Perioperative Broad-spectrum Antibiotics are Associated With Decreased Surgical Site Infections Compared to 1st-3rd Generation Cephalosporins After Open Pancreaticoduodenectomy in Patients With Jaundice or a Biliary Stent.

OBJECTIVE: Compare the effectiveness of 1st-3rd generation cephalosporins (1st-3rdCE) to broad-spectrum antibiotics in decreasing surgical site infections (SSI) after pancreatectomy. SUMMARY OF BACKGROUND DATA: SSI is one of the most common complications after pancreatic surgery. Various antibiotic regimens are utilized nationwide with no clear guidelines for pancreatectomy. As we await results of a recently initiated prospective trial, this study retrospectively evaluates over 15,000 patients using the same administrative data abstraction tools as in the trial. METHODS: All relevant clinical variables were collected from the 2016-2018 targeted-pancreatectomy database from the American College of Surgeon National Surgical Quality Improvement Program. Preoperative antibiotics were initially collected as first-generation cephalosporin, second or third-generation cephalosporin, and broad-spectrum antibiotics (Broad-abx). RESULTS: Of the 15,182 patients who completed a pancreatic surgery between 2016 and 2018, 6114 (40%) received a first-generation cephalosporin, 4097 (27%) received a second or third-generation cephalosporin, and 4971 (33%) received Broad-abx. On multivariate analysis, Broad-abx was associated with a decrease in all-type SSI compared to 1st-3rdCE (odds ratio = 0.73-0.77, P < 0.001) after open pancreaticoduodenectomy (PD). There was no difference in SSI between antibiotic-types after distal pancreatectomy. Subgroup multivariate analysis of open PD revealed decrease in all-type SSI with Broad-abx amongst patients with jaundice and/or biliary stent only, regardless of wound protector use (odds ratio = 0.69-0.70, P < 0.001). Propensity score matching of open PD patients with jaundice and/or biliary stent confirmed a decrease in all-type SSI (19% vs 24%, P = 0.001), and organ-space SSI (12% vs 16%, P < 0.001). CONCLUSION: Broad-abx are associated with decreased SSI after open PD and may be preferred specifically for patients with preoperative biliary stent and/ or jaundice.

Surgeon-Placed Continuous Wound Infusion Pain Catheters Markedly Decrease Narcotic Use and Improve Outcomes After Pancreatic Tumor Resection.

BACKGROUND: Pancreatectomy results in significant postoperative pain and typically requires opioid analgesia for adequate pain control. Local anesthetics may decrease postoperative pain and opioid requirements but can be limited by onset of action, duration of effect, and inability to titrate dosing after administration. This can be overcome by surgeon placement of tunneled peri-incisional catheters with continuous wound infusion (CWI). METHODS: This retrospective cohort study analyzed patients undergoing open pancreatic tumor resection. All the patients received patient-controlled analgesia (PCA), enabling an objective comparison of opioid requirements, and underwent the same recovery pathway. The patients received CWI (n = 45), PCA alone (n = 11), or epidural analgesia (EA) (n = 9). The primary outcome was total opioid use in terms of intravenous morphine milligram equivalents (MMEs) and patient-reported pain scores on a numeric rating scale (NRS) of 0 to 10. RESULTS: No differences in baseline patient or tumor characteristics were observed. In both the uni- and multivariate analyses, CWI was associated with lower opioid use than PCA (MME, 83 vs 207 mg; p = 0.004) or EA (MME, 83 vs 156 mg; p < 0.001) without having a negative impact on pain scores. Furthermore, CWI was associated with a greater percentage of time that patients experienced optimal pain control (NRS, ≤ 4: 63% vs 50%; p = 0.033) and a shorter time to PCA independence (4.0 vs 4.9 days; p = 0.004) than PCA alone. In addition, CWI was associated with earlier ambulation [EA vs CWI: odds ratio (OR), 0.05; p = 0.021], improved spirometry performance (CWI vs PCA: regression coefficient (coef), 267; p = 0.013), and earlier urinary catheter removal (EA vs CWI: coef, 1.30; p = 0.013). The findings showed no differences in time to return of bowel function, antiemetic use, or hospital length of stay. CONCLUSIONS: After open pancreatic tumor resection, CWI is safe and associated with decreased opioid requirements and improved functional outcomes without a negative impact on pain scores, supporting its potential for preferred use over PCA or EA alone.

A propensity score analysis of over 12,000 pancreaticojejunal anastomoses after pancreaticoduodenectomy: does technique impact the clinically relevant fistula rate?

