Neoadjuvant Chemotherapy and Radiation Improves Recurrence-free and Overall Survival in Resectable and Borderline Resectable Pancreatic Ductal Adenocarcinoma.

OBJECTIVE: The objective of this study is to analyze the outcomes of patients with resectable/borderline resectable PDAC who receive total neoadjuvant therapy vs upfront surgery. METHODS AND ANALYSIS: Patients who were treated at a single institution from 2006 to 2021 were included. The primary outcome was overall survival (OS). Secondary outcomes included disease free survival (DFS), rates of lymph node positivity, and R0 resection. All survival analyses were performed with intention-to-treat. RESULTS: 26 patients received neoadjuvant chemotherapy and radiation (TNT), 28 received neoadjuvant chemotherapy only (NAC), and 168 received upfront surgery. Demographics were comparable across all three groups. Patients who received TNT or NAC had longer OS and DFS compared to the surgery first patients (P < .01). Patients who received TNT had a lymph node positivity rate of 0% at time of surgery compared to 5.3% and 13.3% in the NAC and surgery-first groups, respectively (P < .01). The rate of R0 resection did not differ between groups (P = .17). CONCLUSION: Patients with resectable/borderline resectable PDAC who receive neoadjuvant therapy have longer OS and RFS relative to those who receive upfront surgery.

Can we let our patients sleep in the hospital? A randomized controlled trial of a pragmatic sleep protocol in surgical oncology patients.

BACKGROUND: Postoperative inpatients experience increased stress due to pain and poor restorative sleep than non-surgical inpatients. OBJECTIVES AND METHODS: A total of 101 patients, undergoing major oncologic surgery, were randomized to a postoperative sleep protocol (n = 50) or standard postoperative care (n = 51), between August 2020 and November 2021. The primary endpoint of the study was postoperative sleep time after major oncologic surgery. Sleep time and steps were measured using a Fitbit Charge 4®. RESULTS: There was no statistically significant difference found in postoperative sleep time between the sleep protocol and standard group (median sleep time of 427 min vs. 402 min; p = 0.852, respectively). Major complication rates were similar in both groups (7.4% vs. 8.9%). Multivariate analysis found sex and Charlson Comorbidity Index to be significant factors affecting postoperative sleep time and step count. Postoperative delirium was only observed in the standard group, although this did not reach statistical significance. There were no in hospital mortalities. CONCLUSION: The use of a sleep protocol was found to be safe in our study population. There was no statistical difference in postoperative sleep time or major complications. Institution of a more humane sleep protocol for postoperative inpatients should be considered.

Expecting the unexpected: incidental findings at a level 1 trauma center.

INTRODUCTION: Incidental findings on comprehensive imaging in the adult trauma population occur at rates as high as 54.8%. We sought to determine the incidence of potentially malignant or pre-malignant incidental findings in a high-volume level 1 trauma center and to evaluate follow-up recommendations. METHODS: This was a retrospective review of all patients with incidental findings on imaging who were admitted to the trauma service at our level 1 trauma center between January 1st, 2014, and October 1st, 2019. A multi-disciplinary team characterized findings as potentially malignant or pre-malignant. RESULTS: The study included 495 patients who had incidental findings, 410 of whom had potentially malignant or pre-malignant findings on imaging, resulting in a cumulative incidence of 6.6%. The mean age was 65 and 217 (52.9%) patients were male. The majority of "incidentalomas" were discovered on CT imaging (n=665, 98.1%); over half were solid (n=349, 51.5%), while 27.4% were cystic (n=186) in nature. The lungs (n=199, 29.4%), kidneys (n=154, 22.8%), liver (n=74, 10.9%), thyroid gland (n=58, 8.6%), and adrenal glands (n=53, 7.8%) harbored the most incidentalomas. Less than half of patients with incidental findings received specific follow-up recommendations on the radiologist's report (n=150, 39%). Sixty-one percent of patients (n=250) had their incidentalomas detailed in the discharge paperwork. CONCLUSION: The results of our study suggest that potentially malignant or pre-malignant incidental findings are common among trauma patients. Specific follow-up recommendations were not presented in 61% of the radiology reports, highlighting the need to standardize medical record capture of an incidentaloma to ensure adequate and appropriate follow-up.

Out of sight, out of mind? The impact on trauma patient opioid use when the medicine administration schedule is not displayed.

