Advances in the Diagnosis and Treatment of Appendiceal Mucinous Neoplasms

Primary appendiceal neoplasms represent a relatively low percentage of all gastrointestinal cancers. A subset of these neoplasms, those of epithelial origin, are characterised by the production of a considerable amount of mucus, which is referred to as appendiceal mucinous neoplasms (AMN). Appendiceal mucinous neoplasms (AMN) have a low incidence, are easily misdiagnosed, depend on postoperative examination for confirmation of the diagnosis, are prone to form a “diagnosis”, and have a high incidence of the disease. Furthermore, they are prone to form peritoneal pseudomyxoma peritonei (PMP), are controversial in surgical decision-making, are prone to recurring after surgery alone, and are tricky to manage clinically. In this paper, we review the pathological characteristics, diagnosis and treatment of appendiceal mucinous tumours in the light of recent literature reports, with a view to providing certain references for the clinical diagnosis and treatment of this disease. .

Surgical management of pancreatic neuroendocrine neoplasms

Pancreatic neuroendocrine neoplasms are a rare and complex group of neoplastic lesions that develop from pancreatic islet cells.Their incidence has dramatically increased during the last two decades.Due to its complex nature and pathophysiological behaviour,surgical management continues to evolve.Surgery remains the cornerstone of treatment for most non-functional and functional pancreatic neuroendocrine tumours,while lymphadenectomy remains a controversial subject.Different techniques,such as pancreas-preserving and minimally invasive approaches,continue to evolve and offer the same overall outcomes as open surgery.This comprehensive review describes in detail the current and most up-todate classification and staging of pancreatic neuroendocrine tumours,explores the rationale for nonsurgical and surgical management,and focuses on surgical treatment and more specifically,on minimally invasive approaches.

Solid pseudopapillary tumor of the pancreas:A systematic review of clinical,surgical and oncological characteristics of 1384 patients underwent pancreatic surgery

Background:Pancreatic solid pseudopapillary tumors(SPTs)are rare clinical entity,with low malignancy and still unclear pathogenesis.They account for less than 2%of exocrine pancreatic neoplasms.This study aimed to perform a systematic review of the main clinical,surgical and oncological characteristics of pancreatic SPTs.Data sources:MEDLINE/PubMed,Web of Science and Scopus databases were systematically searched for the main clinical,surgical and oncological characteristics of pancreatic SPTs up to April 2021,in accordance with the preferred reporting items for systematic reviews and meta-analyses(PRISMA)standards.Primary endpoints were to analyze treatments and oncological outcomes.Results:A total of 823 studies were recorded,86 studies underwent full-text reviews and 28 met inclusion criteria.Overall,1384 patients underwent pancreatic surgery.Mean age was 30 years and 1181 patients(85.3%)were female.The most common clinical presentation was non-specific abdominal pain(52.6%of cases).Mean overall survival was 98.1%.Mean recurrence rate was 2.8%.Mean follow-up was 4.2 years.Conclusions:Pancreatic SPTs are rare,and predominantly affect young women with unclear pathogenesis.Radical resection is the gold standard of treatment achieving good oncological impact and a favorable prognosis in a yearly life-long follow-up.

Risk of appendiceal neoplasm in patients with appendix disorders

The most common appendicular disease is acute appendicitis,with a lifetime risk of 7%–8%.Complicated cases,which can occur in 2%–7%of patients,can signi-ficantly impact the severity of the condition and may require different manage-ment approaches.Nonoperative management with possible delayed appende-ctomy has been suggested for selected patients,however,there is a non-negligible risk of missing an underlying malignancy,which is reported to be as high as 11%.Diagnostic work-up is paramount to achieve optimal treatment with good results.

External validation of nomograms for predicting cancer-specific mortality in penile cancer patients treated with definitive surgery

Using a population-based cancer registry,Thuret et al.developed 3 nomograms for estimating cancerspecific mortality in men with penile squamous cell carcinoma.In the initial cohort,only 23.0% of the patients were treated with inguinal lymphadenectomy and had pN stage.To generalize the prediction models in clinical practice,we evaluated the performance of the 3 nomograms in a series of penile cancer patients who were treated with definitive surgery.Clinicopathologic information was obtained from 160 M0 penile cancer patients who underwent primary tumor excision and regional lymphadenectomy between 1990 and 2008.The predicted probabilities of cancer-specific mortality were calculated from 3 nomograms that were based on different disease stage definitions and tumor grade.Discrimination,calibration,and clinical usefulness were assessed to compare model performance.The discrimination ability was similar in nomograms using the TNM classification or American Joint Committee on Cancer staging(Harrell's concordance index = 0.817 and 0.832,respectively),whereas it was inferior for the Surveillance,Epidemiology and End Results staging(Harrell's concordance index = 0.728).Better agreement with the observed cancer-specific mortality was shown for the model consisting of TNM classification and tumor grade,which also achieved favorable clinical net benefit,with a threshold probability in the range of 0 to 42%.The nomogram consisting of TNM classification and tumor grading was shown to have better performance for predicting cancer-specific mortality in penile cancer patients who underwent definitive surgery.Our data support the integration of this model in decision-making and trial design.

