Zollinger-Ellison Research Articles

Weight Gain in Zollinger-Ellison Syndrome After Acid Suppression.

Zollinger-Ellison syndrome (ZES) is characterized by hypergastrinemia and gastric acid hypersecretion resulting in peptic ulcer disease, diarrhea, and weight loss. Acid secretion can be controlled with medication, and biochemical cure is possible with surgery. Data on how these interventions affect patients' weight are lacking. We aimed to determine how medical and surgical acid control affects weight over time. We performed a retrospective cohort study on 60 ZES patients. Acid control was achieved with appropriate-dose proton pump inhibitor (PPI) therapy. Surgery was performed for curative intent when appropriate. Weight change was assessed versus pre-acid control or immediate preoperative weights and expressed as absolute and percent change from baseline at 6, 12, 18, and 24 months. A total of 30 PPI-controlled patients and 20 surgery-controlled patients were analyzed. Weight gain was noted at all time points while on appropriate-dose PPI therapy (P < 0.005). Of patients who had surgery with curative intent, weight gain was noted at 12 months (7.9%, P = 0.013) and 18 months (7.1%, P = 0.007). There was a trend toward weight gain seen at all time points in the patients who were surgically cured. These data represent a novel description of weight gain after acid suppression in ZES.

Helicobacter pylori Association with Acid Peptic Disease: It’s Incidence in Population Having Increase Junk Food Intake

Helicobacter pylori (H. pylori) is an organism that causes several gastric issues in majority of the formulation, it is a gram negative bacteria that increases the secretion of acid in stomach causing ulcer of stomach and duodenum that may lead to several other conditions like Zollinger Ellison syndrome (ZES), gastro esophageal reflux disease (GERD) etc. A study was conducted on population of Karachi (n=400 i.e. 200 males and 200 females) having junk food in their diet either daily, per week, or in 15 days and those visiting OPD of different hospitals with having complain of acidity, to find out either the acidity was due to H. pylori or not, and found out that in majority of population H. pylori is the cause behind acidity, thus indicating the increased prevalence of H. pylori in the population having acidity issues, for which several measures should be taken.

Management of gastric and duodenal neuroendocrine tumors.

Gastrointestinal neuroendocrine tumors (GI-NETs) are rare neoplasms, like all NETs. However, the incidence of GI-NETS has been increasing in recent years. Gastric NETs (G-NETs) and duodenal NETs (D-NETs) are the common types of upper GI-NETs based on tumor location. G-NETs are classified into three distinct subgroups: type I, II, and III. Type I G-NETs, which are the most common subtype (70%-80% of all G-NETs), are associated with chronic atrophic gastritis, including autoimmune gastritis and Helicobacter pylori associated atrophic gastritis. Type II G-NETs (5%-6%) are associated with multiple endocrine neoplasia type 1 and Zollinger-Ellison syndrome (MEN1-ZES). Both type I and II G-NETs are related to hypergastrinemia, are small in size, occur in multiple numbers, and are generally benign. In contrast, type III G-NETs (10%-15%) are not associated with hypergastrinemia, are large-sized single tumors, and are usually malignant. Therefore, surgical resection and chemotherapy are generally necessary for type III G-NETs, while endoscopic resection and follow-up, which are acceptable for the treatment of most type I and II G-NETs, are only acceptable for small and well differentiated type III G-NETs. D-NETs include gastrinomas (50%-60%), somatostatin-producing tumors (15%), nonfunctional serotonin-containing tumors (20%), poorly differentiated neuroendocrine carcinomas (< 3%), and gangliocytic paragangliomas (< 2%). Most D-NETs are located in the first or second part of the duodenum, with 20% occurring in the periampullary region. Therapy for D-NETs is based on tumor size, location, histological grade, stage, and tumor type. While endoscopic resection may be considered for small nonfunctional D-NETs (G1) located in the higher papilla region, surgical resection is necessary for most other D-NETs. However, there is no consensus regarding the ideal treatment of D-NETs.

