Recent advances for treatment of upper gastrointestinal malignancy.

Recent prospective trials for esophageal cancer, gastric cancer, and gastrointestinal stromal tumor (GIST) are encouraging. This manuscript reviews selected recently published studies. Not surprisingly, immunotherapy dominates the current clinical trial landscape. However, targeted biologic therapies and standard chemotherapy remain critical to the treatment of gastric and esophageal cancer while imatinib remains the backbone for advanced or metastatic GISTs. For all three cancers, surgical resection remains important when intent of treatment is potential cure.

Oncologic Outcomes of Multi-Institutional Minimally Invasive Inguinal Lymph Node Dissection for Melanoma Compared with Open Inguinal Dissection in the Second Multicenter Selective Lymphadenectomy Trial (MSLT-II).

BACKGROUND: Minimally invasive inguinal lymphadenectomy (MILND) is safe and feasible, but limited data exist regarding oncologic outcomes. METHODS: This study performed a multi-institutional retrospective cohort analysis of consecutive MILND performed for melanoma between January 2009 and June 2016. The open ILND (OILND) comparative cohort comprised patients enrolled in the second Multicenter Selective Lymphadenectomy Trial (MSLT-II) between December 2004 and March 2014.The pre-defined primary end point was the same-basin regional nodal recurrence, calculated using properties of binomial distribution. Time to events was calculated using the Kaplan-Meier method. The secondary end points were overall survival, progression-free survival, melanoma-specific survival (MSS), and distant metastasis-free survival (DMFS). RESULTS: For all the patients undergoing MILND, the same-basin regional recurrence rate was 4.4 % (10/228; 95 % confidence interval [CI], 2.1-7.9 %): 8.2 % (4/49) for clinical nodal disease and 3.4 % (6/179) for patients with a positive sentinel lymph node (SLN) as the indication. For the 288 patients enrolled in MSLT-II who underwent OILND for a positive SLN, 17 (5.9 %) had regional node recurrence as their first event. After controlling for ulceration, positive LN count and positive non-SLNs at the time of lymphadenectomy, no difference in OS, PFS, MSS or DMFS was observed for patients with a positive SLN who underwent MILND versus OILND. CONCLUSION: This large multi-institutional experience supports the oncologic safety of MILND for melanoma. The outcomes in this large multi-institutional experience of MILND compared favorably with those for an OILND population during similar periods, supporting the oncologic safety of MILND for melanoma.

Formal robotic training diminishes the learning curve for robotic pancreatoduodenectomy: Implications for new programs in complex robotic surgery.

INTRODUCTION: The learning curve associated with robotic pancreatoduodenectomy (RPD) is a hurdle for new programs to achieve optimal results. Since early analysis, robotic training has recently expanded, and the RPD approach has been refined. The purpose of this study is to examine RPD outcomes for surgeons who implemented a new program after receiving formal RPD training to determine if such training reduces the learning curve. METHODS: Outcomes for consecutive patients undergoing RPD at a single tertiary institution were compared to optimal RPD benchmarks from a previously reported learning curve analysis. Two surgical oncologists with formal RPD training performed all operations with one surgeon as bedside assistant and the other at the console. RESULTS: Forty consecutive RPD operations were evaluated. Mean operative time was 354 ± 54 min, and blood loss was 300 ml. Length of stay was 7 days. Three patients (7.5%) underwent conversion to open. Pancreatic fistula affected five patients (12.5%). Operative time was stable over the study and lower than the reported benchmark. These RPD operative outcomes were similar to reported surgeon outcomes after the learning curve. CONCLUSION: This study suggests formal robotic training facilitates safe and efficient adoption of RPD for new programs, reducing or eliminating the learning curve.

Association of treatment factors with surgical outcomes in tri-modality therapy for esophageal cancer.

