Association of gravity drainage and complications following Whipple: an analysis of the ACS-NSQIP targeted database.

BACKGROUND: The optimal type of operative drainage following pancreaticoduodenectomy (PD) remains unclear. Our objective is to investigate risk associated with closed drainage techniques (passive [gravity] vs. suction) after PD. METHODS: We assessed operative drainage techniques utilized in patients undergoing PD in the ACS-NSQIP pancreas-targeted database from 2016 to 2018. Using multivariable logistic regression to adjust for characteristics of the patient, procedure, and pancreas, we examined the association between use of gravity drainage and postoperative outcomes. RESULTS: We identified 9665 patients with drains following PD from 2016 to 2018, of which 12.7% received gravity drainage. 61.0% had a diagnosis of adenocarcinoma or pancreatitis, 26.5% had a duct <3 mm, and 43.5% had a soft or intermediate gland. After multivariable adjustment, gravity drainage was associated with decreased rates of postoperative pancreatic fistula (odds ratio [OR] 0.779, 95% confidence interval [CI] 0.653-0.930, p=0.006), delayed gastric emptying (OR 0.830, 95% CI 0.693-0.988, p=0.036), superficial SSI (OR 0.741, 95% CI 0.572-0.959, p=0.023), organ space SSI (OR 0.791, 95% CI 0.658-0.951, p=0.012), and readmission (OR 0.807, 95% CI 0.679-0.958, p=0.014) following PD. CONCLUSIONS: Gravity drainage is independently associated with decreased rates of CR-POPF, DGE, SSI, and readmission following PD. Additional prospective research is necessary to better understand the preferred drainage technique following PD.

No Opioids after Septorhinoplasty: A Multimodal Analgesic Protocol.

From a public health perspective, nasal surgery accounts for many unused opioids. Patients undergoing septorhinoplasty require few opioids, and efforts to eliminate this need may benefit both patients and the public. METHODS: A multimodal analgesic protocol consisting of 15 components encompassing all phases of care was implemented for 42 patients. RESULTS: Median age and BMI were 34 years and 23, respectively. Most were women (79%), White (79%), primary surgeries (62%), and self-pay (52%). Comorbid conditions were present in 74% of the patients, with anxiety (33%) and depression (21%) being the most common. Septoplasties (67%) and osteotomies (45%) were common. The median operative time was 70 minutes. No patients required opioids in recovery, and median time in recovery was 63 minutes. Ten (24%) patients required an opioid prescription after discharge. In those patients, median time to requirement was 27 hours (range 3-81), and median total requirement was 20 mg morphine equivalents (range 7.5-85). Protocol compliance inversely correlated to opioid use (P = 0.007). Compliance with local and regional anesthetic (20% versus 63%, P = 0.030) as well as ketorolac (70% versus 100%, P = 0.011) was lower in patients who required opioids. Patients who required opioids were less likely to be administered a beta blocker (0% versus 34%, P = 0.041). Pain scores were higher in opioid users on postoperative days 1-5 (P < 0.05). No complications occurred in those requiring opioids, and satisfaction rates were equivalent between groups. CONCLUSION: This protocol allowed us to safely omit opioid prescriptions in 76% of patients following septorhinoplasty, without adverse effects on outcomes or patient satisfaction.

A Comparative Analysis of Survival and Funding Discrepancies in Cancers With High Mortality.

OBJECTIVE: Comparative analyses of survival and funding statistics in cancers with high mortality were performed to quantify discrepancies and identify areas for intervention. BACKGROUND: Discrepancies in research funding may contribute to stagnant survival rates in pancreatic ductal adenocarcinoma (PDAC). METHODS: The Surveillance, Epidemiology, and End Results database was queried for survival statistics. Funding data were obtained from the National Cancer Institute (NCI). Clinical trial data were obtained from www.clinicaltrials.gov. Cancers with high mortality were included for analyses. RESULTS: Since 1997, PDAC has received lesser funding ($1.41 billion) than other cancers such as breast ($10.52 billion), prostate ($4.93 billion), lung ($4.80 billion), and colorectal ($4.50 billion). Similarly, fewer clinical trials have been completed in PDAC (n = 608) compared with breast (n = 1904), lung (n = 1629), colorectal (n = 1080), and prostate (n = 1055) cancer. Despite this, since 1997, dollars invested in PDAC research produced a greater return on investment with regards to 5-year overall survival (5Y-OS) compared with breast, prostate, uterine, and ovarian cancer. Incremental cost-effectiveness analysis demonstrates that millions (liver, non-Hodgkin lymphoma, and melanoma) and billions (colorectal and lung) of dollars were required for each additional 1% increase in 5Y-OS compared with PDAC. Funding of research towards early diagnosis of PDAC has decreased by 19% since 2007. For nearly all cancers, treatment-related research receives the highest percentage of NCI funding. CONCLUSIONS: Funding of PDAC research is significantly less than other cancers, despite its higher mortality and greater potential to improve 5Y-OS. Increased awareness and lobbying are required to increase funding, promote research, and improve survival.

