Total gastrectomy for severe proton pump inhibitor-induced hypomagnesemia in a MEN1/Zollinger Ellison syndrome patient

We report here the first case of life-threatening hypomagnesemia in a Zollinger-Ellison syndrome patient with multiple endocrine neoplasia type 1 (MEN1) syndrome. The severe symptomatic hypomagnesemia proved to be due to proton pump inhibitors (PPIs), but withdrawal of PPIs led to early severe peptic complications despite a substitution by histamine H2-receptor antagonist therapy. Simultaneous management of life-threatening hypomagnesemia, severe gastric acid hypersecretion and MEN1-associated gastrinomas was complex. A total gastrectomy was performed in order to definitely preclude the use of PPIs in this frail patient who was not eligible for curative pancreatoduodenal resection.     

Large primary hepatic gastrinoma in young patient treated with trisegmentectomy: A case report and review of the literature

Primary hepatic gastrinoma is a rare disease, with fewer than 40 cases reported in the medical literature. Because it is located in an organ in which metastases are common, its diagnosis is difficult. We report a case of a 19 years old male patient with a history of gastric ulcers since the age of nine. Following gastric surgery, an antrectomy and a vagotomy, there was some alleviation of symptoms. Subsequently, the patient reported various intermittent episodes of diarrhea, diffuse abdominal pain, and vomiting. The patient underwent tomography, which revealed the presence of a hepatic mass measuring 19.5 cm × 12.5 cm × 17 cm. Primary hepatic gastrinoma was diagnosed based on laboratory examinations that indicated hypergastrinemia and a positron emission tomography/magnetic resonance study with somatostatin analogue that confirmed the liver as the primary site. After hepatic trisegmentectomy(Ⅱ, Ⅲ, Ⅳ, Ⅴ, Ⅷ), the patient's symptoms improved. The case is notable for the presence of a rare tumor with uncommon dimensions.     

Irritable bowel syndrome: A disease still searching for pathogenesis,diagnosis and therapy

Irritable bowel syndrome (IBS) is the most frequently diagnosed functional gastrointestinal disorder in primary and secondary care. It is characterised by abdominal discomfort, pain and changes in bowel habits that can have a serious impact on the patient’s quality of life. The pathophysiology of IBS is not yet completely clear. Genetic, immune, environmental, inflammatory, neurological and psychological factors, in addition to visceral hypersensitivity, can all play an important role, one that most likely involves the complex interactions between the gut and the brain (gut-brain axis). The diagnosis of IBS can only be made on the basis of the symptoms of the Rome III criteria. Because the probability of organic disease in patients fulfilling the IBS criteria is very low, a careful medical history is critical and should pay particular attention to the possible comorbidities. Nevertheless, the severity of the patient’s symptoms or concerns sometimes compels the physician to perform useless and/or expensive diagnostic tests, transforming IBS into a diagnosis of exclusion. The presence of alarming symptoms (fever, weight loss, rectal bleeding, significant changes in blood chemistry), the presence of palpable abdominal masses, any recent onset of symptoms in patient aged over 50 years, the presence of symptoms at night, and a familial history of celiac disease, colorectal cancer and/or inflammatory bowel diseases all warrant investigation. Treatment strategies are based on the nature and severity of the symptoms, the degree of functional impairment of the bowel habits, and the presence of psychosocial disorders. This review examines and discusses the pathophysiological aspects and the diagnostic and therapeutic approaches available for patients with symptoms possibly related to IBS, pointing out controversial issues and the strengths and weaknesses of the current knowledge.     

林奇综合征诊疗进展

林奇综合征是一种由错配修复基因突变造成的遗传性结直肠癌综合征,属常染色体显性遗传病,过去又称遗传性非息肉病性大肠癌,约占全部大肠癌的5%~15%,错配修复基因的种系突变和微卫星不稳定是其分子遗传学基础。近年来随着分子生物学的进展,林奇综合征的诊断及治疗越来越受到人们的关注,本文就林奇综合征的诊断与治疗进展做一综述。     

Management of neuroendocrine carcinomas of the pancreas (WHO G3): A tailored approach between proliferation and morphology

