Pathoetiology of Levator Ani Syndrome and Its Treatment With Translumbosacral Neuromodulation Therapy.

INTRODUCTION: The pathoetiology and treatment of levator ani syndrome (LAS) remain unclear. METHODS: We evaluated pathophysiology using translumbosacral motor-evoked potentials and anorectal manometry in patients with LAS and compared with healthy controls. A cohort underwent translumbosacral neuromodulation therapy (TNT). RESULTS: Lumbar and sacral motor-evoked potential latencies were prolonged in 32 patients with LAS compared with 31 controls ( P < 0.013), with higher prevalence of anal neuropathy ( P = 0.026). TNT improved anorectal pain ( P = 0.003) and neuropathy ( P < 0.02) in 13 patients with LAS. DISCUSSION: Patients with LAS demonstrate significant lumbosacral neuropathy that may cause anorectal pain. TNT improved anorectal pain and neuropathy, providing a novel therapeutic option.

The impact of the speed of food intake on gastroesophageal reflux events in obese female patients.

Obesity increases the risk of gastroesophageal reflux disease (GERD). The majority of the reflux attacks occur postprandially. The influence of the speed of food intake on gastroesophageal reflux events is unclear in obese patients. To determine the influence of the speed of food intake on intraesophageal reflux events in obese patients with and without GERD. A total of 26 obese female patients were recruited. The patients underwent esophageal manometry to evaluate the upper limit of the lower esophageal sphincter and subsequently placement of a Multichannel intraluminal impedance-pH (MII-pH) catheter. All patients were asked to eat the same standard meal (double cheeseburger, 1 banana, 100 g yogurt and 200 mL water; total energy value, 744 kcal; 37.6% carbohydrates, 21.2% proteins and 41.2% lipids) within 5 or 30 minutes under observation in a random order on two consecutive days. All reflux episodes over a 3-hour postprandial period were manually analyzed and compared. The mean age was 46 ± 12 (18-66) years. The mean body mass index (BMI) was 39.9 ± 8.4 kg/m2. There was no difference between the fast- and slow-eating group in the number of refluxes within the 3-postprandial hours. The patients were divided into 2 groups according to the 24-hour MII-pH monitoring results, that is, 16 subjects with normal MII-pH monitoring and 10 patients with pathologic MII-pH monitoring. There was no effect of the speed of food intake in either the patients with or without GERD. In contrast to the general belief, this study suggested that the speed of food intake does not influence the number of refluxes in obese female patients with or without GERD.

Small intestinal fungal overgrowth.

Small intestinal fungal overgrowth (SIFO) is characterized by the presence of excessive number of fungal organisms in the small intestine associated with gastrointestinal (GI) symptoms. Candidiasis is known to cause GI symptoms particularly in immunocompromised patients or those receiving steroids or antibiotics. However, only recently, there is emerging literature that an overgrowth of fungus in the small intestine of non-immunocompromised subjects may cause unexplained GI symptoms. Two recent studies showed that 26 % (24/94) and 25.3 % (38/150) of a series of patients with unexplained GI symptoms had SIFO. The most common symptoms observed in these patients were belching, bloating, indigestion, nausea, diarrhea, and gas. The underlying mechanism(s) that predisposes to SIFO is unclear but small intestinal dysmotility and use of proton pump inhibitors has been implicated. However, further studies are needed; both to confirm these observations and to examine the clinical relevance of fungal overgrowth, both in healthy subjects and in patients with otherwise unexplained GI symptoms. Importantly, whether eradication or its treatment leads to resolution of symptoms remains unclear; at present, a 2-3-week course of antifungal therapy is recommended and may be effective in improving symptoms, but evidence for eradication is lacking.

Treatment of esophageal (noncardiac) chest pain: an expert review.