BACKGROUND AND OBJECTIVES: To identify the impact of the interval between chemoradiation to surgery on morbidity and mortality in patients undergoing tri-modality therapy for esophageal cancer. METHODS: Eighty-five patients completed chemoradiation followed by esophagectomy between 2006 and 2011. The interval between completion of chemoradiation and surgery was calculated for each patient. We evaluated the association of quartiles and 3-week groups with morbidity and mortality using logistic regression. Other treatment and clinical factors were also assessed. RESULTS: A total of 59 patients(69%) experienced at least one complication. When examining specific complications, patients with pulmonary complications had a longer mean time interval from chemoradiation to surgery (P = 0.02). Linear regression showed an association between longer interval between chemoradiation to surgery and hospital length of stay (LOS) >14 days when analyzing by both interval quartile (P = 0.04) and 3-week intervals (P = 0.04). On multivariable analysis, increased time interval predicted for pulmonary complications (P < 0.01) and LOS >14 days (P = 0.03). When examining other treatment factors, squamous cell histology (P = 0.02) also predicted for a hospital length of stay >14 days. CONCLUSIONS: Factors such as interval between completion of chemoradiation and surgery and squamous cell histology may be associated with surgical morbidity. Further data is warranted to confirm these findings.

The Right Hand Must Know What the Left Hand is Doing: A False-Positive Hotspot on the Sestamibi Scan.

Objective: Imaging studies in the setting of primary hyperparathyroidism are performed to rule out an ectopic parathyroid adenoma. Although rare, false-positive scans can cause confusion and possibly more extensive procedures. Method: A 68-year-old woman with parathyroid hormone-dependent hypercalcemia was found to have uptake in the left midclavicular area on the parathyroid scan with sestamibi. Retention of the isotope was considered a possibility, and the sestamibi scan was repeated after injecting the isotope in the right hand and this did not show uptake in the left midclavicular area. Results: Sestamibi is taken up by the mitochondrial-rich adenoma cells and can help identify an ectopic location of the adenoma. Sestamibi scans are commonly performed before neck exploration to rule out an ectopic adenoma and to localize the parathyroid adenoma. Thyroid adenoma and thyroid cancer can also cause retention of isotopes. Retention of the isotope in the vein can also give an illusion of an ectopic parathyroid adenoma. Injecting the isotope in the contralateral hand can overcome this retention issue. Conclusion: Uptake on parathyroid scan outside of normal embryologic decent of the parathyroid gland should raise the possibility of a false-positive uptake.

Toll-like receptor 4 signaling regulates the acute local inflammatory response to injury and the fibrosis/neovascularization of sterile wounds.

The role of Toll-like receptor 4 (TLR4) in the regulation of inflammation and fibrosis in sterile wounds was investigated in TLR4 signal-deficient (C3H/HeJ or TLR4(-/-) ) and control mice using the subcutaneously implanted polyvinyl alcohol sponge wound model. Total and differential wound cell counts 1, 3, and 7 days after injury did not differ between C3H/HeJ and C3H/HeOuJ animals. Blood monocytes from both strains expressed CCR2 equally. Day one wounds in C3H/HeJ mice contained fewer Gr-1(high) wound macrophages, CCL3, and CCL5, and more CCL17 than those in controls. The accumulation of CCL2, CX3CL1, tumor necrosis factor-α, interleukin (IL)-6, IL-10, IL-12, and interferon-γ in wound fluids was not TLR4 dependent. Wound macrophages from C3H/HeJ and C3H/HeOuJ mice expressed CCR4 and CCR5, but not CCR1 or CCR3. Wound macrophage recruitment was not altered in CCR5(-/-) mice or in C3H/HeOuJ animals injected with neutralizing anti-CCL3 and anti-CCL5 antibodies. Neutralization of the CCR4 ligand CCL17 in C3H/HeJ mice did not alter wound macrophage populations. There was a twofold increase in collagen content and number of neovessels in 21-day-old wounds in C3H/HeJ vs. C3H/HeOuJ mice. There were no differences between strains in the number of myofibroblasts in the wounds 7 or 21 days postwounding. The increased fibrosis and angiogenesis in wounds from /HeJ mice correlated with higher concentrations of transforming growth factor-ß and fibroblast growth factor 2 in wound fluids from these animals. Wound fluids did not contain detectable lipopolysaccharide and did not induce IκBα degradation in J774.A1 macrophages. Results support a role for endogenous ligands of TLR4 in the regulation of inflammation and repair in sterile wounds.

