The Added Value of Technetium-99 m Sestamibi Scan in Patients with Primary Hyperparathyroidism and Positive Ultrasound.

BACKGROUND: Neck ultrasound (US) and Technetium-99 m Sestamibi (MIBI) scan are the most commonly used imaging studies for preoperative localization of parathyroid adenomas. The aim of this study was to determine the added value of MIBI scan and its effect on the operative plan via a hypothetical model where a stepwise approach is conducted and MIBI is considered only after the ultrasound is evaluated. METHODS: Patients who underwent parathyroidectomy for primary hyperparathyroidism (PHPT) between 2012 and 2019 at two tertiary centers were included. Data collected included demographic data, preoperative workup, operative findings and follow-up. The added value of MIBI scans was determined for patients with positive ultrasound. RESULTS: A total of 513 patients with positive US result and a MIBI scan were included. If a stepwise approach was conducted then MIBI scan would not change the operative plan in 492 (95.9%). Among the remaining 21 patients, MIBI scan would correctly change the ultrasound-based operative plan in only 12 (2.3%) patients, while incorrectly change the plan in 9 (1.8%), resulting in unnecessary exploration of the contralateral side. In patients with sonographic appearance of a parathyroid gland larger than 1.2 cm, MIBI scan would correctly change the operative plan in only 1 of the 287 (0.35%) patients. CONCLUSIONS: Our study suggests that the routine use of MIBI scans may have limited added value in patients with PHPT and a positive neck ultrasound, especially in those with adenoma size larger than 1.2 cm. Positive ultrasound alone may be sufficient for the preoperative localization of parathyroid disease.

Rapid Cancer Diagnosis and Early Prognosis of Metastatic Risk Based on Mechanical Invasiveness of Sampled Cells.

We provide an innovative, bioengineering, mechanobiology-based approach to rapidly (2-h) establish the in vivo metastatic likelihood of patient tumor-samples, where results are in direct agreement with clinical histopathology and patient outcomes. Cancer-related mortality is mostly due to local recurrence or to metastatic disease, thus early prediction of tumor-cell-fate may critically affect treatment protocols and survival rates. Metastasis and recurrence risks are currently predicted by lymph-node status, tumor size, histopathology and genetic testing, however, these are not infallible and results may require days/weeks. We have previously observed that subpopulations of invasive cancer-cells will rapidly (1-2 h) push into the surface of physiological-stiffness, synthetic polyacrylamide gels, reaching to cell-scale depths, while normal or noninvasive cells do not considerably indent gels. Here, we evaluate the mechanical invasiveness of established breast and pancreatic cell lines and of tumor-cells from fresh, suspected pancreatic cancer tumors. The mechanical invasiveness matches the in vitro metastatic potential in cell lines as determined with Boyden chamber assays. Moreover, the mechanical invasiveness directly agrees with the clinical histopathology in primary-site, pancreatic-tumors. Thus, the rapid, patient-specific, early prediction of metastatic likelihood, on the time-scale of initial resection/biopsy, can directly affect disease management and treatment protocols.

Proceedings of resources for optimal care of acute care and emergency surgery consensus summit Donegal Ireland.

BACKGROUND: Opportunities to improve emergency surgery outcomes exist through guided better practice and reduced variability. Few attempts have been made to define optimal care in emergency surgery, and few clinically derived key performance indicators (KPIs) have been published. A summit was therefore convened to look at resources for optimal care of emergency surgery. The aim of the Donegal Summit was to set a platform in place to develop guidelines and KPIs in emergency surgery. METHODS: The project had multidisciplinary global involvement in producing consensus statements regarding emergency surgery care in key areas, and to assess feasibility of producing KPIs that could be used to monitor process and outcome of care in the future. RESULTS: Forty-four key opinion leaders in emergency surgery, across 7 disciplines from 17 countries, composed evidence-based position papers on 14 key areas of emergency surgery and 112 KPIs in 20 acute conditions or emergency systems. CONCLUSIONS: The summit was successful in achieving position papers and KPIs in emergency surgery. While position papers were limited by non-graded evidence and non-validated KPIs, the process set a foundation for the future advancement of emergency surgery.

Erratum to: The management of intra-abdominal infections from a global perspective: 2017 WSES guidelines for management of intra-abdominal infections.

[This corrects the article DOI: 10.1186/s13017-017-0141-6.].

Erratum to: 2016 WSES guidelines on acute calculous cholecystitis.

[This corrects the article DOI: 10.1186/s13017-016-0082-5.].