BACKGROUND & AIMS: Chest pain is a common and frightening symptom. Once cardiac disease has been excluded, an esophageal source is most likely. Pathophysiologically, gastroesophageal reflux disease, esophageal dysmotility, esophageal hypersensitivity, and anxiety disorders have been implicated. However, treatment remains a challenge. Here we examined the efficacy and safety of various commonly used modalities for treatment of esophageal (noncardiac) chest pain (ECP) and provided evidence-based recommendations. METHODS: We reviewed the English language literature for drug trials evaluating treatment of ECP in PubMed, Cochrane, and MEDLINE databases from 1968-2012. Standard forms were used to abstract data regarding study design, duration, outcome measures and adverse events, and study quality. RESULTS: Thirty-five studies comprising various treatments were included and grouped under 5 broad categories. Patient inclusion criteria were extremely variable, and studies were generally small with methodological concerns. There was good evidence to support the use of omeprazole and fair evidence for lansoprazole, rabeprazole, theophylline, sertraline, trazodone, venlafaxine, imipramine, and cognitive behavioral therapy. There was poor evidence for nifedipine, diltiazem, paroxetine, biofeedback therapy, ranitidine, nitrates, botulinum toxin, esophageal myotomy, and hypnotherapy. CONCLUSIONS: Ideally, treatment of ECP should be aimed at correcting the underlying mechanism(s) and relieving symptoms. Proton pump inhibitors, antidepressants, theophylline, and cognitive behavioral therapy appear to be useful for the treatment of ECP. However, there is urgent and unmet need for effective treatments and for rigorous, randomized controlled trials.

High resolution and high definition anorectal manometry and pressure topography: diagnostic advance or a new kid on the block?

The recent development of closely spaced circumferential solid state transducers has paved the way for novel technology that includes high resolution anorectal manometry and topography (HRAM) and 3-D high definition anorectal manometry (HDAM). These techniques are increasingly being used for the assessment of anorectal neuromuscular function. However, whether they constitute a diagnostic advantage or a mere refinement of an old technology is unknown. Unlike the traditional manometry that utilized 3 or 6 unidirectional sensors, the closely spaced circumferential arrangement facilitates superior spatiotemporal mapping of pressures at rest and during various dynamic maneuvers. HDAM can provide knowledge of the three muscles that govern the anal continence namely, the puborectalis, and the internal and external anal sphincters, and can show how they mediate the rectoanal inhibitory reflex and sensorimotor responses and the spatiotemporal orientation of these muscles. Also, anal sphincter defects can be mapped and readily detected using 3-D technology. Similarly, HRAM has facilitated confirmation and development of phenotypes of dyssynergic defecation. Recently, normative data have also been reported with HRAM and HDAM, together with the influence of age, gender, and test instructions. The greater yield of anatomical and functional information may supersede the limitations of costs, fragility, and shorter life-span associated with these new techniques. Thus, HDAM and HRAM are not just new gadgets but constitute a significant and novel diagnostic advance. However, more prospective studies are needed to better define anorectal disorders with these techniques and to confirm their superiority.

Barostat or syringe-assisted sensory biofeedback training for constipation with rectal hyposensitivity: A randomized controlled trial.

BACKGROUND: Rectal hyposensitivity (RH) is a well-known pathophysiological dysfunction in chronic constipation. Whether biofeedback training improves RH and restores bowel function is unknown. AIM: To investigate the efficacy of barostat-assisted sensory training (BAST) with syringe-assisted sensory training (SAST) in patients with RH in a randomized controlled trial. METHODS: Patients with RH and chronic constipation (Rome III) were randomized to receive 6 biweekly sessions of BAST or SAST. Verbal/visual feedback was provided during repeated rectal distensions to improve defecation desire/urge and first sensations with either 10-cm balloon connected to barostat (BAST) or 4-cm balloon connected to syringe and manometry probe (SAST). Sensory thresholds, bowel symptoms, and therapist and patient's rating of treatments were compared. The primary outcome (responders) was the improvement in ≥2 sensory thresholds. RESULTS: Sixty-six patients were enrolled: 32 received BAST, 34 received SAST, and 56 completed study. There were significantly more responders in BAST group than SAST (78% vs. 53%, p = 0.0320). Rectal sensation normalized in 81% with BAST compared to 56% with SAST (p = 0.0270). When compared to baseline, desire and urge to defecate thresholds and bowel satisfaction improved with BAST (p = 0.0013; p = 0.0002; p = 0.0001) and SAST (p = 0.0012; p = 0.0001; p < 0.0001) and number of complete spontaneous bowel movements with BAST (p = 0.0029) but without inter-group differences. Therapists rated BAST as superior to SAST (p < 0.0001), but patients rated both equally. CONCLUSIONS: Sensory biofeedback training was effective and significantly improved rectal sensation and constipation symptoms. Although both techniques were useful, the novel BAST was more efficacious and easier to administer for treating RH.