Clinicopathologic characteristics and prognosis of gastroenteropancreatic neuroendocrine neoplasms: a multicenter study in South China

Background: Gastroenteropancreatic neuroendocrine neoplasms(GEP-NENs) are a heterogeneous group of rare tumors. Many issues in terms of epidemiologic features, pathogenesis, and treatment of GEP-NENs are still under discussion. Our study aimed to analyze the clinicopathologic characteristics and prognosis of Chinese patients with GEP-NENs.Methods: Complete clinicopathologic data and survival information of 1183 patients with GEP-NENs treated between 2005 and 2015 were collected from five medical centers in Guangdong Province, China. Patient survival was estimated using the Kaplan–Meier method and analyzed using the log-rank test; prognostic factors were analyzed using the Cox proportional hazards model.Results: The most common tumor location was the rectum(37.4%), followed by the pancreas(28.1%), stomach(20.7%), small intestine(7.2%), appendix(3.4%), and colon(3.3%). After initial definitive diagnosis, 1016(85.9%) patients underwent surgery. The 1-, 3-, and 5-year overall survival(OS) rates for the entire cohort were 87.9%, 78.5%, and 72.8%, respectively. The 3-year OS rates of patients with G1, G2, and G3 tumors were 93.1%, 82.7%, and 43.1%, respectively(P < 0.001). The 3-year OS rates of patients with stage I, II, III, and IV tumors were 96.0%, 87.3%, 64.0%, and 46.8%, respectively(P < 0.001). Patients with distant metastasis who underwent palliative surgery had a longer survival than those who did not(P = 0.003). Similar survival benefits of palliative surgery were observed in patients with neuroendocrine tumor(P y, M category, and sur= 0.031) or neuroendocrine carcinoma(P gery were found to be independent prog= 0.046). In multivariate analysis, age, grade, N categornostic factors.Conclusions: Patients with GEP-NENs who are women, younger than 50 years old, have smaller tumor size, have lower tumor grade, have lower T/N/M category, and who undergo surgery can have potentially longer survival time. Our data showed that surgery can improve the prognosis of GEP-NEN patients with distant metastasis. However, randomized controlled trials need to be conducted to establish the optimal criteria for selecting patients to undergo surgery.

Current perspectives on pancreatic serous cystic neoplasms:Diagnosis, management and beyond

Pancreatic cystic neoplasms have been increasingly recognized recently. Comprising about 16% of all resected pancreatic cystic neoplasms, serous cystic neoplasms are uncommon benign lesions that are usually asymptomatic and found incidentally. Despite overall low risk of malignancy, these pancreatic cysts still generate anxiety, leading to intensive medical investigations with considerable financial cost to health care systems. This review discusses the general background of serous cystic neoplasms, including epidemiology and clinical characteristics, and provides an updated overview of diagnostic approaches based on clinical features, relevant imaging studies and new findings that are being discovered pertaining to diagnostic evaluation. We also concisely discuss and propose management strategies for better quality of life.

Differences between main-duct and branch-duct intraductal papillary mucinous neoplasms of the pancreas

In the last decade,intraductal papillary mucinous neoplasms(IPMNs) have become commonly diagnosed.From a morphological standpoint,they are classified in main-duct IPMNs(MD-IPMNs) and branch-duct IPMNs(BD-IPMNs),depending on the type of involvement of the pancreatic ductal system by the neoplasm.Despite the fact that our understanding of their natural history is still incomplete,recent data indicate that MD-IPMNs and BD-IPMNs show significant differences in terms of biological behaviour with MD-IPMNs at higher risk of malignant degeneration.In the present paper,clinical and epidemiological characteristics,rates of malignancy and the natural history of MD-IPMNs and BD-IPMNs are analyzed.The profile of IPMNs involving both the main pancreatic duct and its side branches(combined-IPMNs) are also discussed.Finally,general recommendations for management based on these differences are given.

