Interpectoral nerve blocks may lower postoperative narcotic use after mastectomy.

BACKGROUND: Pain management following mastectomy is a significant challenge often requiring opioids. Nonopioid pain management utilizing nerve blocks has been shown in other fields to reduce postoperative opioid use and may be effective for postoperative pain in mastectomy patients. The primary purpose of this study was to compare postoperative opioid use, measured in morphine milligram equivalents (MME), between mastectomy patients who underwent interpectoral nerve block (IPNB) and a historical control group. Secondary outcomes included length of stay (LOS) and postoperative pain scores. METHODS: This is a single-center, retrospective cohort study. The charts of women who underwent mastectomy for cancer without immediate reconstruction from 10/2017-12/2019 were reviewed. Wilcoxon rank sum test was used for unadjusted analysis and multiple linear regression for adjusted analysis. RESULTS: There were 105 patients included in this study, of which 37 (35%) underwent IPNB. In unadjusted analysis, median MME use was significantly lower in patients that received IPNB compared to the control group (IPNB = 5, controls = 17, p = 0.03). Patients that received IPNB had an observed reduction in LOS and postoperative pain, though these results failed to reach statistical significance. There were no IPNB-related complications. CONCLUSIONS: IPNB may be an effective strategy to decrease postoperative opioid use in mastectomy patients. Larger, prospective studies are needed to further investigate the effectiveness of IPNB.

Changes in Stage at Presentation among Lung and Breast Cancer Patients During the COVID-19 Pandemic.

BACKGROUND: The COVID-19 pandemic altered access to healthcare by decreasing the number of patients able to receive preventative care and cancer screening. We hypothesized that, given these changes in access to care, radiologic screening for breast and lung cancer would be decreased, and patients with these cancers would consequently present at later stages of their disease. STUDY DESIGN: This is a retrospective cross-sectional study of 2017 to September 2021 UMass Memorial Tumor Registry data for adult breast and lung cancer patients. Changes in stage at presentation of breast and lung cancer during the COVID-19 pandemic were measured, defined as before and during COVID-19. RESULTS: There were no statistically significant changes in the overall stage of presentation before or during the COVID-19 pandemic for either breast or lung cancer patients. Analysis of case presentation and stage during periods of COVID-19 surges that occurred during the time of this study compared with prepandemic data demonstrated a statistically significant decrease in overall presentation of breast cancer patients in the first surge, with no other statistically significant changes in breast cancer presentation. A nonstatistically significant decrease in lung cancer presentation was seen during the initial surge of COVID-19. There was also a statistically significant increase in early-stage presentation of lung cancer during the second and third COVID-19 surges. CONCLUSIONS: In the 2 years after the COVID-19 pandemic, we were not able to demonstrate stage migration at presentation of breast and lung cancer patients to later stages despite decreases in overall presentation during the initial 2 years of the COVID pandemic. An increase in early-stage lung cancer during the second and third surges is interesting and could be related to increased chest imaging for COVID pneumonia.

Update on the Financial Well-Being of Surgical Residents in New England.

BACKGROUND: Poor personal financial health has been linked to key components of health including burnout, substance abuse, and worsening personal relationships. Understanding the state of resident financial health is key to improving their overall well-being. STUDY DESIGN: A secondary analysis of a survey of New England general surgery residents was performed to understand their financial well-being. Questions from the National Financial Capability Study were used to compare to an age-matched and regionally matched cohort. RESULTS: Overall, 44% (250 of 570) of surveyed residents responded. Residents more frequently reported spending less than their income each year compared to the control cohort (54% vs 34%, p < 0.01). However, 17% (39 of 234) of residents reported spending more than their income each year. A total of 65% of residents (152 of 234), found it "not at all difficult" to pay monthly bills vs 17% (76 of 445) of the control cohort (p < 0.01). However, 32% (75 of 234) of residents reported it was "somewhat" or "very" difficult to pay monthly bills. Residents more frequently reported they "certainly" or "probably" could "come up with" $2,000 in a month compared to the control cohort (85% vs 62% p < 0.01), but 16% (37 of 234) of residents reported they could not. In this survey, 21% (50 of 234) of residents reported having a personal life insurance policy, 25% (59 of 234) had disability insurance, 6% (15 of 234) had a will, and 27% (63 of 234) had >$300,000 worth of student loans. CONCLUSIONS: Surgical residents have better financial well-being than an age-matched and regionally matched cohort, but there is still a large proportion who suffer from financial difficulties.

