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Background  Liquid biopsy is mainly used to identify tumor cells in pulmonary neoplasms. It is more often used in research than in clinical practice. The BL-MOL-AR study aims to investigate the efficacy of next-generation sequencing (NGS) and clinical interpretation of the circulating free DNA (cfDNA) levels. This study reports the preliminary results from the first samples analyzed from patients affected by various neoplasms: lung, intestinal, mammary, gastric, biliary, and cutaneous. Methods  The Biopsia Liquida-Molecolare-Arezzo study aims to enroll cancer patients affected by various malignancies, including pulmonary, intestinal, advanced urothelial, biliary, breast, cutaneous, and gastric malignancies. Thirty-nine patients were included in this preliminary report. At time zero, a liquid biopsy is executed, and two types of NGS panels are performed, comprising 17 genes in panel 1, which is already used in the routine tissue setting, and 52 genes in panel 2. From the 7th month after enrollment, 10 sequential liquid biopsies are performed up to the 17th month. The variant allele frequency (%) and cfDNA levels (ng/mL) are measured in every plasmatic sample. Results  The NGS results obtained by different panels are similar even though the number of mutations is more concordant for lung pathologies. There are no significant differences in the actionability levels of the identified variants. Most of the molecular profiles of liquid biopsies reflect tissue data. Conclusions  Preliminary data from this study confirm the need to clarify the limitations and potential of liquid biopsy beyond the lung setting. Overall, parameters related to cfDNA levels and variant allele frequency could provide important indications for prognosis and disease monitoring., Competing Interests: Conflict of Interest None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. ( https://creativecommons.org/licenses/by/4.0/ ).)

Acute appendicitis (AA) is among the most common causes of acute lower abdominal pain leading patients to the emergency department. Significant debate remains on whether AA should be operated or not. A propensity score-matched analysis was performed in seven Italian Hospitals, with the aim to assess safety and feasibility both nonoperative management with antibiotics (AT) and surgical therapy with appendectomy (ST) for patients with AA. Data regarding all patients discharged from the participating centers with a diagnosis of appendicitis from January 1st, 2014 to December 31st, 2014 were collected retrospectively. Follow-up data were collected from January 1st, 2015 to December 31st, 2016. The complication-free treatment success of AT (53.7%) was significantly inferior to that of ST (86.4%) (P < 0.0001). Patients initially treated with antibiotics reported an index admission AT failure rate of 20.9% and a recurrence rate at 1-year follow-up of 20.3%. No statistically significant difference was found when comparing AT and ST groups for the outcome of interest post-operative complications (13.5 vs 13.6%, P = 0.834). Patients treated with AT were discharged home earlier than patients in the ST group (3.38 ± 1.89 vs 4.84 ± 2.69 days, P < 0.0001). Due to the low rates of complications occurred in the ST group and the high efficacy of the surgical therapy, laparoscopic appendectomy still represents the most effective treatment for patients with AA. AT is associated with shorter hospital stay and faster return to normal activity, and may prevent from appendectomies around 80% of patients who leave the hospital with clinical recovery.

Adnexal tumors with follicular differentiation in the breast parenchyma are rarely encountered. The authors present a unique case arising in a 64-year-old woman, in whom they observed composite differentiation toward follicular germinative cells of the hair follicle with focal areas of outer root sheath differentiation and pilar-type keratinization. The histogenesis of this tumor is analyzed in light of the peculiar pathological, immunohistochemical, and molecular genetic findings.

Aim of the Study: Post-gastrectomy syndromes (PGS) are iatrogenic conditions which may arise from partial gastrectomies, independently from their indications (cancer or ulcer) and the reconstruction technique (Billroth I, Billroth II or Roux-en-Y). They are usually less frequent in patients with a Roux-en-Y reconstruction, but also this technique does not surely prevent SPG. Recently, some new technique have been proposed in order to prevent the PGS. Most of them are based upon a less extensive resection of the viscus, replaced by application of simple stapler mediated interruptions (the so called "uncut" technique). We aimed to verify whether such less invasive technique were also able to exert a therapeutic role for various type of PGS with the same efficiency of the traditional ri-resection techniques, which are known to generally have a major morbidity impact., Material and Methods: Nineteen patients, 12 male and 7 female, aged between 44 and 67 years, have been operated since 1985 up to 2004. All of them had an overt SPG (2 with efferent loop syndrome, 10 with gastro-esophageal biliary reflux, 3 with an afferent loop disease and, finally, 4 with a late dumping disease. The series has been divided into two groups depending on the type of surgical technique we chose for the correction of their SPG: "high surgery" patients (HS), operated with Roux re-resection and TADE, "low surgery" (LS) patients treated with "uncut" techniques and or Braun/GEA anastomosis. Both group were comparatively analyzed for the surgical outcome using an Eckhauser and a Visick scale., Results: Out of the 11 patients of the first group 8 had a Roux ri-resection and 3 a TADE, whereas subjects from the second group underwent in four cases to a Braun/uncut afferent loop closer, which was associated to a GEA in the remnant ones. In both group there was no mortality rate, whereas only one subjects from the HS group had a post-operative complication. Either the Visick and the Eckauser score was better in the LS group., Discussion: Data collected show that SPG, even if represented an heterogeneous group of clinical conditions, can be generally treated following a surgical procedure as conservative as possible. Such conclusion may open further views in the laparoscopic management of SPG.