Drug Interactions of H2 Receptor Antagonists-Ranitidine: A Review

Ranitidine has OTC drug status as well as it is an essential drug by WHO, hence it is popularly selling drug from community and hospital pharmacy. Many prescription and nonprescription drugs were found having drug interaction with ranitidine which may lead to either drug toxicity or therapy failure. This review compiles potential drug interactions of ranitidine with several categories of drugs along with effective measures. Ranitidine is in a group of drugs called histamine-2 blockers. H2 receptor antagonists continue to be prescribed usually for acid –peptic disease. Their safety record finally led to their availability as “Over the Counter” drugs. Histamine is a naturally-occurring chemical that stimulates cells in the stomach (parietal cells) to produce acid. H2-blockers inhibit the action of histamine on the cells, thus reducing the production of acid by the stomach. Ranitidine hydrochloride is prescribed for conditions such as gastroesophageal reflux disease (GERD), ulcers, Zollinger-Ellison syndrome, erosive esophagitis, upper gastrointestinal bleeding, heartburn, and other conditions where reduction of gastric secretion and acid output is desirable.

Syndromic versus non-syndromic sporadic gastrin-producing neuroendocrine tumors of the duodenum: comparison of pathological features and biological behavior

Sporadic gastrin-producing neuroendocrine tumors of the duodenum present either with the Zollinger-Ellison syndrome (ZES) or with unspecific symptoms. While syndromic gastrin-producing neuroendocrine tumors often show metastases at the time of diagnosis, those without a syndrome do not. The aim of the study was to search for clinicopathological features that may distinguish the two categories of gastrin-producing duodenal tumors. In a retrospective study, we analyzed the clinical and pathological data in a series of 41 patients with syndromic (i.e., gastrinomas) or non-syndromic duodenal gastrin-producing neuroendocrine tumors (ns-gas-NETs). Twenty-four (59 %) of the 41 patients had tumors that were associated with a ZES and were classified as gastrinomas. These tumors showed a higher Ki-67 index than that of the ns-gas-NETs (1.74 vs. 0.85 %, p = 0.012). In addition, they had more lymph node metastases (75 vs. 6 %, p < 0.001) and showed liver metastases and thus presented much more frequently in TNM stage ≥III (75 vs. 6 %; p < 0.001) than their non-syndromic counterparts. Gastrinomas were removed surgically, ns-gas-NETs endoscopically. We did not observe any significant differences in overall survival or recurrence of disease. Duodenal gastrinomas show no clear morphological features that distinguish them from their non-syndromic counterparts. However, the patients with gastrinomas present in a more advanced stage of disease and need surgical treatment, while non-syndromic gastrin-producing duodenal NETs may be cured by complete endoscopical removal.

Gastric neuroendocrine tumors with manifestations of Zollinger-Ellison syndrome

Gastric neuroendocrine tumors with manifestations of Zollinger-Ellison syndrome

Controversies in Surgery for Multiple Endocrine Neoplasia Type 1-Associated Zollinger–Ellison Syndrome

Zollinger–Ellison syndrome (ZES) is a common manifestation of multiple endocrine neoplasia type 1 (MEN1). At least 90% of MEN1-ZES patients have multiple duodenal gastrinomas, making the duodenum the target organ of ZES. The indication and the timing of surgery in MEN1-ZES is controversial, since there is yet no parameter that indicates an aggressive course of disease and long-term survival is generally good. An imageable, most likely nonfunctioning pancreatic neuroendocrine neoplasm (pNEN) &gt;1–2 cm seems to be a good surrogate parameter to indicate surgery in order to prevent distant metastatic pNEN disease, although some groups indicate surgery at the time of biochemical ZES evidence. The optimal surgical procedure is also controversial. Different strategies encomprise local excision via duodenotomy with or without distal pancreatic resection and regional lymphadenectomy to partial pancreaticoduodenectomy. At present, the timing and type of surgery for MEN1-ZES should be individualized according to patient’s characteristics and preference.

