Downstaging after preoperative chemoradiation for locally advanced rectal cancer is associated with better survival than pathologic stage 0-1 disease treated with upfront surgery.

BACKGROUND AND OBJECTIVES: It is unknown how patients with locally advanced rectal cancer with significant response to preoperative radiotherapy/chemoradiotherapy fare relative to patients with true pathologic 0-1 disease undergoing upfront surgery. We aimed to determine whether survival is improved in locally advanced rectal cancer downstaged to pathologic stage 0-1 disease compared to true pathologic stage 0-1 tumors. METHODS: A retrospective review of the National Cancer Database between 2004 and 2016 was conducted. Three groups were identified: (1) clinical stage 2-3 disease downstaged to pathologic stage 0-1 disease after radiotherapy, (2) clinical stage 2-3 disease not downstaged after radiotherapy, and (3) true pathologic 0-1 tumors undergoing upfront surgery. The primary endpoint was overall survival and was compared using Kaplan-Meier and multivariate Cox regression analyses. RESULTS: The study population consisted of 59,884 patients. Of the 40,130 patients with locally advanced rectal cancer treated with preoperative radiation, 12,670 (31.5%) had significant downstaging (group 1), while 27,460 (68.4%) had no significant downstaging (group 2). A total of 19,754 had pathologic 0-1 disease treated with upfront resection (group 3). On Kaplan-Meier analysis, downstaged patients had significantly better overall survival compared to both non-downstaged and true pathologic stage 0-1 patients (median 156 vs. 99 and 136 months, respectively, p < 0.001). On multivariate analysis, downstaged patients had significantly better survival (HR 0.88, p < 0.001) compared to true pathologic 0-1 patients. CONCLUSIONS: Locally advanced rectal cancer downstaged after preoperative radiotherapy has significantly better survival compared to true pathologic stage 0-1 disease treated with upfront surgery. Response to chemoradiotherapy likely identifies a subset of patients with a particularly good prognosis.

Ablation techniques or active surveillance compared to surgical resection in patients with low-risk papillary thyroid cancer: a systematic review and meta-analysis.

BACKGROUND: The global prevalence of thyroid cancer is on the rise. About one-third of newly diagnosed thyroid cancer cases comprise low-risk papillary thyroid cancer (1.5 cm or more minor). While surgical removal remains the prevailing approach for managing low-risk papillary thyroid cancer (LPTC) in patients, other options such as active surveillance (AS), radiofrequency ablation (RFA), microwave ablation (MWA), and laser ablation (LA) are also being considered as viable alternatives. This study evaluated and compared surgical thyroid resection (TSR) versus non-surgical (NS) methods for treating patients with LPTC. METHODS: The study encompassed an analysis of comparisons between surgical thyroid resection (TSR) and alternative approaches, including active surveillance (AS), radiofrequency ablation (RFA), microwave ablation (MWA), or laser ablation (LA). The focus was on patients with biopsy-confirmed low-risk papillary thyroid cancer (LPTC) of less than 1.5 cm without preoperative indications of local or distant metastasis. The primary outcomes assessed were recurrence rates, disease-specific mortality, and quality of life (QoL). Data were collected from prominent databases, including Cochrane Database, Embase, MEDLINE, and Scopus, from inception to June 3rd, 2020. The CLARITY tool was utilized to evaluate bias risk. The analysis involved odds ratios (OR) with 95% confidence intervals (CI) for dichotomous outcomes, as well as mean differences (MD) and standardized mean differences (SMD) for continuous outcomes. The study is registered on PROSPERO under the identifier CRD42021235657. RESULTS: The study incorporated 13 retrospective cohort studies involving 4034 patients. Surgical thyroid resection (TSR), active surveillance (AS), and minimally invasive techniques like radiofrequency ablation (RFA), microwave ablation (MWA), and laser ablation (LA) were performed in varying proportions of cases. The analysis indicated that specific disease mortality rates were comparable among AS, MWA, and TSR groups. The risk of recurrence, evaluated over different follow-up periods, showed no significant differences when comparing AS, RFA, MWA, or LA against TSR. Patients undergoing AS demonstrated better physical health-related quality of life (QoL) than those undergoing TSR. However, no substantial differences were observed in the overall mental health domain of QoL when comparing AS or RFA with TSR. The risk of bias was moderate in nine studies and high in four. CONCLUSION: Low-quality evidence indicates comparable recurrence and disease-specific mortality risks among patients with LPTC who underwent ablation techniques or active surveillance (AS) compared to surgery. Nevertheless, individuals who opted for AS exhibited enhanced physical quality of life (QoL). Subsequent investigations are warranted to validate these findings.