In a review of 109 cases reported in the literature, including our own experience with two successful right laparoscopic adrenalectomies performed in a 3-year old girl for androgen-secreting adenoma and in a 9-year-old male for pheochromocytoma, we analysed the indications, surgical techniques and results of video-assisted (laparoscopic or retroperitoneoscopic) adrenalectomy in children. The indications are no different from those for traditional surgery. It seems that there are no age or tumour size limits for a well-trained surgical team. The best endoscopic approach needs to be more clearly defined. Experience shows that laparoscopy is undoubtly preferred for right adrenalectomy (95.2% of cases), while left adrenalectomy has been performed by retroperitoneoscopy in 30% of cases. Considering the conversion rate of laparoscopy vs retroperitoneoscopy (12.5% vs 28.5%), right laparoscopic vs right retroperitoneoscopic adrenalectomy (4.7% vs 100%) and left laparoscopic vs left retroperitoneoscopic adrenalectomy (5% vs 16.6%) and on the basis of our experience in adults, we recommend laparoscopic adrenalectomy via a transperitoneal route in 45-degree flank decubitus for both right and left adrenal lesions. However, we think that the best surgical result can be achieved if the paediatric and adult surgeon collaborate with their different experience and expertise. As a technical point, we would like to stress that because of the child's small peritoneal cavity, trocar placement must be lower than in adults. Lastly, we suggest the use of new technological devices such as the Ultracision Harmonic Scalpel, which was a critical factor in our two successful right laparoscopic adrenalectomies.

Background: At the present time, the precise indications for laparoscopic surgery of adrenal incidentaloma (AI) have yet to be completely clarified. The most controversial issue is the role of laparoscopy in the treatment of potentially malignant and large adrenal masses. Trying to address these questions, we retrospectively examined a group of patients with AIs., Materials and Methods: Forty-two patients with AIs who were laparoscopically treated since 1995 were enrolled in this study. The patients were divided into two groups: the 27 patients of the immediate surgery (IS) group were operated on immediately, whereas the 15 subjects in the delayed surgery (DS) group needed further evaluations and/or a follow-up period before surgery. Surgical timing for both groups was decided according to a widely accepted decision-making algorithm. Many outcome parameters of laparoscopy (operative time, blood loss, conversion rate, time to liquid and solid food nutrition, drainage removal, resumption of normal bowel habits, and average hospital stay) were analyzed in the two groups. The subjects had AIs of various sizes and different histotypes., Results: Patients in the DS group had a higher risk for malignancy. The definitive pathology revealed a malignant biology in 26.6% of DS vs. 0% of IS cases. No difference in the outcome parameters of laparoscopy was observed between the two groups or among pathologically different AIs. A significant correlation was found between the operative time and the size of the AI (r=0.836, P<0.001, linear regression test)., Conclusion: Our study shows that laparoscopy is feasible and safe for AIs, regardless of the preoperative probability of malignancy. The size of the AI was the only determinant for choosing a laparotomy. Further long-term studies are necessary to confirm the laparoscopic efficacy in terms of oncologic safety.

