Safety and Efficacy of Oxaliplatin Pressurized Intraperitoneal Aerosolized Chemotherapy (PIPAC) in Colorectal and Appendiceal Cancer with Peritoneal Metastases: Results of a Multicenter Phase I Trial in the USA.

BACKGROUND: Pressurized intraperitoneal aerosolized chemotherapy (PIPAC) is a laparoscopic locoregional treatment for peritoneal metastases (PM) from colorectal cancer (CRC) or appendiceal cancer (AC) in patients who cannot undergo cytoreductive surgery (CRS). While PIPAC has been studied in Europe and Asia, it has not been investigated in the USA. PATIENTS AND METHODS: We evaluated PIPAC with 90 mg/m2 oxaliplatin alone (cycle 1) and preceded by systemic chemotherapy with fluorouracil (5-FU) and leucovorin (LV) (cycle 2-3) as a multicenter prospective phase I clinical trial (NCT04329494). The primary endpoint was treatment-related adverse events (AEs). Secondary endpoints included survival and laparoscopic, histologic, and radiographic response. RESULTS: 12 patients were included: 8 with CRC and 4 with AC. Median prior chemotherapy cycles was 2 (interquartile range (IQR) 2-3). All patients were refractory to systemic oxaliplatin-based chemotherapy. Median peritoneal carcinomatosis index (PCI) was 28 (IQR 19-32). Six (50%) of twelve patients completed three PIPAC cycles. No surgical complications or dose-limiting toxicities were observed. Two patients developed grade 3 treatment-related toxicities (one abdominal pain and one anemia). Median overall survival (OS) was 12.0 months, and median progression-free survival (PFS) was 2.9 months. OS was correlated with stable disease by Response Evaluation Criteria in Solid Tumors (RECIST) criteria but not with laparoscopic response by PCI or histologic response by peritoneal regression grading system (PRGS). CONCLUSIONS: This phase I trial in the USA demonstrated safety, feasibility, and early efficacy signal of PIPAC with oxaliplatin and chemotherapy in patients with PM from AC or CRC who are refractory to standard lines of systemic chemotherapy.

Osteopontin Levels Are Persistently Elevated for 4 weeks Following Minimally Invasive Colorectal Cancer Resection.

INTRODUCTION: Osteopontin (OPN) is an integrin binding phosphorylated glycoprotein secreted by macrophages and leukocytes that is found in extracellular fluids and sites of inflammation; various forms of CD44 serve as receptors. Osteopontin, expressed by numerous cancers, enhances tumor progression and angiogenesis via the PI3K/AKT and ERK mediated pathways in concert with Vascular Endothelial Growth Factor (VEGF); OPN also plays a role in wound healing. The impact of minimally invasive colorectal resection (MICR) for colorectal cancer (CRC) on plasma OPN levels is unknown. This study's goal was to assess blood levels during the first month after MICR. METHOD: Patients undergoing MICR for CRC who were enrolled in an IRB approved tissue/prospective data bank for whom preoperative, postop Day (POD) 1, POD 3, and at least 1 late postop plasma sample (POD 7-34) were available were studied. Osteopontin levels were determined in duplicate via enzyme linked immunosorbent assay (ELISA) (results reported as mean ± SD). The Wilcoxon signed rank test was used for analysis (significance P < .05). RESULTS: A total of 101 CRC patients (63% colon and 37% rectal) met study criteria. The mean preop OPN level was 89.2 ± 36.8 (ng/ml) for the entire group. Significantly elevated (P < .001) mean plasma levels were detected, vs preop, on POD1 (198.0 ± 67.4; n = 101), POD 3 (186.0 ± 72.6, n = 101), POD 7-13 (154.1 ± 70.2, n = 70), POD14-20 (146.7 ± 53.4, n=32), and POD 21-27 (123.0 ± 56.9, n = 25). No difference was noted at the POD 27-34 timepoint (P > .05). CONCLUSION: Plasma OPN levels are significantly elevated over baseline for a month after MICR for CRC. The early rise in OPN levels may be related to the postop acute inflammatory response. The persistent elevation noted in weeks 2-4, however, may be a manifestation of wound healing in which OPN plays a role. Similar persistent plasma elevations of VEGF, angiopoietin 2 (ANG 2), and 11 other proangiogenic proteins have been noted and, collectively, may promote angiogenesis in residual tumors.

