Opioid-free anesthesia for patients undergoing mastectomy: A matched comparison.

Opioid-free anesthesia (OFA) is being implemented in breast surgery due to increased awareness of adverse effects and the national opioid crisis. The objective of this study was to examine the effect of OFA on postoperative pain and postoperative nausea and vomiting (PONV) in mastectomy patients. A single-institution matched-cohort study was conducted from 2014 to 2017 on 48 women undergoing mastectomy, with the majority also undergoing immediate prosthetic-based reconstruction. Patients received either conventional anesthesia (CA) or a novel OFA regimen. Primary outcomes included postoperative pain scores, opioid use, and need for antiemetics that were evaluated both in the PACU and on the hospital floors. No significant differences were found in PACU opioid or antiemetic use between OFA and CA. Pain scores in PACU and on POD0 were not significantly different. There was a significant but modest decrease on POD1 in OFA patients (3.9 vs. 5.1, P = .046). Additionally, patients with higher intraoperative opioid regimens experienced significantly increased PONV (P = .023). This study demonstrated the efficacy of OFA in controlling postoperative pain and nausea compared to a traditional opioid-based regimen. Regardless of intraoperative opioids, patients experienced similar postoperative opioid requirements and PONV with decreased pain scores. Thus, OFA is feasible in mastectomy patients and should be further evaluated in select patients.

Appendiceal goblet cell carcinomatosis treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

BACKGROUND: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is a treatment commonly applied to peritoneal surface disease from low-grade mucinous tumors of the appendix. Some centers have extended this therapy to carcinomatosis from more aggressive malignancies. Therefore, we reviewed our experience with CRS/HIPEC for patients with goblet cell carcinomatosis. METHODS: Patients with carcinomatosis from appendiceal primaries with goblet cell features were identified in a prospectively maintained database of 1198 CRS/HIPEC procedures performed between 1991 and 2014. Patient demographics, disease characteristics, morbidity, mortality, and survival were reviewed. RESULTS: A total of 31 patients with carcinomatosis originating from appendiceal goblet cell tumors underwent CRS/HIPEC during the study period. Patients were generally young (mean age, 53 y) and otherwise healthy (84% without comorbidities) with good performance status (94% Eastern Cooperative Oncology Group 0 or 1). The mean number of visceral resections was 3.5, and complete cytoreduction of macroscopic disease was accomplished in 36%. Major 90-d morbidity and mortality rates were 38.7% and 9.7%, respectively. Median overall survival (OS) for all patients was 18.4 mo. Patients with negative nodes had better survival than those with positive nodes (median OS, 29.2 versus 10.2 mo), respectively (P = 0.002). Although complete cytoreduction was associated with longer median OS after CRS/HIPEC (R0/R1 28.6 versus R2 17.2 mo, P = 0.47), the observed difference did not reach statistical significance. CONCLUSIONS: CRS/HIPEC may improve survival in patients with node negative goblet cell carcinomatosis when a complete cytoreduction is achieved. Patients with disease not amenable to complete cytoreduction should not be offered CRS/HIPEC.

Acute Postoperative Complications in Prepectoral versus Subpectoral Reconstruction following Nipple-Sparing Mastectomy.