An Atypical Endoscopic Presentation of Zollinger-Ellison Syndrome

Zollinger-Ellison syndrome (ZES) is a rare condition characterized by gastrointestinal (GI) ulceration due to a gastrin-secreting tumor and hyper-secretion of gastric acid. Recent studies have shown thickened gastric folds and duodenal ulcers as the two most common endoscopic findings occurring in up to 80.3% and 15.3% of patients. We present a case of ZES with atypical endoscopic findings. A 52 year-old female with type 2 diabetes and hypertension presented with peri-umbilical pain. She described 7 out of 10, dull, aching pain with brown, mucus-like emesis. In the emergency department (ED), she was diagnosed with diverticulitis, prescribed antibiotics, and discharged. Due to severe nausea she did not finish the medications. She returned to the ED in 5 days with worsening pain. A CT abdomen/pelvis with contrast showed a 6.5x4.6x5.5 cm lobular enhancing mass lateral to the 4th part of the duodenum with multiple enlarged lymph nodes and wall thickening of the duodenum, suspicious for malignancy. Gastroenterology was consulted. Push enteroscopy showed severe LA class D esophagitis, and a normal stomach. The proximal duodenum had erosions and small clean based ulcers. Distal to the duodenal bulb, circumferential ulcers were seen with overlying eschar on each duodenal and proximal jejunal fold. There was a high suspicion for ZES given the CT and endoscopic findings. Fasting serum gastrin level was 3804 pg/mL (normal).Figure 1Figure 2Figure 3GI ulcerations are common endoscopic findings in ZES with 91-93% having peptic or duodenal ulcers when diagnosed. ZES is usually characterized by solitary ulcers < 1cm in diameter, with the majority in the 1st part of the duodenum. However, it is not uncommon for ulcers to be located in the distal duodenum or jejunum. Circumferential ulcers of the small bowel are often related to non-steroidal anti-inflammatory medications, or thiazide potassium-chloride use. In this case of Zollinger-Ellison we found multiple, circumferential ulcers extending from the duodenal bulb to the jejunum, which has not been previously reported endoscopically.

Microscopic Carcinoid: An Unusual Presentation of Gastric Carcnioid

51 year old Caucasian male with history of hyperlipidemia presented with complain of melena. Patient had noticed one episode of bright red blood per rectum. On questioning patient also complained of feeling tired lately with generalized body aches. He also had some numbness and tingling in both lower extremities which had been gradually worsening. Neurological exam showed decreased sensation, vibration and position sensation in both lower extremities. Digital rectal exam was positive for frank blood in rectal vault. Initial laboratory work up showed hemoglobin of 8.5 with MCV of 110. Patient underwent upper endoscopy which showed non-bleeding gastric ulcer. Also there were few scattered small focal areas of erythematous lesions in gastric cardia and proximal body with significant loss of the gastric folds. Biopsy of the lesions showed increase in fibrous tissue with moderate active inflammation of lamina propria and Chronic atrophic gastritis while rapid urease test was negative. Interestingly, carcinoid changes with chronic intestinal metaplasia were found on biopsy suspicious for carcinoid tumor. Given the finding on biopsy, fasting serum Gastrin Chromogranin A levels, Parietal cell antibodies, Intrinsic Factor antibodies, 24 hour urine for 5-HIAA, Computerized tomography (CT) scan of the abdomen and pelvis, and Octreotide scan were ordered to look for primary location of carcinoid tumor. Fasting serum Gastrin Chromogranin A levels, Parietal cell antibodies, Intrinsic Factor antibodies were found to be elevated the diagnosis of Carcinoid Tumor but there were no mass lesions but only scattered cells in the stomach. Patient subsequently underwent frequent endoscopies with biopsies which reconfirmed well differentiated carcinoid tumor cells scattered in the stomach but no mass lesion. Meanwhile patient underwent extensive work up for peripheral neuropathy and was found to have vitamin B12 deficiencies in setting of atrophic gastritis leading towards diagnosis of pernicious anemia which was likely cause of the underlying carcinoid changes. Patient is currently treated with vitamin B12 with marked improvement in his symptoms and is undergoing Surveillance endoscopies of carcinoid changes. Discussion: Carcinoid tumors Originate from Enterochromaffin-like (ECL) cells, found in gastric wall. There are three types of gastric carcinoid tumors. Type 1 are smaller and less than 1 cm, multiple, polypoid lesions with central ulceration associated with chronic atrophic gastritis and pernicious anemia. Type 2 occurs in association with gastrinomas (Zollinger-Ellison syndrome), often in setting of MEN type 1 and are mostly indolent in nature. While type 3 are Sporadic as they occur in the absence of atrophic gastritis or the Zollinger-Ellison /MEN1 syndromes and are very aggressive in nature. They are characterized by normal gastrin level. Diagnosis for carcinoid tumors include biochemical testing including urinary excretion of 5-HIAA, Chromogranin level, Blood serotonin concentration, Gastrin level and Anti parietal cell antibodies. Tumor localization is done by CT, Magnetic resonance Imaging, Octreotide scan. Type 1 and 2 are treated with endoscopic resections and survelliant endoscopies. Treatment for type 3 gastric carcinoid tumors is partial or total gatstrectomy considering the aggressive nature. Conclusions: Carcinoid tumors usually appear as discrete masses but microscopic carcinoid tumor in stomach is a very rare.

