 1-year OS was 58%. There was a statistically significant worsening of overall survival from diagnosis between ECOG 2+ and ECOG 0/1 patients (HR 1.94, 1.05-3.57). 27 (27%) patients went on to have surgical resection with 23 (82%) having R0 resection, and 3 (11%) have an R1 resection. Improved OS was seen in patients with surgical resection (HR 0.06, 0.02-0.23). Acute grade 3+ GI toxicity from radiation was seen in 4 (4%) patients and late toxicity from radiation was seen in 6 (6%) patients. GI bleeding was seen in 16(16%) patients, 10 (62%) of which were on anticoagulation at the time of GI bleed and 5 (19%) of which had surgery. Portal vein complications occurred with 7 (7%) having portal vein thrombosis and 6 (6%) portal vein stenosis. Conclusions: SMART showed durable responses in pancreatic cancer patients with an acceptable toxicity profile. Attention needs to be paid to the moderate incident of GI bleeding, however further work is necessary to determine if bleeding was due to radiation, surgery, or disease progression. Surgical resection as well as performance status of ECOG 0-1 were associated with improved overall survival. Further follow up will be necessary to determine further durability of treatment response and long-term survival in these patients

Disparity Outcomes in Patients Undergoing Pancreas Surgery at an Urban Tertiary Care Center

INTRODUCTION: Previous studies have shown significant disparities in pancreas cancer outcomes in African American (AA) compared to non-AA patients. Pancreas surgery continues to be associated with significant morbidity, however, there is little reported data on pancreas surgical outcomes by race. We sought to evaluate how race would affect surgical outcomes in an urban tertiary care center for patients undergoing pancreas surgery. METHODS: A retrospective single-center analysis of patients undergoing pancreas surgery between January 2013 and September 2021 was performed. Patient demographics and post-surgical complications were collected and stratified by race. Area Deprivation Index (ADI) was used to determine patient socioeconomic status. Charlson Comorbidity Index (CCI) was calculated for comorbidities. Clavien-Dindo (CD) complications, as well as postoperative pancreatic fistula (POPF), delayed gastric emptying (DGE) and postpancreatectomy hemorrhage (PPH) were evaluated. Patient reoperation, readmission, and mortality in the 30- and 90- day period were collected and univariate and multivariate analyses were performed. RESULTS: Among 461 patients, 82% (N = 378) were nonAA and 18% (N = 83) were AA. Age and sex were found to be significantly different between the two groups, while ADI and CCI were not. Length of stay (LOS), POPF, PPH, PPH grade C and intra-abdominal abscess (IAA) were found to be significant on univariate analysis in the AA cohort. On multivariate analysis, LOS (OR 4.0; 95% CI 2.0-5.7; p \u3c 0.001), POPF (OR 0.6; 95% CI 0.4-1.0; p = 0.043), PPH (OR 0.5; 95% CI 0.2-0.9; p = 0.022), PPH grade C (OR 0.2; 95% CI 0.1-0.7; p = 0.017) and IAA (OR 0.4; 95% CI 0.2-0.9; p = 0.017) were still significantly higher in the AA cohort. CONCLUSIONS: AA patients undergoing pancreas surgery were noted to have a longer LOS, higher incidence of POPF, PPH and IAA compared to non-AA patients. However, no significant difference was seen in reoperation rates, major CD complications, or 30- and 90-day readmission. Elucidating patient selection, tumor biology, and preoperative treatment algorithms may shed additional insight on the differences in surgical outcomes in this particular patient cohort

Surgery After Neoadjuvant Stereotactic MRI Guided Adaptive Radiation in Pancreatic Cancer: Multi-institutional Toxicity and Survival Outcomes