[Investigation of verotoxigenic Escherichia coli O157:H7 incidence in gastroenteritis patients]. / Gastroenteritli olgularda verotoksijenik escherichia coli O157:H7 insidansinin arastirilmasi.

Escherichia coli O157:H7 is the most common serotype among verotoxigenic E.coli (VTEC) strains that cause haemolytic uremic syndrome. Although sporadic VTEC cases originating from Turkey and small outbreaks have been reported from our country, VTEC has not been routinely investigated in most of the diagnostic microbiology laboratories in Turkey and studies related to this topic are limited. In this study, the incidence of E.coli O157:H7 in patients who were admitted to Alanya Research and Application Hospital of Baskent University with the complaints of acute gastroenteritis between September 2005 and September 2008, was investigated. Stool samples collected from 1815 diarrheal patients (of them 50.5% were male; 49.3% were ? 5 years old; 10.2% were tourists) were evaluated initially by direct microscopy and then inoculated to hectoen enteric agar, EMB agar, Skirrow agar and cefixime tellurite sorbitol MacConkey (CT-SMC) agar media for cultivation. The sorbitol-negative colonies which were compatible with E.coli according to the conventional methods were tested with E.coli polyvalent and 0157 and H7 monovalent antisera and agglutination positive strains were also investigated for verotoxin production in Vero cell cultures. VTEC RPLA toxin detection kit (Oxoid, UK) was used for further identification of toxin type of verotoxin positive strains. Fecal leukocytes were detected in 41.3% of the samples in direct microscopy, while 27% (173/639) of the samples were also found positive for amoeba antigen, 6% (24/396) for rotavirus antigen, 1.2% (22/1815) for Salmonella spp., 0.6% (11/1815) for Shigella spp., 0.2% (4/1815) for Giardia trophozoites and 0.06% (1/1815) for Campylobacter jejuni. The isolation rate of sorbitol-negative E.coli strains was %0.8 (14/1815), and two of them were identified as E.coli O157:H7 by monovalent antisera, and both of them were determined as verotoxin-producers in cell culture. Verotoxin types of those isolates were found as verotoxin 1 in one strain and verotoxin 1 + verotoxin 2 in the other. The two patients infected with verotoxigenic E.coli O157:H7 were both tourists (one was 7 and the other was 35 years old) and admitted to the emergency room of hospital with complaints of bloody diarrhea. No further investigation directed towards the origin of the pathogen could be performed in the hotels of these patients. These data indicated that VTEC O157:H7 incidence was low (2/1815; 0.1%) in our area during the study period. Thus, routine testing of stool samples for E.coli O157:H7 does not seem to be cost-effective. However, E.coli O157:H7 should necessarily be investigated at least in bloody diarrhea cases since this pathogen has serious morbidity, mortality and complications like haemolytic uremic syndrome, hemorrhagic colitis and also due to its epidemiological significance.

Sensory Adaptation Training or Escitalopram for IBS With Constipation and Rectal Hypersensitivity: A Randomized Controlled Trial.

INTRODUCTION: Rectal hypersensitivity is an important pathophysiological dysfunction in irritable bowel syndrome with predominant constipation (IBS-C), whose treatment remains challenging. In a randomized controlled trial, we compared the efficacy and safety of a novel sensori-behavioral treatment, sensory adaptation training (SAT) with escitalopram. METHODS: Patients with IBS-C (Rome III) with rectal hypersensitivity received 6 biweekly sessions of SAT or escitalopram 10 mg daily for 3 months. SAT was performed by repetitive gradual distension of 10-cm long highly compliant rectal balloon above tolerability thresholds using barostat. Treatment effects on sensory thresholds and symptoms were compared. Coprimary outcome measures were those achieving improvements in rectal hypersensitivity (≥20% increase in ≥2/3 sensory thresholds) and pain (≥30% decrease). RESULTS: We randomized 49 patients; 26 received SAT and 23 escitalopram. SAT significantly improved desire to defecate (Δ 13.5 ± 2.3 vs 2.2 ± 1.1 mm Hg, P = 0.0006) and maximum tolerability (Δ 14.8 ± 1.9 vs 1.6 ± 0.9 mm Hg, P < 0.0001) thresholds compared with escitalopram. There were significantly greater percentage of hypersensitivity responders with SAT than escitalopram (69% vs 17%, P < 0.001), but not pain responders (58% vs 44%, P = 0.4). Daily pain scores did not differ between groups (P = 0.8) or escitalopram (P = 0.06) but decreased with SAT (P = 0.0046) compared with baseline. SAT significantly increased rectal compliance (P < 0.019) and complete spontaneous bowel movements per week than escitalopram (P = 0.04). Five withdrew from adverse events with escitalopram and none with SAT. DISCUSSION: SAT was significantly more efficacious in improving hypersensitivity and bowel symptoms in IBS-C than escitalopram. SAT is a promising novel treatment for IBS with rectal hypersensitivity.

