Perioperative systemic immunophenotype following irreversible electroporation (IRE) predicts recurrence.

Comprehensive understanding of the immunophenotypic response to local therapy will likely be required to improve outcomes for pancreatic ductal adenocarcinoma (PDAC). While the desmoplastic stroma has rendered PDAC resistant to immunotherapies, irreversible electroporation (IRE), a non-thermal method of tumor ablation, can overcome some of this resistance and immune suppression. We studied the systemic immunophenotype of patients following local treatment of PDAC. Stored lymphocytes from peripheral blood collected pre- and post-operatively for patients with PDAC who underwent surgical treatment from 12/2018 until 12/2019 were prepared for mass cytometry and a 30-marker panel identifying 37 immune-cell clusters were analyzed and compared to all clinical parameters. Stored lymphocytes from patient samples were collected pre-operatively postoperatively (Day 1, 3, 5 and 14) and during surveillance (Month 3, 6, 9 and 12). Thirty patients with locally advanced pancreatic cancer (LAPC) who underwent IRE were evaluated prospectively for changes in their immunophenotype. No significant differences in baseline demographics or tumor markers were identified. CA19-9 levels were significantly higher among patients who developed a recurrence (P=0.03). In the early perioperative period, CD4 and CD8 central memory cells were significantly higher among patients who did not recur (P=0.02 and 0.009 respectively). These findings were maintained in the late (>3 month) surveillance period. Early natural killer (NK) cells were significantly higher among those who did not recur (P=0.004) in the early postoperative period. The early immune-cell populations of CD4 and CD8 central memory cells and early NK cells were significantly higher among populations who did not recur following IRE for PDAC during the study period, with maintenance of the CD4 and CD8 central memory populations during later surveillance. Monitoring the early immunophenotype may offer opportunities to augment the immune response following tumor-disruptive IRE for PDAC.

Role of Surgery in Stage IV Melanoma.

Stage IV melanoma has a 5-year survival rate of 6%, but considerable advances have been made in systemic therapies. Systemic immunotherapy has achieved durable responses in up to 40% of patients, with similar improvements with targeted therapies. This has reshaped the landscape for surgery in stage IV melanoma. Metastasectomy can be considered in patients on systemic immunotherapy or targeted therapy with responding, stable, or isolated progressing lesions, oligometastatic disease, or long disease-free intervals. Surgery plays a role in providing tumor tissue for preparation of tumor-infiltrating lymphocytes for adoptive cell therapy. Surgical palliation plays a role in patients with symptomatic metastases.

Cardiac synchronization and arrhythmia during irreversible electroporation.

BACKGROUND AND OBJECTIVES: Irreversible electroporation (IRE) is a nonthermal electrical tumor ablative strategy for unresectable tumors. IRE is relatively safe around critical structures but may induce cardiac arrhythmia when its delivery is not synchronized to the cardiac cycle. We performed a systematic literature review to determine rates of arrhythmia when IRE was utilized with or without cardiac synchronization. METHODS: An online literature search was conducted with additional hand selection of articles. Data were extracted and pooled analyses were performed. RESULTS: Twelve articles were included in analysis. IRE was performed for 481 patients; 46% hepatic tumors (n = 223), 36% pancreatic lesions (n = 168), and multiple other locations including prostate. Synchronization was performed on 422 patients. Arrhythmias were noted in 3.7% of cases (n = 18/481); cardiac synchronization: 1.2% (n = 5/422) vs unsynchronized: 22.0% (n = 13/59), P < .0001. These events occurred in every organ except the prostate. CONCLUSIONS: IRE remains a potent technology for unresectable tumors, but arrhythmia is a clinical concern. This literature review confirms that cardiac gating should be used in all cases outside of prostate to prevent this potentially serious adverse event.

Negative-pressure wound therapy does not reduce superficial SSI in pancreatectomy and hepatectomy procedures.