INTRODUCTION: The impact of a visual pain medication schedule on opioid use among hospitalized trauma patients is unknown. We examined whether removal of this displayed schedule would decrease oral morphine equivalent (OME) use. METHODS: This retrospective cohort study compared OME use in trauma patients in the inpatient setting before and after removing the patient-facing pain medication schedule that is typically displayed on the patient's white board for all trauma admissions. RESULTS: 707 patients were included. The control (n = 308, 43.6%) and intervention (n = 399, 56.4%) groups were similar in age (p = 0.06). There was no difference in total inpatient OME use between the control and intervention groups, median 50 (IQR: 22.5-118) vs 60 (IQR: 22.5-126), p = 0.79, respectively. No difference in total OME use was observed when patients were stratified by age, sex, race, ISS, and length of hospital stay. CONCLUSION: Removing a visual display of the pain medication schedule did not decrease OME use in inpatient trauma patients.

Bleeding After Hemorrhoidectomy in Patients on Anticoagulation Medications.

BACKGROUND: Post-hemorrhoidectomy bleeding is a serious complication after hemorrhoidectomy. In the setting of a new wave of anticoagulants, we aimed to investigate the relationship of post-operative anticoagulation timing and delayed bleeding. METHODS: We performed a retrospective analysis of all patients undergoing hemorrhoidectomy at a single institution over a 10-year period. Fisher's exact and Wilcoxon Rank Sum tests were utilized to test for association between delayed bleeding and anticoagulation use. RESULTS: Between January 2011 and October 2020, 1469 hemorrhoidectomies were performed. A total of 216 (14.7%) were taking platelet inhibitors and 56 (3.8%) other anticoagulants. Delayed bleeding occurred in 5.2% (n = 76) of which 47% (n = 36) required operative intervention. Mean time to bleeding was 8.7 days (SD ±5.9). Time to bleeding was longer in those taking antiplatelet inhibitors vs. non-platelet inhibitors vs. none (11 vs. 8 vs. 7 days, P = .05). Among anticoagulants (n = 56), novel oral anticoagulants were more common than warfarin (57% vs 43%) and had a nonsignificant increase in delayed bleeding (31% vs 16%, P = .21). Later restart (>3 days) of novel anticoagulants after surgery was associated with increased bleeding (10.5% vs 61.5%, P=.005). On multivariable analysis, only anticoagulation use (OR 4.5, 95% CI: 2.1-10.0), male sex (OR 1.8, 95% CI: 1.1-2.9), and operative oversewing (OR 3.5, 95% CI: 1.8-6.9) were associated with delayed bleeding. CONCLUSION: Post-hemorrhoidectomy bleeding is more likely to occur with patients on anticoagulation. Later restart times within the first week after surgery was not associated with a decrease in bleeding.

Pancreatic Cancer: A Review of Current Treatment and Novel Therapies.

Pancreatic cancer is one of the leading causes for cancer-related deaths in the United States. Majority of patients present with unresectable or metastatic disease. For those that present with localized disease, a multidisciplinary approach is necessary to maximize survival and optimize outcomes. The quality and safety of surgery for pancreatic cancer have improved in recent years with increasing adoption of minimally invasive techniques and surgical adjuncts. Systemic chemotherapy has also evolved to impact survival. It is now increasingly being utilized in the neoadjuvant setting, often with concomitant radiation. Increased utilization of genomic testing in metastatic pancreatic cancer has led to better understanding of their biology, thereby allowing clinicians to consider potential targeted therapies. Similarly, targeted agents such as PARP inhibitors and immune checkpoint- inhibitors have emerged with promising results. In summary, pancreatic cancer remains a disease with poor long-term survival. However, recent developments have led to improved outcomes and have changed practice in the past decade. This review summarizes current practices in pancreatic cancer treatment and the milestones that brought us to where we are today, along with emerging therapies.

Kirsten rat sarcoma (KRAS) oncogene mutation predicts magnitude of response and outcomes in hepatic arterial infusion pump therapy of unresectable colorectal liver metastases.

