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Introduction: Everolimus is a treatment option for patients with pancreatic NETs, while its use in patients with gastrointestinal NETs still remains to be defined. Aim(s): To test the efficacy and side effects of Everolimus in six patients with differentiated NET refractory to other therapies. Materials and methods: Everolimus (10 mg/day; compassionate use) was administered until disease progression or unacceptable toxicity. Three patients had metastases of ileal neuroendocrine carcinoma; one of typical lung carcinoid; one of ovary carcinoid and one of pancreatic insulinoma. Results: Two patients showed stable disease at imaging after six and 12 months of treatment. One patient showed biochemical remission. Two patients discontinued treatment due to adverse events. One patient did not reach the six months followup. Side effects were: stomatitis (2); thrombocytopenia (2); nausea (2); fatigue (2) that in one case determined definitive therapy discontinuation after eight months; skin infected lesions (1) leading to definitive discontinuation after three months of therapy. In one case, Everolimus was discontinued after 17 months for severe tricuspid valve insufficiency. Finally, one patient discontinued therapy after three months for worsening dyspnea. The only patient currently under treatment had no side effects. During therapy, lipid and glucose profile did not show significant alterations. Conclusion: Everolimus induces disease stabilization but may have several side effects which should be monitored. [ABSTRACT FROM AUTHOR]

Purpose: Decompressive craniectomy (DC) is a life-saving procedure conducted to treat refractory intracranial hypertension. Although DC reduces mortality of severe Acquired Brain Injury (sABI) survivors, it has been associated with severe long-term disability. This observational study compares functional outcomes at discharge from an Intensive Rehabilitative Unit (IRU) between sABI patients with and without DC., Material and Methods: sABI patients undergoing DC before entering the Don Gnocchi Foundation IRU were compared with a group of sABI patients who did not undergo DC (No-DC group), after matching it by age, sex, aetiology, time post-onset, and clinical status. Inclusion criteria were: diagnosis of sABI, age 18+, time from the event <90 days., Results: A total of 87 (DC: 47) patients were included (median age: 60.5 [IQR = 17.47]). The two groups did not differ for admission clinical features except for the tracheostomy presence (more frequent in DC, p  < 0.001). No significant differences were also found at discharge. DC group presented a significantly longer length-of-stay than No-DC group ( p  < 0.001) and a longer time to tracheostomy removal ( p  = 0.036). DC was not found to influence outcomes as consciousness improvement, tracheostomy removal, oral intake and functional independence., Conclusions: sABI patients with DC improved after rehabilitation as much as No-DC patients did but they required a longer stay.Implications for RehabilitationDecompressive craniectomy (DC) is practiced during the acute phase after hemorrhagic, ischemic, traumatic severe brain injury as a life-saving procedure to treat refractory intracranial hypertensionDC has been associated with follow-up severe long-term disability, but no study yet addressed whether DC may affect intensive rehabilitation outcomes.Undergoing a DC is not a negative prognostic factor for achieving rehabilitation goals after a severe acquired brain injuryDC must be taken into account when customizing rehabilitation pathway especially because these patients required a longer time to reach the outcomes.