Outcomes in patients with mucosal melanomas.

BACKGROUND AND OBJECTIVE: Our goal was to evaluate the different subtypes of mucosal melanoma and describe specific variables that predict outcomes. METHODS: Prospective review of two tertiary care center databases identified 76 mucosal melanoma patients; 73 with complete records were included. Demographic and clinical data were analyzed. Cox regression determined variables impacting recurrence and survival. RESULTS: In the 73 patients, the mean age was 64 years, and 74% were female. Sixty-seven percent presented with lymph node involvement, and 73% had ulcerated tumors. Major sites affected were nasal/palate/oral (36%), vulvar/vaginal/cervical (48%), and anorectal (15%). Mean overall and disease-free survival were 56.9 and 27.2 months. Variables associated with decreased survival included: lymphovascular invasion (HR17.70, P = 0.0093), Caucasian race (HR3.02, P = 0.0362), nasal/palate/oral sub-group (HR1.85, P = 0.026), Breslow thickness (HR1.23, P = 0.00004), T stage (HR1.34, P = 0.0075), M stage (HR3.03, P = 0.0039), and chemotherapy (HR3.13, P = 0.0002). The worst prognosis was seen in the nasal/palate/oral sub-group, with a median overall survival of 9.7 months and recurrence-free time of 4.5 months. This subtype also demonstrated high lymph node positivity, ulceration, and larger tumor size. CONCLUSION: The nasal, palate, oral subtype has the worst prognosis compared to other mucosal melanoma locations. Studies are ongoing to evaluate pathologic and genomic variables that may predict outcomes.

Radioactive Seed Localization for Non-Breast Tissue Excision.

Lymph nodes are common basins for cancer recurrence; however, during surgery, lymphatic tissue is often indistinguishable from surrounding tissue making local excision difficult. Novel breast surgery techniques have utilized radioactive seed localization (RSL) to preoperatively tag tissue so it can be identified intraoperatively with a gamma probe. Our goal was to assess the use of RSL in non-breast tissues. This was a retrospective case series of non-breast cancer patients undergoing RSL. Overall, 42 patients met inclusion criteria. Pathology results indicated benign findings in 20 patients (47.62%), toxoplasma in 1 patient (2.38%), non-necrotizing granulomatous disease in 2 patients (4.76%), and malignant progression in 19 patients (45.24%). Two patients had non-lymphatic tissue removed: one in the abdominal wall and one in the lower lumbar region. Radioactive seed localization is an effective technique to localize and excise non-palpable lymph nodes and masses identified on imaging, highlighting its wide variety of uses in non-breast cancer cases.

Medical Students' Communication Preferences for the Ideal Surgical Educator.

OBJECTIVE: Medical students have expectations and preferences for how they are taught by clinical surgical educators. The goal of this study was to (a) determine medical students' prioritizations of ideal teaching behaviors and characteristics for surgical educators, and (b) delineate which teaching behaviors and characteristics were considered to be less important for surgical education. DESIGN: Using a necessity (low) and luxury (high) budget allocation methodology to build their ideal surgical educator, MSIII and MSIV students (N = 82) completed a survey to prioritize and invest in 10 effective teaching behaviors and characteristics identified in the instructional communication literature (assertiveness, responsiveness, clarity, relevance, competence, character, caring, immediacy, humor, and disclosure). RESULTS: Repeated-measures ANOVAs indicated MSIII and MSIV students invested significantly more of their teaching budget allocations for their ideal surgical educator into instructor clarity, competence, relevance, responsiveness, and caring, both within a (low) necessity budget (F[5.83, 472.17] = 24.09, p < 0.001, η2p = 0.23) and (high) luxury budget (F(7.65, 619.76) = 67.56, p < 0.001, η2p = 0.46). Using paired t-tests, comparisons of repeated investments in low and high budget allocations revealed that students invested slightly more of a percentage of funds in instructor immediacy (+2.62%; t(81) = 2.90, p = 0.005; d = 0.32) and disclosure (+1.44%; t(81) = 3.26, p = 0.002; d = 0.36), indicating they viewed these teaching behaviors more as luxury components of surgical education rather than necessities, but these behaviors were significantly less important than their ideal prioritizations of instructor clarity, competence, relevance, responsiveness, and caring. CONCLUSIONS: Results indicated that medical students want a surgical educator who is largely a rhetorical educator; that is, a surgical specialist who clearly communicates expertise and relevant content that students can apply to their careers as future surgeons. However, a relational component was viewed as ideal by students as students also preferred surgical educators to be sensitive and sympathetic to their academic needs.