Clinical Impact of Immune Checkpoint Inhibitor (ICI) Response, DNA Damage Repair (DDR) Gene Mutations and Immune-Cell Infiltration in Metastatic Melanoma Subtypes.

Molecular and histopathological analysis of melanoma subtypes has revealed distinct epidemiological, genetic, and clinical features. However, immunotherapy for advanced metastatic melanoma patients does not differ based on subtype. Response to immune checkpoint inhibitors (ICI) has been shown to vary, therefore, predictive biomarkers are needed in the design of precision treatments. Targeted sequencing and histopathological analysis (CD8 and CD20 immunohistochemistry) were performed on subtypes of metastatic melanoma (cutaneous melanoma (CM, n = 10); head and neck melanoma (HNM, n = 7); uveal melanoma (UM, n = 4); acral lentiginous melanoma (AM, n = 1) and mucosal melanoma (MM, n = 1) treated with ICI). Progression-free survival (PFS) was significantly associated with high CD8 expression (p = 0.025) and mutations in DNA damage repair (DDR) pathway genes (p = 0.012) in all subtypes but not with CD20 expression. Our study identified that immune cell infiltration and DDR gene mutations may have an impact in response to ICI treatment in metastatic melanoma but differs among subtypes. Therefore, a comprehensive understanding of the immune infiltration cells' role and DDR gene mutations in metastatic melanoma may identify prognostic biomarkers.

Update on the Personal and Professional Well-Being of Surgical Residents in New England.

BACKGROUND: Surgical culture has shifted to recognize the importance of resident well-being. This is the first study to longitudinally track regional surgical resident well-being over 5 years. STUDY DESIGN: An anonymous cross-sectional, multi-institutional survey of New England general surgery residents using novel and published instruments to create three domains: health maintenance, burnout, and work environment. RESULTS: Overall, 75% (15 of 20) of programs participated. The response rate was 44% (250 of 570), and 53% (133 of 250) were women, 94% (234 of 250) were 25 to 34 years old, and 71% (178 of 250) were in a relationship. For health maintenance, 57% (143 of 250) reported having a primary care provider, 26% (64 of 250) had not seen a primary care provider in 2 years, and 59% (147 of 250) endorsed being up to date with age-appropriate health screening, but only 44% (109 of 250) were found to actually be up to date. Only 14% (35 of 250) reported exercising more than 150 minutes/week. The burnout rate was 19% (47 of 250), with 32% (81 of 250) and 25% (63 of 250) reporting high levels of emotional exhaustion and depersonalization, respectively. For program directors and attendings, 90% of residents reported that they cared about resident well-being. Eighty-seven percent of residents believed that it was acceptable to take time off during the workday for a personal appointment, but only 49% reported that they would personally take the time. CONCLUSIONS: The personal health maintenance of general surgery residents has changed little over the past five years, despite an overwhelming majority of residents reporting that attendings and program directors care about their well-being. Further study is needed to understand the barriers to improvement of resident wellbeing.

Accelerated Graduation and the Deployment of New Physicians During the COVID-19 Pandemic.

