IGF2BP3 as a Prognostic Biomarker in Well-Differentiated/Dedifferentiated Liposarcoma.

BACKGROUND: Although IGF2BP3 has been implicated in tumorigenesis and poor outcomes in multiple cancers, its role in soft-tissue sarcoma (STS) remains unknown. Preliminary data have suggested an association with IGF2BP3 expression among patients with well-differentiated/dedifferentiated liposarcoma (WD/DD LPS), a disease where molecular risk stratification is lacking. METHODS: We examined the survival associations of IGF2BP3 via univariate and multivariate Cox regression in three unique datasets: (1) the Cancer Genome Atlas (TCGA), (2) an in-house gene microarray, and (3) an in-house tissue microarray (TMA). A fourth dataset, representing an independent in-house TMA, was used for validation. RESULTS: Within the TCGA dataset, IGF2BP3 expression was a poor prognostic factor uniquely in DD LPS (OS 1.6 vs. 5.0 years, p = 0.009). Within the microarray dataset, IGF2BP3 expression in WD/DD LPS was associated with worse survival (OS 7.7 vs. 21.5 years, p = 0.02). IGF2BP3 protein expression also portended worse survival in WD/DD LPS (OS 3.7 vs. 13.8 years, p < 0.001), which was confirmed in our validation cohort (OS 2.7 vs. 14.9 years, p < 0.001). In the multivariate model, IGF2BP3 was an independent risk factor for OS, (HR 2.55, p = 0.034). CONCLUSION: IGF2BP3 is highly expressed in a subset of WD/DD LPS. Across independent datasets, IGF2BP3 is also a biomarker of disease progression and worse survival.

Laparoscopic compared to open approach for distal gastrectomy may reduce pneumonia risk for patients with gastric cancer.

Background: Whether laparoscopic approach to gastrectomy for gastric cancer (GC) reduces the risk of pneumonia remains unknown. In this study, we compared pneumonia outcomes for patients with GC who underwent either laparoscopic gastrectomy (LG) or open gastrectomy (OG). Methods: The ACS NSQIP database was queried to identify patients with GC who underwent LG or OG between Jan 2012 - Dec 2018. Outcomes were compared using regression models. A post-hoc analysis was performed for elderly patients. Results: The study cohort included 2661 patients, 23.4 % undergoing LG. Laparoscopic approach lowered pneumonia risk (OR 0.47, p = .028) and reduced hospital length of stay, (5.3 vs 7.1 days, p < .001). Elderly patients undergoing LG demonstrated similar benefits. Risk factors for pneumonia included advanced age, dyspnea and weight-loss, whereas laparoscopic approach reduced this risk. Conclusions: LG in patients with GC has both statistically and clinically significant advantages over OG with respect to pneumonia. Further studies are needed to validate the relationship between postoperative pneumonia and surgical approach for gastrectomy.

The Role of Antibiotic Prophylaxis in Primary and Secondary Implant-Based Breast Augmentation: A Systematic Review and Meta-Analysis.

BACKGROUND: The administration of antibiotic prophylaxis for implant-based breast augmentation (IBBA) is commonplace among many plastic surgeons. However, the current literature lacks evidence-based recommendations to support this practice. Although few studies have demonstrated a reduction in surgical site infection (SSI) and capsular contracture (CC) with antibiotics, these studies were underpowered and poorly designed. The aim of this study was to provide an updated comprehensive analysis of the literature to revisit the benefit of antibiotic prophylaxis. METHODS: A comprehensive literature search of PubMed, Embase, Web of Science, and Cochrane was performed from January 1989 to January 2022. Observational studies and randomized controlled trials (RCTs) involving primary and secondary IBBA and use of antibiotic prophylaxis were included. Primary outcomes included SSI and CC. Study quality and risk of bias were evaluated using standardized tools. A meta-analysis was performed for eligible studies. Trial Sequential Analysis was used to assess the need for future RCTs. RESULTS: A total of 5 studies (3 observational and 2 RCTs) with 2383 patients were included in this study. Rates of SSI ranged from 0% to 2.3%, whereas CC ranged from 0% to 53%. Antibiotic prophylaxis showed no benefit for both SSI (odds ratio, 1.77; 95% confidence interval, 0.76-4.13) and CC (odds ratio, 0.46; 95% confidence interval, 0.00-45.72). Trial Sequential Analysis demonstrated that further high-quality RCTs are needed. CONCLUSIONS: Antibiotic prophylaxis for IBBA failed to demonstrate improvements in SSI and CC in this comprehensive review. Current evidence was shown to be of low quality because of heterogeneity and high risk for bias. Further high-quality multicentered RCTs are warranted to fully evaluate the role of antibiotic prophylaxis for IBBA.