Background: Favorable toxicity and survival outcomes after dose escalated stereotactic MR guided adaptive radiation therapy (SMART) have been recently published for locally advanced (LA) and borderline resectable (BR) pancreatic cancer. Perioperative morbidity and mortality are not well understood after ablative radiation therapy, which may temper enthusiasm for offering surgery. Objectives: The purpose of this study was to investigate survival and toxicity in resected pancreas cancer patients after neoadjuvant ablative SMART. Methods: In this IRB approved analysis, we retrospectively reviewed 33 consecutive patients with resectable, BR, and LA pancreatic cancer based on NCCN 2.2021 staging criteria who were treated at 2 institutions from 2017-2020 with neoadjuvant SMART 50 Gy in 5 fractions on a 0.35T MR Linac and later underwent definitive surgical resection. Overall survival (OS) and locoregional control (LRC) were evaluated by Kaplan-Meier method. Results: Median follow up was 22.4 months from diagnosis and 17.8 months from last day of RT. Most had BR (55%), otherwise initially resectable (33%) or LA (12%) pancreatic cancer. Median duration of induction chemotherapy was 3.5 (SD 1.6) months with most common regimens being FOLFIRINOX (74%), gemcitabine/abraxane (24%) and FOLFOX (3%). Performance status was ECOG 0, 1, 2 in 16 (48.5%), 12 (36.4%), and 5 (15.2%), respectively. Whipple was performed in 27 (82%) of patients, distal pancreatectomy in 4 (12%), and total pancreatectomy in 2 (6%). The median duration from SMART completion to surgery was 6.9 weeks (4.7-44.1). R0 resections were achieved in 28 (84.8%) of patients with the rest being R1, all in BR patients. Vascular resection/reconstruction was performed of the portal vein (PV) in 8 (24.2%) patients, SMV in 4 (12%), SMA in 1 (3%), and common hepatic artery in 2 (6%). Vascular resection/reconstruction was performed in all LA patients. Median OS, 1-year OS, and 2-year OS from diagnosis were 29.6 months, 93.8%, 81.5%, respectively. Median OS from RT was not yet reached; 1-year OS was 90.9%. LRC at 1 and 2 years was 97% and 93%, respectively. Radiation related acute and late grade 3+ gastrointestinal toxicity was seen in 2 (6%) and 2 (6%) patients. Post-op mortality at 30 and 90 days was seen 2 (6%) and 3 (9%) of patients with 1 death from GI bleed attributed to surgery and 1 death from hepatic ischemia related to PV resection. Conclusions: To the best of our knowledge, this is the first report suggesting that surgery for pancreas cancer after dose escalated 5-fraction SMART is feasible. Further clarification is needed with respect to ideal patient selection and timing for surgery, the safety of arterial versus venous resection/reconstruction, and histopathologic response after delivery of ablative versus non-ablative radiation dose

Surgery After Neoadjuvant Stereotactic MRI Guided Adaptive Radiation in Pancreatic Cancer: Multi-institutional Toxicity and Survival Outcomes

Background: Favorable toxicity and survival outcomes after dose escalated stereotactic MR guided adaptive radiation therapy (SMART) have been recently published for locally advanced (LA) and borderline resectable (BR) pancreatic cancer. Perioperative morbidity and mortality are not well understood after ablative radiation therapy, which may temper enthusiasm for offering surgery. Objectives: The purpose of this study was to investigate survival and toxicity in resected pancreas cancer patients after neoadjuvant ablative SMART. Methods: In this IRB approved analysis, we retrospectively reviewed 33 consecutive patients with resectable, BR, and LA pancreatic cancer based on NCCN 2.2021 staging criteria who were treated at 2 institutions from 2017-2020 with neoadjuvant SMART 50 Gy in 5 fractions on a 0.35T MR Linac and later underwent definitive surgical resection. Overall survival (OS) and locoregional control (LRC) were evaluated by Kaplan-Meier method. Results: Median follow up was 22.4 months from diagnosis and 17.8 months from last day of RT. Most had BR (55%), otherwise initially resectable (33%) or LA (12%) pancreatic cancer. Median duration of induction chemotherapy was 3.5 (SD 1.6) months with most common regimens being FOLFIRINOX (74%), gemcitabine/abraxane (24%) and FOLFOX (3%). Performance status was ECOG 0, 1, 2 in 16 (48.5%), 12 (36.4%), and 5 (15.2%), respectively. Whipple was performed in 27 (82%) of patients, distal pancreatectomy in 4 (12%), and total pancreatectomy in 2 (6%). The median duration from SMART completion to surgery was 6.9 weeks (4.7-44.1). R0 resections were achieved in 28 (84.8%) of patients with the rest being R1, all in BR patients. Vascular resection/reconstruction was performed of the portal vein (PV) in 8 (24.2%) patients, SMV in 4 (12%), SMA in 1 (3%), and common hepatic artery in 2 (6%). Vascular resection/reconstruction was performed in all LA patients. Median OS, 1-year OS, and 2-year OS from diagnosis were 29.6 months, 93.8%, 81.5%, respectively. Median OS from RT was not yet reached; 1-year OS was 90.9%. LRC at 1 and 2 years was 97% and 93%, respectively. Radiation related acute and late grade 3+ gastrointestinal toxicity was seen in 2 (6%) and 2 (6%) patients. Post-op mortality at 30 and 90 days was seen 2 (6%) and 3 (9%) of patients with 1 death from GI bleed attributed to surgery and 1 death from hepatic ischemia related to PV resection. Conclusions: To the best of our knowledge, this is the first report suggesting that surgery for pancreas cancer after dose escalated 5-fraction SMART is feasible. Further clarification is needed with respect to ideal patient selection and timing for surgery, the safety of arterial versus venous resection/reconstruction, and histopathologic response after delivery of ablative versus non-ablative radiation dose

The Landmark Series: Appendiceal Primary Peritoneal Surface Malignancy

Appendiceal primary peritoneal surface malignancies are rare and include a broad spectrum of pathologies ranging from indolent disease to aggressive disease. As such, the data that drive the management of appendiceal peritoneal surface malignancies is generally not based on prospective clinical trial data, but rather consists of level 1 data based on retrospective studies and high-volume institutional experiences. Complete surgical debulking typically offers the best chance for long-term survival. This review highlights the landmark articles on which management of primary appendiceal peritoneal surface malignancies are based