Neuroendocrine carcinomas(NEC) of the pancreas are defined by a mitotic count 20 mitoses/10 high power fields and/or Ki67 index 20%, and included all the tumors previously classified as poorly differentiated endocrine carcinomas. These latter are aggressive malignancies with a high propensity for distant metastases and poor prognosis, and they can be further divided into small- and large-cell subtypes. However in the NEC category are included also neuroendocrine tumors with a well differentiated morphology but ki67 index 20%. This category is associated with better prognosis and does not significantly respond to cisplatin-based chemotherapy, which represents the gold standard therapeutic approach for poorly differentiated NEC. In this review, the differences between well differentiated and poorly differentiated NEC are discussed considering both pathology, imaging features, treatment and prognostic implications. Diagnostic and therapeutic flowcharts are proposed. The need for a revision of current classification system is stressed being well differentiated NEC a more indolent disease compared to poorly differentiated tumors.     

Nature and management of pancreatic mucinous cystic neoplasm (MCN): A systematic review of the literature

BackgroundThe current management of pancreatic mucinous cystic neoplasms (MCN) is defined by the consensus European, International Association of Pancreatology and American College of Gastroenterology guidelines. However, the criterion for surgical resection remains uncertain and differs between these guidelines. Therefore through this systematic review of the existing literature we aimed to better define the natural history and prognosis of these lesions, in order to clarify recommendations for future management.MethodsA systematic literature search was performed (PubMed, EMBASE, Cochrane Library) for studies published in the English language between 1970 and 2015.ResultsMCNs occur almost exclusively in women (female:male 20:1) and are mainly located in the pancreatic body or tail (93–95%). They are usually found incidentally at the age of 40–60 years. Cross-sectional imaging and endoscopic ultrasound are the most frequently used diagnostic tools, but often it is impossible to differentiate MCNs from branch duct intraductal papillary mucinous neoplasms (BD-IPMN) or oligocystic serous adenomas pre-operatively. In resected MCNs, 0–34% are malignant, but in those less than 4 cm only 0.03% were associated with invasive adenocarcinoma. No surgically resected benign MCNs were associated with a synchronous lesion or recurrence; therefore further follow-up is not required after resection. Five-year survival after surgical resection of a malignant MCN is approximately 60%.ConclusionsCompared to other pancreatic tumors, MCNs have a low aggressive behavior, with exceptionally low rates of malignant transformation when less than 4 cm in size, are asymptomatic and lack worrisome features on pre-operative imaging. This differs significantly from the natural history of small BD-IPMNs, supporting the need to differentiate mucinous cyst subtypes pre-operatively, where possible. The findings support the recommendations from the recent European Consensus Guidelines, for the more conservative management of MCNs.     

Gemcitabine-Induced Hemolytic Uremic Syndrome in Pancreatic Cancer: A Case Report and Review of the Literature

Hemolytic uremic syndrome (HUS) is a rare thrombotic complication characterized by a triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. HUS may be caused by several different conditions, including infection, malignancy, and chemotherapeutic agents, such as mitomycin, cisplatin, and most recently, gemcitabine. The outcome of gemcitabine-induced HUS is poor, and the disease has a high mortality rate. This study reports a case of gemcitabine-induced HUS in a patient with pancreatic cancer in Korea.     

Review of lymphoma in the duodenum: An update of diagnosis and management

The presentation, subtype, and macroscopic images of lymphoma vary depending on the site of the tumor within the gastrointestinal tract. We searched PubMed for publications between January 1, 2012 and October 10, 2022, and retrieved 130 articles relating to duodenal lymphoma. A further 22 articles were added based on the manual screening of relevant articles, yielding 152 articles for full-text review. The most predominant primary duodenal lymphoma was follicular lymphoma. In this review, we provide an update of the diagnosis and man-agement of representative lymphoma subtypes occurring in the duodenum: Follicular lymphoma, diffuse large B-cell lymphoma, extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue, mantle cell lymphoma, and T-cell lymphomas.     

Diagnosis and management of postural orthostatic tachycardia syndrome: A brief review

Postural orthostatic tachycardia syndrome (POTS) has been recognized since at least 1940. A review of the literature identifies differences in the definition for this condition and wide variations in treatment and outcomes. This syndrome appears to describe a group of conditions with differing pathophysiology, which requires treatment tailored to the true underlying disorder. Patients need to be fully evaluated to guide treatment. Further research is required to effectively classify the range of underlying pathophysiology that can produce this syndrome and to guide optimal management.     