Background: Intraoperative ultrasonography (IOUS) in traumatic brain injury is a fast, easy, and low-cost technique that has been poorly investigated so far even though it could potentially answer many of the intraoperative needs of the surgeon. The aim of this study was to investigate the role of IOUS in patients undergoing surgery for traumatic acute subdural hematoma (aSDH), focusing on its influence on intraoperative surgical strategy, particularly regarding the management of intracerebral contusions (ICCs) associated with aSDH., Methods: Data of patients who consecutively underwent surgical evacuation of traumatic aSDH with IOUS assistance at our institution from May 2017 to December 2020 were retrospectively analyzed. Patients were dichotomized into an ICC group (ICCs associated with aSDH on preoperative computed tomography scan) and no ICC group (no ICCs associated with aSDH on preoperative computed tomography scan)., Results: The study included 41 patients. Before aSDH evacuation, IOUS findings were similar to preoperative computed tomography data. After aSDH evacuation, IOUS detected a new-onset ICC in 13% of patients in the no ICC group and a volume increase of the known ICCs in 22% of patients in the ICC group. Therefore, IOUS made it possible to evacuate these new-onset or expanding hematomas in the same operation, changing our surgical strategy and avoiding a delayed reintervention., Conclusions: Our study suggests that IOUS in patients undergoing surgery for traumatic aSDH can promptly identify possible evolution of a primary head injury, leading to early and effective treatment., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Patients with idiopathic normal pressure hydrocephalus (iNPH) frequently show pathologic CSF Aβ 42 levels, comparable with Alzheimer's Disease (AD). Nevertheless, the clinical meaning of these findings has not been fully explained. We aimed to assess the role of AD CSF biomarkers (Aβ 42 , Aβ 42 /Aβ 40 , p-tau, t-tau) in iNPH. To this purpose, we enrolled 44 patients diagnosed with iNPH and 101 with AD. All the patients underwent CSF sampling. We compared CSF biomarker levels in iNPH and AD: Aβ 42 levels were not different between iNPH and AD, while Aβ 42 /Aβ 40 , p-tau, and t-tau were significantly different and showed excellent accuracy in distinguishing iNPH and AD. A multiple logistic regression analysis showed that Aβ 42 /Aβ 40 was the variable that most contributed to differentiating the two groups. Furthermore, iNPH patients with positive Aβ 42 /Aβ 40 had higher p-tau and t-tau than iNPH patients with negative Aβ 42 /Aβ 40 . Those iNPH patients who showed cognitive impairment had lower Aβ 42 /Aβ 40 and higher p-tau than patients without cognitive impairment. We concluded that positive CSF Aβ 42 with negative Aβ 42 /Aβ 40 , p-tau, and t-tau is a typical CSF profile of iNPH. On the contrary, positive Aβ 42 /Aβ 40 in iNPH patients, especially when associated with positive p-tau, may lead to suspicion of a coexistent AD pathology.

Background: The Subdural Hematoma in the Elderly (SHE) score has been recently developed to assess the 30-day mortality in acute and chronic subdural hematomas in patients >65 years and has shown good reliability. We aimed to validate the SHE score's accuracy to predict 30-day mortality on a homogeneous cohort of patients undergoing surgical chronic subdural hematoma evacuation at our Institution. We also investigated whether the SHE score could reliably predict the occurrence of 30-day chronic subdural hematoma recurrence needing surgery., Methods: We included patients from our prospectively collected database from January 2018 to January 2021. Patients with the availability of the following information were enrolled: age, Glasgow Coma Scale score on admission, hematoma volume, medical history, and outcome at 30 days. The SHE score was calculated for each patient, and the association between greater scores and 30-day mortality was investigated and its ability to predict 30-day and disease recurrence. Statistical significance was assessed for P < 0.05., Results: Three hundred twenty-one patients were included. Of them, 40 (12.5%) displayed mortality within 30-day: specifically, 0% of the group of patients with SHE score = 0, 4.3% of SHE score = 1, 14.5% of SHE score = 2, 39.3% of SHE score = 3, and 37.5% of SHE score = 4, with a statistically significant linear trend between greater SHE scores and 30-day mortality rates (P < 0.001, area under the curve 0.75 [0.67-0.82]). No significant association of the SHE score with the risk of recurrence needing surgery was detected (P = 0.4)., Conclusions: The SHE score proved helpful in predicting 30-day mortality in patients with chronic subdural hematomas, but no utility was observed to predict disease recurrence., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Gastrointestinal stromal tumors (GISTs) are rare tumors of the gastrointestinal tract, which cover about 1-2% of gastrointestinal neoplasms with an unadjusted incidence of around 1/100,000/year. They are also the most common non-epithelial neoplasms of the gastrointestinal tract and they are associated with a high rate of malignant transformation. They are more common in the stomach (40-60%) while a minor part repeatedly involves jejunum/ileus (25-30%), duodenum (5%), colorectal (5-15%) and esophagus (<1%). There are also much rarer extragastrointestinal stromal tumor (EGIST): these tumors have immunohistochemical and molecular characteristics similar to GISTs and for this reason, they are called this way, EGIST can involve retroperitoneum, mesentery, and omentum, without affecting the gastrointestinal tract. The clinical presentation depends on the primary localization of the neoplasm, however in 18% it is asymptomatic, and it is accidentally discovered during endoscopies, radiological examinations or surgical operations performed for other reasons, especially if it is small in size. More often, they are associated with non-specific symptoms such as early satiety, nausea or vomiting. Gastrointestinal bleeding is the most dangerous complication, often necessitating emergency surgery. The purpose of this case report is to describe our experience in the management of a young patient with gastrointestinal bleeding caused by an unknown voluminous retroperitoneal GIST with metastatic progression using a combined endovascular embolization and debulking-surgery approach for emergency and imatinib therapy combined with radiofrequency for the oncological approach. GIST requires multidisciplinary management, which improves both prognosis and quality of life., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/acr-20-70). The authors have no conflicts of interest to declare., (2020 AME Case Reports. All rights reserved.)