Novel antibiotic irrigation device versus standard O-ring wound retractor in the prevention of surgical site infection following colorectal resection.

PURPOSE: We sought to compare the effectiveness of a novel antibiotic irrigation device to the standard O-ring wound retractor in preventing surgical site infections (SSIs) following colorectal resections. METHODS: This single-arm clinical trial included patients undergoing colorectal resections utilizing the novel device. A retrospective cohort of patients undergoing the same procedures with the O-ring retractor was selected as the control group. The primary outcome assessed was SSI. Secondary outcomes assessed were overall complications, hospital length of stay (LOS), and 30-day readmission. A univariable and multivariable logistic regression model was built to evaluate the association between SSI as the outcome variable and the use of the novel device as the main independent variable. The model was adjusted for any confounding variables. RESULTS: Eighty-six novel device cases and 170 O-ring retractor cases were enrolled. There were no significant differences between the two groups in terms of demographics and preoperative comorbidities. Cases with the novel device had fewer Pfannenstiel incisions (1.2% vs. 14.6%, p < 0.001). There were no other significant differences in intraoperative variables. SSI rates were significantly lower in the novel device group (1.2% vs. 9.1%, p = 0.014). There were no other significant differences in postoperative complications. Multivariable logistic regression with backward elimination showed that the use of the novel device was significantly more effective against SSI by 92.5% compared to the use of the O-ring retractor. CONCLUSION: The novel device may contribute to lower SSI rates compared to the O-ring retractor following colorectal resection.

Does coffee affect bowel recovery following minimally invasive colorectal operations? A three-armed randomized controlled trial.

PURPOSE: Previous studies have suggested that coffee may shorten the postoperative ileus period. We sought to evaluate the impact of both coffee and caffeine on shortening the return of postoperative bowel function following minimally invasive colectomy. METHODS: This was a single-center, randomized controlled clinical trial conducted in a tertiary hospital. Patients undergoing an elective robotic or laparoscopic small or large bowel operation were included in this study. Patients were randomized into one of three groups: warm water, decaffeinated coffee, and caffeinated coffee. Subjects were assigned to drink a 4-oz cup three times daily starting on postoperative day one. The primary endpoint was time to first bowel movement. Secondary endpoints included time to first flatus, length of hospital stay, and postoperative morbidity. RESULTS: A total of 99 patients were included in this study: 31 warm water, 31 decaffeinated coffee, and 37 caffeinated coffee. The groups were similar in age and sex (p = 0.51 and 0.91, respectively). Mean (SD) time to the first bowel movement in days was 2.94 (1.4), 2.58 (1.2), and 2.86 (1.3), respectively (p = 0.53). There were no significant differences observed in postoperative morbidity (p = 0.52) between groups. Multivariate linear regression analysis did not reveal a statistically significant association between any interventions and time to first bowel movement or length of hospital stay. CONCLUSIONS: Coffee (caffeinated or decaffeinated) does not expedite the return of bowel function following minimally invasive operation. TRIAL REGISTRATION: https://classic. CLINICALTRIALS: gov/ct2/show/NCT02639728 NCT02639728.

Hartmann's Reversal is More Complex Than Elective Left Colectomy.