Through a review of 83 cases reported in literature, including our experience of two successful right laparoscopic adrenalectomies performed in a 3-year-old girl for androgen-secreting adenoma and in a 9-year-old male for pheochromocitoma, we have anaIyzed the indications, the techniques and the results of laparoscopic or retroperitoneoscopic adrenalectomy in children. Nineteen pheochromocytomas, 18 neuroblastomas, 15 adenomas, 12 ganglioneuromas, 9 hyperplasias, 2 carcinomas, 1 teratoma and 1 adrenogenital syndrome have been treated with excellent results (follow-up 1 month to 4 years) with no evidence of recurrence. The age range is from 1 month to 16 years with an equal female/male ratio. The tumor size range from 10 mm to 80 mm with approximately a mean of 40 mm. Sixty-three laparoscopies of which 54 lateral and 9 anterior have been performed versus 14 posterior retroperitoneoscopies. Regarding right adrenalectomy, 29 were laparoscopic and only 2 retroperitoneoscopic. With regards to left adrenalectomy, 23 were laparoscopic and 9 retroperitoneoscopic. Looking at bilateral lesions, these tumors were approached laparoscopically in 6 cases alternating both sides and 1 retroperitoneoscopically (this case was already operated on the other side). The operative time ranged from 25 minutes in newborn to 320 minutes in bilateral cases with an average of 120 minutes. Conversion rate is higher in retroperitoneoscopy (30%) (4 cases out of 13), than laparoscopy (6%) (4 cases out of 63). Specifically, for right retroperitoneoscopic adrenalectomy conversion rate was 100% (2 cases out 2), for left retroperitoneoscopic adrenalectomy 22.2% (2 cases out 9), for right laparoscopic adrenalectomy 6.8% (2 cases out of 29) and for left laparoscopic adrenalectomy 8.6% (2 cases out of 23). Only in 1 case were blood transfusions requested. Hospital stays ranged from 35 hours to 17 days with an average of 4 days. In conclusion the indications of endoscopic adrenalectomy in children are not different from those of traditional surgery and the well-known advantages of laparoscopic adrenal surgery should be applied to pediatric patients. It seems that there is no age and tumor size limits for a well-trained surgical team. Lateral transperitoneal approach is the most utilized with the child positioned in 90-degree flank decubitus. Laparoscopy is undoubtly preferred for right adrenalectomy (93% of cases), while for left adrenalectomy retroperitoneoscopy has been used in 39% of the cases. Considering the conversion rate and on the basis of our experience with adults, we recommend laparoscopic adrenalectomy for both right and left adrenal lesions, but we think that the pediatric surgeon should feel free to choose the approach in which he/she is more skilled. However, the best surgical result will be achieved if the pediatric and adult surgeon collaborate with their different experiences. Lastly, we suggest the use of new technological devices such as Ultracision Harmonic Scalpel which was a critical factor in our two successful right adrenalectomies.

The authors retrospectively analyse 39 patients affected by Conn's syndrome, which have been observed since 1985, and discuss the results of surgical approach using the new technologies. In particular, the introduction of laparoscopy, technique that has been applied almost exclusively since the last seven years, has revealed being the "gold standard" for the surgical treatment of this disease. The adrenal underlying lesions are indeed almost always monolateral, small in size and present very rarely malignancy in their biological behaviour. Furthermore, the authors, although lacking of personal experience, propose the possibility of a more conservative treatment of the adrenal lesions with a simple "enucleation", whose feasibility also in laparoscopy has recently been shown by some authors. Anyway, the Authors believe that this technique of a partial adrenalectomy could be chosen in selective cases of bilateral adenomas or hyperplasia or in those lesions which are placed in an easily accessible peripheral site.

Various authors have suggested that laparoscopic adrenalectomy (LA) leads to better surgical outcomes than open surgery. The debate is still open, however, and indications and limitations of minimally invasive surgery have not been completely established. The objective of our study was to compare surgical outcomes of LA and open adrenalectomy (OA), using multivariate analysis to adjust for potential confounding factors (e.g., size of the lesion, histology). Between 1995 and June 2000 at "Careggi" Hospital in Florence, Italy patients with an indication for adrenalectomy were treated laparoscopically if the lesion was < 10 cm and there was no clinical evidence of malignancy. All 79 patients who underwent LA have been included in this study. Among 152 patients who underwent OA at "La Sapienza" University in Rome, 93 had an adrenal lesion < 10 cm and no clinical evidence of malignancy; they were selected for comparison. Multivariate analysis has been used to analyze the effect of the surgical approach (OA vs. LA) on the surgical outcome, controlling for potential confounders. Multiple logistic regression showed that there is no significant difference in intraoperative outcomes (i.e., surgical time > 2 hours, blood loss > or = 500 ml) between patients operated on through a traditional approach and those who underwent LA. On the other hand, patients operated on laparoscopically have a significantly higher probability than the OA group of experiencing a better recovery from surgery (i.e., require less postoperative analgesics and return to normal activities earlier). The results of the present study show that, although LA does not add much benefit in terms of expected intraoperative outcomes, it dramatically speeds patients' recovery from surgery. The two approaches are complementary and should both be integrated into the technical background of all endocrine surgeons.