Massive gastrointestinal bleed due to multiple gastric neuroendocrine tumors

AbstractGastric neuroendocrine tumors (G-NETs) are uncommon lesions which are usually diagnosed on histological evaluation of gastric polyps. These may occur sporadically or due to hypergastrinemia in the setting of atrophic gastritis or Zollinger-Ellison Syndrome. Large lesions may ulcerate and result in gastrointestinal bleeding. However, massive gastrointestinal bleeding is rare in patients with NETs. We report a 60-year-old lady who presented with massive gastrointestinal bleeding due to multiple G-NETs.

Gastric Hypersecretory States: Investigation and Management.

Hypersecretory conditions affecting the stomach account for significant morbidity and mortality manifested in some cases with peptic ulcer, gastrointestinal hemorrhage, and/or gastroesophageal reflux disease (GERD). The diagnosis of gastric acid hypersecretory states can be challenging and relies on the use of quantitative assays to measure gastric acid secretion and serum gastrin. The most common etiology for hypergastrinemia is the use of potent gastric acid inhibitors such as the proton pump inhibitors. The differential diagnosis of this condition is of critical importance, and will dictate management decisions. Conditions such as atrophic gastritis are relatively benign and can lead to hypergastrinemia without the presence of gastric acid hypersecretion. Zollinger-Ellison syndrome, on the other hand, causes hypergastrinemia with profound gastric acid hypersecretion [1]. More common causes of hypergastrinemia include gastric outlet obstruction, ileus, and chronic renal failure [2]. In most cases, proton pump inhibitors will be used to manage these conditions. In some instances, surgical therapy may be required. This chapter will review the important clinical causes of gastric acid hypersecretion and provide insights to the best medical management options to better care for patients with these disorders.

Development and Evaluation of Optimized Gastroretentive Mucoadhesive Tablets of Famotidine for Gastro-Esophageal Reflux Disease

The aim of the present investigation was to increase the gastric residence time of Famotidine by designing and optimization of gastroretentive mucoadhesive tablet, thereby improving bioavailability of Famotidine. Famotidine conventional tablets have been reported by many Scientists to exhibit poor oral bioavailability and fluctuations in plasma drug concentration. This results, either in precipitation of side effects or reduction in drug concentration at the target site. Famotidine is a histamine H2-receptor antagonist. It is widely prescribed in active duodenal ulcers, gastric ulcers, Zollinger-Ellison syndrome and gastro esophageal reflux disease. The effective treatment requires administration of 20 mg of Famotidine 4 times a day. A conventional dose of 20 mg can inhibit gastric acid secretion up to 6 hours but not up to 12 hours. An alternative dose of 40 mg leads to plasma fluctuations; thus a sustained release dosage form of famotidine is desirable. The short biological half-life of drug (2.5-4 hours) also favors development of a sustained release formulation. Thus objective of present study to reduce the dosing frequency by developing, optimizing and evaluating gastroretentive mucoadhesive tablet for sustain release. A 32 full factorial design is employed to study the effect of independent variables like Carbopol-940 and HPMC K100M, which significantly influence characteristics like ex-vivo mucoadhesive strength and in-vitro drug release. Tablets were prepared by direct compression technique. No significant change was observed in physical appearance, drug content, hardness, mucoadhesive strength, in vitro dissolution pattern after the stability tasting for one month.&#x0D;