BACKGROUND: Hartmann's reversal (HR) is associated with significant technical complexity and morbidity. The decision to perform HR is difficult and up to 50% of patients with colostomies do not undergo a reversal. To better guide surgeons and patients with this decision, we sought to assess the surgical risks and outcomes of HR as compared to elective left colectomy (LC). METHODS: We conducted a retrospective analysis of a prospective database at a tertiary medical center. Patients undergoing elective Hartmann's reversal and left colectomy between January 2014 and November 2021 were identified. We compared preoperative variables, intraoperative events, and short-term postoperative outcomes. RESULTS: 135 patients were identified: 30 HR and 105 LC. There were no significant differences in demographics or preoperative comorbidities between HR and LC. There were more open and fewer robotic cases in HR (23.3% vs 2.9%, P < .0001; 46.6% vs 76.0%, P < .01). Total operative time was significantly longer in HR than LC (261.8 vs 211.7 minutes, P = .02). There was a significantly higher percentage of intraoperative complications in HR (13.3% vs 1.9%, P < .01). There was a significantly higher rate of minor postoperative complications in HR than LC (46.7% vs 26.7%, P = .04), but not major (6.7% vs 5.8%, P = .85). Time to first flatus/bowel movement was significantly longer in HR than LC (3.6 vs 2.5 days, P < .001). CONCLUSION: Hartmann's reversal is a more technically challenging operation than elective left colectomy and is associated with significantly higher rates of intraoperative and minor postoperative complications. Future studies should focus on mitigating these risk factors to optimize patient outcomes.

Hartmann's reversal is associated with worse outcomes compared to elective left colectomy: A NSQIP analysis of 36,794 cases.

BACKGROUND: Hartmann's reversal (HR) is associated with significant technical difficulty and morbidity. Using the ACS-NSQIP database, we assessed the outcomes of HR as compared to elective left colectomy (LC). METHODS: The 2016-2019 ACS-NSQIP datasets were queried to identify patients undergoing HR and elective LC. Patients' demographics, comorbidities, and short-term surgical outcomes were evaluated using both univariable and multivariable methods. RESULTS: The study included 7,632 HR cases and 29,162 LC cases. The HR group had more patients with ASA grade III (50% vs. 42.4%). HR had more open-operative cases (69.4 vs. 18.5%) and longer mean operative times (213 vs. 191 min) than LC. Postoperatively, the HR group had a longer mean hospital stay (5.5 vs. 4.1 days) and higher complication rate (18.3% vs. 10.3%). HR was associated with increased odds of having a concurrent ileostomy (OR 2.11), deep space/organ infection (OR 1.55), and at least one complication (OR 1.56). CONCLUSION: HR is a more challenging operation with patients who fared worse than their LC counterparts. Consideration should be given to alternatives of the index Hartmann's procedure.

Robotic colorectal procedures: does operative start time impact short-term outcome?

BACKGROUND: Previous publications revealed more complications in afternoon versus morning surgeries. With much attention given to robotic surgery outcomes, we sought to evaluate whether morning versus afternoon start time matters. METHODS: In a retrospective review of a prospective database, 210 robotic colorectal surgeries were grouped into 97 morning versus 113 afternoon cases. Preoperative risk factors, intraoperative events, and 30-day postoperative outcomes were compared. An independent samples t-test, Fisher's exact test, and linear regression were used for categorical and continuous variables. RESULTS: Morning patients were significantly younger than afternoon patients (59.5 vs. 65.5, p = 0.004), but there were no significant differences in gender, mean BMI, Charlson Comorbidity Index score, total operative time, console time, estimated blood loss, indications for surgery, and resection type. Morning patients had a significantly shorter mean length of stay (6.0 vs. 8.0 days, p = 0.021), but no significant differences in overall postoperative complications (0.30 vs. 0.30, p = 0.715), wound infection (5.2% vs. 7.1%, p = 0.564), anastomotic leak (0% vs. 2.7%, p = 0.251), ileus/small bowel obstruction (29.9% vs. 22.1%, p = 0.199), and 30-day readmission (8.2% vs. 7.1%, p = 1.000). When analyzing time of day as a continuous variable, we found no significant associations with intra- or postoperative complications. CONCLUSION: We found no correlation between surgery start time and intra- or postoperative outcomes. This can be partly attributed to these cases being non-emergent and performed primarily by two experienced surgeons with highly trained operating room robotic staff in a large volume tertiary center. This, along with decreased fatigue attributed to superior ergonomics of robotic surgery, may have mitigated previously reported differences between morning and afternoon procedures.

