β-Hydroxy-β-Methylbutyrate Supplementation Promotes Antitumor Immunity in an Obesity Responsive Mouse Model of Pancreatic Ductal Adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related deaths in the United States, and effective therapies for PDAC are currently lacking. Moreover, PDAC is promoted and exacerbated by obesity, while cachexia and sarcopenia are exceptionally common comorbidities that predict both poor survival and treatment response. Managing PDAC with immunotherapies has thus far proven ineffective, partly due to the metabolically hostile tumor microenvironment. β-hydroxy-β-methylbutyrate (HMB), a metabolite of leucine commonly used as a dietary supplement to boost muscle growth and immune function, may be an attractive candidate to augment PDAC therapy. We therefore sought to test the hypothesis that HMB would enhance antitumor immunity while protecting mouse muscle mass. Control and diet-induced obese C57BL/6 male mice bearing subcutaneously injected Panc02 tumors were supplemented with 1% HMB and treated with or without 50 mg/kg gemcitabine (n = 15/group). HMB was associated with reduced muscle inflammation and increased muscle fiber size. HMB also reduced tumor growth and promoted antitumor immunity in obese, but not lean, mice, independent of the gemcitabine treatment. Separately, in lean tumor-bearing mice, HMB supplementation promoted an anti-PD1 immunotherapy response (n = 15/group). Digital cytometry implicated the decreased abundance of M2-like macrophages in PDAC tumors, an effect that was enhanced by anti-PD1 immunotherapy. We confirmed that HMB augments M1-like macrophage (antitumor) polarization. These preclinical findings suggest that HMB has muscle-sparing and antitumor activities against PDAC in the context of obesity, and that it may sensitize otherwise nonresponsive PDAC to immunotherapy.

The Benefits of a Muscle-Sparing Below Knee Amputation in the Elderly Population

Background It is well accepted that good muscle coverage of the bones at the end of a below knee amputation (BKA) stump is preferable, for both weight bearing and protection against prosthesis failure. Elderly patients often have atrophy of the leg musculature secondary to age-related physiological changes and decreased use. These patients often have poor coverage and bulk in their stumps after the standard BKA. We propose a selective muscle-sparing approach to these patients, utilizing selective removal of muscle bundles with regard to their blood supply and fascial planes. The surgical method technique along with outcomes of patients undergoing the procedure is presented here. Methods A retrospective chart review was performed to identify patients who had undergone a muscle-sparing BKA from March 2008 to October 2017 by a single surgeon. Estimated blood loss, operative time, and perioperative and postoperative complications were assessed. Results Forty-six patients greater than 60 years of age underwent muscle-sparing BKA procedures. Complete healing was seen in 30 (65%) patients, while 7 (15%) were lost to follow-up and 9 (20%) required conversion to an above knee amputation (AKA). Intraoperative outcomes in our series were notable for an average estimated blood loss (EBL) of 84.3 ml, lower than the traditional BKA (average EBL 150-500 ml), with comparable operative times averaging 131 minutes and as short as 85 minutes (skin incision to dressing). No patients in the cohort required postoperative blood transfusions (day 0–4), significantly less than the reported 3–7 ml/kg body weight blood requirements in similar patient populations. Conclusions The muscle-sparing BKA technique should be considered in elderly patients, where the normally bulky posterior calf muscle mass is lacking. The selective removal of muscle bundles with regard to their blood supply leaves maximum coverage of the bone with decreased potential hematoma formation and blood loss.

Functional Shoulder Outcome and Quality of Life Following Modified Muscle-Sparing Pectoralis Major Flap Surgery

Background: The pedicled pectoralis major muscle flap (PMMF) is a well established flap for fistula prophylaxis after salvage laryngectomy. To reduce donor site morbidity, we established a modified muscle-sparing harvesting technique. We herein investigate postoperative shoulder function and health-related quality of life (HRQOL). Methods: A chart review of patients receiving the modified muscle-sparing pectoralis major muscle flap between 2013–2020 was performed. Nineteen patients (male = 18, female = 1) were potentially eligible and six male patients were ultimately enrolled. Postoperative shoulder function was assessed on both sides (flap side versus non-flap side) using the Constant Murley Score and the Bak criteria. Health-related quality of life was assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire in cancer patients (EORTC QLQ-C30) and head and neck cancer patients (EORTC H&N35). Results: No Constant Murley Score subscale was statistically significant (p ≥ 0.180). Bak criteria was overall rated “Good“. Solely upper extremity adduction force was significantly altered on the flap side (p = 0.039). Median EORTC QLQ-C30 score was 82.2 (IQR 11.1) on the functional scale and 10.3 (IQR 2.6) on the symptomatic scale. Median quality of life score was 75.0 (IQR 33.3) and median EORTC QLQ-H&N35 was 20.6 (IQR 9.8). Conclusions: Postoperative shoulder function after modified muscle-sparing pectoralis major muscle flap surgery is comparable to function of the healthy side with a significant deficiency in adduction force not compromising daily life in this small study cohort.