Intraoperative near-infrared fluorescence visualization of the duodenal gastrinoma in a patient with Zollinger–Ellison syndrome

DISEASE AND ESOPHAGITIS, controlled with protonpump inhibitors during the last 5 years, was admitted to our hospital for evaluation with suspected Zollinger–Ellison syndrome (ZES). The basal acid output was 24 mEq/hr and fasting serum gastrin concentration 1874 pg/mL. On abdominal ultrasonography and magnetic resonance imaging a 15-mm juxta-duodenal pathologic lymph node (LN) of the anterior pancreaticoduodenal artery was detected and no liver metastases. The endoscopic ultrasonography with contrast did not find the primary tumor. Endoscopic fineneedle aspiration cytology with Ki67 proliferation index and Chromogranin A immunohistochemistry from the juxta-duodenal LN confirmed the diagnosis of well-differentiated neuroendocrine carcinoma. Somatostatin receptor scintigraphy was not available. Abdominal exploration, inspection, palpation after Kocher maneuver, and intraoperative ultrasonography only identified but the 15-mm juxta-duodenal LN. Indocyanine-green (ICG) 0.1 mg/kg was administered intravenously, with near-infrared fluorescence (NIRF) visualization (NIRF-800 probe, ArteMIS Handheld System, Quest Medical Imaging BV, Wieringerwerf, the Netherlands) of the duodenum and pancreas. The absolute values of

Multiple neuro-endocrine tumours complicating chronic atrophic gastritis: the cloak that hides the dagger

Neuro-endocrine tumours of the stomach are most likely to be seen as a complication of chronic atrophic gastritis and are usually multiple, small and indolent. Much more rarely, similar tumours can occur in Zollinger-Ellison syndrome and those tumours are also usually relatively benign. Thus most neuro-endocrine tumours of the stomach, especially when multiple, are treated relatively conservatively. Here we present two cases where the initial biopsies suggested that scenario but further investigations indicated more aggressive tumours, which ultimately represented mixed adeno-neuroendocrine carcinomas (MANECs) and frank adenocarcinomas, demanding a much more radical management strategy. Whislt therapeutic conservatism is appropriate for small and multiple neuro-endocrine tumours complicating chronic atrophic gastritis, the potential for other complications of chronic atrophic gastritis in the stomach, namely MANECs and adenocarcinoma, should always be borne in mind and evidence for those tumours sought by the multi-disciplinary team.

Gastric neuroendocrine neoplasms and proton pump inhibitors: fact or coincidence?

Objective. Reporting on three cases of gastric neuroendocrine tumors (g-NETs) in patients taking long-term proton pump inhibitors (PPIs). These tumors are not classifiable considering current criteria. g-NETs are currently grouped as: types 1 and 2, related to hypergastrinemia due to chronic atrophic gastritis and Zollinger-Ellison syndrome respectively, and type 3, normogastrinemic and more aggressive. Although the g-NETs onset in patients taking PPIs is biologically plausible, only a few cases have been reported so far. Materials and methods. From January 2005 to July 2014, 31 g-NETs were referred to our Unit: 24 (77%), one (3%) and three (10%) resulted types 1, 2 and 3, respectively. Three cases (10%) did not meet the current classification criteria. Results. The three patients were administered long-term PPIs for gastro-esophageal reflux disease. Patient 1: a 78-year-old man, with a 4-mm well-differentiated g-NET (Ki-67<1%) and marked hypergastrinemia. Patient 2: a 58-year-old man affected by a 6-mm well-differentiated (Ki-67 = 4%) g-NET, with normal gastrin levels. Patients 3: a 67-year-old woman with an 18-mm well-differentiated g-NET (Ki-67 <2%), with mild hypergastrinemia. In the three patients, histology and pertinent blood tests excluded chronic atrophic gastritis, Helicobacter pylori infection or Zollinger-Ellison syndrome. The first two patients underwent endoscopic polypectomy; in the third case total gastrectomy was performed. Further clinical, endoscopic and imaging follow-up did not show any g-NET recurrence. Conclusions.The present data point to the existence and epidemiological relevance of g-NETs associated with PPIs intake. These neoplasms are not included in the current classification, thus their treatment and follow-up have not been established.