INTRODUCTION: Surgical site infections (SSIs) lead to increased morbidity and cost. Negative-pressure wound therapy (NPWT) removes wound exudate and improves local blood flow, but its effect on SSI is unproven following hepatectomy and pancreatectomy. The aim of this trial was to evaluate the effect of NPWT on SSI in this population. METHODS: Patients were randomized to incisional NPWT or sterile island dressing following surgery. SSI predictive factors were recorded as well as patient comorbidities. Wound complications and type of SSI were recorded prospectively. RESULTS: Forty patients received the standardized perioperative bundle. Twenty patients received sterile island: 11 hepatic and 9 pancreatic resections; 20 patients received NPWT: 11 hepatic and 9 pancreatic resections; 23 patients were male; mean age 60.8 years (SD ±10.3); mean BMI 31.7 (SD ±7.0). There were three incisional wound infections: two with sterile island, one with NPWT; six organ space infections: four sterile island and two NPWT. There were no significant differences in SSI rates between groups (P = .57). CONCLUSION: NPWT does not improve SSI rates over simple sterile dressing following hepatectomy or pancreatectomy. Improvements in SSI must be directed toward organ-space infections, which are unaffected by NPWT.

Complications of Jejunostomy Feeding Tubes: A Single Center Experience of 546 Cases.

INTRODUCTION: Adequate perioperative nutrition is critical for the success of surgical outcomes. Jejunostomy feeding tube placement may ensure enteral feeding access; however, these types of tubes have had variable reported rates of dysfunction/morbidity. The aim of our study was to report our experience with jejunostomy feeding tube placement and the long-term outcomes following complex foregut surgery. METHODS: We performed a review of all of our jejunostomy feeding tube placement patients from 1/1/2010 until 7/1/2018. The indication for surgery and primary operation were recorded. All adverse events related to the jejunostomy were recorded during the entire duration of tube access. Social "hassle-factor" issues were also reported, including the number of "jejunostomy-related" phone calls, reinsertion and related placement studies, and readmissions pertaining to jejunostomy-associated complications. RESULTS: During the study period, 542 primary procedures were performed with secondary jejunostomy placement. Jejunostomy-related adverse events occurred in 22.0% of patients (n = 119/542); 12.0% (n = 65/542) were dislodged tubes, 6.0% (n = 30/542) clogged tubes; 5% (n = 25/542) leaking tubes, and 2.8% (n = 15/542) site infections. Tube dysfunctions initiated 244 reinsertion/placement studies in 107 patients, 20 jejunostomy tube-related readmissions, and 78 phone calls to providers for tube dysfunction. Adverse event rates differed significantly between groups (p < 0.001), with esophagogastric resection adverse event rates of 42.3% versus 19.2% for pancreatic ablations. DISCUSSION: Jejunostomy feeding tubes resulted in adverse events in less than a third of patients. Patient-related hassle must be communicated preoperatively in order to prevent jejunostomy tube-related morbidity. Optimal early and late jejunostomy feeding optimization varies based on preoperative patient comorbidities, type of operation, and the need for adjuvant oncology therapy.

Melanoma.

Current recommendations by the United States Preventive Services Task Force do not support screening for skin cancer. Melanoma is unique among cancers because detection is through visual inspection. Development of technologies that aid visual inspection have supported screening strategies in high-risk populations such as older fair skinned males with personal or family history of melanoma. Clearly delineating these populations and appropriate utilization of these newer technologies will be imperative in future screening paradigms.

Transanal Endoscopic Microsurgery for Early Rectal Cancer: A Single-Center Experience.