Background: The Kirsten rat sarcoma (KRAS) mutation predicts negative outcomes following resection of colorectal liver metastases (CRLM) and adjuvant hepatic arterial infusion (HAI) pump chemotherapy. Less is known on the effects of KRAS mutation on tumor response in patients with unresectable CRLM undergoing HAI chemotherapy with floxuridine. Methods: This is a retrospective cohort study investigating the effects of KRAS mutation on tumor response in patients with unresectable CRLM treated with HAI chemotherapy. Primary endpoint was objective response rate (ORR), secondary endpoints included overall tumor response and conversion to resectability. Results: Twenty-five patients with unresectable liver metastases from colorectal cancer were treated with HAI chemotherapy between 2017-2019. Median number of liver lesions was 12 (range, 1-59) and almost all (n=24) had prior chemotherapy before starting HAI therapy. Median number of cycles administered via HAI pump was 6 (range, 3-12). Overall decrease in liver tumor burden was 63.5% (median; range, -257-100%) with an ORR of 20/25 (80%) and 10 (40%) patients converting to resectable status. Eleven (44%) patients had KRAS positive tumors. When compared to wild-type, KRAS positive tumors had less overall percent decrease (58% vs. 70%; P=0.04) and ORR (7/11 vs. 13/13; P=0.03). Fewer patients with KRAS positive tumors converted to resectable status during HAI therapy (2/11 vs. 8/13; P=0.05). At a median follow-up of 14.6 months (range, 4.0-36.6 months), overall survival is 45% among KRAS-positive and 77% for wild type patients. Conclusions: KRAS mutational status in patients with unresectable liver metastases from colorectal cancer predicts worse response to HAI chemotherapy compared to wild type.

Ileal Pouch Anal Anastomosis (IPAA) for colitis; development of Crohn's and Pouchitis.

BACKGROUND: Chronic pouchitis and Crohn's disease after Ileal pouch anal anastomosis (IPAA) for ulcerative colitis could be a larger issue than previously reported. METHODS: All patients receiving care for their IPAA over a 10-year period at a community hospital were included. Primary outcomes were incidence of Crohn's disease and pouchitis. RESULTS: The study included 380 IPAA patients. Indication for pouch creation was either UC (n = 362) or indeterminate colitis (n = 18). Cumulative incidence of Crohn's was 19.5%. Five-, 10- and 20-year incidence of Crohn's was 3.4%, 8.4% and 16.9%. Chronic pouchitis occurred in 28.7%. Mean time to pouchitis and Crohn's diagnosis was 8.4 (SD ± 8.0) and 11.6 (SD ± 7.5) years. Pouch failure occurred in 12.4%. Patients who developed Crohn's were more likely to suffer pouchitis and pouch failure (OR 3.5, 95%CI 2.0-6.0 and 5.3, 95%CI 2.8-10.1). CONCLUSION: During long term follow up, almost 20% are diagnosed with Crohn's contributing significantly to pouch failure.

Treatment of Gastroesophageal Reflux Disease After Lung Transplant Using Radiofrequency Ablation to the Lower Esophageal Sphincter (Stretta Procedure).

BACKGROUND: Gastroesophageal reflux disease (GERD) is associated with chronic lung allograft dysfunction after lung transplant. Treating GERD after lung transplant has been shown to improve lung allograft function. This case series describes the efficacy of the Stretta procedure to control GERD after lung transplant at our institution. METHODS: Eleven patients underwent the Stretta procedure at our institution for GERD after lung transplant during the years 2016-2017. Pre- and post-Stretta reflux parameters were gathered. Pulmonary function was followed up until subsequent fundoplication surgery, death, or end of study observation. RESULTS: Reflux on esophagram was noted in 9 patients before Stretta and 8 patients after Stretta. The median number of acid reflux events was 31.5 vs. 26 after Stretta (P = .95), and median percent time in reflux was 17.7% before vs. 14.5% after Stretta (P = .76). Median DeMeester score before Stretta was 65.5 (range: 33.2-169.8) vs. 42.5 (range: 19.2-109.8) after the procedure (P = .14). Median lower esophageal resting pressure was 20.7 mm Hg (n = 7) compared to 25.9 mm Hg (n = 9) on post-Stretta follow-up (P = .99). Median FEV1% predicted was 84% (41-97%) before compared to 71% (23-108%) at 1 year after the procedure (P = .14). Seven patients required fundoplication surgery for continued reflux. All patients were on triple immunosuppression, most commonly prednisone, tacrolimus, and mycophenolate (n = 9). DISCUSSION: The Stretta procedure did not provide expected results at our institution after lung transplant surgery. Based on our limited series, we do not recommend routine use of the Stretta procedure for management of GERD in lung transplant patients.