The PASS Course: Practical Anatomy and Surgical Skills Course as a Pragmatic Primer for Senior Medical Students Pursuing Surgical Residency.

The senior year of undergraduate medical education has been scrutinized for lacking emphasis from educators and value for students. Surgical residency program directors and medical students have reported different sets of perceived weaknesses as surgical trainees enter residency. With this in mind, we developed a novel rotation for senior medical students pursuing surgical residency. The rotation incorporates practical didactics, robust skill and simulation training, and an enriching anatomy experience that entails dissections and operations on embalmed and fresh tissue cadavers. To our knowledge, this is the first reported formal training experience for medical students that involves working with fresh tissue cadavers, which have been described as effective models for live human tissue in the operating room. We describe our multifaceted curriculum in detail, discuss its organization, and elaborate on its potential value. We also provide detailed explanations of the curriculum components so that other surgical educators may consider adopting them.

"The Benefit Of Positron Emission Tomography/Computed Tomography In Stage I And Stage II Melanomas With High-Risk Decisiondx-Melanoma Scores".

INTRODUCTION: Early detection of melanoma is instrumental as the 5-year survival decreases from 93.3% to <50% when metastases are present.1-3 Distinguishing which patients require closer follow-up can be difficult for melanoma patients. Developments by Castle Biosciences' (Friendswood, TX) DecisionDx-Melanoma (DDx-M) use 31 melanoma associated genes to stratify melanomas into 4 classes with 1A having lowest risk of morbidity and mortality and 2B the highest.5 We assessed the benefit of providing additional 18FDG-PET-CT and brain MRI to genetically high-risk patients who may have otherwise been overlooked. METHODS: 297 patients at our institution had biopsies sent for DDx-M between 2014 and 2021. Patients found to have Class 2 melanomas received additional screening with yearly 18FDG-PET-CT scans and brain MRIs. Patients with Class 2 DDx-M scores and negative SLNB were included in the study. 66 met inclusion criteria and received imaging. RESULTS: Within 3 years of follow-up, 8/66 (12.1%) patients had metastases detected by 18FDG-PET-CT scans. No patients with stage IA or IB went on to develop metastases. DISCUSSION: 18FDG-PET-CT scans detect metastases in < 3% of the time when all stage I and II patients are scanned; however, by using DDx-M in our screening protocols, we achieved a detection rate of 12.1%.6,7 These patients went on to receive treatment and would have otherwise progressed undetected, leading to higher morbidity and mortality. CONCLUSION: We suggest all patients with initial stage II or above melanomas receive a DDx-M score and those with class 2 receive yearly 18FDG-PET-CT/brain MRI imaging.

Congenital adrenal hyperplasia with associated giant adrenal myelolipoma, testicular adrenal rest tumors and primary pigmented nodular adrenocortical disease: A case report and brief review of the literature.

Congenital adrenal hyperplasia is an autosomal recessive disease most commonly associated with 21-hydroxylase deficiency, an enzyme integral in the biosynthesis of mineralocorticoids and glucocorticoids. We present a case of a 49-year-old male with congenital adrenal hyperplasia and commonly associated findings of adrenal myelolipoma, testicular adrenal rest tumors, as well as primary pigmented nodular adrenocortical disease. Adrenal myelolipoma is a rare, benign disease process associated with exogenous steroid treatment noncompliance in the setting of congenital adrenal hyperplasia. Testicular adrenal rest tumors are benign testicular tumors associated with congenital adrenal hyperplasia. Primary pigmented nodular adrenocortical disease is an ACTH-independent cortisol producing lesion. Our case emphasizes the association of congenital adrenal hyperplasia with adrenal myelolipoma and testicular adrenal rest tumors as well as the importance of familiarity with these associations to guide patient management.