772 Surgery for Bullous Lung Disease

Aim The aim of this study to assess the surgical presentation and outcome for bullous lung disease in Sudanese patients. Method A cross sectional hospital based descriptive retrospective study. Procedures were conducted at Al-Shaab Teaching Hospital Sudan during the period from November 2009 to September 2012. Results 11 patients had lung bullae in the given period. Smoking does not play an important role in the development of bullae in healthy young adults in our patients. Vanishing Lung syndrome (VLS) was seen in 18% of patients without history of smoking. The patients presenting in the fifth decade of life constituted (36.3%) of total number. symptoms of presentation were chest pain and SOB and half of them (45.5%) had exertional dyspnoea. The duration of symptoms before presentation was more than 2 months. Asthma was the only respiratory disease associated seen in 45%. HBV and HTN were the most associated diseases seen in 27% and 18% respectively without significant findings in the history. The diagnosis was made by highresolution CT. Chest in all patients. Bullectomy was done to majority of patients. Muscle sparing thoracotomy is the standard approach (Posterolateral Thoracotomy). improved regarding symptoms and signs (90.9%) and) and no death reported. Conclusions Bullous lung disease with bilateral lung involvement is common in our patients. However, there was no association between lung bullae and smoking in our population. lt's associated with other respiratory disease. The outcome was excellent, and no death was reported. To prevent the miss diagnosis we need sensitive and noninvasive investigation tools.

Minimally Invasive Approach for Dorsal Arachnoid Web: 2-Dimensional Operative Video

A 67-yr-old patient presented with severe paraparesis and lower limb spasticity. The spinal cord magnetic resonance imaging (MRI) revealed the “scalpel sign” 1,2 at the T7 level, suggesting a diagnosis of a dorsal arachnoid web. This video demonstrates a microsurgical technique for the excision of a dorsal arachnoid web with a minimally invasive approach. A paramedian skin incision, understanding the muscular aponeurosis, was performed from T7 to T8. Then, we inserted the tubular dilators until the lamina, to perform a muscle-sparing approach. An expandable tubular retractor of adequate length was passed over the widest dilator and docked into place along the subperiosteal plane. The T7 lamina was drilled, and the resection of the superior and inferior adjacent spine levels was completed with a rongeur. Additional contralateral bone resection was performed after tubular retractor tilt to the midline.3 After dura mater opening, it was carefully suspended and the dorsal arachnoid leaflet was cut to drain the dorsolateral and lateral spinal cisterns.4 The dorsal arachnoid web was, first, disconnected from its lateral anchorages. It was then gently removed with microsurgical forceps, to help its microdissection from the spinal cord surface. At this step, peculiar attention was paid to limit the traction or displacements of the spinal cord and surrounding vessels. Once the dorsal arachnoid web was removed, the quality of the spinal cord decompression was confirmed by its re-expansion. In conclusion, the minimally invasive approach is a safe and appropriate technique for dorsal arachnoid web excision.2,5,6-7 The patient gave her informed and signed consent for the writing and publication of this article. Image at 1:00 reused with permission from Castelnovo G et al, Spontaneous transdural spinal cord herniation, Neurology, 2014;82(14):1290.

Limited effects on patient outcomes of conjoint tendon release in anterolateral muscle-sparing total hip arthroplasty

Background The anterolateral muscle-sparing total hip arthroplasty (THA) in the supine position is advantageous owing to the very low-dislocation rate and excellent leg length discrepancy control. However, femur exposure is challenging. Although the conjoined external rotators tendon (CERT) release is effective in improving femoral access, the effects on clinical outcomes remain unclear. The purpose of this study was to evaluate the clinical and radiographic results of CERT release in the anterolateral muscle-sparing THA approach. Methods The study was performed as a retrospective cohort study and included 85 hips in 85 patients who underwent primary anterolateral THA. Clinical and radiographic outcomes were investigated 6 months and 1 year after THA (CERT-preserved and non-released patients). The Japanese Orthopaedic Association (JOA) hip score, JOA Hip-disease Evaluation Questionnaire (JHEQ), forgotten joint score (FJS), and the 36 short-form questionnaires (SF-36 mental and physical) were evaluated. The leg length discrepancy, cup inclination and stem orientation were evaluated with radiographs. Results Among all the included hips, 37 patients (43.5%) retained the CERT, and 48 patients (56.5%) included the released CERT. There were no significant differences in the JOA hip scores, JHEQ, FJF-12 and SF-36 between the released and non-released groups. There were significant differences in sagittal stem alignments between groups. Conclusion The CERT release in anterolateral muscle-sparing THA has a limited effect on post-operative clinical outcomes. The CERT release improved the femur exposure and is more invasive than the preserved CERT. We infer that the CERT should be maintained in patients with a wide range of motions, and release the CERT in inadequate femur canal preparation cases.