BACKGROUND: Clinically relevant postoperative pancreatic fistula (CR-POPF) remains a major cause of morbidity in patients undergoing pancreatic surgery. Controversy exists as to whether there is any difference in CR-POPF with a Duct-to-Mucosa (DTM) versus an Invagination (IG) pancreaticojejunostomy (PJ). METHODS: Demographic, perioperative, intraoperative, and postoperative data were captured from the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) 2014-2017 databases. Potential confounders were included in a logistic regression and a propensity score model. The primary outcome was CR-POPF. RESULTS: A total of 12,361 pancreaticojejunal anastomoses were performed with 11,168 patients undergoing DTM (90%) and 1193 undergoing IG (10%) after pancreaticoduodenectomy. Amongst all patients, there was no significant difference in CR-POPF between DTM and IG on multivariate (OR = 0.95, p = 0.64) or propensity score analysis (OR = 0.99, p = 0.93). After stratification by pancreatic gland texture and duct size, there was a decrease in CR-POPF with DTM amongst patients with duct size greater than 6 mm on multivariate analysis (OR = 0.35, p = 0.009) and propensity score analysis (OR = 0.40, p = 0.018). There were no significant differences in any other strata. CONCLUSION: DTM or IG technique are not associated with CR-POPF for patients with average size pancreatic ducts; however, DTM is preferable in patients with large pancreatic duct diameter (>6 mm).

The impact of surgical resection on headache disability and quality of life in patients with colloid cyst.

Introduction Colloid cysts are histologically benign but can present with a broad spectrum of symptoms. A systematic review of the literature did not reveal any patient-centered data on the headache disability and quality of life (QoL) of these patients. Methods This is a retrospective cohort study of 187 colloid cyst patients from the Colloid Cyst Survival Group who completed a survey that included demographic data, clinical data, a modified QoL survey (SF36v2), and a headache disability inventory or index (HDI). Results Using multivariable linear regressions, we confirmed that the physical (PCS) and mental (MCS) components of SF-36 were significantly increased in the surgery group after adjustment for various baseline characteristics ( p = 0.025; p = 0.006). Self-reported headache disability was significantly decreased with surgery when adjusted for the same baseline characteristics ( p = 0.02). Finally, patients with an incidental diagnosis of colloid cyst reported similar benefits from surgery in PCS, MCS and HDI. Conclusion Our results suggest that colloid cyst patients who underwent a surgical resection self-report a better QoL and less headache disability compared with patients who did not undergo surgery. Future prospective studies with baseline measures of QoL are indicated to confirm our findings.

Regulation of brain tumor dispersal by NKCC1 through a novel role in focal adhesion regulation.

Glioblastoma (GB) is a highly invasive and lethal brain tumor due to its universal recurrence. Although it has been suggested that the electroneutral Na(+)-K(+)-Cl(-) cotransporter 1 (NKCC1) can play a role in glioma cell migration, the precise mechanism by which this ion transporter contributes to GB aggressiveness remains poorly understood. Here, we focused on the role of NKCC1 in the invasion of human primary glioma cells in vitro and in vivo. NKCC1 expression levels were significantly higher in GB and anaplastic astrocytoma tissues than in grade II glioma and normal cortex. Pharmacological inhibition and shRNA-mediated knockdown of NKCC1 expression led to decreased cell migration and invasion in vitro and in vivo. Surprisingly, knockdown of NKCC1 in glioma cells resulted in the formation of significantly larger focal adhesions and cell traction forces that were approximately 40% lower than control cells. Epidermal growth factor (EGF), which promotes migration of glioma cells, increased the phosphorylation of NKCC1 through a PI3K-dependant mechanism. This finding is potentially related to WNK kinases. Taken together, our findings suggest that NKCC1 modulates migration of glioma cells by two distinct mechanisms: (1) through the regulation of focal adhesion dynamics and cell contractility and (2) through regulation of cell volume through ion transport. Due to the ubiquitous expression of NKCC1 in mammalian tissues, its regulation by WNK kinases may serve as new therapeutic targets for GB aggressiveness and can be exploited by other highly invasive neoplasms.

Drain Placement After Pancreatic Resection: Friend or Foe For Surgical Site Infections?