Priapism secondary to penile metastasis of rectal cancer

Metastatic penile carcinoma is rare and usually originates from genitourinary tumors. The presenting symptoms or signs have been described as nonspecific except for priapism. Rectal adenocarcinoma is a very unusual source of metastatic penile carcinoma. We report a case of metastatic penile carcinoma that originated from the rectum. Symptomatic improvement occurred with palliative radiotherapy.

The penile tourniquet

Tourniquets are commonly used in penile surgery to achieve a bloodless operating field or produce artificial erections intraoperatively. Several techniques have been described, but there is a paucity of data and a lack of guidelines to direct their safe use. In penile surgery, it is the local rather than systemic effects of tourniquet use that are the main concern. Tourniquet time should be kept to a minimum, as the limited data available suggests that reperfusion injury can occur even after short periods of ischaemia. High risk groups such as diabetics and arteriopaths are at particular risk. Further studies are needed to determine safe tourniquet times and pressures.

Gastric neuroendocrine neoplasms type 1: A systematic review and meta-analysis

BACKGROUND To date, the histopathological parameters predicting the risk of lymph node (LN) metastases and local recurrence, associated mortality and appropriateness of endoscopic or surgical resection in patients with gastric neuroendocrine neoplasms type 1 (GNENs1) have not been fully elucidated. AIM To determine the rate of LN metastases and its impact in survival in patients with GNEN1 in relation to certain clinico-pathological parameters. METHODS The PubMed, EMBASE, Cochrane Library, Web of Science and Scopus databases were searched through January 2019. The quality of the included studies and risk of bias were assessed using the Newcastle-Ottawa Scale (NOS) in accordance with the Cochrane guidelines. A random effects model and pooled odds ratios (OR) with 95%CI were applied for the quantitative meta-analysis. RESULTS We screened 2933 articles. Thirteen studies with 769 unique patients with GNEN1 were included. Overall, the rate of metastasis to locoregional LNs was 3.3%(25/769). The rate of LN metastases with a cut-off size of 10 mm was 15.3% for lesions > 10 mm (vs 0.8% for lesions < 10 mm) with a random-effects OR of 10.5 (95%CI: 1.4 -80.8;heterogeneity: P = 0.126;I2 = 47.5%). Invasion of the muscularis propria was identified as a predictor for LN metastases (OR: 17.2;95%CI: 1.8-161.1;heterogeneity: P = 0.165;I2 = 44.5%), whereas grade was not clearly associated with LN metastases (OR: 2;95%CI: 0.3-11.6;heterogeneity: P = 0.304;I2 = 17.4%). With regard to GNEN1 local recurrence, scarce data were available. The 5-year disease-specific survival for patients with and without LN metastases was 100% in most available studies irrespective of the type of intervention. Surgical resection was linked to a lower risk of recurrence (OR: 0.3;95%CI: 0.1-1.1;heterogeneity: P = 0.173;I2 = 31.9%). The reported complication rates of endoscopic and surgical intervention were 0.6 and 3.8%, respectively. CONCLUSION This meta-analysis confirms that tumor size ≥ 10 mm and invasion of the muscularis propria are linked to a higher risk of LN metastases in patients with GNEN1. Overall, the metastatic propensity of GNEN1 is low with favorable 5- year disease-specific survival rates reported;hence, no clear evidence of the prognostic value of LN positivity is available. Additionally, there is a lack of evidence supporting the prediction of local recurrence in GNEN1, even if surgery was more often a definitive treatment.

Tunica albuginea allograft： a new model of LaPeyronie＇s disease with penile curvature and subtunical ossification

The pathophysiology of LaPeyronie＇s disease （PD） is considered to be multifactorial, involving genetic predisposition, trauma, inflammation and altered wound healing. However, these factors have not yet been validated using animal models. In this study, we have presented a new model obtained by tunica albuginea allograft. A total of 40, 16-week-old male rats were used. Of these, 8 rats served as controls and underwent a 10 × 2-mm-wide tunical excisionwith subsequent autografting, whereas the remaining 32 underwent the same excision with grafting of the defect with another rat＇s tunica. Morphological and functional testing was performed at 1, 3, 7 and 12 weeks after grafting. Intracavernous pressure, the degree of penile curvature and elastic fiber length were evaluated for comparison between the allograft and control groups. The tissues were obtained for histological examination. The penile curvature was significantly greater in the allografted rats as compared with the control rats. The erectile function was maintained in all rats, except in those assessed at 12 weeks. The elastin fiber length was decreased in the allografted tunica as compared to control. SMAD2 expression was detected in the inner part of the allograff, and both collagen-Ⅱ- and osteocalcin-positive cells were also noted. Tunica albuginea （TA） allograft in rats is an excellent model of PD. The persistence of curvature beyond 12 weeks and the presence of ossification in the inner layer of the TA were similar to those observed in men with PD. Validation studies using this animal model would aid understanding of the PD pathophysiology for effective therapeutic interventions.