PIPAC for the Treatment of Gynecologic and Gastrointestinal Peritoneal Metastases: Technical and Logistic Considerations of a Phase 1 Trial.

BACKGROUND: Peritoneal metastases (PM) from ovarian, gastric, appendiceal, or colorectal origin can be treated via cytoreductive surgery with or without the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) for selected patients. Unfortunately, not all patients are candidates for aggressive surgical debulking. For these patients, pressurized intraperitoneal aerosolized chemotherapy (PIPAC) has emerged as an alternative method for intraperitoneal (IP) chemotherapy administration. This report presents the design and implementation of the first phase 1 trial to evaluate the safety and efficacy of PIPAC in the United States. METHODS: This is an ongoing prospective phase 1 clinical trial of PIPAC for patients who have histologically confirmed ovarian, uterine, gastric, appendiceal, or colorectal cancer with PM and have progressed to at least one evidence-based chemotherapeutic regimen. The trial has two clinical arms. The patients in arm 1 have gynecologic and gastric malignancies treated with IP cisplatin and doxorubicin, and the arm 2 patients have colorectal and appendiceal malignancies treated with intravenous fluorouracil and leucovorin followed by IP oxaliplatin. All the patients are monitored for dose-limiting toxicities and adverse events. RESULTS: Practical and technical considerations for the phase 1 PIPAC trial are presented. These considerations include patient selection, operating room setup, and technical details for successful aerosolized chemotherapy delivery. The phase 1 study results will be reported separately at completion of the trial. CONCLUSIONS: The PIPAC treatment is a feasible, minimally invasive approach that permits IP delivery of chemotherapy. Once completed, the ongoing phase 1 trial will help to provide safety and initial efficacy data.

A colonoscopic overtube system that creates a 'therapeutic zone' and permits retraction facilitates endoscopic submucosal dissection, was associated with fewer deep bowel wall injuries and instrument exchanges, and required less lifting solution vs classic endoscopic submucosal dissection in an ex vivo bovine model.

INTRODUCTION: Endoscopic submucosal dissection (ESD) is the 'gold standard' for large flat polyps; nevertheless, the rate of adoption in the USA is low. In ESD, the polyp is 'surgically' detached with a needle knife after a submucosal lift; gravity and the dissection cap are used for retraction. ESD would be easier if active retraction were possible. In an ex vivo bovine colon model, this study assessed an overtube system (Boston Scientific ORISE Tissue Retraction System, TRS) that permits retraction and creates 'an operative field' for removal of rectal/sigmoid lesions. METHOD: Classic ESD (C-ESD) was compared to TRS-facilitated ESD (TRS-ESD). Cleaned/preserved bovine large bowel was used, and two 2-cm 'lesions'/colon were branded onto the mucosal surface 25 and 35 cm from the anus. Submucosal saline lifts were made using a thin catheter and a standard needle knife. We tracked case length, number of instrument exchanges (to refresh lift), the volume of lift solution, the fullness of resection, and deep muscle injuries. RESULTS: Fifty ESDs were carried out in 25 colons (25 C-ESD, 25 TRS-ESD). Complete resections were noted in all cases. The TRS method required fewer instrument exchanges (median 5) vs C-ESD (median 9, p < 0.0001) and less lift solution (median 39 ml) than the C-ESD cases (median 55 ml, p = 0.0003). TRS-ESD was associated with fewer deep muscle injuries (median 2) than C-ESD (median 3, p = 0.0191). Finally, the TRS group's median case length (34.5 min) was shorter than that of C-ESD (41 min, p = 0.0543). CONCLUSION: The TRS system provides retraction and facilitates ESD regarding the number of lift injections, the volume of lift solution needed, and avoidance of muscle injuries. Of note, there is an apparent TRS learning curve, and the device mandates a distal-to-proximal approach and initial 360 degree mucosal incision. Further study is warranted.

Pressurized Intraperitoneal Aerosol Chemotherapy, a Palliative Treatment Approach for Patients With Peritoneal Carcinomatosis: Description of Method and Systematic Review of Literature.