Does "Low-Grade" Dedifferentiated Liposarcoma Exist? The Role of Mitotic Index in Separating Dedifferentiated Liposarcoma From Cellular Well-differentiated Liposarcoma.

BACKGROUND: Subjective, varying criteria identify "low-grade" dedifferentiation in well-differentiated/dedifferentiated liposarcoma (WD/DDLPS). The value of mitotic rate (MR) in defining DDLPS is not confirmed. We studied all patients with the resection of their primary or first recurrence retroperitoneal WD/DDLPS at our institution to determine the value of MR in diagnosing DDLPS and if MR associates with patient survival. DESIGN: Ninety-eight patients with retroperitoneal WD/DDLPS operated at our institution from January 1, 1989 to December 31, 2013 were included. Cases were defined as acellular (AC) WDLPS, LS0-4 (tumors with non-lipogenic areas and MR 0-4/10HPFs) or LS5+(non-lipogenic areas, MR≥5/10 HPFs) and graded using the French system. Kaplan-Meier survival estimates with log-rank test and multivariate Cox (mCox) analyses were performed. RESULTS: Follow-up was available on all patients (median 9.3 y, range 0.02-23.16 y). Kaplan-Meier demonstrated a significant ( P =0.004) difference in disease-specific survival (DSS) among the 3 groups. mCox demonstrated no difference in DSS between the AC and LS0-4 groups (HR 1.51; 95% CI 0.57-3.99, P =0.412) but significantly lower DSS in the LS5+group compared with the AC group (HR 2.68; 95% CI 1.07-6.71, P =0.035). The difference in DSS was not significant between grade 2 and 3 tumors ( P =0.094). DSS between MR 5-19/10 HPFs and MR20+/10 HPFs subgroups was significant ( P =0.007) but by mCox did not reach significance (HR 2.47; 95% CI 0.96-6.35, P =0.060). CONCLUSION: This study confirms that MR distinguishes DDLPS from WDLPS with non-lipogenic areas, also known as cellular WDLPS. For consistency in diagnosis and research, only WD/DDLPS with≥5 mitoses/10 HPFs should be considered DDLPS.

Management of small bowel obstruction and systematic review of treatment without nasogastric tube decompression.

Background: Small bowel obstruction (SBO) is common and its management has evolved in recent years. Study design: The literature describing adhesive small bowel obstruction (aSBO) treatment was reviewed, and a formal systematic review was performed to identify publications reporting results of aSBO treatment without NGTs. Results: The annual rate of hospital admission for SBO in the US has increased, with 340,100 admissions in 2019 alone. SBO is usually treated with bowel rest, intravenous hydration and NGT placement. In recent years, water soluble contrast (WSC) has been used as a cathartic to simulate bowel function and may reduce hospital length of stay (HLOS) by 1.95 days (95%CI 0.56-3.3). There were 3 articles of the initial 1650 screened that reported outcomes of SBO treatment without NGTs. These articles included 759 patients, of whom 272 (36%) with aSBO were managed successfully without NGTs. When comparing outcomes to patients who did receive NGT decompression, there were no significant differences in operative rates (28.6% v 16.5%, risk ratio 1.34, 95% CI 1.0, 1.8). Mortality and rates of bowel resection were also not affected by NGT decompression (risk ratio 1.98, 95% CI 0.43, 9.10 and risk ratio 1.56, 95% CI 0.92, 2.65, respectively). Conclusion: SBO is a common disease process with increasing annual incidence. Use of WSC stimulates the bowel and may reduce HLOS. Modern aSBO treatment protocols should include NGT decompression with consideration of WSC administration. Selection of patients for treatment without NGT decompression requires further investigation.