Background: Since the first years of the 1980s, some authors described the use of mechanical stapler for the creation of anastomosis in biliary surgery. However, the use of these devices has not spread during the following decades, and nowadays most centers usually craft hand-sewn anastomosis., Methods: We retrospectively collected data from medical records, surgical registries and computerized databases about the use of mechanical circular staplers for the creation of hepaticojejunostomy at our institution., Results: From 2012 to 2020, 11 stapled hepaticojejunostomy for both neoplastic and non-neoplastic diseases were performed at our institution. The mean age of the patient was 74, with a sex distribution of 5 men and 6 women. The mean preoperative common bile duct diameter was 19 mm. Preoperative blood samples showed mean total bilirubin of 6.95 mg/dL. No intraoperative complications were reported. Two patients (18%) had minor postoperative complications (1 wound dehiscence and 1 episode of melena that required blood transfusions), while no major complications occurred. No patients developed biliary fistula or anastomotic dehiscence. No one dies within 30 days from surgery. The mean postoperative length of stay was 13 days., Conclusions: According to our limited experience, stapled hepaticojejunostomy seems to be a safe and effective technique in selected patients., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/gs-20-387). The authors have no conflicts of interest to declare., (2020 Gland Surgery. All rights reserved.)

Acquired diaphragmatic hernia, non-related to trauma, is a very rare condition. It can constitute a therapeutic problem and the surgical solution is not always immediately clear. We report the case of a 73-year-old woman with a history of spleno-distal pancreatectomy for a neuroendocrine tumour performed in 2009, who came back to Emergency Room 2 years later, complaining of abdominal pain. Chest radiography and computed tomography were performed; they showed a diaphragmatic hernia with visceral migration into the thorax. The diaphragmatic defect was surgically repaired and the patient had an uneventful post-operative recovery.

The truncated somatostatin receptor variant sst5TMD4 associates with increased invasiveness and aggressiveness in breast cancer. We previously found that sst5 activation may counteract sst2 selective agonist effects in a medullary thyroid carcinoma (MTC) cell line, the TT cells, and that sst5TMD4 is overexpressed in poorly differentiated thyroid cancers. The purpose of this study is to evaluate sst5TMD4 expression in a series of human MTC and to explore the functional role of sst5TMD4 in TT cells. We evaluated sst5TMD4 and sst5 expression in 36 MTC samples. Moreover, we investigated the role of sst5TMD4 in TT cells evaluating cell number, DNA synthesis, free cytosolic calcium concentration ([Ca(2+)]i), calcitonin and vascular endothelial growth factor levels, cell morphology, protein expression, and invasion. We found that in MTC the balance between sst5TMD4 and sst5 expression influences disease stage. sst5TMD4 overexpression in TT cells confers a greater growth capacity, blocks sst2 agonist-induced antiproliferative effects, modifies the cell phenotype, decreases E-cadherin and phosphorylated β-catenin levels, increases vimentin, total β-catenin and phosphorylated GSK3B levels (in keeping with the development of epithelial to mesenchymal transition), and confers a greater invasion capacity. This is the first evidence indicating that sst5TMD4 is expressed in human MTC cells, where it associates with more aggressive behavior, suggesting that sst5TMD4 might play a functionally relevant role.