Development of a Senior Medical Student Robotic Surgery Training Elective.

As robotic surgery has become more widespread, early exposure to the robotic platform is becoming increasingly important, not only to graduate medical education, but also for medical students pursuing surgical residency. In an effort to orient students to robotic technology and decrease the learning curve for what is likely to become an integral part of residency training, we created a formal, elective robotic surgery curriculum for senior medical students. Throughout this 2-week fourth year rotation, students completed online training modules and assessment; mastered exercises on the simulator system related to the console, camera, energy, dexterity, and suturing skills; attended didactics; utilized the dual console during one-on-one simulation lab sessions with attending robotic surgery experts; and translated new skills to biotissue anastomoses as well as bedside-assisting in the operating room. During cases, students were able to have more meaningful observation experiences, recognizing the significance of various robotic approaches employed and utilization of specific instruments. Future aims of this rotation will assess student experience as it impacts readiness for surgical residency.

Outside the Thorax: Doege-Potter Syndrome Presenting as a Retroperitoneal Abdominal Mass.

OBJECTIVE: We present a case of refractory hypoglycemia, weight loss, and retroperitoneal solitary fibrous tumor. Case report. A 68-year-old female presented with symptomatic hypoglycemia, weight loss, and abdominal mass identified on CT scan of the abdomen. Blood work during symptomatic hypoglycemia was consistent with an IGF-2-producing tumor. The abdominal mass pathology was consistent with solitary fibrous tumor surrounding the adrenal gland, and resection resulted in complete resolution of hypoglycemia. Discussion. Understanding the biochemical mechanisms behind glucose regulation is necessary to diagnose and adequately treat Doege-Potter syndrome, a paraneoplastic syndrome observed in patients with solitary fibrous tumors. Solitary fibrous tumors can be characterized by specific histologic and immunohistochemical studies. CONCLUSION: This report describes the clinical workup of a patient presenting with hypoglycemia and a retroperitoneal tumor. This case is unique because of its presentation with severe, refractory hypoglycemia and the tumor's location in the retroperitoneum, given the majority of solitary fibrous tumors are found in the lungs originating from the pleura.

Disruption of interleukin-1 signaling improves the quality of wound healing.

In this study, we investigated the role of interleukin (IL)-1 signaling in wound healing. IL-1 receptor type I (IL-1R) knockout (KO) mice showed reduced fibrosis in both cutaneous and deep tissue wounds, which was accompanied by a reduction in inflammatory cellular infiltration in cutaneous but not in deep tissue wounds. There were no differences in either total collagenolytic activity or in the expression of selected matrix metalloproteinases or tissue inhibitors of metalloproteinases between the wound fluids from wild-type or IL-1R KO mice. However, wound fluids from IL-1R KO mice contained lower levels of IL-6 compared with wild-type controls. In addition, the infusion of IL-6 into wounds in IL-1R KO mice did not increase fibrosis. Skin wounds in IL-1R KO animals had lower levels of collagen and improved restoration of normal skin architecture compared with skin wounds in wild-type mice. However, neither the tensile strength of incisional skin wounds nor the rate of closure of excisional wounds differed between IL-1R KO and wild-type animals. The reduced fibrotic response in wounds from IL-1R KO mice could be reproduced by the administration of an IL-1R antagonist. These findings suggest that pharmacological interference with IL-1 signaling could have therapeutic value in the prevention of hypertrophic scarring and in the treatment of fibrotic diseases.

Optimizing resection for "responding" hepatic metastases after neoadjuvant chemotherapy.

Fifty percent of patients with colorectal cancer will develop metastases at some time during their disease, with the liver being the most common site. Recent advances in the treatment of metastatic colorectal cancer have led to a change in treatment paradigm. What follows is a review of the surgical management of hepatic colorectal metastases responding to neoadjuvant chemotherapy. In addition, the complexity of treating patients with "disappearing" colorectal liver metastases is discussed.