BACKGROUND: Peritoneal metastases arise in patients with a variety of primary cancers, and are associated with a poor prognosis. Systemic chemotherapy is the mainstay of treatment; however, the morbidity is considerable and the survival benefit is modest. Cytoreductive surgery and heated intraperitoneal chemotherapy is a potentially curative treatment available to a minority of patients; however, most develop recurrent disease. A novel palliative treatment for peritoneal metastases, pressurized intraperitoneal aerosol chemotherapy, has recently been introduced. Pressurized intraperitoneal aerosol chemotherapy utilizes an aerosol of chemotherapy in carbon dioxide gas. It is instilled into the abdomen under pressure via laparoscopic ports. No cytoreduction is performed. Pressurized intraperitoneal aerosol chemotherapy can be repeated at 6-week intervals. Oxaliplatin or cis-platinum and doxorubicin have been used to date. OBJECTIVE: This study aims to systematically review and evaluate the method, and the preclinical and early clinical results of pressurized intraperitoneal aerosol chemotherapy. DATA SOURCES: Medline and the Cochrane Library were the data sources for the study. STUDY SELECTION: Peer-reviewed series of greater than 10 patients, with sufficient patient data, through April 2019, were selected. INTERVENTION: Patients with peritoneal metastases underwent pressurized intraperitoneal aerosol chemotherapy. MAIN OUTCOME MEASURES: Patient dropout, histologic tumor response, adverse events, and 30-day mortality were the primary outcomes measured. RESULTS: A total of 921 patients with peritoneal metastases were brought to the operating room for pressurized intraperitoneal aerosol chemotherapy. The number of pressurized intraperitoneal aerosol chemotherapy treatments administered was as follows: 1 treatment, 862 (94%); 2 treatments, 645 (70%); and 3 treatments, 390 patients (42%). Initial laparoscopic access was not possible in 59 patients (6.4%). Common Terminology Criteria for Adverse Events grade 3 or higher were noted in 13.7% of the patients who, collectively, underwent a total of 2116 treatments. The 30-day mortality was 2.4% (22/921). LIMITATIONS: This study was limited by the heterogeneity of reported data and primary tumor types and by the lack of long-term survival data. CONCLUSIONS: Early clinical results are encouraging, but tumor-specific, prospective, randomized trials are needed to compare pressurized intraperitoneal aerosol chemotherapy to systemic chemotherapy. This method has yet to be introduced to the United States. It is another therapeutic option for patients with peritoneal metastases and will broaden the patient base for future clinical trials.

Sclerotherapy needle injections can expand the subserosal and muscularis propria layers and cause a stable mucosal lift in ESD/EMR patients.

BACKGROUND: A mucosal lift is needed for ESD and EMR. Most lifts are made via sclerotherapy needle injection. The firm push needed to penetrate the mucosa often leaves the needle tip in the deep wall. The needle is next withdrawn and fluid injected until a sharp lift (due to submucosal expansion) begins to form; the needle is then held steady and the injection finished. The initial injection may result in a subtle deep lift that resolves quickly. It was the authors' belief that only submucosal expansion could lead to a stable mucosal lift. A colonic ESD case in which a polyp was inadvertently resected via needle knife in an expanded subserosal plane led to a questioning of this position. This study's purpose was to determine if stable deep wall mucosal lifts can be generated via bowel wall injection. METHODS: Transmucosal and intramural injections into bovine large bowel were carried out. Stable lifts and lift cross sections were made and examined grossly and histologically to determine the location of the lift fluid. Clinical ESD videos were also reviewed. RESULTS: Over 200 intact and cross-sectioned lifts were assessed. Gross inspection revealed two types of lifts (superficial and deep), whereas cross sections and histologic analyses revealed examples of stable expansion of the submucosal, muscularis propria, and subserosal layers post injection. Clinical "deep" lifts were also found. Superficial lifts are more focal and taller, whereas deep wall lifts are broader and less prominent. CONCLUSION: Stable deep wall mucosal lifts occur and are likely due to the deep starting point of the needle post insertion. If ESD/EMR are attempted with a deep lift, the chances of failure or perforation are high. Lifts must be carefully scrutinized before starting ESD/EMR. Other means of lift establishment should be evaluated and considered.

Plasma levels of the proangiogenic protein CXCL16 remains elevated for 1 month after minimally invasive colorectal cancer resection.