Neonatal diabetes, with hypoplastic pancreas, intestinal atresia and gall bladder hypoplasia: search for the aetiology of a new autosomal recessive syndrome

Aims/hypothesis Neonatal diabetes is a rare disease with several identified molecular aetiologies. Despite associations with other malformations, neonatal diabetes with intestinal and biliary anomalies has not been described. The current study aims to describe a new syndrome, and to examine a possible link with one of three genes known to cause neonatal diabetes.Methods Five clinical cases are described. Immunohistochemical staining for pancreatic islet hormones was performed on three of the infants. DNA from one infant was analysed for abnormalities of the PLAGL-1 (ZAC), glucokinase and PDX-1 (IPF-1) genes.Results Five infants (two sibling pairs from two families, and an isolated case) presented with neonatal diabetes, hypoplastic or annular pancreas, jejunal atresia, duodenal atresia and gall bladder aplasia or hypoaplasia. One sibling pair was born to consanguineous parents. One patient with a milder form is surviving free of insulin. Four children died in the first year of life despite aggressive medical management. Pancreatic immunohistochemistry revealed few scattered chromogranin-A-positive cell clusters but complete absence of insulin, glucagon and somatostatin. Exocrine histology was variable. In one case from the consanguineous family, molecular analysis showed no duplication or uniparental isodisomy of PLAGL-1 at 6q24, no contiguous gene deletion involving the glucokinase gene, and no mutation in the coding sequences or splice sites of PDX-1.Conclusions/interpretation This combination of multiple congenital abnormalities has not been previously described and probably represents a new autosomal recessive syndrome involving a genetic abnormality that interferes with normal islet development and whose aetiology is as yet unknown.     

Acupuncture and related therapies for carpal tunnel syndrome: A protocol for systematic review and Bayesian network meta-analysis

Background:Carpal tunnel syndrome (CTS) is the most common peripheral nerve compression syndrome of the upper limb. Plenty of studies showed the effects of acupuncture therapy on relieving pain and improving functional status for CTS patients. Diverse types of acupuncture therapies have been used in the treatment for CTS, but their relative treatment effects are poorly understood. This study will evaluate the effects of different acupuncture and related therapies for CTS by conducting a systematic review and Bayesian network meta-analysis (NMA).Methods:We will search randomized controlled trials (RCTs) of acupuncture and related therapies for CTS in MEDLINE (via PubMed), EMBASE, Web of Science, Cochrane Library, Chinese Biomedical Database, China National Knowledge Infrastructure, VIP Database, Wanfang Database, WHO International Clinical Trials Registry Platform, ClinicalTrials.gov, Chinese Clinical Trial Register, and OpenGrey from inception to November 2021. Then, we will select eligible studies, extract data, and conduct risk of bias assessment using the Cochrane tool. Pairwise meta-analysis and Bayesian NMA will be performed in Stata 15.1 software and Aggregate Data Drug Information System 1.16.8 software. We will assess the quality of the evidence using the Confidence in Network Meta-Analysis application.Results:In this study, the treatment effects and safety of different acupuncture and related therapies for CTS will be evaluated.Conclusion:This study will provide evidence for choosing the optimal acupuncture and related therapies in the treatment for CTS.     

Diagnosing irritable bowel syndrome: poor agreement between general practitioners and the Rome II criteria

Background: The new guidelines for diagnosing irritable bowel syndrome (IBS) in clinical practice recommend the use of the Rome II criteria. In this study the agreement between general practitioners (GPs) and the Rome II criteria for diagnosing of IBS and functional bowel disorders (FBD) is examined. Methods: Consecutive patients in general practice were asked to report on abdominal complaints, for which they had consulted or wanted to consult a GP. Patients with such complaints completed a questionnaire based on the Rome II criteria for FBD. After consultations, the GPs reported their diagnoses on the abdominal complaints. Results: Of 3097 screened patients, 553 patients were diagnosed by their GP and had complete data in the questionnaire. Of these patients, 107 had IBS according to the GPs and 209 had IBS according to the Rome II criteria (agreement 58%, kappa 0.01 (CI: ?0.06; 0.09)). Agreement on IBS and FBD in patients without organic disease, without reflux or dyspepsia and in patients with a verified diagnosis was 45%–58%, with kappa values from ?0.02 to 0.13. IBS and FBD cases were diagnosed by the Rome II criteria more often than by the GPs in all these groups of patients (P?Conclusions: This study shows poor agreement in the diagnosis of IBS between GPs and the Rome II criteria. Therefore, current knowledge about IBS based on strict criteria is not necessarily transferable to patients with IBS in general practice.     