BACKGROUND: There is debate regarding the appropriate use of transanal endoscopic microsurgery for rectal cancer. OBJECTIVE: This study analyzed our single-center experience with transanal endoscopic microsurgery for early rectal cancer. DESIGN: Medical charts of patients who underwent transanal endoscopic microsurgery were reviewed to determine lesion characteristics, as well as operative and treatment characteristics. Complications and recurrences were recorded. SETTINGS: The study was conducted at a single academic medical center. PATIENTS: Patients with early stage cancer (T1 or T2, N0, and M0) of the rectum were included. MAIN OUTCOME MEASURES: Local and overall recurrence and disease-specific survival were measured. RESULTS: A total of 92 patients were analyzed. Median follow-up was 4.6 years. Negative margins were obtained in 98.9%. Length of stay was 1 day for 95.4% of patients. The complication rate was 10.9% (n = 10), including urinary retention at 4.3% (n = 4) and postoperative bleeding at 4.3% (n = 4). Preoperative staging included 54 at T1 (58.7%) and 38 at T2 (41.3%). Adjuvant therapy was recommended for all of the T2 and select T1 lesions with adverse features on histology. The final pathologic stages of tumors were ypT0 at 8.7% (n = 8), pT1 at 58.7% (n = 54), pT2 at 23.9% (n = 22), and ypT2 at 8.7% (n = 8). The 3-year local recurrence risk was 2.4% (SE = 1.7), and overall recurrence was 6.7% (SE = 2.9). There were no recurrences among patients with complete pathologic response to neoadjuvant therapy. Mean time to recurrence was 2.5 years (SD = 1.43). A total of 89.2% of patients with very low tumors underwent curative resection without a permanent stoma (33/37). The 3-year disease-specific survival rate was 98.6% (95% CI, 90.4%-99.8%), and overall survival rate was 89.4% (95% CI, 79.9%-94.6%). LIMITATIONS: The study was limited by its single-center retrospective experience. CONCLUSIONS: Transanal endoscopic microsurgery provides comparable oncologic outcomes to radical resection in properly selected patients with early rectal cancer. Sphincter preservation rates approach 90% even in patients with very distal rectal cancer.

Protective Actions of Epithelial 5-Hydroxytryptamine 4 Receptors in Normal and Inflamed Colon.

BACKGROUND & AIMS: The 5-hydroxytryptamine receptor 4 (5-HT4R or HTR4) is expressed in the colonic epithelium but little is known about its functions there. We examined whether activation of colonic epithelial 5-HT4R protects colons of mice from inflammation. METHODS: The 5-HT4R agonist tegaserod (1 mg/kg), the 5-HT4R antagonist GR113808 (1 mg/kg), or vehicle (control) were delivered by enema to wild-type or 5-HT4R knockout mice at the onset of, or during, active colitis, induced by administration of dextran sodium sulfate or trinitrobenzene sulfonic acid. Inflammation was measured using the colitis disease activity index and by histologic analysis of intestinal tissues. Epithelial proliferation, wound healing, and resistance to oxidative stress-induced apoptosis were assessed, as was colonic motility. RESULTS: Rectal administration of tegaserod reduced the severity of colitis compared with mice given vehicle, and accelerated recovery from active colitis. Rectal tegaserod did not improve colitis in 5-HT4R knockout mice, and intraperitoneally administered tegaserod did not protect wild-type mice from colitis. Tegaserod increased proliferation of crypt epithelial cells. Stimulation of 5-HT4R increased Caco-2 cell migration and reduced oxidative stress-induced apoptosis; these actions were blocked by co-administration of the 5-HT4R antagonist GR113808. In noninflamed colons of wild-type mice not receiving tegaserod, inhibition of 5-HT4Rs resulted in signs of colitis within 3 days. In these mice, epithelial proliferation decreased and bacterial translocation to the liver and spleen was detected. Daily administration of tegaserod increased motility in inflamed colons of guinea pigs and mice, whereas administration of GR113808 disrupted motility in animals without colitis. CONCLUSIONS: 5-HT4R activation maintains motility in healthy colons of mice and guinea pigs, and reduces inflammation in colons of mice with colitis. Agonists might be developed as treatments for patients with inflammatory bowel diseases.

Parastomal hernia repair.

Parastomal herniation is a common clinical occurrence. Historically, there has been a high recurrence rate after repair, and conservative management is usually recommended for patients with mild symptoms. When operative intervention is warranted, we opt for a laparoscopic mesh sublay over the fascial defect and lateralization of the stoma limb, or the Sugarbaker technique. In patients who are considered poor risk for laparoscopy/laparotomy requiring repair, we perform a fascial onlay with mesh utilizing an anterior circumstomal approach.