BACKGROUND: Inflammation-induced endothelial precursor cell recruitment and angiogenesis are thought to be associated with CXCL16-CXCR6 pair activity. This study's main purpose was to determine plasma CXCL16 levels after minimally invasive colorectal resection (MICR) for colorectal cancer (CRC); an adjunct study assessed wound fluid (WF) and plasma CXCL16 levels in a separate group of CRC patients. METHODS: CRC patients who had MICR and for whom plasma was available in a tissue bank were eligible. Plasma samples were collected preoperatively from all patients. Samples were also collected on postoperative days (POD) 1 and 3 and at various late postoperative time points (POD 7-34). In a separate study, blood and intra-abdominal wound fluid (WF) samples were collected from CRC MICR patients (pts). Samples were stored at - 80 °C. CXCL16 levels were determined via ELISA. The Wilcoxon signed-rank and Mann and Whitney tests were used for analysis. RESULTS: Main study: 86 CRC pts. were included. The mean preoperative plasma CXCL16 level was 2.36 ± 0.57 ng/ml. Elevated mean plasma levels (p <  0.0001 × first 4 time points) were noted on POD 1 (2.82 ± 0.81, n = 86), POD 3 (3.12 ± 0.77, n = 82), POD 7-13 (3.28 ± 0.88, n = 64), POD 14-20 (3.03 ± 0.62, n = 24), POD 21-27 (3.06 ± 0.67, n = 20, p = 0.0003), and POD 28-34 (3.17 ± 0.43, n = 11, p = 0.001) vs. preop levels. WF study: In the adjunct study, plasma and WF CXCL16 levels were determined for 23 CRC MICR pts. WF levels at all time points were significantly elevated over plasma levels. CONCLUSION: Plasma CXCL16 levels were elevated for 4 weeks after minimally invasive colorectal resection for cancer. Also, WF CXCL16 levels were 3-10 times greater than the corresponding plasma concentrations. The source of the late plasma elevations may be the healing wound. Increased plasma CXCL16 levels may promote tumor angiogenesis in the first month after MICR.

Risk factors for superficial surgical site infection after elective rectal cancer resection: a multivariate analysis of 8880 patients from the American College of Surgeons National Surgical Quality Improvement Program database.

BACKGROUND: Superficial surgical site infection (sSSI) is one of the most common complications after colorectal resection. The goal of this study was to determine the comorbidities and operative characteristics that place patients at risk for sSSI in patients who underwent rectal cancer resection. METHODS: The American College of Surgeons National Surgical Quality Improvement Program database was queried (via diagnosis and Current Procedural Terminology codes) for patients with rectal cancer who underwent elective resection between 2005 and 2012. Patients for whom data concerning 27 demographic factors, comorbidities, and operative characteristics were available were eligible. A univariate and multivariate analysis was performed to identify possible risk factors for sSSI. RESULTS: A total of 8880 patients met the entry criteria and were included. sSSIs were diagnosed in 861 (9.7%) patients. Univariate analysis found 14 patients statistically significant risk factors for sSSI. Multivariate analysis revealed the following risk factors: male gender, body mass index (BMI) >30, current smoking, history of chronic obstructive pulmonary disease (COPD), American Society of Anesthesiologists III/IV, abdominoperineal resection (APR), stoma formation, open surgery (versus laparoscopic), and operative time >217 min. The greatest difference in sSSI rates was noted in patients with COPD (18.9 versus 9.5%). Of note, 54.2% of sSSIs was noted after hospital discharge. With regard to the timing of presentation, univariate analysis revealed a statistically significant delay in sSSI presentation in patients with the following factors and/or characteristics: BMI <30, previous radiation therapy (RT), APR, minimally invasive surgery, and stoma formation. Multivariate analysis suggested that only laparoscopic surgery (versus open) and preoperative RT were risk factors for delay. CONCLUSIONS: Rectal cancer resections are associated with a high incidence of sSSIs, over half of which are noted after discharge. Nine patient and operative characteristics, including smoking, BMI, COPD, APR, and open surgery were found to be significant risk factors for SSI on multivariate analysis. Furthermore, sSSI presentation in patients who had laparoscopic surgery and those who had preoperative RT is significantly delayed for unclear reasons.

Warm and Humidified Versus Cold and Dry CO2 Pneumoperitoneum in Minimally Invasive Colon Resection: A Randomized Controlled Trial.