Background: Angiomyolipoma (AML) is a rare mesenchymal tumor composed by blood vessels, adipose tissue and smooth muscle cells in variable proportions. Although it is most often diagnosed in the kidney, this tumor may originate from any part of the liver. It is often misdiagnosed as hepatocellular carcinoma (HCC) or other benign liver tumor. We describe a case of spontaneous rupture of hepatic angiomyolipoma in a young woman, with evidence of internal hemorrhage and hemoperitoneum., Case Report: Liver tumor rupture is a rare but real surgical emergency. In our case it has been managed according to the trauma principles of the damage control surgery. At the time of the observation, the patient presented an instable condition, so the decision-making was oriented toward a less invasive first step of liver packing instead of a more aggressive intervention such as one shot hepatic resection., Conclusion: Damage control surgery with deep parenchymal sutures of the liver and pro-coagulant tissue adhesives packing abbreviates surgical time before the development of critical and irreversible physiological endpoints and permits a more confident second time surgery. This surgical management concept helps to reduce the mortality rate and the incidence of complications not only in traumatic liver damages, it works very well in spontaneous liver ruptures as well.

Liver damage induced by ovarian stimulation has been demonstrated in some cases reported in the literature. However, there has never been a fruitful debate on this topic. The present manuscript tried to fill this gap. We reported a case of a 35-year-old nulliparous woman admitted to our obstetric emergency room for severe pre-eclampsia. She had been subjected to four cycles of controlled ovarian stimulation for intrauterine insemination. At 32 weeks of gestation, she developed severe pre-eclampsia, which led to HELLP syndrome complicated by fatal liver failure. The etiological link between ovarian stimulation and HELLP syndrome is intriguing. Further investigations are needed to understand whether repeated ovarian stimulation may represent a risk factor in pre-eclamptic patients.

We investigate the role of protein kinase C (PKC) in the control of medullary thyroid carcinoma (MTC) cell proliferation by a PKC inhibitor, Enzastaurin, in human MTC primary cultures and in the TT cell line. We found that PKC inhibition reduces cell proliferation by inducing caspase-mediated apoptosis and blocks the stimulatory effect of IGF-I on calcitonin secretion. Enzastaurin reduces PKCβII (Thr500) phosphorylation, indicating a direct involvement of this isoform as well as the phosphorylated levels of Akt (Ser 473) and glycogen synthase kinase (Ser9), PKC pathway downstream targets and pharmacodynamic markers for PKC inhibition. PKCβII and PKCδ enzyme isoforms expression and localization were investigated. These data indicate that in vitro PKC is involved in the control of human MTC proliferation and survival by modulating apoptosis, with a mechanism that implicates PKCβII inhibition and translocation in different subcellular compartments. Targeting PKC may represent a useful therapeutic approach for controlling MTC proliferation.

In this case report, the authors discuss clinical presentation, surgical procedure and early results of chemotherapy of pancreatic carcinoma with liver metastases diagnosed a few days after delivery. Pancreatic adenocarcinoma occurs infrequently in pregnant and childbearing women: only ten cases have been reported in the literature. The early diagnosis of pancreatic cancer is difficult because symptoms appear when cancer is about to reach an advanced stage. In pregnancy, it is even more difficult because symptoms like dyspepsia, vomiting and epigastric pain may result confusing. The authors outline the difficulties in diagnosis and treatment of this kind of disease during pregnancy.