Changing trends in the clinicopathological features,practices and outcomes in the surgical management for cystic lesions of the pancreas and impact of the international guidelines: Single institution experience with 462 cases between 1995-2018

IntroductionThe impact on clinical practice of the international guidelines including the Sendai Guidelines (SG06) and Fukuoka Guidelines (FG12) on the management of cystic lesions of the pancreas (CLP) has not been well-studied. The primary aim was to examine the changing trends and outcomes in the surgical management of CLP in our institution over time and to determine the impact of these guidelines on our institution practice.Methods462 patients with surgically-treated CLP were retrospectively reviewed and classified under the 2 guidelines. The cohort was divided into 3 time periods: 1998–2006, 2007–2012 and 2013 to 2018.ResultsComparison across the 3 time periods demonstrated significantly increasing frequency of older patients, asymptomatic CLP, male gender, smaller tumor size, elevated Ca 19-9, use of magnetic resonance imaging (MRI) and use of endoscopic ultrasound (EUS) prior to surgery. There was also significantly increasing frequency of adherence to the international guidelines as evidenced by the increasing proportion of HR^SG06 and HR^FG12 CLP with a corresponding lower proportion of LR^SG06 and LR^FG12 being resected. This resulted in a significantly higher proportion of resected CLP whereby the final pathology confirmed that a surgery was actually indicated.ConclusionsOver time, there was increasing adherence to the international guidelines for the selection of patients for surgical resection as evidenced by the significantly increasing proportion of HR^SG06 and HR^FG06 CLPs undergoing surgery. This was associated with a significantly higher proportion of patients with a definitive indication for surgery.These suggested that over time, there was a continuous improvement in our selection of appropriate CLP for surgical treatment.     

Current and emerging therapies for managing hyperphagia and obesity in Prader‐Willi syndrome: A narrative review

In early childhood, individuals with Prader‐Willi syndrome (PWS) experience excess weight gain and severe hyperphagia with food compulsivity, which often leads to early onset morbid obesity. Effective treatments for appetite suppression and weight control are currently unavailable for PWS. Our aim to further understand the pathogenesis of PWS led us to carry out a comprehensive search of the current and emerging therapies for managing hyperphagia and extreme weight gain in PWS. A literature search was performed using PubMed and the following keywords: “PWS” AND “therapy” OR “[drug name]”; reference lists, pharmaceutical websites, and the ClinicalTrials.gov registry were also reviewed. Articles presenting data from current standard treatments in PWS and also clinical trials of pharmacological agents in the pipeline were selected. Current standard treatments include dietary restriction/modifications, exercise, and growth hormone replacement, which appear to have limited efficacy for appetite and weight control in patients with PWS. The long‐term safety and effectiveness of bariatric surgery in PWS remains unknown. However, many promising pharmacotherapies are in development and, if approved, will bring much needed choices into the PWS pharmacological armamentarium. With the progress that is currently being made in our understanding of PWS, an effective treatment may not be far off.     

Why the current diagnostic criteria of Takotsubo syndrome are outmoded: A proposal for new criteria

Diagnosis of Takotsubo syndrome (TTS), the reversible, acute heart failure pathological entity, precipitated by stress, is based on the fulfillment of sets of criteria, developed by careful characterization of the precipitants, symptoms, results of imaging testing, clinical course, and follow-up of many patients presented with this affliction. As understanding of TTS, increase in its awareness, and the diversion in its presentation have evolved, the various proposed diagnostic criteria, naturally have started to appear outmoded. The author argues that the initially proposed Mayo Clinic criteria, the subsequently revised Mayo Clinic criteria, the Japanese Circulation Society guidelines, the Johns Hopkins criteria, and the Gothenburg criteria for the diagnosis of TTS have been outpaced by the rapidly accumulating clinical experience, and thus need to be replaced by more realistic sets of diagnostic rules. To this effect the author proposes a set of diagnostic criteria for TTS, which include 2 plausible, albeit speculative, notions, that of the milder forms or formes frustes of TTS, and the existence of “TTS comorbidity” in patients with various other illnesses, which either precipitate TTS, or are being brought about by TTS.     