2016 WSES guidelines on acute calculous cholecystitis.

Acute calculus cholecystitis is a very common disease with several area of uncertainty. The World Society of Emergency Surgery developed extensive guidelines in order to cover grey areas. The diagnostic criteria, the antimicrobial therapy, the evaluation of associated common bile duct stones, the identification of "high risk" patients, the surgical timing, the type of surgery, and the alternatives to surgery are discussed. Moreover the algorithm is proposed: as soon as diagnosis is made and after the evaluation of choledocholitiasis risk, laparoscopic cholecystectomy should be offered to all patients exception of those with high risk of morbidity or mortality. These Guidelines must be considered as an adjunctive tool for decision but they are not substitute of the clinical judgement for the individual patient.

A Decade of Advances in Military Trauma Care.

BACKGROUND: While combat casualty care shares many key concepts with civilian trauma systems, its unique features mandate certain practices that are distinct from the civilian ones. METHODS: This is a review of the most current literature on combat casualty care, based on computer database searches for studies on combat casualty care and military medicine. Studies were selected for inclusion in this review based on their relevance and contribution. RESULTS: Over the last decade, meticulous, international data collection and research efforts have led to significant improvements in military trauma care. Combat medicine has focused on the causes of preventable deaths and targeted on bleeding control and resuscitation strategies, as well as improved evacuation. En route care and forward surgical interventions have resulted in unprecedented low fatality rates and the saving of more lives. CONCLUSION: This overview of the developments in combat casualty care in recent years emphasizes medical practices that are characteristic of combat medicine, yet with the potential to save lives in other scenarios, as well.

PD-L1 Expression in Clear Cell Renal Cell Carcinoma: An Analysis of Nephrectomy and Sites of Metastases.

BACKGROUND: Expression of programmed death ligand (PD-L1/B7-H1/CD274) represents a mechanism of immune escape for renal cell carcinoma (RCC) cells. Drugs blocking PD-L1 or its receptor are in clinical development and early data suggests that tumor PD-L1 expression may predict response. PATIENTS AND METHODS: A tissue microarray (TMA) consisting of four biopsy cores from 34 matched pairs of nephrectomy and metastatic sites of clear cell RCC was used to assess PD-L1 expression by quantitative immunofluorescence. Assessment of intra- and inter-tumor heterogeneity and primary and metastatic tumor expression was performed using a method of Automated Quantitative Analysis (AQUA). RESULTS: The median AQUA scores were higher in metastatic than primary specimens (P < 0.0001). The correlation between PD-L1 expression in matched primary and metastatic specimens was weak (R= 0.24). Within a given tumor, variable PD-L1 staining heterogeneity was seen, however the degree of heterogeneity was similar in primary and metastatic sites (P = 0.482). CONCLUSIONS: The weak correlation between PD-L1 expression in primary and metastatic sites for a given patient suggests that expression in nephrectomy specimens cannot be used to select metastatic RCC patients for PD-L1 and PD-1 inhibitors. The intra-tumor heterogeneity seen in both primary and metastatic specimens indicates that a single core biopsy might not be sufficient to determine PD-L1 expression.

PTEN functions as a melanoma tumor suppressor by promoting host immune response.

Cancer cells acquire several traits that allow for their survival and progression, including the ability to evade the host immune response. However, the mechanisms by which cancer cells evade host immune responses remain largely elusive. Here we study the phenomena of immune evasion in malignant melanoma cells. We find that the tumor suppressor phosphatase and tensin homolog (PTEN) is an important regulator of the host immune response against melanoma cells. Mechanistically, PTEN represses the expression of immunosuppressive cytokines by blocking the phosphatidylinositide 3-kinase (PI3K) pathway. In melanoma cells lacking PTEN, signal transducer and activator of transcription 3 activates the transcription of immunosuppressive cytokines in a PI3K-dependent manner. Furthermore, conditioned media from PTEN-deficient, patient-derived short-term melanoma cultures and established melanoma cell lines blocked the production of the interleukin-12 (IL-12) in human monocyte-derived dendritic cells. Inhibition of IL-12 production was rescued by restoring PTEN or using neutralizing antibodies against the immunosuppressive cytokines. Furthermore, we report that PTEN, as an alternative mechanism to promote the host immune response against cancer cells, represses the expression of programmed cell death 1 ligand, a known repressor of the host immune response. Finally, to establish the clinical significance of our results, we analyzed malignant melanoma patient samples with or without brisk host responses. These analyses confirmed that PTEN loss is associated with a higher percentage of malignant melanoma samples with non-brisk host responses compared with samples with brisk host responses. Collectively, these results establish that PTEN functions as a melanoma tumor suppressor in part by regulating the host immune response against melanoma cells and highlight the importance of assessing PTEN status before recruiting melanoma patients for immunotherapies.

Growth factor receptor-bound protein-7 (Grb7) as a prognostic marker and therapeutic target in breast cancer.