Lifelong Imaging Surveillance is Indicated for Patients with Primary Retroperitoneal Liposarcoma.

BACKGROUND: Surveillance imaging of patients with retroperitoneal liposarcoma (RP-LPS) after surgical resection is based on a projected risk of locoregional and distant recurrence. The duration of surveillance is not well defined because the natural history of RP-LPS after treatment is poorly understood. This study evaluated the long-term risk of recurrence and disease-specific survival (DSS) for a cohort of patients with at least 10 years of progression-free survival (10yr-PFS) from their primary resection. METHODS: The prospective University of California, Los Angeles (UCLA) Sarcoma Database identified RP-LPS patients with 10yr-PFS after initial resection. The patients in the 10yr-PFS cohort were subsequently evaluated for recurrence and DSS. The time intervals start at date of initial surgical resection. Cox proportional hazards models were used to determine factors associated with recurrence and DSS. RESULTS: From 1972 to 2010, 76 patients with RP-LPS had at least 10 years of follow-up evaluation. Of these 76 patients, 39 (51%) demonstrated 10yr-PFS. The median follow-up period was 15 years (range 10-33 years). Among the 10yr-PFS patients, 49% (19/39) experienced a recurrence at least 10 years after surgery. Of those who experienced recurrence, 42% (8/19) died of disease. Neither long-term recurrence nor DSS were significantly associated with age, sex, tumor size, LPS subtype, surgical margin, or perioperative treatment with radiation or chemotherapy. CONCLUSION: Patients who have primary RP-LPS treated with surgical resection ± multimodality therapy face a long-term risk of recurrence and disease-specific death unacknowledged by current surveillance imaging guidelines. Among the patients with 10yr-PFS, 49% experienced a recurrence, and 42% of those died of disease. These findings suggest a need for lifelong surveillance imaging for patients with RP-LPS.

The Effect of Hyperosmolar Water-Soluble Contrast for the Management of Adhesive Small Bowel Obstruction: A Systematic Review and Meta-Analysis.

OBJECTIVE: To better understand the efficacy of water-soluble contrast (WSC) in the treatment of adhesive small bowel obstruction (SBO). BACKGROUND: Guidelines recommend using WSC to treat adhesive SBO nonoperatively by acting as a cathartic agent. The evidence supporting this practice is mixed. METHODS: A systematic review and meta-analysis of published articles describing the effect of WSC compared with control treatments was performed for the period of January 1, 1990 to November 1, 2021. Study quality was assessed using the Cochrane risk-of-bias and the Newcastle-Ottawa tools. The therapeutic effect of WSC was assessed by operative rates and hospital length of stay (HLOS) in nonsurgical patients. RESULTS: The initial search yielded 4879 articles, of which, 28 were selected for full text review. We identified 11 eligible randomized controlled trials (RCTs) which included 817 patients and 9 observational studies of 3944 patients. HLOS in nonsurgical patients decreased by 1.95 days (95% confidence interval: 0.56-3.3) in the RCTs and could not be assessed in the observational studies. WSC did not significantly affect operative rates in the RCTs (19.8% vs. 21.4%) but did reduce rates in the observational studies (11% vs. 16%, risk ratio: 0.56, 95% confidence interval: 0.39-0.82). CONCLUSION: WSC studies may reduce HLOS for patients who have SBO and do not require surgery. However, the current literature is heterogenous with considerable design limitations. High-quality RCTs are needed using standardized protocols to determine the full benefit of WSC for the management of SBO.

Muir-Torre Syndrome.

A 64-year-old man was referred to our dermatology clinic with a diagnosis of Muir-Torre syndrome (MTS), he had a history of multiple sebaceous carcinomas and sebaceous adenomas removed over the years. The patient has also had visceral cancer and had undergone a colon resection 17 years before to treat colon cancer and was recently diagnosed with invasive high-grade urothelial carcinoma of the right ureter. In addition, the patient has an extensive family history of cancer; a pedigree was constructed to document this history (Figure 1). Of note is that the patient's mother and father were second cousins. The patient's father was diagnosed with lung cancer at age 57 and died of colon cancer at the age of 72. The patient's mother died of colon cancer at age 74. The patient has three siblings: a sister and two brothers. The sister died of bone cancer at age 42. One brother had a number of cancers including colon, kidney, and skin cancers and died at age 53. His other brother is alive and has a history of colon cancer, kidney cancer, and ureteral cancer. The patient has five children. He has a 40-year-old son who, at the age of 30, was diagnosed with testicular cancer. His daughters are 47, 44, 39, and 34, with no history of malignancy to date. The patient had three maternal aunts, all of whom succumbed to colon cancer, as well as two paternal uncles who died of lung cancer. The patient's maternal grandfather was a smoker and he also died of lung cancer.