The clinical profiles,management, and prognostic factors of biliary mixed neuroendocrine nonneuroendocrine neoplasms: A systematic review of the literature

Background:Mixed neuroendocrine nonneuroendocrine neoplasms (MiNENs) originating from the biliary system (gallbladder, biliary tract, or ampulla of Vater) are extremely rare and have not been discussed in detail or systematically. We aimed to present the demographics, clinicopathological characteristics, management, and prognostic factors of biliary MiNENs.Methods:A systematic search of electronic biomedical databases (Web of Science, PUBMED, and Embase) was performed to identify eligible studies. Survival was analyzed with the Kaplan–Meier method. Log-rank tests were used to evaluate the differences between groups, and the effects of various clinical and histopathological features on prognosis were analyzed by univariate and multivariate Cox regression.Results:Fifty-three publications (patients, n = 67) were included. The median overall survival time was 21.0 months. Fifty-one patients (76.1%) underwent radical surgery and median survival for 41 months (P < .001). Twenty-two patients who received adjuvant radiochemotherapy treatment after radical surgery had a median survival for 43 months (P = .076). Radical resection (P < .001), Ki-67 index (P = .011), tumor stage (P < .001), neuroendocrine (NEC) grade (P = .011), and non-NEC grade (P = .017) were independent statistically significant prognostic factors according to univariate analysis; radical resection (P = .010) and small morphological subtype (P = .036) were independent statistically significant prognostic factors associated with higher overall survival according to multivariate analysis, and radical resection (P = .005) and age < 65 years (P = .026) were associated with higher recurrence free survival time.Conclusion:Radical resection is essential for long-term survival. Aggressive multimodality therapy with adjuvant radiochemotherapy and biotherapy may improve survival of biliary MiNENs. Further randomized controlled trials are needed to determine the standard treatment.     

Moving towards the New International Study Group for Pancreatic Surgery (ISGPS) definitions in pancreaticoduodenectomy: a comparison between the old and new

BackgroundThe International Study Group for Pancreatic Surgery (ISGPS) has proposed several definitions for postoperative pancreatic fistula (POPF), delayed gastric emptying (DGE) and post-pancreatectomy haemorrhage (PPH). We assessed the effects of implementing these definitions on predicting outcomes.MethodsA database of 77 patients who underwent pancreaticoduodenectomy between January 2005 and December 2009 was analysed. Morbidities were defined and classified using the ISGPS definitions and recalculated based on the definitions adopted by our institution (‘Old’ definitions) prior to the implementation of ISGPS definitions. Data for the two groups were then compared.ResultsThe morbidity rate rose to 70.1% from 27.2% when ISGPS rather than Old definitions were used to define morbidities (P < 0.001). Incidences of DGE, POPF and PPH were 20.7%, 39.0% and 10.4%, respectively. Rates of DGE and POPF were significantly higher according to ISGPS definitions than to Old definitions (20.7% vs. 5.2% [P= 0.001] and 39.0% vs. 15.6% [P= 0.004], respectively). According to the ISGPS definitions, all of the 12 additional patients with DGE and 12 of the 18 additional patients with POPF had grade A morbidities. Patients with ISGPS-defined morbidity had a longer intensive care unit (ICU) stay, longer postoperative stay and longer total stay (P= 0.030, P= 0.007 and P= 0.001, respectively).ConclusionsThe morbidity rate more than doubled when ISGPS definitions were applied (an additional 42.9% of patients demonstrated morbidities). The majority of patients with DGE and POPF had grade A morbidities. The ISGPS definitions correlate well with ICU stay, postoperative stay and total length of stay.Use of ISGPS definitions increased markedly the morbidity rate in patients undergoing pancreatic resection and correlated well with hospital stay