Penile revascularization--contemporary update

Contemporary therapies for erectile dysfunction are generally targeted towards older men and universally engage pharmacological and/ or device related treatment options. Penile revascularization, using microvascular arterial bypass surgical techniques, is a non-pharmacological, non-device-related, and reconstructive surgical strategy for men with erectile dysfunction that was first described by Dr Vaclav Michal in 1973.

An update on penile reconstruction

Penile reconstruction still represents a formidable challenge for the urologist. In this review, the most recent advances in penile reconstruction after trauma, excision of benign and malignant disease and in patients with micropenis, aphallia or female to male gender dysphoria are reported.

Update on surgical treatment of pancreatic neuroendocrine neoplasms

Pancreatic neuroendocrine neoplasms(PNENs) are rare and account for only 2%-4% of all pancreatic neoplasms. All PNENs are potential(neurendocrine tumors PNETs) or overt(neuroendocrine carcinomas PNECs) malignant,but a subset of PNETs is low-risk. Even in case of low-risk PNETs surgical resection is frequently required to treat hormone-related symptoms and to obtain an appropriate pathological diagnosis. Low-risk PNETs in the body and the tail are ideal for minimallyinvasive approaches which should be tailored to the individual patient. Generally,surgeons must aim for parenchyma sparing in these cases. In high-risk and malignant PNENs,indications for tumor resection are much wider than for pancreatic adenocarcinoma,in many cases due to the relatively benign tumor biology. Thus,patients with locally advanced and metastatic PNETs may benefit from extensive resection. In experienced hands,even multi-organ resections are accomplished with acceptable perioperative morbidity and mortality rates and are associated with excellent long term survival. However,poorly differentiated neoplasms with high proliferation rates are associated with a dismal prognosis and may frequently only be treated with chemotherapy. The evidence on surgical treatment of PNENs stems from reviews of mostly singlecenter series and some analyses of nation-wide tumor registries. No randomized trial has been performed to compare surgical and non-surgical therapies in potentially resectable PNEN. Though such a trial would principally be desirable,ethical considerations and the heterogeneity of PNENs preclude realization of such a study. In the current review,we summarize recent advances in the surgical treatment of PNENs.

Endoscopic submucosal dissection for colorectal neoplasms

Although endoscopic submucosal dissection(ESD) gains acceptance as one of the standard treatments for esophageal and stomach neoplasms in Japan,it is still in the developing stage for colorectal neoplasms.In terms of indications,little likelihood of nodal metastasis and technical resectability are principally considered.Some of intramucosal neoplasms,carcinomas with minute submucosal invasion,and carcinoid tumors,which are technically unresectable by conventional endoscopic treatments,may become good candidates for ESD,considering substantial risks and obtained benefits.ESD as a staging measure to obtain histological information of the invasion depth and lymphovascular infiltration is acceptable because preoperative prediction is difficult in some cases.In terms of techniques,advantages of ESD in comparison with other endoscopic treatments are to be controllable in size and shape,and to be resectable even in large and fibrotic neoplasms.The disadvantages may be longer procedure time,heavier bleeding,and higher possibility of perforation.However,owing to refinement of the techniques,invention of devices,and the learning curve,acceptable technical safety has been achieved.Colorectal ESD is very promising and become one of the standard treatments for colorectal neoplasms in the near future.

Therapeutic strategies for gastroenteropancreatic neuroendocrine neoplasms: State-of-the-art and future perspectives

Although gastroenteropancreatic neuroendocrine neoplasms(GEP-NENs)have always been considered rare tumors,their incidence has risen over the past few decades.They represent a highly heterogeneous group of neoplasms with several prognostic factors,including disease stage,proliferative index(Ki67),and tumor differentiation.Most of these neoplasms express somatostatin receptors on the cell surface,a feature that has important implications in terms of prognosis,diagnosis,and therapy.Although International Guidelines propose algorithms aimed at guiding therapeutic strategies,GEP-NEN patients are still very different from one another,and the need for personalized treatment continues to increase.Radical surgery is always the best option when feasible;however,up to 80%of cases are metastatic upon diagnosis.Regarding medical treatments,as GEP-NENs are characterized by relatively long overall survival,multiple therapy lines are adopted during the lifetime of these patients,but the optimum sequence to be followed has never been clearly defined.Furthermore,although new molecular markers aimed at predicting the response to therapy,as well as prognostic scores,are currently being studied,their application is still far from being part of daily clinical practice.As they represent a complex disease,with therapeutic protocols that are not completely standardized,GEP-NENs require a multidisciplinary approach.This review will provide an overview of the available therapeutic options for GEP-NENs and attempts to clarify the possible approaches for the management of these patients and to discuss future perspectives in this field.