Perioperative Management and Factors Associated With Transfusion in Cranial Vault Reconstruction.

BACKGROUND: Bleeding is the most common adverse event in patients undergoing cranial vault reconstruction. The authors compare the transfusion rates against a national sample to determine whether the patients experience lower transfusion rates. METHODS: The authors queried the Pediatric National Surgical Quality Improvement Program (Peds-NSQIP) for patients who underwent cranial vault reconstruction (CPT 61559) and compared them to patients who underwent cranial vault reconstruction for sagittal craniosynostosis at Children's Hospital and Medical Center (CHMC) in Omaha, Nebraska. Patients over the age of 24 months were excluded. Binary logistic regression analysis was performed using IBM-SPSS v24.0 to determine factors associated with transfusion at CHMC. RESULTS: Patient demographics, preoperative hematocrit and platelet counts, readmission rates, and reoperation rates did not differ between CHMC (N = 54) and Peds-NSQIP (N = 1320) cohorts. Patients in the CHMC cohort had shorter preincision anesthesia times (47 versus 80 minutes, P < 0.001), shorter operative times (108 versus 175 minutes, P < 0.001), lower transfusion rates (50% versus 73%, P < 0.001), and smaller mean transfusion volumes (16 versus 33 mL/kg, P < 0.001); however mean length of stay was longer (4.1 versus 3.6 days, P < 0.001). Factors independently associated with transfusion at CHMC included preoperative hematocrit (odds ratio [OR] 0.423, P = 0.002), administration of an antifibrinolytic agent (OR 0.004, P = 0.001) and temperature at the time of incision (OR 0.020, P = 0.043). CONCLUSION: Patients at CHMC require less transfused blood and experience low transfusion rates. Preoperative hematocrit, administration of antifibrinolytic agents, and temperature at the time of incision are all modifiable factors associated with perioperative transfusion.

Risk factors for anastomotic leak after esophagectomy for cancer: A NSQIP procedure-targeted analysis.

BACKGROUND: Anastomotic leak is the most common major complication after esophagectomy. We investigated the 2016 American College of Surgeons National Surgical Quality Improvement Program esophagectomy targeted database to identify risk factors for anastomotic leak. METHODS: Patients who underwent esophagectomy for cancer were included. Patients experiencing an anstomotic leak were identified, and univariate and multivariable logistic regression was performed to identify variables independently associated with anastomotic leak. RESULTS: Of 915 patients included, 83% were male and the median age was 64 years. Patients with anastomotic leak more frequently had additional complications (87% vs 36%, P < .001). Rates of reoperation (64% vs 11%, P < .001) and mortality (8% vs 2%, P = .001) were higher in patients with anastomotic leak. After adjusting for patient and procedure characteristics, prolonged operative time (for each additional 30-minutes; adjusted odds ratios (AOR) 1.068, 95% CI, 1.022-1.115, P = .003), increased preoperative WBC count (for each 3000/µL increase; AOR 1.323, 95% CI, 1.048-1.670, P = .019), pre-existing diabetes (AOR 1.601, 95% CI, 1.012-2.534, P = .045), and perioperative transfusion (AOR 1.777, 95% CI, 1.064-2.965, P = .028) were independently associated with anastomotic leak. CONCLUSION: Both patient and procedure-related factors are associated with anastomotic leak. Though frequently non-modifiable, these findings could facilitate risk stratification and early detection of anastomotic leak to reduce associated morbidity.

Factors Predictive of Reoperation After Pancreaticoduodenectomy for Pancreatic Cancer.