Minimally invasive right versus left colectomy for cancer: does robotic surgery mitigate differences in short-term outcomes?

Studies comparing right (RC) and left colectomies (LC) show higher rates of ileus in RC and higher wound infection and anastomotic leak rates in LC. However, prior studies did not include robotic procedures. We compared short-term outcomes of laparoscopic and robotic RC and LC for cancer, with sub-analysis of robotic procedures. In a retrospective review of a prospective database, preoperative factors, intraoperative events, and 30-day postoperative outcomes were compared. Student's t tests and Chi-square tests were used for continuous and categorical variables, respectively. A logistic binomial regression was performed to assess whether type of surgery was associated with postoperative complications. Between January 2014 and August 2020, 115 patients underwent minimally invasive RC or LC for cancer. Sixty-eight RC [30 (44.1%) laparoscopic, 38 (55.9%) robotic] and 47 LC [13 (27.6%) laparoscopic, 34 (72.4%) robotic] cases were included. On univariate analysis, RC patients had significantly higher overall postoperative complications but no differences in rates of ileus/small bowel obstruction, wound infection, time to first flatus/bowel movement, length of hospital stay, and 30-day readmissions. On multivariate analysis, there was no significant difference in overall complications and laparoscopic surgery had a 2.5 times higher likelihood of complications than robotic surgery. In sub-analysis of robotic cases, there was no significant difference among all outcome variables. Previously reported outcome differences between laparoscopic RC and LC for cancer may be mitigated by robotic surgery.

An introduction to the Cyrcadia Breast Monitor: A wearable breast health monitoring device.

BACKGROUND: The most common breast cancer detection modalities are generally limited by radiation exposure, discomfort, high costs, inter-observer variabilities in image interpretation, and low sensitivity in detecting cancer in dense breast tissue. Therefore, there is a clear need for an affordable and effective adjunct modality that can address these limitations. The Cyrcadia Breast Monitor (CBM) is a non-invasive, non-compressive, and non-radiogenic wearable device developed as an adjunct to current modalities to assist in the detection of breast tissue abnormalities in any type of breast tissue. METHODS: The CBM records thermodynamic metabolic data from the breast skin surface over a period of time using two wearable biometric patches consisting of eight sensors each and a data recording device. The acquired multi-dimensional temperature time series data are analyzed to determine the presence of breast tissue abnormalities. The objective of this paper is to present the scientific background of CBM and also to describe the history around the design and development of the technology. RESULTS: The results of using the CBM device in the initial clinical studies are also presented. Twenty four-hour long breast skin temperature circadian rhythm data was collected from 93 benign and 108 malignant female study subjects in the initial clinical studies. The predictive model developed using these datasets could differentiate benign and malignant lesions with 78% accuracy, 83.6% sensitivity and 71.5% specificity. A pilot study of 173 female study subjects is underway, in order to validate this predictive model in an independent test population. CONCLUSIONS: The results from the initial studies indicate that the CBM may be valuable for breast health monitoring under physician supervision for confirmation of any abnormal changes, potentially prior to other methods, such as, biopsies. Studies are being conducted and planned to validate the technology and also to evaluate its ability as an adjunct breast health monitoring device for identifying abnormalities in difficult-to-diagnose dense breast tissue.

Role of right hemicolectomy in patients with low-grade appendiceal mucinous adenocarcinoma.