The COVID-19 pandemic has presented unprecedented challenges and opportunities for medical schools in the United States. In this Invited Commentary, the authors describe a unique collaboration between the University of Massachusetts Medical School (UMMS), the only public medical school in the state; the University of Massachusetts Memorial Medical Center (UMMMC); and the Commonwealth of Massachusetts. Through this partnership, UMMS was able to graduate fourth-year medical students 2 months early and deploy them to UMMMC to care for patients and alleviate workforce shortages during the COVID-19 surge, which peaked in Massachusetts in April 2020. The authors describe how they determined if students had fulfilled graduation requirements to graduate early, what commencement and the accompanying awards ceremony looked like this year as virtual events, the special emergency 90-day limited license these new graduates were given to practice at UMMMC during this time, and the impact these new physicians had in the hospital allowing residents and attendings to be redeployed to care for COVID-19 patients.

PRDX3 is associated with metastasis and poor survival in uveal melanoma.

AIMS: Uveal melanoma (UM) is the most common primary intraocular malignancy in adults, and 40% develop fatal metastatic disease. Overexpression of thioredoxin-dependent peroxidase reductase (PRDX3) has been implicated in several cancers, including prostate, breast, colorectal and lung cancer. The aim of this study was to compare the immunohistochemical expression of PRDX3 in formalin-fixed, paraffin-embedded (FFPE) primary UM tissues of patients who did and did not develop metastatic disease. METHODS: Immunohistochemical staining of PRDX3 was performed on FFPE tissue microarray samples of 92 primary UM tumours from patients who did and did not develop metastatic disease. The immunohistochemical staining was assessed by two observers who were blinded to all clinicopathological and cytogenetic details including metastatic/non-metastatic information. Based on a scoring system, expression of PRDX3 was graded as high or low. RESULTS: There were 55 tumours (59.8%) from patients who developed metastatic disease, while 37 (40.2%) were from patients who did not develop metastasis. A statistically significant difference in PRDX3 expression was observed in patients who did and did not develop metastasis (p=0.001). A significant positive correlation between high PRDX3 expression and metastasis was observed (p=0.001). A significant negative correlation between PRDX3 expression and survival was found (p=0.005). Kaplan-Meier survival analysis showed a statistically significant difference in overall survival between tumours that demonstrated low and high expression of PRDX3 (67.61 vs 130.64 months, respectively, p=0.013). CONCLUSIONS: High immunohistochemical expression of PRDX3 in primary UM tissue is associated with metastasis and poor survival.

Prophylactic Versus Therapeutic Mastectomy: A Contemporary Analysis of the ACS-NSQIP Database.

INTRODUCTION: The objective of the study was to evaluate the morbidity, mortality, and postoperative outcomes associated with simple or subcutaneous mastectomy in the management of prophylactic versus therapeutic resection. In this study we aimed to assess if simple or subcutaneous mastectomy for prophylaxis affects perioperative outcomes compared with resection performed for biopsy proven malignancy. MATERIALS AND METHODS: The American College of Surgeons National Surgical Quality Improvement Program database was queried for subjects who underwent simple or subcutaneous mastectomy between 2007 and 2012. Patient demographic characteristics, comorbid conditions, and postoperative complications were analyzed. RESULTS: Of the 30,803 patients, 30,644 (99.5%) underwent therapeutic mastectomy and 159 (0.5%) underwent prophylactic mastectomy. Subjects who underwent prophylactic surgery were more likely to be younger (45 vs. 58 years; P < .01) and white (134 [84%] vs. 20,647 [67%]; P < .01). Surgery time was significantly greater in the prophylactic group (265 vs. 166 minutes; P < .01). There was no significant difference in mortality between groups. There was a trend toward greater 30-day morbidity (15 [9%] vs. 1835 [6%]; P = .09) and occurrence of deep venous thrombosis (DVT; 2 [1%] vs. 74 [0.2%]; P = .06) in those who underwent prophylactic mastectomy. After age adjustment, the prophylactic group showed a nearly sixfold increase in DVT (odds ratio [OR], 5.77; 95% confidence interval [CI], 1.37-24.22), which persisted when controlling for surgery time (OR, 4.95; 95% CI, 1.18-20.86). CONCLUSION: Prophylactic simple or subcutaneous mastectomy incurs significant additional 30-day postoperative morbidity related to perioperative DVT. Risk-mitigating strategies should be considered in the perioperative care of this patient population.