BACKGROUND: Growth factor receptor-bound protein-7 (Grb7) is an adapter-type signaling protein recruited to various tyrosine kinases, including HER2/neu. Grb7-specific inhibitors are in early development. As with other targeted therapies, response to therapy might be associated with target expression. MATERIALS AND METHODS: Tissue microarrays containing 638 primary breast cancer specimens with 15-year patient follow-up were employed to assess Grb7 expression using our Automated QUantitative Analysis method; cytokeratin defines pixels as breast cancer (tumor mask) within the histospot, and Grb7 expression within the mask is measured with Cy5-conjugated antibodies. RESULTS: High Grb7 expression was strongly associated with decreased survival in the entire cohort and in the node-positive subset (P = 0.0034 and P = 0.0019, respectively). On multivariable analysis, it remained an independent prognostic marker (P = 0.01). High Grb7 was strongly associated with high HER2/neu, and coexpression of these molecules was associated with worse prognosis than HER2/neu overexpression alone. CONCLUSIONS: High Grb7 defines a subset of breast cancer patients with decreased survival, indicating that Grb7 might be a valuable prognostic marker and drug target. Coexpression with HER2/neu indicates that cotargeting these molecules might be an effective approach for treating HER2/neu-positive breast cancers. Future studies using Grb7-targeting agents should include assessment of Grb7 levels.

HSP90 as a marker of progression in melanoma.

BACKGROUND: HSP90 chaperones molecules critical for cell survival and malignant progression, including mutated B-raf. HSP90-targeting agents are in clinical trials. No large studies have been conducted on expression of HSP90 in melanomas. MATERIALS AND METHODS: Tissue microarrays containing 414 nevi, 198 primary and 270 metastatic melanomas were assessed using our automated quantitative analysis (AQUA) method of in situ protein measurement; we use S-100 to define pixels as melanocytes (tumor mask) within the array spot, and measure HSP90 expression within the mask using Cy5-conjugated antibodies. RESULTS: HSP90 expression was higher in melanomas than nevi (P < 0.0001) and higher in metastatic than primary specimens (P < 0.0001). No association was seen between high HSP90 expression and survival in the primary or metastatic patient subsets. In primary melanomas, high HSP90 expression was associated with higher Clark level (P = 0.0167) and increased Breslow depth (P < 0.0001). CONCLUSIONS: HSP90 expression was significantly higher in tumors than nevi and was associated with disease progression, indicating that it might be a valuable drug target in melanoma, as well as a useful diagnostic marker. Prospective studies are needed to confirm the diagnostic role of HSP90, as well as the predictive role of HSP90 expression in patients treated with HSP90 inhibitors.

Microsurgical management of penetrating peripheral nerve injuries: pre, intra- and postoperative analysis and results.

BACKGROUND AND METHODS: Clinical and electrophysiological motor function data were compared before and after microsurgical repair of penetrating peripheral nerve injuries. Sixty-four patients totaling 74 injured nerves (25 gunshot wounds, 49 stab wounds) were treated with external and interfascicular neurolysis and/or interfascicular nerve grafts. Microsurgery was performed 2-12 months after the injury (Group 1, 33 patients,) and 12 months-60 years after the injury (Group 2, 31 patients). The postoperative clinical and electrophysiological follow-up period ranged between 1 and 5 years. RESULTS: A statistically significant improvement in muscle strength occurred after the microsurgery, compared to before repair, gunshot wounds (p < 0.001), stab wounds (p < 0.001). Intraoperative and postoperative electrophysiological analysis showed statistically significant improvement. TIMING OF SURGERY: No statistically significant difference in muscle strength occurred between the 2 groups after the surgery, each showing statistically significant improvement, Group 1 (p < 0.001), Group 2 (p < 0.001). Patients above and below age of 40 showed an improvement in muscle strength after microsurgery, (p < 0.001) and (p < 0.001), respectively. CONCLUSION: Microsurgery can progressively improve nerve function in penetrating peripheral nerve injuries and lead to significant functional improvement, even when it is delayed for more than one year after the injury.

Endoscopic sphincterotomy and temporary internal stenting for bile leaks following complex hepatic trauma.

BACKGROUND: Biliary leak secondary to blunt or penetrating hepatic trauma and damage to the intrahepatic biliary tree remains a challenging problem. The role and safety of endoscopic retrograde cholangiopancreatography (ERCP) and stenting in this setting were studied. METHODS: All trauma victims who developed a bile leak secondary to hepatic trauma were included. Bile leak was defined as the appearance of bile in a surgical wound or intra-abdominal drain after surgery, following percutaneous drainage of a perihepatic bile collection, or evidence of a leak on hepatobiliary scintigraphy. ERCP was performed within 24 h of diagnosis and included biliary sphincterotomy and internal stenting. Recovery was defined as cessation of leakage. RESULTS: Between 1996 and 2004, six patients with penetrating injuries and five with blunt abdominal injuries were treated according to the study protocol. Eight underwent surgery to control bleeding or for additional intra-abdominal injuries. All bile leaks resolved completely within 10 days of ERCP. One patient died from pulmonary sepsis; ten recovered without hepatobiliary sequelae. CONCLUSION: ERCP, biliary sphincterotomy and temporary internal stenting, together with percutaneous drainage of intra-abdominal or intrahepatic bile collections, represent a safe and effective strategy for the management of bile leaks following both blunt and penetrating hepatic trauma.