Pilot study to determine improvements in subjective penile morphology and personal relationships following a Nesbit plication procedure for men with congenital penile curvature

Aim： To determine whether the surgical straightening of congenital penile curvature can improve intromission comfort, penile features, personal relationships and psychogenic erectile dysfunction （ED）. Methods： Fifty-four patients （mean age 24 years, range 20-31 years） whose congenital penile deviation due to physiological curvature was ≥ 25 degrees, as measured on a graph, and who were experiencing penetration discomfort were assessed specifically for the present study. Of these, 14 patients suffered from psychogenic ED. The assessment included a case history, an objective examination, a pharmacologically-induced erection with prostaglandin E1 10-20 g, a graph taken during erection, a basal and dynamic Duplex ultrasonograph, penile length measurement, nocturnal penile tumescence recording, hormonal profiles and a psychological interview to evaluate the quality of their personal relationships according to Hinde＇s parameters （contents, number, features, frequency, ability to perceive limits of mutuality, subjective perception of the other person[s], and reliability）. All patients underwent the Nesbit procedure. The initial assessment was repeated at 3 and 12 months after surgery. Data analyses were carried out using the z test. Results： Subjective judgement of cosmetic penile features and vaginal intromission comfort improved significantly after surgery whereas the quality of personal relationships and ED did not. Conclusion： The surgical straightening of congenital penile curvature improved intromission comfort and penile features, but it failed to improve interpersonal relationships or psychogenic ED.

Hypothesis of human penile anatomy,erection hemodynamics and their clinical applications

Aim： To summarize recent advances in human penile anatomy, hemodynamics and their clinical applications. Methods： Using dissecting, light, scanning and transmission electron microscopy the fibroskeleton structure, penile venous vasculature, the relationship of the architecture between the skeletal and smooth muscles, and erection hemodynamics were studied on human cadaveric penises and clinical patients over a period of 10 years. Results： The tunica albuginea of the corpora cavernosa is a bi-layered structure with inner circular and outer longitudinal collagen bundles. Although there is no bone in the human glans, a strong equivalent distal ligament acts as a trunk of the glans penis. A guaranteed method of local anesthesia for penile surgeries and a tunical surgery was developed accordingly. On the venous vasculature it is elucidated that a deep dorsal vein, a couple of cavernosal veins and two pairs of para-arterial veins are located between the Buck＇s fascia and the tunica albuginea. Furthermore, a hemodynamic study suggests that a fully rigid erection may depend upon the drainage veins as well, rather than just the intracavemosal smooth muscle. It is believed that penile venous surgery deserves another look, and that it may be meaningful if thoroughly and carefully performed. Accordingly, a penile venous surgery was developed. Conclusion： Using this new insight into penile anatomy and physiology, exact penile curvature correction, refined penile implants and promising penile venous surgery, as well as a venous patch, for treating Peyronie＇s deformity might be performed under pure local anesthesia on an outpatient basis. （Asian J Androl 2006 Mar; 8： 225-234）

CONGENITAL EXPRESSION OF mdr-1 GENE IN FRESH CANCER TISSUES FROM SEVERAL HIGH-INCIDENCE NEOPLASMS WITHOUT PREOPERATIVE CHEMOTHERAPY

Objective: The purpose of the present study is to detect characteristics of primary expression of mdr 1 gene in several neoplasms which has high morbidity in clinic. Methods: 151 resected samples, which are pathologically malignant and clinically untreated before operation, were obtained from Anyang Cancer Hospital. All of them were investigated with RT PCR for the expression of mdr 1 gene and correlated each other. Besides, we evaluated the advantages of RT PCR in this study. Results: The mdr 1 gene expression rate of these 151 samples, including cancers of stomach and gastric cardia (n=51), esophagus (n=46), colorectum (n=16), breast (n=15), thyroid (n=10), lung (n=9), uterine cervix (n=4), was 33.3%, 37%, 31.3%, 13.2%, 40%, 55%, 0%, respectively. Conclusion: Compared with other methods, RT PCR for studying mdr 1 gene expression had certain advantages in simplicity, reliability, and accuracy. Overexpression of mdr 1 gene in these neoplasms suggested that cases should be distinguished before treatment according to MDR of tumor and to choose effective drugs for individual cancer patient.