While mortality is low, morbidity remains high for patients undergoing pancreas resections, especially for those who return to the operating room (RTOR). The aim of this study is to identify risk factors for RTOR following pancreaticoduodenectomy (PD) for ductal adenocarcinoma. Logistic regression models were constructed using the 2014 and 2015 National Surgical Quality Improvement Program (NSQIP) Pancreas Targeted database. Preoperative and procedure-related risk factors predictive of RTOR for patients undergoing either classic or pylorus-preserving pancreaticoduodenectomy for pancreatic ductal adenocarcinoma (PDAC) were identified. A total of 1736 patients were included. Multivariable analysis of patients undergoing classic PD demonstrated that an abnormally low preoperative WBC count was significantly associated with RTOR (OR 2.78, 95% CI 1.27-6.06, p = 0.010). For patients who underwent pylorus-preserving PD, the wound classification (OR 3.99, 95% CI 1.75-9.11, p = 0.001) and arterial resection (OR 26.3, 95% CI 7.96-87.20, p < 0.001) were associated with a higher rate of RTOR. When analyzing both approaches (classic and pylorus-preserving PD) together, only isolated arterial (OR 9.98, 95% CI 3.81-26.18, p < 0.001) and isolated venous (OR 1.79, 95% CI 1.05-3.05, p = 0.032) resections were independently associated with RTOR. The results of our study demonstrate that few factors are predictive of RTOR. Knowledge of these few variables in combination with a focus on the components of medical care in the immediate postoperative period may help identify individuals at risk for RTOR and improve patient care.

Utilizing cell line-derived organoids to evaluate the efficacy of a novel LIFR-inhibitor, EC359 in targeting pancreatic tumor stroma.

Survival of pancreatic cancer (PC) patient is poor due to lack of effective treatment modalities, which is partly due to the presence of dense desmoplasia that impedes the delivery of chemotherapeutics. Therefore, PC stroma-targeting therapies are expected to improve the efficacy of chemotherapeutics. However, in vitro evaluation of stromal-targeted therapies requires a culture system which includes components of both tumor stroma and parenchyma. We aim to generate a cell line-derived 3D organoids to test the efficacy of stromal-targeted, LIFR-inhibitor EC359. Murine PC (FC1245) and stellate (ImPaSC) cells were cultured to generate organoids that recapitulated the histological organization of PC with the formation of ducts by epithelial cells surrounded by activated fibroblasts, as indicated by CK19 and α-SMA staining, respectively. Analysis by qRT-PCR demonstrated a significant downregulation of markers of activated stroma, POSTN, FN1, MMP9, and SPARC (p<0.0001), when treated with gemcitabine in combination with EC359. Concurrently, collagen proteins including COL1A1, COL1A2, COL3A1, and COL5A1 were significantly downregulated (p <0.0001) after treatment with gemcitabine in combination with EC359. Overall, our study demonstrates the utility of cell lines-derived 3D organoids to evaluate the efficacy of stroma-targeted therapies as well as the potential of EC359 to target activated stroma in PC.

Prolonged non-operative management of clostridium difficile colitis is associated with increased mortality, complications, and cost.

BACKGROUND: We aim to investigate the effects of delaying surgery on outcomes and cost in patients admitted with severe clostridium difficile infection (CDI). METHODS: The Vizient database was queried for patients with CDI who underwent open total abdominal colectomy (TAC). Patients operated on the day of admission were excluded. Chi-square, Fisher's exact, student T-test, and logistic regression were performed with α = 0.05. RESULTS: Logistic regression analyses using days from admission to surgery (DATO), age, race, and gender demonstrated that increased DATO was associated with higher 30-day mortality (OR 1.022, 95% CI 1.001-1.044, p = 0.040), overall complications (OR 1.034, 95% CI 1.014-1.054, p = 0.001), and infectious complications (OR 1.040, 95% CI 1.018-1.062, p < 0.001) compared to age for all three outcomes. Total length of stay (LOS), intensive care unit LOS, and direct cost increased in conjunction with DATO (p < 0.001). CONCLUSIONS: Early surgical intervention in appropriately selected patients should be considered when there is a high suspicion for prolonged non-operative treatment.

Cancer-associated mucins: role in immune modulation and metastasis.

Mucins (MUC) protect epithelial barriers from environmental insult to maintain homeostasis. However, their aberrant overexpression and glycosylation in various malignancies facilitate oncogenic events from inception to metastasis. Mucin-associated sialyl-Tn (sTn) antigens bind to various receptors present on the dendritic cells (DCs), macrophages, and natural killer (NK) cells, resulting in overall immunosuppression by either receptor masking or inhibition of cytolytic activity. MUC1-mediated interaction of tumor cells with innate immune cells hampers cross-presentation of processed antigens on MHC class I molecules. MUC1 and MUC16 bind siglecs and mask Toll-like receptors (TLRs), respectively, on DCs promoting an immature DC phenotype that in turn reduces T cell effector functions. Mucins, such as MUC1, MUC2, MUC4, and MUC16, interact with or form aggregates with neutrophils, macrophages, and platelets, conferring protection to cancer cells during hematological dissemination and facilitate their spread and colonization to the metastatic sites. On the contrary, poor glycosylation of MUC1 and MUC4 at the tandem repeat region (TR) generates cancer-specific immunodominant epitopes. The presence of MUC16 neo-antigen-specific T cell clones and anti-MUC1 antibodies in cancer patients suggests that mucins can serve as potential targets for developing cancer therapeutics. The present review summarizes the molecular events involved in mucin-mediated immunomodulation, and metastasis, as well as the utility of mucins as targets for cancer immunotherapy and radioimmunotherapy.