Fluoroscopic placement of nasojejunal feeding tubes in COVID-19 patients in the prone position.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has caused an increase in patients requiring enteral feeding access while undergoing proning for severe acute respiratory distress syndrome (ARDS). We investigated the safety and feasibility of fluoroscopy-guided nasojejunal (NJ) feeding tube placement in the prone position. METHODS: This is a retrospective cohort study of all patients who underwent fluoroscopic placement of NJ feeding tubes at a single institution between March 2020 and December 2020. Primary end points were success rate and number of attempts. Chi-squared and Fischer exact tests were used to compare prone and supine groups. RESULTS: A total of 210 patients were included in the study: 53 patients received NJ feeding tubes while prone and 157 while supine. All but one patient in the prone group had ARDS secondary to COVID-19, whereas 47 (30.3%) had COVID-19 in the supine group. The rate of successful placement was 94.3% in the prone group and 100% in the supine group. Mean number of attempts was 1.1 (SD, ±0.4) in the prone and 1.0 (SD, ±0.1) in the supine group (P = .14). Prone patients had a longer median fluoroscopy time (69 s, interquartile range [IQR] = 92; vs 48 s, IQR = 43; P < .001) and received a higher radiation dose during the procedure (47 mGy, IQR = 50; vs 25 mGy, IQR = 33; P = .004). No procedural complications were reported. CONCLUSION: Fluoroscopy-guided NJ feeding tube placement in prone patients is feasible and safe. Patient positioning should not delay obtaining postpyloric feeding access.

Recurrence and survival after curative-intent treatment for colorectal liver metastases: Implications for adjuvant liver-directed regional chemotherapy.

BACKGROUND: This study investigates tumor recurrence patterns and their effect on postrecurrence survival following curative-intent treatment of colorectal liver metastases (CRLM) to identify those who stand to benefit the most from adjuvant liver-directed therapy. METHODS: This is a retrospective analysis of all patients that underwent liver resection and/or ablation for CRLM between 2007 and 2019. Postrecurrence survival was compared between recurrence locations. Risk factors for liver recurrence were sought. RESULTS: The study included 227 patients. Majority were treated with resection (71.0%) while combination resection/ablation (18.9%) and ablation alone (11.0%), were less common. At a median follow-up of 3.0 years, recurrence was observed in 151 (66.5%) patients. Of those, liver, lung, and peritoneal recurrence were most common at 66.9%, 49.6%, and 9.2%, respectively. Median postrecurrence survival after liver, lung, and multisite recurrence was 39.6-, 68.4-, and 33.6 months, respectively. High tumor grade (p < 0.014), perineural invasion (p = 0.002), and N0 node status (p = 0.017) of primary tumor correlated with liver recurrence on multivariate analysis. CONCLUSIONS: Tumor grade, perineural invasion, and N0 node status of the primary tumor are associated with increased risk of liver recurrence after CRLM resection and represent a target population that may benefit the most from adjuvant liver-directed regional chemotherapy.

Recurrence patterns and postrecurrence survival after curative intent resection for pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma has a high rate of recurrence after resection. We aimed to investigate patterns of recurrence of pancreatic ductal adenocarcinoma to identify opportunities for targeted intervention toward improving survival. METHODS: This was a retrospective analysis of consecutive patients that underwent curative-intent resection for pancreatic ductal adenocarcinoma between 2007 and 2015. Recurrence and survival were analyzed based on site of recurrence. Multiple clinicopathologic factors were calculated for likelihood of site-specific recurrence. RESULTS: The study included 221 patients with median follow-up of 83 months. Median overall and recurrence-free survival was 19 and 13 months, respectively. Recurrence was observed in 71.9% patients. Local recurrence occurred in 16.4%, distant recurrence in 67.3%, and combined in 15.9%. The most common site of distant recurrence was the liver (49.7%) followed by lung (31.8%) and peritoneum (16.6%). Median time to liver recurrence was shortest (5 months, 95% confidence interval 1.7-8.3) and post recurrence survival was poor (4 months, 95% confidence interval 1.9-6.1). Patients with poorly differentiated tumors on pathology were 4.8 times more likely to recur in the liver (odds ratio 4.83, 95% confidence interval 1.7-13.9). CONCLUSION: Liver metastasis after resection of pancreatic ductal adenocarcinoma occurs most frequently, earliest after surgery, and is rapidly fatal. Liver-directed therapies represent a target for future study.

[Sigmoid volvulus at the University Hospital of Iceland 2000-2013].