BACKGROUND: Despite multiple studies and randomized trials, there remains controversy over whether drains should be placed, and if so for how long, after pancreas resection. The aim was to determine if post-pancreatectomy drain placement and timing of drain removal were associated with differences in infectious outcomes and, if so, which specific procedures and infectious sites were most at risk. METHODS: The ACS-NSQIP targeted pancreatectomy database was utilized to identify patients who underwent pancreatectomies between 2015 and 2020 with postoperative drain placement for retrospective cohort analysis. A propensity score matching analyses was conducted to determine associations between drain placement and surgical site infections (SSI). RESULTS: Of 39,057 pancreatic resections, 66.4% were proximal pancreatectomies, and 33.6% were distal pancreatectomies. After propensity score matching, drain placement was not associated with significantly lower rates of superficial SSI (7% vs 9%, p = 0.755) or organ/space SSI (17% vs 16%, p = 0.647) after proximal pancreatectomy. After distal pancreatectomy, drain placement was associated with higher rates of organ/space SSI (12% vs 9%, p = 0.010). Drain removal on or after postoperative day 3 was significantly associated with higher rates of SSI in both proximal and distal pancreatectomy. CONCLUSIONS: Drain placement is associated with an increased rate of organ/space SSI after distal pancreatectomy and not after pancreaticoduodenectomy. When drains are utilized, early removal is associated with a reduction of SSI after all types of pancreatectomy. In surgical units where post-pancreatectomy SSI is a concern, selective drain placement for high-risk glands or after distal pancreatectomy, combined with early drain removal, may be considered.

Non-Canonical Activin A Signaling Stimulates Context-Dependent and Cellular-Specific Outcomes in CRC to Promote Tumor Cell Migration and Immune Tolerance.

We have shown that activin A (activin), a TGF-ß superfamily member, has pro-metastatic effects in colorectal cancer (CRC). In lung cancer, activin activates pro-metastatic pathways to enhance tumor cell survival and migration while augmenting CD4+ to CD8+ communications to promote cytotoxicity. Here, we hypothesized that activin exerts cell-specific effects in the tumor microenvironment (TME) of CRC to promote anti-tumoral activity of immune cells and the pro-metastatic behavior of tumor cells in a cell-specific and context-dependent manner. We generated an Smad4 epithelial cell specific knockout (Smad4-/-) which was crossed with TS4-Cre mice to identify SMAD-specific changes in CRC. We also performed IHC and digital spatial profiling (DSP) of tissue microarrays (TMAs) obtained from 1055 stage II and III CRC patients in the QUASAR 2 clinical trial. We transfected the CRC cells to reduce their activin production and injected them into mice with intermittent tumor measurements to determine how cancer-derived activin alters tumor growth in vivo. In vivo, Smad4-/- mice displayed elevated colonic activin and pAKT expression and increased mortality. IHC analysis of the TMA samples revealed increased activin was required for TGF-ß-associated improved outcomes in CRC. DSP analysis identified that activin co-localization in the stroma was coupled with increases in T-cell exhaustion markers, activation markers of antigen presenting cells (APCs), and effectors of the PI3K/AKT pathway. Activin-stimulated PI3K-dependent CRC transwell migration, and the in vivo loss of activin lead to smaller CRC tumors. Taken together, activin is a targetable, highly context-dependent molecule with effects on CRC growth, migration, and TME immune plasticity.

Robotic Surgery for Biliary Tract Cancer.

Biliary tract cancer consists of cholangiocarcinoma (CC) and gallbladder cancer (GBC). When resectable, surgery provides the best chance at long-term survival. Unfortunately, surgery for these tumors is associated with long operative times, high morbidities, and prolonged hospital stays. Minimally invasive surgery has been shown to impact selected outcomes, including length of stay, in other diseases, and robotic surgery may offer additional advantages compared to laparoscopic surgery in treating bile duct cancers. This is a systematic review of robotic surgery for biliary tract cancer. Predetermined selection criteria were used to appraise the literature. The PRISMA guidelines were followed. In total, 20 unique articles with a total of 259 patients with biliary tract cancer undergoing robotic surgery met the inclusion criteria. For CC and GBC, respectively, the weighted average operative time was 401 and 277 min, the estimated blood loss was 348 and 260 mL, the conversion rate to open was 7 and 3.5%, the all-cause morbidity was 52 and 9.7%, the major morbidity was 12 and 4.4%, the perioperative mortality was 1.4 and 0%, the length of stay was 15 and 4.8 days, the positive margin rate was 27 and 9%, and the number of lymph nodes retrieved was 4.2 and 8. Robotic surgery for biliary tract cancer appears non-inferior to open surgery when compared to the published contemporary data. However, the current literature on the topic is of low quality, and future prospective/randomized studies are needed.