INTRODUCTION: Peritoneal insufflation with warm-humidified (WH) CO2 gas during minimally invasive surgical procedures is purported to prevent hypothermia and peritoneal desiccation and is associated with decreased postoperative IL-6 levels. This randomized study's purpose was to determine the clinical impact of WH versus cold-dry (CD) CO2 in minimally invasive colon resection (MICR), and to assess perioperative plasma levels of IL-6, TIMP-1, sVEGF-R1, and HSP-70 after MICR. METHODS: Operative and short-term clinical data plus perioperative blood samples were collected on MICR patients randomized to receive either WH (36.7°C, 95% humidity) or CD (room temperature, 0% humidity) CO2 perioperatively. Peritoneal biopsies were taken at the start and end of surgery. Outcomes tracked included core temperature, postoperative in-hospital pain levels, analgesia requirements, and standard recovery parameters. Preoperative and postoperative days (PODs) 1 and 3 plasma protein levels were determined via ELISA. RESULTS: A total of 101 patients were randomized to WH CO2 (50) or CD CO2 (51). The WH group contained more diabetics ( P = .03). There were no differences in indication, minimally invasive surgical method used, or core temperature. Pain scores were similar; however, the WH patients required less narcotics on PODs 1 to 3 ( P < .05), and less ketorolac on PODs 1 and 2 ( P < .03). No differences in length of stay, complication rates, or time to flatus/diet tolerance were noted. Plasma levels of the 4 proteins were similar postoperatively. Though insignificant, the WH group had less marked histologic changes on "end-of-case" peritoneal biopsies. CONCLUSION: This study found significantly lower pain medication requirements for PODs 1 to 3 for the WH group; however, because there were no differences in the pains scores between the groups, firm conclusions regarding WH CO2 cannot be made.

Cancer prevention and therapy through the modulation of the tumor microenvironment.

Cancer arises in the context of an in vivo tumor microenvironment. This microenvironment is both a cause and consequence of tumorigenesis. Tumor and host cells co-evolve dynamically through indirect and direct cellular interactions, eliciting multiscale effects on many biological programs, including cellular proliferation, growth, and metabolism, as well as angiogenesis and hypoxia and innate and adaptive immunity. Here we highlight specific biological processes that could be exploited as targets for the prevention and therapy of cancer. Specifically, we describe how inhibition of targets such as cholesterol synthesis and metabolites, reactive oxygen species and hypoxia, macrophage activation and conversion, indoleamine 2,3-dioxygenase regulation of dendritic cells, vascular endothelial growth factor regulation of angiogenesis, fibrosis inhibition, endoglin, and Janus kinase signaling emerge as examples of important potential nexuses in the regulation of tumorigenesis and the tumor microenvironment that can be targeted. We have also identified therapeutic agents as approaches, in particular natural products such as berberine, resveratrol, onionin A, epigallocatechin gallate, genistein, curcumin, naringenin, desoxyrhapontigenin, piperine, and zerumbone, that may warrant further investigation to target the tumor microenvironment for the treatment and/or prevention of cancer.

A multi-targeted approach to suppress tumor-promoting inflammation.

Cancers harbor significant genetic heterogeneity and patterns of relapse following many therapies are due to evolved resistance to treatment. While efforts have been made to combine targeted therapies, significant levels of toxicity have stymied efforts to effectively treat cancer with multi-drug combinations using currently approved therapeutics. We discuss the relationship between tumor-promoting inflammation and cancer as part of a larger effort to develop a broad-spectrum therapeutic approach aimed at a wide range of targets to address this heterogeneity. Specifically, macrophage migration inhibitory factor, cyclooxygenase-2, transcription factor nuclear factor-κB, tumor necrosis factor alpha, inducible nitric oxide synthase, protein kinase B, and CXC chemokines are reviewed as important antiinflammatory targets while curcumin, resveratrol, epigallocatechin gallate, genistein, lycopene, and anthocyanins are reviewed as low-cost, low toxicity means by which these targets might all be reached simultaneously. Future translational work will need to assess the resulting synergies of rationally designed antiinflammatory mixtures (employing low-toxicity constituents), and then combine this with similar approaches targeting the most important pathways across the range of cancer hallmark phenotypes.

Immune evasion in cancer: Mechanistic basis and therapeutic strategies.