Backround Sigmoid volvulus is an uncommon cause of bowel obstruction in most western societies. Treatment options include colonoscopy in uncomplicated disease with elective surgery later on. The aim of this study was to assess what treatment sigmoid volvulus patients receive along with long-term outcomes at Landspitali University Hospital. Methods The study was retrospective. Patients diagnosed with sigmoid volvulus at Landspitali University Hospital from 2000-2013 were included. Information regarding age, sex, and duration of hospital stay, treatment, short and long-term outcomes were gathered. Results Forty-nine patients were included in the study, of which 29 men and 20 women. Mean age was 74 (25-93). One patient underwent acute surgery on first arrival due to signs of peritonitis. Others (n=48) were treated conservatively in the first attempt with colonoscopy (n=45), barium enema (n=2) and rectal tube (n=1). Three other patients underwent acute surgery due to failed colonoscopy, 8 patients had planned surgery during the index admission. Thirty-six patients were discharged after conservative treatment with colonoscopy (n=35), barium enema (n=1) or rectal tube (n=1). Two patients came in for elec-tive surgery later on. Twenty-two patients (61%) had recurrence. Median time to recurrence was 101 days (1-803). Disease-free probability in 3, 6 and 24 months was 66%, 55% and 22% respec-tively. Total disease related mortality was 10.2%. Mortality (30 days) after acute surgery was 25% (1/4) and 16,6% (3/18) after planned surgery. Conclusions Sigmoid volvulus has high recurrence rate if not treated operatively. Total mortality due to sigmoid volvulus at Landspitali is low but surgery related mortality high.

[Outcome after surgical resection for rectal cancer and its precursors in Landspitali University Hospital 2008-2012].

BACKGROUND: Rectal cancer makes up 2-3% of all cancers in Iceland and surgery is the mainstay of its treatment. Information regarding those who undergo resection of the rectum because of rectal cancer or its precursors in Iceland today is lacking. The aim of this study was to evaluate what kind of surgical treatment rectal cancer patients receive at Landspitali University Hospital along with peri-operative and long-term outcomes. METHODS: The study was retrospective. All patients undergoing total or partial resection of the rectum for rectal cancer or its precursor from 2008-2012 in Landspitali University hospital were included. Information regarding age, sex, surgery, neoadjuvant and adjuvant treatment along with reoperations and survival were gathered. RESULTS: The total number of patients included were 144. Mean age was 66 years (33-89). Neoadjuvant treatment was used in 65 (45%) cases. Most of the patients (65%) underwent anterior resection of the rectum, 21% abdominoperineal resection, 11% Hartmann´s procedure and 3% other surgery. Majority of the patients had a cancer diagnoses (88%) but 12% had dysplastic adenomas. An anastomosis was made in 67% of cases, others (33%) got a permanent stoma. Reoperation rate within 30 days was 12%. Thirty day and 1 year mortality were 0.7% and 6.2% respectively. Average follow up time was 56 months (1-98). Local recurrence rate was 7,1%, five year survival rate was 77%. CONCLUSION: The surgical treatment for rectal cancer in Landspitali is up to international standard. Perioperative and long-term outcomes are similar to what other authors have reported.

[Gallstone disease during pregnancy at Landspitali University Hospital 1990-2010].

INTRODUCTION: Gallstone disease in pregnant patients and their management in Iceland has not been studied. Management of these patients changed after the introduction of laparoscopic cholecystectomy. The aim of this study was to investigate the incidence, symptoms, diagnostic methods and management of gallstone disease during pregnancy at the National University Hospital of Iceland during the years 1990-2010. MATERIAL AND METHODS: This was a retrospective study and included all pregnant women admitted with gallstone diseases to the National University Hospital of Iceland which is the only tertiary hospital in Iceland. Information regarding age, symptoms and diagnostic methods for all women with gallstone disease along with BMI, ASA scores, pathology results and pregnancy related outcomes for women who underwent cholecystectomy were gathered. RESULTS: During the twenty year time period 77 women were admitted with gallstone disease in 139 admissions which makes incidence 0,1% amongst pregnant women. Diagnoses incuded biliary colic (n=59), common bile duct stones (n=10), acute cholecystitis (n=7) and gallstone pancreatitis (n=1). The most common symptom was RUQ pain (n=63). Two preterm births were a direct consequence of gallstone disease. Fifteen women underwent cholecystectomy during pregnancy and 17 during the six week period after birth. Mean BMI was 31,1 and median ASA score was 1. Pathology reports showed chronic inflammation (n=24) and acute inflammation (n=5), one case included gallstones without inflammation Adverse outcomes of surgeries were two cases of gallstones left in the common bile duct. No stillbirths or preterm births resulted from cholecystectomies during pregnancy. CONCLUSION: Gallstone disease during pregnancy is rare and readmissions are frequent. Pregnancy related complications are rare. Laparoscopic cholecystectomy is safe during pregnancy. Key words: gallstones, pregnancy, laparoscopic cholecystectomy. Correspondence: Pall Helgi Moller pallm@landspitali.is.