Current and future biomarkers for risk-stratification and treatment personalisation in multiple myeloma.

Multiple myeloma, an incurable malignancy of the plasma cells in the bone marrow, has a complex pathogenesis due to clonal heterogeneity. Over the years, many clinical trials and researches have led to the development of effective myeloma treatments, resulting in survival prolongation. Molecular prognostic markers for risk-stratification to predict survival, and predictive markers for treatment response are being extensively explored. This review discusses the current risk-adaptive strategies based on genetic and molecular risk signatures that are in practice to predict survival and describes the future prognostic and predictive biomarkers across the fields of genomics, proteomics, and glycomics in myeloma. Gene expression profiling and next generation sequencing are coming to the forefront of risk-stratification and therapeutic-response prediction. Similarly, proteomic and glycomic-based platforms are gaining momentum in biomarker discovery to predict drug resistance and disease progression.

Rosai-Dorfman Disease of the Breast.

Rosai-Dorfman disease (also known as sinus histiocytosis with massive lymphadenopathy) is a rare benign proliferative disorder of histiocytes that typically involves the lymph nodes and can also involve extranodal sites. Rosai-Dorfman disease confined to the breast is extremely rare, but important to recognize as it can mimic malignancy. We present the case of a 63-year-old woman who presented with a palpable breast lump that was highly suspicious for malignancy based on mammogram and ultrasound appearance. Biopsy revealed inflammatory tissue with lymphoplasmacytic and histiocytic predominance. The diagnosis of Rosai-Dorfman was made based on characteristic staining of histiocytes with S-100 and the presence of emperipolesis. Early recognition of this benign disease entity spared the patient further investigation and surgical intervention.

Teaching of Independent Exercises for Prehabilitation in Breast Cancer.

We attempted to determine the feasibility of studying prehabilitation exercises to improve shoulder pain and abduction range of motion (ROM) after breast cancer surgery. We evaluated methods of exercise teaching and assessed effect on postsurgical seroma formation. This was a feasibility study with two non-blinded groups of subjects randomized by timing of appointment. This single-site study was performed at an academic tertiary medical center. Sixty cancer patients were randomly assigned to either group 1, in-person teaching arm, n = 36, or group 2, video-only teaching arm, n = 24. Forty-five patients completed the study. Shoulder exercises were assigned to both groups 1 month prior to surgery during evaluation. Group 1 received in-person instruction on exercises, plus an information sheet with exercises and a link to an online video. Group 2 received only the information sheet with exercises and a link to the online video. The primary outcomes considered are as follows: exercise compliance, shoulder pain (via visual analog scale), shoulder abduction ROM (via goniometer), and presence or absence of seroma. Seventy-six percent of study patients chose to exercise. There was no difference in exercise compliance between in-person teaching versus video teaching (75 %, 24/32 vs. 77 %, 10/13, OR = 1.03). Sixty-six of patients (20/30) lost greater than 10° shoulder abduction ROM at 1 month post surgery. Twenty-nine of patients (9/31) had worse shoulder pain than baseline at 1 month post surgery (24 %, 6/25 exercisers, and 50 %, 3/6 non-exercisers). Fifteen percent of patients (4/27) had worse shoulder pain than baseline at 3 months post surgery (8 %, 2/23 exercisers, and 100 %, 2/2 non-exercisers). Prehabilitation exercise program inferred no additional risk of seroma formation (Exercisers 21 %, 7/33 vs. non-exercisers 22 %, 2/9, OR = 0.94). Our subjects were able to perform three exercises independently in the preoperative period. A high-quality randomized controlled trial is necessary to assess the appropriate timing and efficacy of this intervention.

Polyclonal Immunoglobulin G N-Glycosylation in the Pathogenesis of Plasma Cell Disorders.