Cancer immune evasion is a major stumbling block in designing effective anticancer therapeutic strategies. Although considerable progress has been made in understanding how cancers evade destructive immunity, measures to counteract tumor escape have not kept pace. There are a number of factors that contribute to tumor persistence despite having a normal host immune system. Immune editing is one of the key aspects why tumors evade surveillance causing the tumors to lie dormant in patients for years through "equilibrium" and "senescence" before re-emerging. In addition, tumors exploit several immunological processes such as targeting the regulatory T cell function or their secretions, antigen presentation, modifying the production of immune suppressive mediators, tolerance and immune deviation. Besides these, tumor heterogeneity and metastasis also play a critical role in tumor growth. A number of potential targets like promoting Th1, NK cell, γδ T cell responses, inhibiting Treg functionality, induction of IL-12, use of drugs including phytochemicals have been designed to counter tumor progression with much success. Some natural agents and phytochemicals merit further study. For example, use of certain key polysaccharide components from mushrooms and plants have shown to possess therapeutic impact on tumor-imposed genetic instability, anti-growth signaling, replicative immortality, dysregulated metabolism etc. In this review, we will discuss the advances made toward understanding the basis of cancer immune evasion and summarize the efficacy of various therapeutic measures and targets that have been developed or are being investigated to enhance tumor rejection.

Surgical Treatment of Diverticulitis: Hand-Assisted Laparoscopic Resection Is Predominantly Used for Complex Cases and Is Associated With Increased Postoperative Complications and Prolonged Hospitalization.

Introduction Laparoscopic (LAP) colectomy is now the "gold" standard for diverticulitis; the role of hand-assisted LAP (HAL) and Open methods today is unclear. This study assessed the elective use of these methods for diverticulitis. Methods A retrospective review of demographic, comorbidity (Carlson Comorbidity Index [CCI]), resection type, and short-term outcomes was carried out. Results There were 125 (44.5%) LAP, 125 (44.5%) HAL, and 31 (11%) Open cases (overall N = 281). The mean age, body mass index, and percentage of high-risk patients (CCI score >2) of the HAL group were greater (P < .05) than the LAP group (vs Open, P = ns). The Open group's mean age and percent with CCI >2 was greater when compared with the LAP group (P < .05). More Open (P < .05) and HAL patients had complex disease (Open, 63%; HAL, 40%, LAP, 22%) and were diverted (Open, 35%; HAL, 10%; LAP, 3%). Time to bowel movement was not different; however, there was a stepwise increase in median length of stay (LOS; days) from the LAP (5 days) to HAL (6 days) to Open group (7 days) (P < .05 for all). The LAP complication rate (22.4%) was lower (P < .05) than the HAL (42.4%) or Open groups' (45.2%) rates. The LAP surgical site infection rate (5.6%) was lower (P < .05) than the HAL (12.8%) or Open groups (19.6%). Conclusion The HAL and Open groups had more high risk, complex disease, diverted, and older patients than the LAP group; likewise, the overall complication rate and LOS was higher in the HAL and Open groups. Use of HAL methods likely contributed to the high minimally invasive surgery utilization rate (89%).

Efficacy of laparoscopic-assisted approach for reversal of Hartmann's procedure: results from the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database.

INTRODUCTION: Morbidity after reversal of Hartmann's procedure remains high. The laparoscopic approach (LAP) may be associated with lower morbidity versus open Hartmann's closure. This study's aim is to compare results after LAP and OPEN colostomy takedown and Hartmann's reversal. METHODS: The American College of Surgeons National Surgical Quality Improvement Program database was queried from 2005 to 2012 for CPT procedure codes 44227 (LAP) and 44626 (OPEN). Exclusion criteria included: ventilator dependence, ASA class 4 or 5, SIRS, sepsis, emergency case, and advanced malignancy. Demographic parameters were assessed as well as comorbidities and short-term outcomes. Statistical methods used include Fisher's exact test for categorical variables and Student's t test for continuous variables. RESULTS: In total, 4,148 patients underwent stoma closure and Hartmann's reversal (LAP 732 [17.6 %], OPEN 3,416 [82.3 %]). The mean BMI was lower in the LAP (mean ± SD 27.6 ± 6.6) versus OPEN group (28.3 ± 6.8, p = 0.012). The groups were similar as regards comorbidities except for dyspnea (LAP 5.6 %, OPEN 7.8 %, p = 0.043). The mean surgery times were similar and the median LOS shorter in the LAP versus OPEN groups (5 vs 6 days, p < 0.0001). A lower overall morbidity rate was noted for the LAP group (18.4 % vs OPEN 27 %, p < 0.0001) but mortality was statistically similar. Lower rates were noted in the LAP group for the following complications: incisional SSI (10.4 vs 14.1 %, p = 0.033), organ space SSI (3.1 vs 5.0 %, p = 0.033), UTI (1.6 vs 3.3 %, p = 0.005), sepsis (3.4 vs 6.0 %, p = 0.038), and reoperation (3.1 vs 5.4 %, p = 0.011). CONCLUSION: Only 18 % of Hartmann's reversal's were done using LAP methods. The LAP and OPEN groups were similar except for gender, BMI, and dyspnea history. LAP methods were associated with a 1 day LOS benefit and significantly lower overall morbidity and lower rates of incisional and deep SSI, UTI, sepsis, and reoperations. Operative length was similar. The short-term results of the LAP approach are superior to the OPEN results.