Terror bombing-mechanisms, consequences and implications.

Our objective in this review is to describe the unique features of bombing injury and to outline some special elements of their management. This is to allow the timely improvement and adjustment of existing mass casualty protocols. Forensic studies, detonation and explosion, mechanisms of injury in explosion and their bodily effects, chemical effects of the explosive, site of the explosion and the wounding potential, the Multidimensional Injury Pattern, diagnostic evaluation of Multidimensional Injury Pattern, and surgical and treatment dilemmas associated with it are described and discussed.

Peritoneal cultures and antibiotic treatment in patients with perforated appendicitis.

OBJECTIVE: To question the common practice of sending material for microbiological examination during appendicectomy for perforated appendixes. DESIGN: Uncontrolled retrospective study. SETTING: Teaching hospital, Israel. SUBJECTS: 89 patients who had their perforated appendixes removed. INTERVENTIONS: Appendicectomy and antibiotic treatment. MAIN OUTCOME MEASURE: Whether a change in antibiotic regimen was required after bacteriological identification of bacteria isolated during the operation. RESULTS: In only 43 of the cultures (48%) taken during the operation were bacteria grown, and these were mainly Escherichia coli. In 65 patients (73%) there was no need to change the previously initiated antibiotic regimen, and in 23 (26%) it was changed purely on clinical grounds. In only one patient (1%) was the change the consequence of microbiological testing, as the organisms identified in 42 of the 43 cultures (98%) were sensitive to at least one of the antibiotics that had already been given. CONCLUSION: The practice of culturing samples taken from a ruptured appendix is redundant, because the antibiotic that has already been initiated is effective in most of the patients and the decision to modify the therapeutic regimen is dominated by clinical considerations.

Stab wounds to the gluteal region: a management strategy.

OBJECTIVE: To examine the utility of a protocol for treating stab wounds to the gluteal region. These are uncommon and potentially lethal, and the location of injury influences the rate and severity of associated injuries. This was a retrospective, uncontrolled study. METHODS: Patients who sustained gluteal stab wounds and were treated according to our predetermined protocol that classifies injuries as upper or lower zone were reviewed, and associated injuries and outcome were measured. RESULTS: Of 27 gluteal stab wounds in 17 patients, 53% were classified as upper zone and 47% as lower zone injuries. Sixty-six percent of the upper zone injuries had associated neurologic, vascular, or visceral injuries that required invasive procedures or surgery, compared with 12.5% for lower zone injuries (p < 0.05). CONCLUSION: Upper zone gluteal stab wounds require prompt multisystem evaluation with mandatory angiography and aggressive management. Lower zone wounds need observation and repeated evaluations.

[Selective embolization of hepatic arteries--an additional precaution to control hemorrhage in the management of severe liver trauma].

Two cases of severe hepatic injury in which selective hepatic artery embolization was used to control hemorrhage are presented. The first case is that of a 35 year old patient who sustained a severe liver injury after a car accident. A CAT scan of the abdomen revealed an AAST grade 5 liver injury, pooling of contrast material within the liver parenchyma, and blood within the peritoneal cavity. The patient was given fluid resuscitation and taken to angiography where bleeding from branches of the right hepatic artery was demonstrated. While angiography was being undertaken the hemodynamic status of the patient deteriorated, blood transfusion was started, and a selective embolization of the right hepatic artery was performed. The bleeding stopped promptly and hemodynamic stability was regained. The second case is that of a 40 year old pedestrian run over by a car. Abdominal ultrasound revealed free fluid in the peritoneal cavity and the patient was rushed to the O.R. Crushed right lobe of the liver, and inferior vena cava and bowel tears were found. After perihepatic packing and resection of the right and sigmoid colons retrohepatic vena cava tear was repaired and perihepatic packing restored. The abdominal cavity was closed and the patient was taken to the ICU for the correction of hypothermia, metabolic acidosis, and coagulopathy that had developed during the surgery. After 8 hours in the ICU the patient was transferred for angiography and a selective embolization of branches of the right hepatic artery was performed. The clinical course of the patients after angiographic embolization of the hepatic arteries is described and the literature that discusses the use of angiography and embolization of hepatic arteries after traumatic hepatic bleeding is reviewed.