No survival advantage exists for patients undergoing loop ileostomy for clostridium difficile colitis.

BACKGROUND: We aim to compare outcomes between loop ileostomy (LI) and total abdominal colectomy (TAC) for clostridium difficile infection (CDI) and hypothesize that LI is associated with fewer complications. METHODS: The 2011-2016 ACS-NSQIP database was queried for patients undergoing LI or TAC for CDI. Patients with high outlying age, LOS, and operative time were excluded. Statistics were performed using IBM-SPSS and NCSS PASS-11. RESULTS: Of 457 patients identified, 47 underwent LI. Predicted morbidity was higher in the TAC cohort (62% vs. 37%, p < 0.001). Patients in the LI cohort experienced fewer complications (72% vs. 87%, p = 0.021); however, mortality did not differ between LI (36%) and TAC (31%). Blood transfusions were more than twice as frequent in the TAC cohort (54% vs. 19%, p < 0.001). Four patients in the LI cohort required reoperation; however, none required colectomy. CONCLUSIONS: No mortality difference was observed between LI and TAC. Prospective studies are required to determine the utility of LI. SUMMARY: An analysis of the ACS-NSQIP database was performed and demonstrates that no survival benefit exists for patients who undergo loop ileostomy for C difficile infection compared to those who undergo total colectomy; however, patients who undergo loop ileostomy are likely to retain their colon with low risk of requiring subsequent colectomy.

Desmoplasia in pancreatic ductal adenocarcinoma: insight into pathological function and therapeutic potential.

Extensive desmoplasia is a prominent feature of the pancreatic ductal adenocarcinoma (PDAC) microenvironment. Initially, studies demonstrated that desmoplasia promotes proliferation, invasion and chemoresistance in PDAC cells. While these findings suggested the therapeutic potential of targeting desmoplasia in PDAC, more recent studies utilizing genetically-engineered mouse models of PDAC, which lack key components of desmoplasia, demonstrated accelerated progression of PDAC. This contrast calls into question the paradigm that desmoplasia unilaterally promotes PDAC progression and the premise of desmoplasia-targeted therapy. This review briefly examines the major reports of the tumor-promoting and -restraining roles of desmoplasia in PDAC with commentary on the gaps in our current understanding of desmoplasia in PDAC. Additionally, we discuss the studies demonstrating the heterogeneous and multifaceted nature of desmoplasia in PDAC and advocate for future areas of research to thoroughly address the various facets of desmoplasia in PDAC, reconcile seemingly contradictory reports of the role of desmoplasia in PDAC progression, and discover aspects of desmoplasia that are therapeutically actionable.

Advanced pancreatic cancer: a meta-analysis of clinical trials over thirty years.

BACKGROUND: In contrast to other cancers, survival rates for pancreatic ductal adenocarcinoma (PDAC) patients have improved but minimally over the past thirty years. The aim of this study was to perform a meta-analysis of clinical trials published since 1986 to determine trends in median overall survival in primarily metastatic PDAC. MATERIALS AND METHODS: All Phase 2-4 clinical trials published during or after 1986 investigating first-line systemic chemotherapy in metastatic PDAC were included in the meta-analysis. Publications obtained through PubMed and www.ClinicalTrials.gov were cross-referenced to identify additional trials. Trials enrolling fewer than 50% of study participants with metastatic disease were excluded. RESULTS: Of 19,488 patients enrolled in 151 clinical trials, 84% had metastatic disease and 16% had locally advanced pancreatic cancer. In clinical trials published from 1986 to 2016, the weighted median overall survival (wMOS) increased by 3.0 months. The median wMOS was higher in combination therapy (7.31 months, IQR 5.4 to 8.5) compared to non-gemcitabine, single-agent therapy (4.76 months, IQR 3.5 to 6.0), gemcitabine monotherapy (6.48 months, IQR 5.9 to 7.2), and gemcitabine plus single-agent therapy (7.09 months, IQR 6.3 to 8.2). Of all regimens used in more than one study arm, FOLFIRINOX had the highest wMOS (10.9 months). CONCLUSIONS: Regardless of treatment regimen, survival rates in PDAC have minimally improved over time. Of drugs used in two or more study arms, only FOLFIRINOX has a wMOS greater than ten months. Emphasis should, therefore, be placed on identification of novel targets that promote early diagnosis and intervention. FUNDING: The authors on this manuscript are in parts, supported by grants from the National Institutes of Health (EDRN U01 CA200466, SPORE P50 CA127297, R01 CA183459, R21 AA026428 and R01 CA 195586).