BACKGROUND: There is little consensus with regards to the most appropriate surgical management for low-grade appendiceal mucinous adenocarcinomas (LAMA), though right hemicolectomy is usually recommended. METHODS: The SEER database was queried for all patients with non-metastatic LAMA. Disease specific and overall survival was compared by surgery type: 1) appendectomy, 2) formal right hemicolectomy 3) non-formal colectomy (including ileocecectomy). RESULTS: A total of 579 patients with non-metastatic LAMA were identified. 133 (23%), 404 (70%), and 42 (7%) of patients had stage I, II, and III disease, respectively. 99 (17.1%) had appendectomy, 87 (15%) had non-formal colectomy, and 302 (52.2%) had formal right hemicolectomy. We observed no significant differences in disease specific or overall survival by surgery type. Controlling for age and stage, surgery type was not a significant predictor of disease specific or overall survival. CONCLUSION: In patients with localized LAMA, right hemicolectomy did not increase disease specific or overall survival. Right hemicolectomy should be reserved for LAMA patients with positive margins post appendectomy.

"But His Yelp Reviews Are Awful!": Analysis of General Surgeons' Yelp Reviews.

BACKGROUND: Patients use Web-based platforms to review general surgeons. However, little is known about the free-form text and structured content of the reviews or how they relate to the physicians' characteristics or their practices. OBJECTIVE: This observational study aimed to analyze the Web-based reviews of general surgeons on the west side of Los Angeles. METHODS: Demographics, practice characteristics, and Web-based presence were recorded. We evaluated frequency and types of Yelp reviews and assigned negative remarks to 5 categories. Tabulated results were evaluated using independent t test, one-way analysis of variance, and Pearson correlation analysis to determine associations between the number of total and negative reviews with respect to practice structure and physician characteristics. RESULTS: Of the 146 general surgeons, 51 (35%) had at least 1 review and 29 (20%) had at least 1 negative review. There were 806 total reviews, 679 (84.2%) positive reviews and 127 (15.8%) negative reviews. The negative reviews contained a total of 376 negative remarks, categorized into physician demeanor (124/376, 32.9%), clinical outcomes (81/376, 22%), office or staff (83/376, 22%), scheduling (44/376, 12%), and billing (44/376, 12%). Surgeons with a professional website had significantly more reviews than those without (P=.003). Surgeons in private practice had significantly more reviews (P=.002) and more negative reviews (P=.03) than surgeons who were institution employed. A strong and direct correlation was found between a surgeon's number of reviews and number of negative reviews (P<.001). CONCLUSIONS: As the most common category of complaints was about physician demeanor, surgeons may optimize their Web-based reputation by improving their bedside manner. A surgeon's Web presence, private practice, and the total number of reviews are significantly associated with both positive and negative reviews.

p53-Reactive T Cells Are Associated with Clinical Benefit in Patients with Platinum-Resistant Epithelial Ovarian Cancer After Treatment with a p53 Vaccine and Gemcitabine Chemotherapy.

Purpose: To conduct a phase I trial of a Modified Vaccinia Ankara vaccine delivering wild-type human p53 (p53MVA) in combination with gemcitabine chemotherapy in patients with platinum-resistant ovarian cancer.Experimental Design: Patients received gemcitabine on days 1 and 8 and p53MVA vaccine on day 15, during the first 3 cycles of chemotherapy. Toxicity was classified using the NCI Common Toxicity Criteria and clinical response assessed by CT scan. Peripheral blood samples were collected for immunophenotyping and monitoring of anti-p53 immune responses.Results: Eleven patients were evaluated for p53MVA/gemcitabine toxicity, clinical outcome, and immunologic response. TOXICITY: there were no DLTs, but 3 of 11 patients came off study early due to gemcitabine-attributed adverse events (AE). Minimal AEs were attributed to p53MVA vaccination. Immunologic and clinical response: enhanced in vitro recognition of p53 peptides was detectable after immunization in both the CD4+ and CD8+ T-cell compartments in 5 of 11 and 6 of 11 patients, respectively. Changes in peripheral T regulatory cells (Tregs) and myeloid-derived suppressor cells (MDSC) did not correlate significantly with vaccine response or progression-free survival (PFS). Patients with the greatest expansion of p53-reactive T cells had significantly longer PFS than patients with lower p53-reactivity after therapy. Tumor shrinkage or disease stabilization occurred in 4 patients.Conclusions: p53MVA was well tolerated, but gemcitabine without steroid pretreatment was intolerable in some patients. However, elevated p53-reactive CD4+ and CD8+ T-cell responses after therapy correlated with longer PFS. Therefore, if responses to p53MVA can be enhanced with alternative agents, superior clinical responses may be achievable. Clin Cancer Res; 24(6); 1315-25. ©2018 AACR.

p53MVA therapy in patients with refractory gastrointestinal malignancies elevates p53-specific CD8+ T-cell responses.