LIGHT enhanced bispecific antibody armed T-cells to treat immunotherapy resistant colon cancer.

Increased tumor infiltrating lymphocytes (TIL) are associated with improved patient responses to immunotherapy. As a result, there is interest in enhancing lymphocyte trafficking particularly to colon cancers since the majority are checkpoint blockade-resistant and microsatellite stable. Here, we demonstrate that activated T-cells (ATC) armed with anti-CD3 x anti-EGFR bispecific antibody increases TIL and mediate anti-tumor cytotoxicity while decreasing tumor cell viability. Furthermore, treatment induces endogenous anti-tumor immunity that resisted tumor rechallenge and increased memory T-cell subsets in the tumor. When combined with targeted tumor expression of the tumor necrosis factor superfamily member LIGHT, activated T-cell proliferation and infiltration were further enhanced, and human colorectal tumor regressions were observed. Our data indicate that tumor-targeted armed bispecific antibody increases TIL trafficking and is a potentially potent strategy that can be paired with combination immunotherapy to battle microsatellite stable colon cancer. SIGNIFICANCE: Enhancing trafficking of tumor infiltrating lymphocytes (TILs) to solid tumors has been shown to improve outcomes. Unfortunately, few strategies have been successful in the clinical setting for solid tumors, particularly for "cold" microsatellite stable colon cancers. In order to address this gap in knowledge, this study combined TNFSF14/LIGHT immunomodulation with a bispecific antibody armed with activated T-cells targeted to the tumor. This unique T-cell trafficking strategy successfully generated anti-tumor immunity in a microsatellite stable colon cancer model, stimulated T-cell infiltration, and holds promise as a combination immunotherapy for treating advanced and metastatic colorectal cancer.

Epidural Analgesia Is Associated with Prolonged Length of Stay After Open HPB Surgery in Over 27,000 Patients.

BACKGROUND: The impact of epidural analgesia (EA) on postoperative morbidity and length of stay (LOS) after HPB surgery remains to be determined. These specific outcomes have been highlighted by the implementation of multiple enhanced recovery pathways (ERAS). The authors hypothesized that EA in the current environment may be associated with LOS and other outcomes. METHODS: The American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) databases from 2014 to 2017 for patients undergoing open hepatopancreaticobiliary (HPB) surgery were included in a retrospective cohort analysis with propensity score matching (PSM) comparing EA with control. RESULTS: Twenty-seven thousand two hundred eighteen patients underwent open HPB surgery, of which 6048 (22%) received EA. There was an increase use of EA over time (from 19.3 to 25.5%, p = 0.001). On PSM, EA was associated with more than half of a day increase in LOS for both pancreatic (p < 0.001) and hepatic surgery (p < 0.001). Furthermore, for pancreatic surgery, there was an increase in urinary tract infection (2.5% vs. 3.3%, p = 0.018), time to drain removal (7.8 vs. 8.7 days, p < 0.001), and discharge to rehabilitation (2.9% vs. 4.3%, p = 0.029). For hepatic surgery, there was an increase in blood transfusion requirements (17% vs. 20%, p = 0.019). There were no differences in overall morbidity and mortality. CONCLUSION: In this cohort of over 27,000 patients with granular surgical details, there was a significant increase in LOS associated with EA after HPB surgery, along with increased procedure-specific UTI and blood transfusion. With the ever-increasing need for standardized and efficient patient care pathways that reduce LOS, alternative analgesic adjuncts may be considered to optimize patient outcomes.

Should Drains Suck? A Propensity Score Analysis of Closed-Suction Versus Closed-Gravity Drainage After Pancreatectomy.

BACKGROUND: Post-operative pancreatic fistula (POPF) remains one of the most common complications after pancreatic surgery. We previously reported that the majority of US surgeons leave drains after pancreatectomy. However, there remains controversy and surgeon bias on the use of gravity compared with suction drainage with limited data on patient outcomes to guide management. METHODS: Demographics, comorbidities, perioperative, and outcome data were captured from the most recent ACS National Surgical Quality Improvement Program (NSQIP)-targeted pancreatectomy databases. This is a retrospective cohort analysis comparing closed-suction to closed-gravity drains with multivariate analysis and propensity score matching (PSM). RESULTS: Of 9232 patients that underwent a pancreatectomy with closed drain placement, 1345 (15%) were to gravity and 7887 (85%) were to suction. On multivariate and PSM, stratified by surgery-type, there was no difference in biochemical leak (Whipple, 4 vs. 4%; distal, 8 vs. 6%) or clinically relevant (CR)-POPF (Whipple, 13 vs. 15%; distal, 12 vs. 15%). On multivariate analysis, there was an increase in organ-space surgical site infections with suction drains for patients undergoing Whipple procedure (12 vs. 16%, p = 0.004), which did not persist on PSM (p = 0.088). Finally, there were no significant differences in amylase level, time to drain removal, or superficial surgical site infections for patients undergoing either procedure based on drain type. CONCLUSION: The majority of drains utilized after pancreatectomy in the USA are placed to suction, though a significant proportion are kept to gravity. Neither type of drain is associated with increased CR-POPF or other post-operative outcomes compared with the other; therefore, both types remain reasonable options if drains are to be placed.