Brucella melitensis infection in total knee arthroplasty: a case report.

We report a case of a 63-year-old female patient who underwent a total knee arthroplasty in which the knee later became infected with Brucella melitensis. Diagnosis was made by positive culture of a sinus tract discharge. Radiological views of the knee did not show signs of implant loosening. The patient was successfully treated with rifampicin and doxycycline without surgery.

Enterohemorrhagic Escherichia coli O157:H7: case report.

Enterohemorrhagic Escherichia coli (EHEC) is a significant bacterial pathogen of bloody diarrhea. Not only does it cause systemic complications, such as hemolytic uremic syndrome (HUS) (the most common cause of potentially preventable pediatric renal failure), but it also leads to large outbreaks of bloody diarrhea. Among EHEC serotypes that cause HUS, E. coli O157:H7 is the most common. Herein, we present the case of a young girl with E. coli O157:H7 infection and review the related literature.

Anorectal Manometry in Defecatory Disorders: A Comparative Analysis of High-resolution Pressure Topography and Waveform Manometry.

BACKGROUND/AIMS: Whether high-resolution anorectal pressure topography (HRPT), having better fidelity and spatio-temporal resolution is comparable to waveform manometry (WM) in the diagnosis and characterization of defecatory disorders (DD) is not known. METHODS: Patients with chronic constipation (Rome III) were evaluated for DD with HRPT and WM during bearing-down "on-bed" without inflated rectal balloon and "on-commode (toilet)" with 60-mL inflated rectal balloon. Eleven healthy volunteers were also evaluated. RESULTS: Ninety-three of 117 screened participants (F/M = 77/16) were included. Balloon expulsion time was abnormal (＞ 60 seconds) in 56% (mean 214.4 seconds). A modest correlation between HRPT and WM was observed for sphincter length (R = 0.4) and likewise agreement between dyssynergic subtypes (κ = 0.4). During bearing down, 2 or more anal pressure-segments (distal and proximal) could be appreciated and their expansion measured with HRPT but not WM. In constipated vs healthy participants, the proximal segment was more expanded (2.0 cm vs 1.0 cm, P = 0.003) and of greater pressure (94.8 mmHg vs 54.0 mmHg, P = 0.010) during bearing down on-commode but not on-bed. CONCLUSIONS: Because of its better resolution, HRPT may identify more structural and functional abnormalities including puborectal dysfunction (proximal expansion) than WM. Bearing down on-commode with an inflated rectal balloon may provide additional dimension in characterizing DD.

How to perform and assess colonic manometry and barostat study in chronic constipation.

Management of chronic constipation with refractory symptoms can be challenging. Although new drugs and behavioral treat-ments have improved outcome, when they fail, there is little guidance on what to do next. At this juncture, typically most doc-tors may refer for surgical intervention although total colectomy is associated with morbidity including complications such as recurrent bacterial overgrowth. Recently, colonic manometry with sensory/tone/compliance assessment with a barostat study has been shown to be useful. Technical challenges aside, adequate preparation, and appropriate equipment and knowledge of co-lonic physiology are keys for a successful procedure. The test itself appears to be safe with little complications. Currently, colon-ic manometry is usually performed with a 6-8 solid state or water-perfused sensor probe, although high-resolution fiber-optic colonic manometry with better spatiotemporal resolutions may become available in the near future. For a test that has evolved over 3 decades, normal physiology and abnormal findings for common phenotypes of chronic constipation, especially slow transit constipation, have been well characterized only recently largely through the advent of prolonged 24-hour ambulatory colonic manometry studies. Even though the test has been largely restricted to specialized laboratories at the moment, emerg-ing new technologies and indications may facilitate its wider use in the near future.(J Neurogastroenterol Motil 2014;20:547-552).

How to assess regional and whole gut transit time with wireless motility capsule.