Physicochemical Investigation of Engineered Nanosuspensions Containing Model Drug, Lansoprazole

Lansoprazole is a proton-pump inhibitor used in treatment of gastric ulcers, gastroesophageal reflux disease (GERD), and Zollinger–Ellison syndrome. The objective of the study was physicochemical investigation and comparative characterization of nanosuspensions of lansoprazole by complexing with β-cyclodextrin and β-cyclodextrin-based nanosponges to enhance its solubility and stability. Inclusion complexes of lansoprazole with β-cyclodextrin and nanosponges were prepared by physical method and polymer condensation method, respectively. Particle size, zeta potential, encapsulation efficiency, in vitro release, FTIR, and Differential Scanning Calorimeter (DSC) studies were used as characterization parameters. The average particle size of lansoprazole nanoparticles was found to be in the range of 178.7 ± 6.39 nm to 204.9 ± 2.91 nm. The high zeta potential values were attained to ensure a high-energy barrier and favor a good stability of nanosuspensions. In vitro release study showed the controlled release of lansoprazole, which was more satisfactory than individual drug. FTIR spectroscopy showed that there was interaction of cyclodextrin and its nanosponges with drug. DSC study revealed that drug was involved in complexion with cyclodextrin and nanosponges. Solubility and stability of lansoprazole were remarkably improved by inclusion complexation. Based on these findings, it can be concluded that engineered nanosuspension of lansoprazole is a promising carrier for nanoparticulate drug delivery in gastric ulcer.

Intraoperative Use of a Portable Large Field of View Gamma Camera and Handheld Gamma Detection Probe for Radioguided Localization and Prediction of Complete Surgical Resection of Gastrinoma: Proof of Concept

Surgical management of Zollinger-Ellison syndrome (ZES) relies on localization and resection of all tumor foci. We describe the benefit of combined intraoperative use of a portable large field of view gamma camera (LFOVGC) and a handheld gamma detection probe (HGDP) for indium-111 ((111)In)-pentetreotide radioguided localization and confirmation of gastrinoma resection in ZES. Five patients (6 cases) with (111)In-pentetreotide-avid ZES were evaluated. Patients were injected with (111)In-pentetreotide for diagnostic imaging the day before surgery. Intraoperatively, an HGDP and LFOVGC were used to localize (111)In-pentetreotide-avid lesions, guide resection, assess specimens for (111)In-pentetreotide activity, and to verify lack of abnormal post-resection surgical field activity. Large field of view gamma camera imaging and HGDP-assisted detection were helpful for localization and guided resection of tumor and removal of (111)In-pentetreotide-avid tumor foci in all cases. In 3 of 5 patients (3 of 6 cases), these techniques led to detection and resection of additional tumor foci beyond those detected by standard surgical techniques. The (111)In-pentetreotide-positive or-negative specimens correlated with neuroendocrine tumors or benign pathology, respectively. In one patient with mild residual focal activity on post-resection portable LFOVGC imaging, thought to be artifact, had recurrence of disease in the same area 5 months after surgery. Real-time LFOVGC imaging and HGDP use for surgical management of gastrinoma improve success of localizing and resecting all neuroendocrine tumor-positive tumor foci, providing instantaneous navigational feedback. This approach holds potential for improving long-term patient outcomes in patients with ZES.