PURPOSE: To conduct a phase I trial of a modified vaccinia Ankara (MVA) vaccine delivering wild-type human p53 (p53MVA) in patients with refractory gastrointestinal cancers. EXPERIMENTAL DESIGN: Three patients were vaccinated with 1.0×10(8) plaque-forming unit (pfu) p53MVA followed by nine patients at 5.6×10(8) pfu. Toxicity was classified using the NCI Common Toxicity Criteria and clinical responses were assessed by CT scan. Peripheral blood samples were collected pre- and post-immunization for immunophenotyping, monitoring of p53MVA-induced immune response, and examination of PD1 checkpoint inhibition in vitro. RESULTS: p53MVA immunization was well tolerated at both doses, with no adverse events above grade 2. CD4+ and CD8+ T cells showing enhanced recognition of a p53 overlapping peptide library were detectable after the first immunization, particularly in the CD8+ T-cell compartment (P=0.03). However, in most patients, this did not expand further with the second and third immunization. The frequency of PD1+ T cells detectable in patients' peripheral blood mononuclear cells (PBMC) was significantly higher than in healthy controls. Furthermore, the frequency of PD1+ CD8+ T cells showed an inverse correlation with the peak CD8+ p53 response (P=0.02) and antibody blockade of PD1 in vitro increased the p53 immune responses detected after the second or third immunizations. Induction of strong T-cell and antibody responses to the MVA backbone were also apparent. CONCLUSION: p53MVA was well tolerated and induced robust CD8+ T-cell responses. Combination of p53MVA with immune checkpoint inhibition could help sustain immune responses and lead to enhanced clinical benefit.

Evaluation of expert criteria for preoperative magnetic resonance imaging of newly diagnosed breast cancer.

Despite 2 randomized trials reporting no reduction in operations or local recurrence at 1 year, preoperative magnetic resonance imaging (MRI) is increasingly used in diagnostic workup of breast cancer. We evaluated 5 utilization criteria recently proposed by experts. Of women (n = 340) newly diagnosed with unilateral breast cancer who underwent bilateral MRI, most (69.4%) met at least 1 criterion before MRI: mammographic density (44.4%), under consideration for partial breast irradiation (PBI) (19.7%), genetic-familial risk (12.9%), invasive lobular carcinoma (11.8%), and multifocal/multicentric disease (10.6%). MRI detected occult malignant lesion or extension of index lesion in 21.2% of index, 3.3% of contralateral, breasts. No expert criterion was associated with MRI-detected malignant lesion, which associated instead with pre-MRI plan of lumpectomy without PBI (48.2% of subjects): Odds Ratio 3.05, 95% CI 1.57-5.91 (p adjusted for multiple hypothesis testing = 0.007, adjusted for index-vs-contralateral breast and covariates). The expert guidelines were not confirmed by clinical evidence.

Overcoming immunosuppression to enhance a p53MVA vaccine.

A Phase I trial of a p53-targeting modified vaccinia Ankara (p53MVA) vaccine in patients afflicted with refractory gastrointestinal cancers demonstrated enhanced T-cell recognition of p53 following vaccination. However, this effect was transient suggesting that p53MVA requires combination with immunomodulatory agents to deliver clinical benefit. Here, we outline our rationale for combining p53MVA with immunomodulatory chemotherapy in a forthcoming trial.

Adipose stromal vascular fraction isolation: a head-to-head comparison of four commercial cell separation systems.