Aim of the Study: To retrospectively evaluate a series of patients with acute and chronic small bowel obstruction and discuss the indications of laparoscopic vs laparotomic approach and the outcome of both these techniques., Patients and Method: 85 patients with acute and chronic small bowel obstruction who underwent to either emergency or elective surgery since January 1999 up to October 2001 were enrolled. Subjects were divided into three groups: 39 treated with emergency laparotomy (group I), 13 with emergency laparoscopy (group II) and 33 with elective laparoscopy for chronic/subacute obstructions (group III)., Results: 1) the most frequent indication of the laparotomic approach was either multiple or major previous surgery as well as neoplastic diseases; 2) patients of the second group had frequently previous either minor or laparoscopic surgery; 3) the incidence of previous emergency surgery were maximum among the III group; 4) both post-operative ileus and mean hospital stay lasted less in the II than in the I group. The mean operative time and the morbidity was equal in the two groups; 5) we observed more intra-operative complications, a higher conversion rate and a longer both post-operative ileus and mean hospital stay in the II than in the III group., Conclusions: Our data support the role of laparoscopy in patients with chronic/subacute small bowel obstruction. Patients with acute obstruction may undergo laparoscopy after a careful selection, excluding subjects with previous either multiple or major surgery as well as neoplastic diseases. Such results need future confirmations from prospective randomized studies.

Splenic cysts are rare in pediatric surgery. Congenital epidermoid cysts are exceptional representing only 2.5% of all splenic cysts in childhood. Nowadays, considering the short- and long-term complications of splenectomy in children, the management of epidermoid cyst consists of partial splenectomy or decapsulation of the cystic wall. To our knowledge, the case reported in this article describes the first successful laparoscopic decapsulation of an epidermoid splenic cyst in an 10-year-old child using the UltraCision LaparoSonic Coagulating Shears (LCS). Follow-up at six months confirms no recurrence. Laparoscopic splenic decapsulation provides minimal access and small surgical trauma for treating the cyst while preserving splenic function. The use of UltraCision LCS makes the laparoscopy safely, expeditiously, with minimal blood loss and short hospital stay.

The aim of this study was to analyse the morphological, kinetic and molecular characteristics of low-grade (LGD) and high-grade dysplasias (HDG) in comparison with intestinal metaplasia type III (IM III) and normal mucosa (NM) as well as with early gastric cancer of the intestinal type (EGC). Based on this it was verified whether these categories are distinct, progressive proliferative steps from IM III to LGD, HGD and EGC, according to Correa's sequence of events. The morphology, mitotic index (MI), and the apoptotic index (AI) were assessed. The E-cadherin expression (E-Cad), matrix-metalloproteinase activity (MMP2), and the number of microvessels (NV) were also evaluated. Among the categories, MI increases from NM to IM III and LGD, and from LGD to HGD and EGC, while AI continues to increase also from HGD to EGC. E-cad decreases from NM to EGC, although not significantly from LGD to HGD; MMP2 is significantly more expressed only in EGC. Three groups are obtained by means of cluster analysis. The first group includes all the NMs and IM IIIs, all except 1 LGD, about half of HGDs, and 1 EGC. E-Cad is highly expressed, MMP2 and angiogenesis are low, the proliferative activity is low and mitoses are partly balanced by apoptoses. The second group includes some EGCs and HGDs and is characterised by a very high proliferative activity and cell death; there is an initial loss of cell adhesion, an increase of MMP2 and NV. The third group includes the majority of EGCs, but also 1 HGD: it has intermediate MI and AI, the lowest expression of E-Cad, the highest expression of MMP2 and the most numerous microvessels. These results underscore the necessity of evaluating each case individually within the same singular category of Correa's sequence. The use of kinetic and molecular parameters in addition to the morphological analysis may give important information on the behaviour of the various lesions.