Assessment of transit through the gastrointestinal tract provides useful information regarding gut physiology and patho-physiology. Although several methods are available, each has distinct advantages and limitations. Recently, an ingestible wire-less motility capsule (WMC), similar to capsule video endoscopy, has become available that offers a less-invasive, standardized, radiation-free and office-based test. The capsule has 3 sensors for measurement of pH, pressure and temperature, and collec-tively the information provided by these sensors is used to measure gastric emptying time, small bowel transit time, colonic transit time and whole gut transit time. Current approved indications for the test include the evaluation of gastric emptying in gastroparesis, colonic transit in constipation and evaluation of generalised dysmotility. Rare capsule retention and malfunc-tion are known limitations and some patients may experience difficulty with swallowing the capsule. The use of WMC has been validated for the assessment of gastrointestinal transit. The normal range for transit time includes the following: gastric empty-ing (2-5 hours), small bowel transit (2-6 hours), colonic transit (10-59 hours) and whole gut transit (10-73 hours). Besides avoiding the use of multiple endoscopic, radiologic and functional gastrointestinal tests, WMC can provide new diagnoses, leads to a change in management decision and help to direct further focused work-ups in patients with suspected disordered motility. In conclusion, WMC represents a significant advance in the assessment of segmental and whole gut transit and mo-tility, and could prove to be an indispensable diagnostic tool for gastrointestinal physicians worldwide.

Single endoscopist-performed percutaneous endoscopic gastrostomy tube placement.

AIM: To investigate whether single endoscopist-performed percutaneous endoscopic gastrostomy (PEG) is safe and to compare the complications of PEG with those reported in the literature. METHODS: Patients who underwent PEG placement between June 2001 and August 2011 at the Baskent University Alanya Teaching and Research Center were evaluated retrospectively. Patients whose PEG was placed for the first time by a single endoscopist were enrolled in the study. PEG was performed using the pull method. All of the patients were evaluated for their indications for PEG, major and minor complications resulting from PEG, nutritional status, C-reactive protein (CRP) levels and the use of antibiotic treatment or antibiotic prophylaxis prior to PEG. Comorbidities, rates, time and reasons for mortality were also evaluated. The reasons for PEG removal and PEG duration were also investigated. RESULTS: Sixty-two patients underwent the PEG procedure for the first time during this study. Eight patients who underwent PEG placement by 2 endoscopists were not enrolled in the study. A total of 54 patients were investigated. The patients' mean age was 69.9 years. The most common indication for PEG was cerebral infarct, which occurred in approximately two-thirds of the patients. The mean albumin level was 3.04 ± 0.7 g/dL, and 76.2% of the patients' albumin levels were below the normal values. The mean CRP level was high in 90.6% of patients prior to the procedure. Approximately two-thirds of the patients received antibiotics for either prophylaxis or treatment for infections prior to the PEG procedure. Mortality was not related to the procedure in any of the patients. Buried bumper syndrome was the only major complication, and it occurred in the third year. In such case, the PEG was removed and a new PEG tube was placed via surgery. Eight patients (15.1%) experienced minor complications, 6 (11.1%) of which were wound infections. All wound infections except one recovered with antibiotic treatment. Two patients had bleeding from the PEG site, one was resolved with primary suturing and the other with fresh frozen plasma transfusion. CONCLUSION: The incidence of major and minor complications is in keeping with literature. This finding may be noteworthy, especially in developing countries.

The influence of the speed of food intake on multichannel impedance in patients with gastro-oesophageal reflux disease.

BACKGROUND: There is a general belief that gastro-oesophageal reflux increases after meals and especially following a rapid intake. OBJECTIVE: To evaluate the impact of rapid vs. slow food intake on gastro-oesophageal reflux disease (GORD) patients. MATERIALS AND METHODS: Forty-six GORD patients with heartburn and / or acid regurgitation once a week or more often common were included in this study. Participants were asked to eat the same standard meal within either 5 or 30 minutes under observation in a random order on 2 consecutive days. A total of 28 hours of recording were obtained by intraoesophageal impedance pH and number of liquid and mixed reflux episodes within 3 hours of the slow- and fast-eating postprandial periods were calculated. RESULTS: While all patients defined GORD symptoms, 10 (21.7%) had pathological 24-h intraoesophageal impedance measurement, 15 (32.6%) had pathological DeMeester and 21.7% had erosive oesophagitis. No difference has been shown according to the eating speed when all reflux episodes were taken together (754 vs. 733). Speed of food intake also did not have an impact on patients with normal vs. pathological 24-h intraoesophageal impedance or erosive vs. non-erosive. During the first postprandial hour, approximately half of the reflux events were non-acid, compared to 34.2% during the second hour and 26.8% during the third hour (p < 0.001). The number of acid reflux episodes was significantly higher than non-acid reflux especially during the second and third hours and in total for 3 hours. CONCLUSIONS: This first study addressing the effect of eating speed on reflux episodes in GORD patients did not support the general belief that reflux increases following fast eating. Acid and non-acid reflux were similar at the first postprandial hour, then acid reflux episodes were predominantly higher, which implicate the importance of acid pockets.