Exposure to recurrent hypoglycemia alters hippocampal metabolism in treated streptozotocin-induced diabetic rats.

AIMS: Exposure to recurrent hypoglycemia (RH) is common in diabetic patients receiving glucose-lowering therapies and is implicated in causing cognitive impairments. Despite the significant effect of RH on hippocampal function, the underlying mechanisms are currently unknown. Our goal was to determine the effect of RH exposure on hippocampal metabolism in treated streptozotocin-diabetic rats. METHODS: Hyperglycemia was corrected by insulin pellet implantation. Insulin-treated diabetic (ITD) rats were exposed to mild/moderate RH once a day for 5 consecutive days. RESULTS: The effect of RH on hippocampal metabolism revealed 65 significantly altered metabolites in the RH group compared with controls. Several significant differences in metabolite levels belonging to major pathways (eg, Krebs cycle, gluconeogenesis, and amino acid metabolism) were discovered in RH-exposed ITD rats when compared to a control group. Key glycolytic enzymes including hexokinase, phosphofructokinase, and pyruvate kinase were affected by RH exposure. CONCLUSION: Our results demonstrate that the exposure to RH leads to metabolomics alterations in the hippocampus of insulin-treated streptozotocin-diabetic rats. Understanding how RH affects hippocampal metabolism may help attenuate the adverse effects of RH on hippocampal functions.

Potential link between post-acute ischemic stroke exposure to hypoglycemia and hemorrhagic transformation.

Hemorrhagic transformation is a severe complication of acute ischemic stroke owing to its limited treatment options and poor prognosis. In the last decade, the rates of hemorrhagic transformation incidence have been associated with blood glucose levels. In particular, hyperglycemia at the time of admission has been associated with increased rates of hemorrhagic transformation in acute ischemic stroke patients. Recent pilot clinical trials have attempted to use intensive insulin therapy during stroke treatment to reduce the severity of cerebral infarction and possibly alleviate the risk of hemorrhagic transformation. However, the results of these studies have shown no clear clinical benefit. In addition, intensive insulin therapy has increased rates of hypoglycemia which may be associated with larger infarct growth. We hypothesize that hypoglycemia, similarly to hyperglycemia, is a risk factor for worse outcomes in acute ischemic stroke by promoting hemorrhagic transformation. This review serves to call attention to patterns present within intensive insulin therapy trials and shed light into the pathophysiological effects of hypoglycemia. It is critical that efforts be directed toward the prevention of hemorrhagic transformation by optimizing insulin therapy during the treatment of acute ischemic stroke.

Carcinosarcoma of the hand.

Carcinosarcomas are rare malignant tumors derived of both epithelial and mesenchymal elements. Herein, we report an elderly man originally diagnosed with a squamous cell carcinoma of the hand. Upon excision, the tumor was found to be a more aggressive carcinosarcoma. Immunohistochemical stains revealed that the sarcoma component of the lesion was vimentin positive, whereas the primary carcinoma tumor cells were positive for p63 and CK903. Both components were negative for CD34 and D2-40. This tumor was found to have angiolymphatic invasion and eventually metastasized to the axillary lymph nodes and lungs.

Acute Trauma Precipitating the Onset of Chest Wall Myxofibrosarcoma.