The pathological progression from benign monoclonal gammopathy of undetermined significance (MGUS) to smoldering myeloma (SMM) and finally to active myeloma (MM) is poorly understood. Abnormal immunoglobulin G (IgG) glycosylation in myeloma has been reported. Using a glycomic platform composed of hydrophilic interaction UPLC, exoglycosidase digestions, weak anion-exchange chromatography, and mass spectrometry, polyclonal IgG N-glycosylation profiles from 35 patients [MGUS (n = 8), SMM (n = 5), MM (n = 8), complete-response (CR) post-treatment (n = 5), relapse (n = 4), healthy age-matched control (n = 5)] were characterized to map glycan structures in distinct disease phases of multiple myeloma. N-Glycan profiles from MGUS resembled normal control. The abundance of neutral glycans containing terminal galactose was highest in SMM, while agalactosylated glycans and fucosylated glycans were lowest in MM. Three afucosyl-biantennary-digalactosylated-sialylated species (A2G2S1, A2BG2S1, and A2BG2S2) decreased 2.38-, 2.4-, and 4.25-fold, respectively, from benign to active myeloma. Increased light chain sialylation was observed in a longitudinal case of transformation from MGUS to MM. Bisecting N-acetylglucosamine was lowest in the CR group, while highest in relapsed disease. Gene expression levels of FUT 8, ST6GAL1, B4GALT1, RECK, and BACH2 identified from publicly available GEP data supported the glycomic changes seen in MM compared to control. The observed differential glycosylation underlined the heterogeneity of the myeloma spectrum. This study demonstrates the feasibility of mapping glycan modifications on the IgG molecule and provides proof of principle that differential IgG glycosylation patterns can be successfully identified in plasma cell disorders.

Randomized trial of a short course of preoperative potassium iodide in patients undergoing thyroidectomy for Graves' disease.

BACKGROUND: A short course of potassium iodide (SSKI) has been traditionally used to prepare patients with Graves' disease for thyroidectomy. The rationale for this treatment has evolved over time; from control of hyperthyroidism to facilitating surgery by making the gland less friable and bloody. METHODS: Randomized trial of preoperative SSKI vs no SSKI to test whether that is true. RESULTS: Mean estimated blood loss in the SSKI group (62 mL) was less than in the control group (162 mL) as was the median estimated blood loss (50 vs 140 mL). Mean (142 vs 162 minutes) and median (138 vs 150 minutes) operative times were also less in the SSKI arm. Subjective difficulty of operation was similar. Multivariable comparisons of groups with analysis of covariance showed the SSKI group suffered a mean blood loss 35% of the no treatment group (P = .036), the 9.2% decrease in Operating Room (OR) time between the SSKI group and the no treatment group was not statistically different (P = .464). CONCLUSIONS: SSKI given before operation in patients with Graves' disease reduces blood loss during thyroidectomy.

Elevated levels of 14-3-3 proteins, serotonin, gamma enolase and pyruvate kinase identified in clinical samples from patients diagnosed with colorectal cancer.

BACKGROUND: Colorectal cancer (CRC), a heterogeneous disease that is common in both men and women, continues to be one of the predominant cancers worldwide. Lifestyle, diet, environmental factors and gene defects all contribute towards CRC development risk. Therefore, the identification of novel biomarkers to aid in the management of CRC is crucial. The aim of the present study was to identify candidate biomarkers for CRC, and to develop a better understanding of their role in tumourogenesis. METHODS: In this study, both plasma and tissue samples from patients diagnosed with CRC, together with non-malignant and normal controls were examined using mass spectrometry based proteomics and metabolomics approaches. RESULTS: It was established that the level of several biomolecules, including serotonin, gamma enolase, pyruvate kinase and members of the 14-3-3 family of proteins, showed statistically significant changes when comparing malignant versus non-malignant patient samples, with a distinct pattern emerging mirroring cancer cell energy production. CONCLUSION: The diagnosis and management of CRC could be enhanced by the discovery and validation of new candidate biomarkers, as found in this study, aimed at facilitating early detection and/or patient stratification together with providing information on the complex behaviour of cancer cells.