Dysregulation of the protein kinase C (PKC) signaling pathway has been implicated in tumor progression. In this study, we investigate the effects of a PKC inhibitor, Enzastaurin, in human pancreatic neuroendocrine neoplasms (PNN) primary cultures and in the human pancreatic endocrine cancer cell line, BON1. To this aim six human PNN dispersed in primary cultures and BON1 cells were treated without or with 1-10 μM Enzastaurin and/or 100 nM IGF1 in the presence or absence of serum. Cell viability and apoptosis were evaluated after 48-72 h; Chromogranin A (CgA) and/or insulin secretion was assessed after 6 h of incubation. PKC expression was investigated by immunofluorescence and western blot. We found that Enzastaurin significantly reduced human PNN primary culture cell viability, as well as CgA and insulin secretion. Moreover, in the BON1 cell line Enzastaurin inhibited cell proliferation at 5 and 10 μM by inducing caspase-mediated apoptosis, and reduced phosphorylation of glycogen synthetase kinase 3β (GSK3β) and of Akt, both downstream targets of PKC pathway and pharmacodynamic markers for Enzastaurin. In addition, Enzastaurin blocked the stimulatory effect of IGF1 on cell proliferation, and reduced CgA expression and secretion in BON1 cells. Two different PKC isoforms are expressed at different levels and have partially different subcellular localization in BON1 cells. In conclusion, Enzastaurin reduces cell proliferation by inducing apoptosis, with a mechanism likely involving GSK3β signaling, and inhibits secretory activity in PNN in vitro models, suggesting that Enzastaurin might represent a possible medical treatment of human PNN.

Lipoastrocytoma is an extremely rare tumor, with only six cases described. We report the case of an astrocytoma involving the upper part of the cerebellar-pontine angle and the right portion of the clivus starting from the brainstem with a diffuse lipomatous component in a 39 year-old man. The patient was admitted with headache of 1 year's duration and diplopia over the previous 3 months. MRI revealed a ponto-cerebellar lesion that showed irregular enhancement after contrast administration. Subtotal excision of the tumor was accomplished. Adjuvant chemotherapy and radiation therapy were not administered. Histologically the tumor showed the classical histology of low-grade astrocytoma and a portion of the lesion was composed of lipid-laden cells. Immunohistochemistry for glial fibrillary acid and S-100 proteins clearly demonstrated the glial nature of these cells. Ki-67/Mib-1 labeling index was low (2%). The patient remains in good neurological conditions after 10 months. Our case has a benign postoperative behavior, also after subtotal excision, with restrictions due to the short follow-up. It is important to record each new case of this rare tumor to produce a better characterization of this lesion., (© 2010 Japanese Society of Neuropathology.)

Background: pituitary tumour transforming gene 1 (PTTG1) is over-expressed in a variety of endocrine-related tumours. We aimed at evaluating PTTG1 expression and function in human neoplastic parafollicular C-cells, represented by medullary thyroid carcinoma (MTC) and C-cell hyperplasia (CCH) samples and by the TT cell line., Methods: TT cells and tissues derived from human CCH (8 samples) and MTC (12 samples) were analyzed by northern blot, furthermore TT cells were subjected to PTTG gene silencing and cells were analyzed for DNA synthesis., Results: PTTG1 expression was significantly higher (p<0.01) in CCH (3-fold), in papillary thyroid cancer and in MTC (5-fold) than in normal thyroid, and in MTC lymph-node metastases as compared to primary lesions (approximately 2-fold; p<0.05). PTTG1 mRNA and protein correlated with tumour diameter and TNM status (p<0.05). In TT cells, PTTG1 silencing did not completely block DNA synthesis, but significantly reduced [3H]Thymidine incorporation (~50%; p<0.01) for up to 3 days., Conclusions: PTTG1 levels correlate with tumour aggressiveness. PTTG1 silencing causes reduced MTC cell proliferation, supporting the hypothesis that PTTG1 might have an important role in C-cell neoplastic proliferation.