BACKGROUND: Nipple-sparing mastectomy is associated with improved aesthetics and oncologic safety. Recently, there has been a resurgence in prepectoral reconstruction. Because of limited data comparing complication rates on patients undergoing prepectoral breast reconstruction, this study compared 30-day postoperative complications by plane of prosthetic placement. METHODS: A retrospective review was conducted on all consecutive patients undergoing nipple-sparing mastectomy with implant-based reconstruction with either prepectoral or subpectoral placement from 2014 to 2018. The primary outcome was a composite, acute 30-day postoperative complication, including nipple-areola complex necrosis, mastectomy flap necrosis, wound dehiscence, infection, hematoma, and seroma. Secondary outcomes included nipple loss and rates of unintended reoperations. Univariate and mixed effects multivariate logistic regression were used to compare outcomes. RESULTS: A total of 228 patients and 405 breasts were included in the final cohort, with 202 in the subpectoral cohort and 203 in the prepectoral cohort. The overall complication rate was 7.65 percent, with no significant difference between subpectoral and prepectoral cohorts (9.41 percent versus 5.91 percent, respectively; p = 0.148). Prepectoral reconstruction was associated with significantly reduced ischemic complications, including nipple loss because of necrosis (2.97 percent versus 0.49 percent, respectively; p = 0.015) and mastectomy flap necrosis (5.45 percent versus 0 percent; p = 0.003). There were no significant differences in rates of infection, hematoma, seroma, or implant loss/exchange. CONCLUSIONS: Prepectoral reconstruction is associated with similar overall 30-day postoperative complications and reoperations compared to traditional subpectoral implants. However, prepectoral reconstruction was associated with significantly decreased ischemic complications, including mastectomy flap necrosis and nipple-areola complex loss because of necrosis. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Intracystic papillary carcinoma of the breast: A SEER database analysis of implications for therapy.

BACKGROUND: Intracystic papillary carcinoma (IPC) of the breast is a rare breast malignancy with an indolent course. However, patients can develop metastatic disease. Indications for surgery and radiotherapeutic management have not been well elucidated. METHODS: We identified 2649 female patients with IPC from the Surveillance, Epidemiology, and End Results (SEER) registry. Differences in demographics, clinical features and survival of patients were assessed using the Kaplan-Meier method and Cox regression. RESULTS: Median age was 67 years. The majority of patients were white with Stage 0 disease. Most patients had lymph node evaluation and only 34% received radiation therapy. Using a log-rank test, survival was significantly better in Caucasian compared to African-American patients, patients with early stage disease, negative lymph nodes and those who received radiation (all p < 0.0001). In a Cox regression survival model adjusting for age, stage and grade, patients who were African-American (hazard ratio [HR] 2.0, CI 1.4-2.8; p < 0.0001) had a significantly higher risk of death than Caucasians. Patients who received radiation therapy (HR 0.5, CI 0.3-0.7; p = 0.0003) had a lower chance of death than patients that did not undergo radiation. CONCLUSION: Overall, IPC has a good prognosis. Survival is improved in Caucasian patients and in patients who receive radiation therapy. Radiation therapy should be offered to women with IPC who undergo breast conserving surgery.

Identification of T-cell Receptors Targeting KRAS-Mutated Human Tumors.

KRAS is one of the most frequently mutated proto-oncogenes in human cancers. The dominant oncogenic mutations of KRAS are single amino acid substitutions at codon 12, in particular G12D and G12V present in 60% to 70% of pancreatic cancers and 20% to 30% of colorectal cancers. The consistency, frequency, and tumor specificity of these "neoantigens" make them attractive therapeutic targets. Recent data associate T cells that target mutated antigens with clinical immunotherapy responses in patients with metastatic melanoma, lung cancer, or cholangiocarcinoma. Using HLA-peptide prediction algorithms, we noted that HLA-A*11:01 could potentially present mutated KRAS variants. By immunizing HLA-A*11:01 transgenic mice, we generated murine T cells and subsequently isolated T-cell receptors (TCR) highly reactive to the mutated KRAS variants G12V and G12D. Peripheral blood lymphocytes (PBL) transduced with these TCRs could recognize multiple HLA-A*11:01(+) tumor lines bearing the appropriate KRAS mutations. In a xenograft model of large established tumor, adoptive transfer of these transduced PBLs reactive with an HLA-A*11:01, G12D-mutated pancreatic cell line could significantly reduce its growth in NSG mice (P = 0.002). The success of adoptive transfer of TCR-engineered T cells against melanoma and other cancers supports clinical trials with these T cells that recognize mutated KRAS in patients with a variety of common cancer types.