BACKGROUND: Supplementation of fat grafts with stromal vascular fraction cells is an emerging technique used to improve graft reliability. A variety of systems for isolating stromal vascular fraction cells are commercially available. The lack of performance data obtained operating the systems in a standardized environment prevents objective assessment of performance. This prospective, blinded study compared performance of four commercially available stromal vascular fraction isolation systems when operated in a clinical outpatient surgery environment. METHODS: Four different systems were compared: (1) PNC's Multi Station, (2) CHA Biotech Cha-Station, (3) Cytori Celution 800/CRS System, and (4) Medi-Khan's Lipokit with MaxStem. Identical lipoaspirate samples from five separate volunteer donors were used to evaluate system process time, viable cell yield, composition, residual enzyme, and operating costs. RESULTS: The mean processing time ranged from 88 to 115 minutes. The highest mean number of viable nucleated cells was obtained using the Celution System (2.41 × 10 cells/g) followed by the Multi Station (1.07 × 10 cells/g). Lipokit and Cha-Station systems yielded nearly a log fewer nucleated cells (0.35 × 10 cells/g and 0.05 × 10 cells/g, respectively). The Celution System also yielded significantly more endothelial cells, CD34/CD31 cells, and adipose-derived stem cells (colony-forming unit-fibroblast). Residual enzyme levels observed with the Multi Station, Cha-Station, and Lipokit, respectively, averaged 5.1-, 13.0-, and 57-fold higher than that observed with the Celution System. CONCLUSIONS: Although all systems generated measurable amounts of stromal vascular fraction, significant variability exists in the number, identity, and safety profiles of recovered viable cells. Side-by-side clinical trials will be required to establish the relevance of these differences.

Systemic delivery of Salmonella typhimurium transformed with IDO shRNA enhances intratumoral vector colonization and suppresses tumor growth.

Generating antitumor responses through the inhibition of tumor-derived immune suppression represents a promising strategy in the development of cancer immunotherapeutics. Here, we present a strategy incorporating delivery of the bacterium Salmonella typhimurium (ST), naturally tropic for the hypoxic tumor environment, transformed with a small hairpin RNA (shRNA) plasmid against the immunosuppressive molecule indoleamine 2,3-dioxygenase 1 (shIDO). When systemically delivered into mice, shIDO silences host IDO expression and leads to massive intratumoral cell death that is associated with significant tumor infiltration by polymorphonuclear neutrophils (PMN). shIDO-ST treatment causes tumor cell death independently of host IDO and adaptive immunity, which may have important implications for use in immunosuppressed patients with cancer. Furthermore, shIDO-ST treatment increases reactive oxygen species (ROS) produced by infiltrating PMNs and, conversely, PMN immunodepletion abrogates tumor control. Silencing of host IDO significantly enhances S. typhimurium colonization, suggesting that IDO expression within the tumor controls the immune response to S. typhimurium. In summary, we present a novel approach to cancer treatment that involves the specific silencing of tumor-derived IDO that allows for the recruitment of ROS-producing PMNs, which may act primarily to clear S. typhimurium infection, but in the process also induces apoptosis of surrounding tumor tissue resulting in a vigorous antitumor effect.

The evolution of surgical technique for total gastrectomy over a 12-year period: a single institution's experience.

Despite the wide acceptance of laparoscopic surgical techniques, its use for gastric cancer has been limited. Laparoscopic total gastrectomy poses many technical challenges when compared with open gastrectomy. Our objective was to evaluate our institutional experience and surgical technique for total gastrectomy. Through a review of patients undergoing total gastrectomy (1999 to 2011), 50 patients were identified. During the first decade, 25 per cent of total gastrectomies were performed laparoscopically compared with 77 per cent since 2009. Compared with open cases, laparoscopic cases yielded a significantly higher number of examined lymph nodes (29 vs 19), lower estimated blood loss (200 vs 450 mL), and shorter length of stay (8 vs 14 days). Median operative time, average tumor size, and number of positive lymph nodes were not different. Morbidity rates were much lower in the laparoscopic series; and 30-day mortality rates were similar in both groups. Laparoscopic total gastrectomy and D2 lymphadenectomy are comparable in safety and have improved efficacy than our open total gastrectomy experience. After initiation of a laparoscopic total gastrectomy program in 2009, the majority of cases in our institution are now performed by laparoscopic techniques.