Objective: To compare characteristics and outcomes of differentiated thyroid cancers < or =10 mm with those 11-20 mm in diameter., Design: Retrospective chart review of 426 patients with thyroid carcinoma < or =20 mm diagnosed and treated between 1990 and 2004 in one university clinic., Main Outcomes: Lymph node metastases were more frequent at diagnosis in 11-20 mm than in < or =10 mm cancers (p < 0.001). The prevalence of distant metastases did not differ between < or =10 mm and 11-20 mm cancers. One hundred and thirty-three patients (73%) with tumors 11-20 mm were disease free 2 years after 131I treatment, and no recurrence has been observed over 2-14 years of follow-up. Forty-one patients (22%) with cancers 11-20 mm (N1 or M1) required 2-4 years to become disease free. Neck lymph node recurrence was observed in nine patients (4.9%) 4 months to 14 years after surgery and (131)I therapy. Four patients (1.6%) with cancers < or =10 mm in diameter had cancer recurrence (p = 0.05 compared to the 11-20 mm cancers). Based on the presence of distant metastases at diagnosis and recurrence of disease during follow-up, cancers 11-20 mm in diameter seemed more aggressive than those < or =10 mm (p < 0.05)., Conclusion: Cancers 11-20 mm seem more aggressive than those < or =10 mm.

Aims: Lymph node metastases for papillary thyroid carcinoma are associated with an increased incidence of locoregional recurrence. The use of preoperative lymphoscintigraphy and intraoperative gamma probe detection to localize the sentinel lymph node in papillary thyroid carcinoma was investigated., Methods: From February 2004 to December 2005 the sentinel lymph node technique was studied in 64 consecutive patients with cytological evidence of papillary thyroid carcinoma. The day before surgery, patients were submitted to US-guided peri-tumoural injection of the radiotracer and a lymphoscintigraphy was performed. In the operating room a total thyroidectomy was done, and thanks to a hand-held gamma probe the sentinel lymph node and all lymph nodes, belonging to the sentinel node compartment, were removed., Results: The gamma probe identified the sentinel lymph node in 62 patients (96.8%). We found 48 (77.5%) sentinel lymph node without metastases; 12 (19.3%) with metastases and 2 (3.2%) with micrometastases. In 7 cases (11.3%), with a negative sentinel lymph node, metastases in other nodes of the same region were recorded. In 22 cases (34.3%) the ultrasound give an erroneous indication (P=0.004). Five patients (8.0%), 4 with multifocal cancer, had a positive postoperative lymphoscintigraphy., Conclusion: This study shows that the sentinel lymph node technique for papillary thyroid carcinoma is feasible, repeatable, and more accurate than preoperative ultrasound. In cases of multifocal thyroid lesions more patients should be enrolled to establish the utility of the radio-guided technique.

Chordoid glioma is a rare low-grade tumor located in the third ventricle-hypothalamic region. Since its first report, 37 cases have been described in the literature. We report on an additional case that we considered significant because of its incidental detection and its uneventful surgical removal.

Aims and Background: Sequential docetaxel and gemcitabine following initial docetaxel plus epirubicin or vinorelbine association could be worthwhile as first-line treatment of metastatic breast cancer., Methods: Fifty-eight patients entered a phase II study that included two sequential phases. In the first phase, 36 and 22 patients previously unexposed or exposed to adjuvant anthracyclines received the association of docetaxel (75 mg/m2, day 1) with epirubicin (75 mg/m2, day 1) or vinorelbine (20 mg/m2, days 1 and 5), respectively, every 21 days for 4 courses. In the second phase, patients who had a response (R) or stable disease (SD) received docetaxel (35 mg/m2) and gemcitabine (800 mg/m2) on days 1, 8 and 15 every 28 days for 4 courses., Results: In the first phase, grade > or = III neutropenia occurred in 51% and 37% of patients during docetaxel-epirubicin and docetaxel-vinorelbine, respectively. In the second phase, it occurred in the 27% and 15% of patients initially treated with docetaxel-epirubicin and docetaxel-vinorelbine, respectively. On an intention to treat basis, the complete (CR) + partial response (PR) rate to the first phase was 71%, and 22% of patients had SD, without a significant difference between the docetaxel-epirubicin and docetaxel-vinorelbine arms. After the second phase, the CR + PR rate was 65%, and 14% of patients had SD. Median time to progression and survival were 12.1 and 22.0 months, respectively, without a significant difference between patients initially treated with docetaxel-epirubicin and docetaxel-vinorelbine., Conclusions: Following an initial docetaxel-based treatment, weekly docetaxel and gemcitabine maintains high percentages of R and SD, with improved toxicity. Survival was similar in patients previously untreated and treated with adjuvant anthracyclines.