Acute symptomatic hyponatremia following elective rhinoplasty: A case report.

We present the first reported case of symptomatic hyponatremia after elective rhinoplasty. A 42-year old female underwent cosmetic rhinoplasty without complication and was discharged home after an uneventful recovery from general anesthesia. Just prior to midnight on the day of surgery, she reported nausea, which was treated with supportive care. Four hours later, she developed emesis, altered mental status, and seizure-like activity prompting medical transport to the emergency department. Upon arrival, she was hypotensive (BP 78/54), tachycardic (HR 112 bpm), hyponatremic (116 mmol/L), hypoosmotic (239 mOsm/kg), and had decreased consciousness (GCS = 10). She was admitted to the intensive care unit and had a central line placed for hypertonic saline infusion. Urinalysis was suggestive of SIADH (UrNa 111 mmol/L, UrOsm 546 mOsm/kg) and Nephrology was consulted. Her serum sodium was corrected over three days and her mental status improved. Surgeons should maintain a low threshold for further evaluation in patients who deviate from the expected postoperative recovery pathway. This report demonstrates that normal postoperative symptoms may mask underlying physiological abnormalities that can progress to acute life-threatening illness and underscores the importance of direct patient observation in the immediate postoperative period.

Salmonella infection of breast implant associated with traveler's diarrhea: A case report.

We present the first case of traveler's diarrhea resulting in breast implant infection. An otherwise healthy 34-year-old female underwent breast augmentation. Five months later, while vacationing in Cancun, Mexico, she developed abdominal pain and diarrhea that progressed to include fevers and chills. Her symptoms persisted until she returned to the United States, at which point her primary care physician evaluated her on the fourth day of her illness. An abdominal CT scan was unremarkable; however, a complete metabolic panel demonstrated elevated transaminases. Her symptoms soon resolved without treatment. Fourteen days after symptom resolution, the patient developed right breast pain. She was evaluated in the surgical clinic where the breast was tender to palpation, swollen and without erythema. An ultrasound demonstrated a small amount of homogenous fluid surrounding the implant. She was prescribed amoxicillin-clavulanate 875-125 mg BID; however, she presented three days later with worsening pain, swelling and new erythema. She was taken to the operating room, where the abscess was incised, drained and the implant removed. Cultures grew Salmonella serogroup C. Patients should be counseled regarding the potential for hematogenous seeding of the breast cavity and implant following severe illness and bacteremia. It may be reasonable to provide patients with breast implants who are traveling to areas at high-risk for traveler's diarrhea or areas with limited medical resources with an antibiotic to take if moderate to severe symptoms of traveler's diarrhea were to develop while away.

Emergent cholecystectomy is superior to percutaneous cholecystostomy tube placement in critically ill patients with emergent calculous cholecystitis.

BACKGROUND: The role of percutaneous cholecystostomy (PC) is undefined in patients with multiple comorbidities presenting with emergent calculous cholecystitis (CC). This study compared outcomes between PC, laparoscopic (LC), and open cholecystectomy (OC). METHODS: The Vizient UHC database was queried for high-risk patients with CC who underwent PC, LC, OC, or laparoscopic converted to open cholecystectomy (CONV). Demographics, outcomes, mortality, length of stay (LOS), and direct cost were compared between the groups. RESULTS: LC was the most common approach with the lowest risk of death, complications, LOS, and cost. Complication risk was highest in OC. Nearly 20% of patients underwent PC. Complication rate, LOS, infection, aspiration pneumonia, and mortality were higher in PC. Direct cost was lowest in LC, followed by CONV, PC, and OC. CONCLUSIONS: Emergent cholecystectomy for CC in high-risk patients is safer and more cost effective than PC and this study supports the use of cholecystectomy as the primary treatment approach in these patients.