Technique of last resort: characteristics of patients undergoing open surgery in the laparoscopic era.

BACKGROUND: The utilization rates for minimally invasive colorectal resection techniques (MICR) continue to increase. In some centers MICR methods are the preferred approach, however, open methods continue to be utilized for select patients. In this study, the profile and short-term outcomes of open colorectal resection (CR) and MICR patients are determined and compared. METHODS: A retrospective review of patients who underwent elective CR over 11 years at two institutions was performed. The MICR group contained both laparoscopic-assisted and hand-assisted cases. The past medical and surgical histories, indications, operations performed, and short-term outcomes were assessed. The Charlson co-morbidity index (CMI) was used to assess risk. RESULTS: During the study period 1080 patients underwent CR (Open, 141; MICR, 939). As judged by the CMI, there were more high-risk patients (score ≥2) in the Open group (34.38%) versus MICR (22.11%) p = 0.0029. Significantly more open patients had prior abdominal surgery and specifically CRs (Open, 15.60% vs. MICR, 2.13%, p < 0.001). Intraoperative transfusion (Open 25.7%; MICR 6.8%, p < 0.001) and diversion (25.53 vs. 11.50%, p < 0.001) were more common in the Open group. Not surprisingly, recovery of bowel function and length of stay were longer for the Open group. The overall complication rate was also higher for the Open patients (p < 0.001). CONCLUSION: When MICR is the procedure of choice, patients selected for Open CR are higher risk and more complex as judged by the CMI and past operative history. Not surprisingly, this translates into a longer length of stay, higher rates of transfusion, diversion, and complications. This disparity in patients undergoing CRs makes direct comparison of MICR and Open resection outcomes not reasonable.

Predictors of mortality after emergency colectomy for Clostridium difficile colitis: an analysis of ACS-NSQIP.

OBJECTIVE: To evaluate clinical factors associated with mortality in emergency colectomies performed for Clostridium difficile colitis. BACKGROUND: The incidence and mortality from C difficile colitis is on the rise. Emergent colectomy performed for C difficile colitis is associated with a high mortality. METHODS: The ACS-NSQIP database from 2005 to 2010 was used to study emergently performed open colectomies for a primary diagnosis of C difficile colitis on the International Classification of Diseases, Ninth Revision. Preoperative, intraoperative, and postoperative factors were noted and compared between survivors and nonsurvivors. We performed multivariate stepwise binomial logistic regression analyses to study clinical factors that may be associated with 30-day mortality. RESULTS: The overall mortality for this cohort was 33% (111/335) with a median time to death of 8 days. On average, survivors were discharged on postoperative day 24. On multivariate analysis, those aged 80 years or older were associated with a ninefold increase in the odds of mortality [95% confidence interval (CI): 3.0-13.0]. Other factors associated with increased mortality were preoperative shock (OR=2.8, 95% CI: 1.6-5.4), preoperative dialysis dependence (OR=2.3, 95% CI: 1.1-4.8), chronic obstructive pulmonary disease (OR=3.7, 95% CI: 2.0-7.1), and wound class III (OR=2.1, 95% CI: 3.0-13). Thrombocytopenia (platelet count < 150×10(3)/mm(3)), coagulopathy (International Normalized Ratio>2.0), and renal insufficiency (blood urea nitrogen>40 mg/dL) were associated with a higher mortality as well. CONCLUSIONS: This is the largest series of colectomies performed for C difficile colitis in the literature. We identified several preoperative clinical risk factors that were associated with increased postoperative mortality. These findings may be useful in selecting appropriate patients for surgical intervention and may help to define a population where surgery may not be beneficial.

Minimally invasive colorectal resection for benign pathology is associated with persistent proangiogenic plasma compositional changes.