Determinants of surgical resection for pancreatic neuroendocrine tumors.

Pancreatic neuroendocrine tumors (pNETs) include functioning and non-functional tumors. Functioning tumors consist of tumors that produce a variety of hormones and their clinical effects. Therefore, determinants of resection of pNETs should be discussed for each group of tumors. Less than 10% of insulinomas are malignant, therefore more than 90% of the cases can be cured by surgical resection. Lymphadenectomy is generally not necessary in insulinoma operation. If preoperative localization of the insulinoma is completed, enucleation from the pancreatic body or tail, and distal pancreatectomy can be performed safely by laparoscopy. When preoperative localization of a sporadic insulinoma is not confirmed, surgical exploration is needed. Intraoperative localization of a tumor, intraoperative insulin sampling and frozen section are required. The crucial purpose of surgical resection is to control inappropriate insulin secretion by removing all insulinomas. Gastrinomas are usually located in the duodenum or pancreas, which secrete gastrin and cause Zollinger-Ellison syndrome (ZES). Duodenal gastrinomas are usually small, therefore they are not seen on preoperative imaging studies or endoscopic ultrasound, and can be found only at surgery if a duodenotomy is performed. In addition, lymph node metastasis is found in 40-60% of cases. Therefore, the experienced surgeons should direct operation for gastrinomas. Surgical exploration with duodenotomy should be performed at a laparotomy. Other functioning pNETs can occur in the pancreas or in other locations. Curative resection is always recommended whenever possible after optimal symptomatic control of the clinical syndrome by medical treatment. Indications for surgery depend on clinical symptom control, tumor size, location, extent, malignancy and presence of metastasis. A lot of non-functioning pNETs are found incidentally according to the quality improvement of imaging techniques. Localized, small, malignant non-functioning pNETs should be operated on aggressively, while in possibly benign tumors smaller than 2 cm the surgical risk-benefit ratio should be carefully weighted. Surgical liver resection is generally proposed in curative intent to all patients with operable metastases from G1 or G2 pNET. The benefits of surgical resection of liver metastases have been demonstrated in terms of overall survival and quality of life. Complete resection is associated with better long-term survival.

Hypergastrinemia.

Gastrin is an important hormone of the digestive system, which assists gastric acid secretion. It may be pathologically elevated in conditions such as Zollinger-Ellison syndrome, or due to common medications such as proton pump inhibitors. In this review we provide an overview of the pathophysiology and medical causes of hypergastrinemia, diagnostic testing and clinical consequences of chronic hypergastrinemia.

How case reports have contributed to the progress of surgery.

Editorial The now well-known Zollinger-Ellison syndrome was recognized by Professor Zollinger at Ohio State University and his student, Dr. Ellison, based on their insightful observations of two young women who suffered from refractory peptic ulcers requiring repeated surgery [1]. The index case for Kasabach-Merritt syndrome was a 2-month-old male infant who underwent radiation therapy for a huge and growing capillary hemangioma in the left thigh causing extensive purpura [2]. Dr. Kasabach was a radiologist and Dr. Merritt was a colleague pediatrician at Columbia University. The first successful right lobectomy of the liver was performed by Professor Honjo at Kyoto University in 1949 to remove a large liver metastasis from rectal cancer in a 22-year-old man [3]. Professor Honjo reported this epoch-making progress in liver surgery as a case report in an English journal. The first three cases of human liver transplantation were reported by Professor Starzl from the University of Colorado in 1963 [4]. Nevertheless, case reports or case series are ranked as low level 4 evidence [5] in the hierarchy of evidence-based medicine. Most of the top medical or surgical journals now restrict the acceptance of case reports to an extreme degree because such reports, in general, are seldom cited and thus would reduce the journal's impact factor. However, we must recognize how previous reports of a few unusual cases, observed and treated by excellent physicians, have contributed greatly to the progress of medical science. In addition to the outstanding case reports mentioned above, there have been a number of amazing discoveries made by surgeons in their daily practice. Sir James Cantlie, a surgeon at the University of Hong Kong, started his anatomical research on the liver after