Preoperative Radiotherapy Is Not Associated with Increased Post-mastectomy Short-term Morbidity: Analysis of 77,902 Patients.

BACKGROUND: Neoadjuvant radiotherapy (NRT) enhances breast-conserving surgery outcomes, reducing local recurrence of breast cancer and increasing median survival. However, its effect on postoperative morbidity remains under-studied. We sought to assess the impact of NRT on 30-day postoperative morbidity after mastectomy. METHODS: We analyzed data from women undergoing mastectomy (with or without immediate reconstruction) using the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) 2005-2011 datasets. ACS-NSQIP is a prospective, risk-adjusted, outcomes-based registry. Data included demographic and perioperative factors. Outcomes studied included surgical site (wound and prosthesis/flap complications), systemic (cardiac, respiratory, neurological, urinary, and venous thromboembolism events), and overall morbidity. Logistic regression was used to estimate the unadjusted odds ratio (uOR) and adjusted odds ratio (aOR) between NRT and postoperative 30-day morbidity. RESULTS: The study population included 77,902 women, of which 61,039 (78.4%) underwent mastectomy only and 16,863 (21.6%) underwent mastectomy with immediate breast reconstruction. NRT was administered to 266 (0.4%) mastectomy-only and 75 (0.4%) immediate breast reconstruction patients. In the mastectomy-only group, there were no significant differences in the rates of postoperative surgical site morbidity (aOR = 1.41; 95% confidence interval (CI): 0.76-2.63; P = 0.276), systemic morbidity (aOR = 0.72; 95% CI: 0.40-1.26; P = 0.252), and overall morbidity (aOR = 0.85; 95% CI: 0.54-1.33; P = 0.477) between NRT and control groups. Similarly, no significant differences were found for these three outcomes in the immediate breast reconstruction population. Statistical power for every comparison was >80%. CONCLUSIONS: This study suggests that NRT is not associated with significantly higher 30-day postoperative complications among breast cancer patients undergoing mastectomy with or without immediate breast reconstruction.

Risk of surgical site infection in 401 consecutive patients with glioblastoma with and without carmustine wafer implantation.

OBJECTIVES: Patients with glioblastoma (GBM) have an inherently shortened survival because of their disease. It has been recently shown that carmustine wafers in addition to other therapies (surgery, temozolomide, and radiation) can further extend survival. There is concern, however, that these therapies may increase infection risk. The goals of this study were to calculate the incidence of postoperative infection, evaluate if carmustine wafers changes the risk of infection and identify factors independently associated with an infection following GBM surgery. METHODS: All patients who underwent non-biopsy, surgical resection of an intracranial GBM from 2007 to 2011 at a single institution were retrospectively reviewed. Stepwise multivariate proportional hazards regression analysis was used to identify factors associated with infection, including the use of carmustine wafers. Variables with P < 0.05 were considered statistically significant. RESULTS: Four hundred and one patients underwent resection of an intracranial GBM during the reviewed period, and 21 (5%) patients developed an infection at a median time of 40 [28-286] days following surgery. The incidence of infection was not higher in patients who had carmustine wafers, and this remained true in multivariate analyses to account for differences in treatment cohorts. The factors that remained significantly associated with an increased risk of infection were prior surgery [RR (95% CI); 2.026 (1.473-4.428), P = 0.01], diabetes mellitus [RR (95% CI); 6.090 (1.380-9.354)], P = 0.02], and increasing duration of hospital stay [RR (95% CI); 1.048 (1.006-1.078); P = 0.02], where the greatest risk occurred with hospital stays > 5 days [RR (95% CI); 3.904 (1.003-11.620), P = 0.05]. DISCUSSION: These findings may help guide treatment regimens aimed at minimizing infection for patients with GBM.