Resection of a colonic mass following trauma: a diagnostic dilemma.

A 53-year-old Caucasian male presented with a 2-week history of abdominal distension, pain, nausea and lethargy. His symptoms began 1 day after an all-terrain vehicle accident during which he suffered blunt-force trauma to his mid-right abdomen. CT scan demonstrated abnormal thickening of the ascending colon and terminal ilium with surrounding inflammation within the retroperitoneum and colonic mesentery. Given his likely mechanism and symptomatic improvement, he was initially managed conservatively. However, he was readmitted with recurrence of symptoms, and a repeat CT scan demonstrated no interval improvement. An exploratory laparotomy was performed and a firm, fixed mass of the right-colon and colonic mesentery was found. Final histopathology of the mass revealed a diffuse lymphoid infiltrate with numerous mitotic figures and apoptotic cells. Immunohistochemical staining was positive for CD45, CD20, CD10, and BCL-6 and negative for CD3, TdT, and BCL-2, indicating a diagnosis of Burkitt lymphoma.

Diagnosis and Surgical Management of a Retroperitoneal Lipoma in Pregnancy.

Retroperitoneal lipomas during pregnancy are very rare. We report a case of a 29-year-old pregnant female who presented with a retroperitoneal lipoma. Our patient presented at 15-week gestation with abdominal pain, distention, and orthopnea. Due to vague symptoms and nonspecific imaging capabilities, retroperitoneal tumors in pregnancy are uniquely challenging with regard to diagnosis and treatment. We describe the unique work up of a retroperitoneal lipoma in pregnancy and the risks and benefits which were considered when optimizing care to the patient. Percutaneous core needle biopsy has accuracy rates for pathologic diagnosis of up to 98% and is largely safe to perform during pregnancy. Surgical resection of this type of tumor does not mandate cesarean delivery in subsequent pregnancies.

Surgical palliation: getting back to our roots.

This article provides an overview of the approach to patients who may benefit from palliative care. While the article's details lend themselves to the treatment of complications secondary to advanced malignancies, the data herein can also be extrapolated to other chronic, terminal diseases. Guidelines for patient selection are discussed, using currently available outcomes data as a platform for the critical decision making process. Suggestions for a multidisciplinary team approach are offered, using the palliative triangle as the ideal model of communication and cooperation. Finally, methods for measuring success are detailed, along with proposals for how to better equip the surgeons of tomorrow with the knowledge and experience needed to tackle these difficult and intimate problems.

Use of Ly6G-specific monoclonal antibody to deplete neutrophils in mice.

The anti-granulocyte receptor-1 (Gr-1) mAb, RB6-8C5, has been used extensively to deplete neutrophils in mice and to investigate the role of these cells in host defense. RB6-8C5 binds to Ly6G, which is present on neutrophils, and to Ly6C, which is expressed on neutrophils, dendritic cells, and subpopulations of lymphocytes and monocytes. It is thus likely that in vivo administration of RB6-8C5 may deplete not only neutrophils but also other Gr-l+ (Ly6C+) cells. This study describes the use of an Ly6G-specific mAb, 1A8, as an alternative means to deplete neutrophils. In vivo administration of RB6-8C5 reduced blood neutrophils and Gr-1+ monocytes, whereas administration of 1A8 reduced blood neutrophils but not Gr-1+ monocytes. Plasma TNF-alpha in endotoxemia was increased 20-fold by RB6-8C5 pretreatment and fourfold by 1A8 pretreatment. In a wound model, pretreatment with either antibody decreased wound neutrophils and macrophages. TNF-alpha staining in brefeldin-treated wound leukocytes was increased by pretreatment with RB6-8C5, but not 1A8. Neutrophil depletion with 1A8 offers advantages over the use of RB6-8C5, as it preserves non-neutrophil Gr-1+ cells depleted by the anti-Gr-1 antibody. The loss of non-neutrophil Gr-1+ populations in RB6-8C5-treated animals is associated with increased TNF-alpha responses, suggesting these cells may function to suppress TNF-alpha production.