Laparoscopic adrenalectomy has proved to be the technique of choice for the treatment of benign pathologies of the adrenals and also for the treatment of isolated adrenal metastases, especially arising from lung tumor, but it shouldn't be performed for primitive adrenal carcinoma. The harmonic scalpel is very useful for laparoscopic adrenalectomy showing a significant reduction in operative time. The Authors retrospectively investigated 78 laparoscopic adrenalectomies performed from April 1995 to April 2000 using a transperitoneal approach with the patient on a lateral position as suggested by Gagner. Special care was taken to improve the surgical approach to the adrenals also by means of new technological devices as the Harmonic scalpel. The 78 laparoscopic adrenalectomies were performed in 70 cases for benign neoplasms: incidentalomas 24, Cushing's disease 16, Conn's disease 20, pheochromocytomas 9, myelolipoma 1. In the remaining 8 patients laparoscopic adrenalectomy was performed in 7 cases for isolated adrenal masses (5 metastases, 2 adenomas) in neoplastic patients, and in 1 patient for a preoperatively diagnosed adrenal carcinoma. Patients operated for functioning neoplasms had all remission or improvement of symptoms and humoral parameters; patients operated for isolated adrenal metastases showed this survival: 3 patients 3 years asymptomatic and disease free, 1 patient 18 months, and 3 patients are still alive and healthy after 6-12-15 months. A fast onset of local recurrence was seen in a patient operated for a preoperatively diagnosed adrenal carcinoma. We analyzed the operating time dividing the patients in three groups: a) 14 patients operated in the first semester of 1998 when we completed the training curve (average operative time 120.7 minutes); b) 14 patients operated from 1998-1999 (average operative time 118 minutes); c) the last 14 patients (operated from December 1999 to April 2000) where surgery was performed using the Harmonic scalpel (HS) (average operative time 94 minutes). The analysis of the average operative time comparing groups B and C using T-Student Test showed a significant reduction (p = 0.004). The morbility rate was 2.6%, mortality 1.3%, and a conversion rate of 2.6%. Laparoscopic approach results to be an extremely reliable procedure also for the treatment of incidentalomas up to 4-5 cm in which the incidence of adrenal carcinoma is about 13%. Doubts may yet result for the treatment of adrenal carcinomas preoperatively diagnosed. When laparoscopic adrenalectomy in performed using HS the operative time is significantly reduced and surgery is easier.

The adrenal pheochromocytoma still arouses great interest among the experts. The Authors give here a report of a study carried out on the personal case history of 32 patients and the concerning literature. A correct clinical and diagnostic approach is important to detect, at a preoperative level, the benign forms from the malignant ones (10-15% of cases according to literature) and the polyendocrine syndromes (21% of our series). Video-laparoscopy technique is recommended in pheochromocytomas surgery, mainly in asymptomatic and incidental forms and in all benign symptomatic forms less than 5 cm in size. At least, uni- or bilateral adrenalectomy associated with total thyroidectomy is also suggested in case of a polyendocrine syndrome.

The protection of Helicobacter pylori from the gastric acid exerted by urease is based on an increase of the bacterial periplasmic pH and membrane potential. Ammonia generated from urea induces apoptosis of gastric cells in vitro, and inhibits gastric somatostatin release in animals, which could have consequences on the physiology of digestion in general. The type s1/m1 structure of the vacA gene is associated with the production of high levels of cytotoxin. Strains with m2 region type, formerly considered devoid of toxic activity, are fully toxic when assayed with cell lines other than HeLa cells, which possibly lack receptors for m2 VacA type. The enhanced gastric mucosa damage associated with infection by cytotoxic organisms could be explained by the varying of effects exerted by VacA on target cells: extracellular secretion of acidic hydrolases, cytoskeletal alterations, actin rearrangement, reduction of epidermal growth factor binding to its receptor, inhibition of the stimulation of CD4+ T cells proliferation induced by the antigen presenting cells. Organisms that possess the pathogenicity island cag (cag+) induce an increased inflammation and transduction of signals to the host cells; however, they reduce the apoptosis of colonised cells. The results of an investigation on the possible influence of a variable cagA status on the extension of apoptosis have indicated that this kind of programmed death is disengaged from the possession of cagA by Helicobacter pylori organisms colonising the same gastric areas. It is likely that the whole pathogenic potential of cag+ organisms is far from being completely explored, as suggested by the recent finding that the expression of a bacterial adhesin (called BabA) involved in binding to the blood group antigen Lewis b is associated with the presence of cag.

Mitotic (MI) and apoptotic index (AI), the sum of the 2, i.e., the turnover index (TI), tumor neovascularization (NV) and p53 expression, as well as tumor grading and node status, are evaluated in early and advanced gastric-cancer cases. T1 cases show significantly less frequent lymph-node invasion and lower tumor grade, and, taken together, have significantly lower MI, Al and TI and higher values of NV than the T2-3 cases. However, correlation of the variables shows that the above-mentioned discrimination is due to a minority of T1 cases (11 out of 33), while the majority of them are allocated in the same 95% ellipse of tolerance of the T2-3 cases.

Villous adenomas of the bladder are rare tumors and up to now they have not been seen to undergo malignant transformation. We report a case of villous adenoma of the bladder with areas of adenocarcinoma in a 72-year-old man. We describe all the morphological, histochemical and immunohistochemical features characterizing this tumor. We recommend adequate pathological sampling and a thorough follow-up of patients with villous adenoma. The prognosis and the behaviour of these adenomatous papillary lesions, morphologically similar to colonic adenomas, in the bladder is unclear. We report a case with focal area of adenocarcinoma and review the literature.