Is there a relationship between Helicobacter pylori and gastric autoimmunity?

BACKGROUND/AIMS: Helicobacter pylori-associated corpus atrophy and autoimmune gastric atrophy share similar histopathologic and clinical aspects. In our study, the relation between Helicobacter pylori and autoimmune gastritis was investigated. METHODS: Eighty-two consecutive histologically and serologically Helicobacter pylori-positive and 96 Helicobacter pylori-negative patients were enrolled in the study. All patients underwent diagnostic upper esophagogastroduodenal endoscopy. Three biopsy specimens from the antrum and corpus greater curvature were obtained for histologic evaluation. Serum samples were collected for detection of anti-parietal cell antibody, anti-Helicobacter pylori IgG and vitamin B12. Statistical analyses were determined with Student t-test and chi-square test. Statistical significance was determined with a p-value <0.05. RESULTS: Of 82 Helicobacter pylori-positive patients, 45 were female and 36 were male, with a mean age 45.1 ± 15.1. There was no significant difference in age, gender and corpus atrophy between the Helicobacter pylori-positive and -negative groups. Eleven Helicobacter pylori-positive patients (13.4%) and 14 (14.6%) Helicobacter pylori-negative patients were positive for anti-parietal cell antibody; the difference between the two groups was not statistically significant (p>0.05). Differences in esophagogastroduodenal endoscopy findings, antrum and corpus inflammation, antrum and corpus atrophy, and vitamin B12 levels were found to be insignificant between parietal cell antibody-positive and -negative groups (p>0.05). CONCLUSIONS: We did not find any relation between Helicobacter pylori infection and anti-parietal cell antibody, a marker of autoimmune gastritis. Long-term follow-up of Helicobacter pylori-infected patients and also determination of the relation between eradication of Helicobacter pylori and autoimmune atrophic gastritis are needed.

Travel-associated Legionnaires disease: clinical features of 17 cases and a review of the literature.

We retrospectively investigated patients with Legionnaires disease (LD) who had been admitted to the Baskent University Alanya Teaching and Research Hospital, Ankara, Turkey, from January 2002 to September 2009. Twenty definitive cases were followed as LD, 17 (85%) of which were travel associated. The mean age was 61.5 ± 9.5 years (range, 39-77 years). Diabetes mellitus was found in 7 (41.2%) of those patients. Gastrointestinal or neurologic abnormalities were found approximately in two-thirds and relative bradycardia in 9 (52.9%). LD was severe in 11 (64.7%) patients, which required intensive care unit follow-up. Although appropriate antibiotic therapy was initiated in all patients on admission day, 4 (23.5%) deaths occurred. In conclusion, clinicians should remain vigilant about the diagnosis of LD in patients with community-acquired pneumonia, especially in the presence of extrapulmonary involvement, risk factors for LD, and a history of recent travel. As in our cases, mortality is still high in sporadic cases despite early appropriate treatment.

Rapidly progressing malignant insulinoma presented with multiple liver metastases: a case report.

INTRODUCTION: A 51-year-old female was admitted to emergency unit with sudden loss of consciousness. Her blood glucose level from fingertip was 33 mg/dl, and insulin level was 55 (normal range, 4-17 IU). Abdominal ultrasonography revealed pancreatic mass with diffuse liver metastases. Biopsy of liver metastases showed differentiated neuroendocrine carcinoma. METHODS AND RESULTS: Diazoxide and chemotherapy stabilized her glucose level for more than 4 months. However, the disease showed progression, and death occurred 8 months later. CONCLUSION: In conclusion, this case may suggest that biologic behavior may differ from histological behavior in insulinoma and platin-based systemic chemotherapy may provide some benefit in patients those who had diazoxide- and octreotide-resistant tumors.