A previously healthy, 47-year-old male presented to his primary care physician with the complaint of a nontender, palpable breast mass discovered coincidentally 1 month after being scratched in the same location by his pet cat. Family history revealed his father was diagnosed with a soft tissue sarcoma of the thigh, 6 months following a traumatic injury in the same location. Cat scratch disease was considered; however, Bartonella Henselae antibody testing was negative. Imaging studies revealed a subpectoral mass without rib involvement. Subsequent core biopsy revealed malignant fibrous histiocytoma, myxoid type, also known as myxofibrosarcoma. The patient underwent complete surgical resection with no complications. Medical advice recommended adjuvant radiation therapy due to the high risk of recurrence; however, the patient refused this option. Twenty-five months later, the patient remains in remission and in overall good health. This case describes the development of a chest wall tumor, diagnosed as myxofibrosarcoma, following acute trauma to the area. The association between acute traumatic injury and the development of a soft tissue sarcoma, as described in this case, continues to be widely reported, suggesting the possibility for an underlying causal mechanism. Future studies are required to unravel the pathogenesis in order to advance the management of this disease.

Eyebrow and Eyelash Hair Transplantation: A Systematic Review.

The objective of this systematic review was to investigate the etiologies of hair loss of the eyebrow and eyelash that required hair transplantation, the optimal surgical technique, patient outcomes, and common complications. A total of 67 articles including 354 patients from 18 countries were included in this study. Most patients were women with an average age of 29 years. The most common etiology requiring hair transplantation was burns, occurring in 57.6 percent of cases. Both eyebrow and eyelash transplantation use follicular unit transplantation techniques most commonly; however, other techniques involving composite grafts and skin flaps continue to be utilized effectively with minimal complication rates. In summary, many techniques have been developed for use in eyebrow/eyelash transplantation and the selection of technique depends upon the dermatologic surgeon's preferences and the unique presentations of their patients.

Severe hypertriglyceridemia presenting as eruptive xanthomatosis.

Eruptive xanthomatosis is described as the sudden eruption of erythematous yellow papules in the presence of hypertriglyceridemia, often associated with serum triglyceride levels above 2000 mg/dl. Severe hypertriglyceridemia can be caused by primary genetic mutations, secondary chronic diseases, or a combination of both. Uncontrolled diabetes mellitus is a known risk factor. It is imperative for physicians to be aware of eruptive xanthomatosis as a warning sign for severe hypertriglyceridemia due to the underlying risk for the potentially fatal complication of acute pancreatitis. Herein, we discuss a case of a 52-year-old man with uncontrolled diabetes mellitus who presented with eruptive xanthomata and a triglyceride level of 7157 mg/dl, the highest recorded value in the absence of acute pancreatitis, with a remarkable response to drug therapy. A review of the literature is included to discuss the clinical relevance and appropriate treatment of this disease entity.

Inflammatory fibroid polyp of the gastric antrum presenting as hypovolemic shock: Case report and literature review.

Inflammatory fibroid polyps (IFP) are an extremely rare entity that arise within the submucosa of the gastrointestinal tract, and represent less than 0.1% of all gastric polyps. They are most commonly localized to the gastric antrum, small intestines and recto-sigmoid colon. IFPs are most commonly found incidentally upon endoscopic evaluation in the absence of symptoms. Presenting symptoms depend on the location of the tumor, although polyps located in the stomach most commonly present with epigastric pain and early satiety. Classic histologic features include perivascular onion skinning of spindle cells with an abundance of eosinophilic infiltration. The prompt diagnosis and management of IFP is essential due to its underlying risk for intussusception, outlet obstruction and acute hemorrhage. In addition, recent evidence has shown that IFP is driven by an activating mutation in the platelet derived growth factor receptor alpha (PDGFRA) gene, suggesting a neoplastic etiology. Herein, we discuss a case of a 65-year-old woman with an inflammatory fibroid polyp of the gastric antrum who initially presented with early hypovolemic shock and melena. Diagnosis was made by endoscopic visualization, biopsy and immunohistochemical analysis.

Low-grade appendiceal mucinous neoplasm and endometriosis of the appendix.