BACKGROUND: Minimally invasive colorectal resection for cancer is associated with increased plasma levels of numerous proangiogenic proteins for 3 to 4 weeks postoperatively, and plasma from postoperative weeks 2 and 3 stimulates proangiogenic endothelial cell behavior in vitro. It is unknown if similar plasma changes occur after minimally invasive colorectal resection for benign pathology. OBJECTIVE: The aim of this study is to assess 1) plasma levels of angiopoetin-2, placental growth factor, and soluble vascular cell adhesion molecule-1 after minimally invasive colorectal resection for benign pathology and 2) postoperative plasma's effects on in vitro endothelial cell proliferation (branch point formation), migration, and invasion. DESIGN: Prospectively gathered plasma samples taken from patients undergoing colorectal resection who consented to participate in an institutional review board-approved plasma and data bank were used for ELISAs and in vitro endothelial cell studies. SETTINGS: The plasma and clinical data used were collected at 3 hospitals. PATIENTS: Patients undergoing minimally invasive colorectal resection for benign indications who were enrolled in a plasma/data bank and for whom adequate samples and volumes of plasma were available were included in the study. MAIN OUTCOME MEASURES: Perioperative plasma levels of angiopoetin-2, placental growth factor, and soluble vascular cell adhesion molecule-1 were the primary outcomes measured. In vitro rates of endothelial cell branch point formation, migration, and invasion were determined after the addition of preoperative and postoperative plasma samples to endothelial cell cultures. RESULTS: Plasma from 86 patients undergoing minimally invasive colorectal resection for benign indications was assessed (diverticulitis, 30; benign polyps, 56). Plasma levels of angiopoetin-2, placental growth factor, and soluble vascular cell adhesion molecule-1 were significantly increased for 3 to 4 weeks postoperatively compared with preoperative levels. In regard to the endothelial cell culture assays, significantly increased endothelial cell branch point formation, invasion, and migration results were noted with plasma from the second and third weeks postoperatively in comparison with preoperative culture results. LIMITATIONS: The weaknesses of this study are the limited numbers of late postoperative plasma samples and the need to bundle late samples into 7- to 12-day time blocks. CONCLUSIONS: Minimally invasive colorectal resection for benign pathology is associated with persistent proangiogenic plasma alterations similar to those found in patients who have cancer. Surgical trauma and not the indication is the likely cause.

The rate for the use of hand-assisted laparoscopic methods is directly proportional to body mass index.

BACKGROUND: Hand-assisted laparoscopic (HAL) colorectal resection remains controversial. Critics believe HAL methods lead to decreased use of laparoscopically assisted (LA) methods. Proponents believe selective HAL use increases minimally invasive surgery (MIS) use rates. This study assessed general and body mass index (BMI)-specific HAL and LA colorectal resection use by surgeons who embraced both methods. METHODS: This study retrospectively investigated 1,122 patients who underwent colorectal resection during an 8-year period. Surgical method, type of colorectal resection, BMI, comorbidities, incision length, and short-term outcomes were collected. RESULTS: The surgical methods included LA (60 %), HAL (25 %), and open (OP 15 %) procedures. The HAL group mean BMI was higher than that of the LA group (P < 0.0001), and the HAL use rate varied directly with BMI. The HAL technique was used for 48 % of the rectal, 36 % of the sigmoid, and 4 % of the right colorectal resections. The incision length was directly proportional to BMI for all the methods. Although the HAL incision lengths were significantly longer than the LA incision lengths for a BMI lower than 40 kg/m(2), there was no difference when the BMI was 40 kg/m(2) or higher. The comorbidities were greater in the HAL group than in the LA sigmoid colorectal resection group (P = 0.001). The mean hospital length of stay (LOS) was similar for the HAL and LA patients but longer for the open surgery patients (P < 0.0001 vs HAL group). The major complications, reoperations, and 30-day mortality rates were low and comparable. CONCLUSIONS: The HAL methods were used primarily for sigmoid and rectal colorectal resections and for higher BMI patients with more comorbidities. The mean incision length difference between the HAL and LA methods was 3.9 cm, but neither the LOS nor the major postoperative complications differed significantly. Selective use of HAL together with LA methods led to a MIS use rate of 85 % and facilitated MIS for high BMI patients. Together, the methods are complementary and may increase the number of minimally invasive surgeries performed.