BACKGROUND: A distended, mucous-filled appendix is known as an appendiceal mucocele. They are a rare form of an appendiceal mass and develop from both benign and malignant processes. Mucoceles can develop secondarily to an obstruction, such as from a fecalith, scarring or, rarely, endometriosis. Only 12 cases of non-neoplastic appendiceal mucoceles caused by endometriosis have been previously described. The association between neoplastic appendiceal mucoceles in the presence of endometriosis is described for the first time in this report. CASE PRESENTATION: A 57-year-old woman presented with a chief complaint of worsening abdominal pain over the past 3 months. Imaging studies revealed an appendiceal mass. Laparoscopic evaluation confirmed an appendiceal mucocele, and the patient underwent complete appendectomy. No evidence of mucinous or endometrial deposits were present within the abdominal cavity. Pathological diagnosis revealed low-grade appendiceal mucinous neoplasm (LAMN) with evidence of endometriosis within the muscularis propria of the appendix. The patient recovered without complications and her abdominal pain completely resolved. CONCLUSIONS: Endometriosis of the appendix is a rare manifestation and is most often identified as an incidental finding. Endometriosis leading to an obstructive mucocele of the appendix is an exceedingly rare finding, having only been described 12 times in the medical literature. LAMN in the presence of endometriosis of the appendix is described for the first time in this report. The association between appendiceal neoplasms in the presence of endometriosis requires further research in order to optimize operative treatment.

Large, extra-abdominal leiomyoma of the round ligament with carneous degeneration.

Round ligament tumours represent a rare entity that can present similarly to an incarcerated hernia. Basic understanding and appropriate preoperative management is imperative in order to differentiate between the two diagnoses. Leiomyoma is the most common type of round ligament tumour. It is associated with oestrogen exposure and is more common in the presence of uterine leiomyomas. Here we discuss a 68-year-old woman who presented with a palpable left inguinal mass that progressively grew in size, associated with pelvic pressure and discomfort. On surgical resection, the mass was found to be derived from the round ligament at the entrance of the external inguinal ring. Pathology confirmed a round ligament leiomyoma, measuring 25×9×8.5 cm. This case is the largest round ligament leiomyoma recorded to date and the first to exhibit carneous degeneration. A review of the current literature is also provided.

Metastatic neuroendocrine tumor of the esophagus with features of medullary thyroid carcinoma.

A 41-year-old female presented with a pedunculated mass in the upper esophagus and bilateral lymphadenopathy. Biopsies suggested a neuroendocrine tumor, possibly carcinoid, and ensuing imaging revealed cervical lymph node metastases. The esophageal mass was removed endoscopically and discovered by pathologists to closely resemble medullary thyroid carcinoma (MTC) on immunohistochemistry staining. Following surgery, further work up demonstrated very high serum calcitonin levels, suggestive of medullary thyroid carcinoma, however the thyroid gland was normal on ultrasound. The patient underwent a neck dissection to remove the lymph node metastases and subsequently her calcitonin levels dropped to 0 ng/mL, indicating remission. It appears that the primary tumor was not in the thyroid, but in the cervical esophagus. The thyroid has appeared normal on multiple ultrasounds without any detectable nodules or masses. This is quite a unique case because this patient presented with a tumor resembling medullary carcinoma of the thyroid that presented as a pedunculated mass in the cervical esophagus. The actual final diagnosis of this mass in the cervical esophagus was neuroendocrine tumor (NET), consistent with a carcinoid tumor, not ectopic MTC. This case report highlights that calcitonin-secreting tumors outside the thyroid should not lead to erroneous recommendations for thyroidectomy.

Novel EYA1 variants causing Branchio-oto-renal syndrome.

INTRODUCTION: Branchio-oto-renal (BOR) syndrome is an autosomal dominant genetic disorder characterized by second branchial arch anomalies, hearing impairment, and renal malformations. Pathogenic mutations have been discovered in several genes such as EYA1, SIX5, and SIX1. However, nearly half of those affected reveal no pathogenic variant by traditional genetic testing. METHODS AND MATERIALS: Whole Exome sequencing and/or Sanger sequencing performed in 10 unrelated families from Turkey, Iran, Ecuador, and USA with BOR syndrome in this study. RESULTS: We identified causative DNA variants in six families including novel c.525delT, c.979T > C, and c.1768delG and a previously reported c.1779A > T variants in EYA1. Two large heterozygous deletions involving EYA1 were detected in additional two families. Whole exome sequencing did not reveal a causative variant in the remaining four families. CONCLUSIONS: A variety of DNA changes including large deletions underlie BOR syndrome in different populations, which can be detected with comprehensive genetic testing.