Mide biyopsisinde tespit edilen nöroendokrin hücre hiperplazisinin hipergastrinemi ile ilişkisi ve eşlik eden endoskopik ve histopatolojik bulguların değerlendirilmesi
The relationship of neuroendocrine cell hyperplasia detected in stomach biopsy with hypergastrinemia and evaluation of the accompanying endoscopic and histopathological findings
Yazar: ESRA ÇİL ÇETİNER
Danışman: DOÇ. DR. HAYDAR ADANIR
Akdeniz Üniversitesi / Tıp Fakültesi / İç Hastalıkları Ana Bilim Dalı
Derece: Tıpta Uzmanlık, 2023
Konu: Gastroenteroloji = Gastroenterology

Özet:
Amaç: Çalışmamızda nöroendokrin hücre hiperplazisi(NEHH) saptanmış hastalarda
hipergastrinemi ile; eşlik eden endoskopik bulguların ve NEHH alt tipleri arasında bir ilişki
olup olmadığını araştırmayı ve literatüre katkıda bulunmayı amaçladık.
Materyal ve Metod: Çalışmaya Akdeniz Üniversitesi Hastanesi Gastroenteroloji Bilim
Dalında takipli 01.07.2021 – 01.07.2022 tarihleri arasında üst GIS endoskopisi yapılmış ve
alınan mide biyopsi materyallerinin patolojik incelemesinde NEHH saptanmış onam veren 511
hastada yaş, cinsiyet, Hashimato tiroiditi ve Tip 1 DM başta olmak üzere eşlik eden diğer
otoimmun hastalıklar, kronik ppi kullanımı, sigara ve alkol kullanımı, obezite varlığı, gastrin
düzeyi, endoskopik eşlik eden bulgular ve nöroendokrin hücre hiperplazisi histolojik alt tipleri
incelendi.
İstatiksel yöntem: Veriler IBM SPSS Statistics 18 © Copyright SPSS Inc. 1989, 2010 yazılımı
kullanılarak analiz edilmiştir. Sürekli değişkenlerin normal dağılıma uygunluğu Shapiro-Wilk
testi ile incelenmiştir. Çalışmada yer alan kategorik değişkenler frekans (n) ve yüzde (%) ile
sürekli değişkenler ortalama±standart sapma (SS), medyan (IQR: 25-75. persentil) değerleri ile
sunulmuştur. Kategorik değişkenlerin analizinde Pearson Ki-kare, Yates düzeltmesi, FisherExact Test, Monte Carlo test ve Bonferroni düzeltmeleri kullanılmıştır. Bağımsız ikiden fazla
grup ortalama karşılaştırmalarında parametrik test varsayımlarının sağlandığı durumlarda One
Way ANOVA ve post hoc LSD testi, sağlanmadığı durumlarda ise Kruskal Wallis H testi ve
post hoc Bonferroni düzeltmesi kullanılmıştır. Çalışmada istatistiksel anlamlılık düzeyi 0,05
olarak kabul edilmiştir.
Bulgular: NEHH saptanan 511 hastanın %64.4'ü kadın olup, NEHH sıklığının kadınlarda daha
fazla olduğu saptanmıştır. NEHH saptanan hastaların yaş ortalaması 54,59±14,46 yıl olarak
hesaplanmıştır. Çalışmamızda NEHH saptanan hastaların %81,6'sında gastrik atrofi
saptanmadı. Hastaların %50.9'unda Helicobacter pylorisi saptandı. NEHH alt tipleri %13,9
diffüz, %39,5 lineer, %15,5 mikronodüler, %3,3 adenamatoid, %27,8 mix (Lineer+Nodüler)
sapatanmış olup en sık saptanan alt tip lineer tip saptanmıştır. Yaş ortalaması gastrin düzeyi
normal olanlarda daha düşük olup 47,73±13,66 yıl, 115-400 arasında olanlarda 56,5±13,33 yıl,
400 ve üzeri olanlarda 56,1±11,94 yıl olarak hesaplanmıştır (p=0,001). Gastrin düzeyi normal
olan grubun %55,2'si, 115-400 arası olan grubun %72,7'si, 400 ve üzeri olan grubun %79,5'i
kadın hastalardan oluşmakta olup istatiksel olarak anlamlıdır (p=0,019). Gastrin düzeyleri ile
atrofik gastrit ve helicobacter pylori varlığı ile anlamlı bir ilişki saptanmadı. İntestinal
metaplazi, displazi, tümör varlığı ve polip varlığı gastrin düzeyi normal olan hastalarda diğer
hastalara göre anlamlı olarak daha düşük bulunmuştur (p<0,001). NEHH alt tiplerinden lineer
tip gastrin düzeyi normal olan hastalarda daha yüksek iken, adenamotid ve mix tip gastrin
düzeyi 400 ve üzeri olan hastalarda daha yüksek bulunmuştur (p<0,001). Gastrin düzeyi ve
NEHH alt tiplerinin, sigara kullanımı, alkol kullanımı, obezite, kronik ppi kullanımı, otoimmun
hastalıklar gibi faktörler ile istatistiksel olarak anlamlı sonuç bulunamamıştır. NEHH alt tipleri
ile ortanca yaş değeri incelendiğinde diffüz tipteki hastaların yaşları mix tipteki hastaların
yaşlarına göre anlamlı olarak daha düşüktür (p=0,015). Ortanca yaş değeri NEHH alt tipi diffüz
olan grupta 49(38-62), lineer olan grupta 57(45-67), mikronodüler olan grupta 53(45-64),
adenamotid olan grupta 53(45-61) ve mix olan grupta 58(49-67) yıl olarak hesaplanmıştır.
NEHH alt tipleri ile atrofik gastrit (p=0,576), helicobacter pylori (p=0,674), polip varlığı
arasında anlamlı bir fark olmadığı görülmüştür. İntestinal metaplazi ve displazi lineer tipte
adenamotid ve mix tipe göre anlamlı olarak daha düşük bulunmuştur (p=0,001). Tümör varlığı
lineer tipte en az, adenamotid tipte diğer tüm gruplara göre en yüksek bulunmuştur (p<0,001).
Sonuçlar: Nöroendokrin hücre hiperplazisinin 50 yaş üzerinde ve kadınlarda daha sık
görüldüğü saptandı. Gastrin düzeyi yüksek olan hastalarda yaş ortalaması daha yüksek ve
kadınlarda görülme olasılığı artmış saptandı. NEHH alt tiplerinden en sık lineer tip saptandı.
Alt tipler incelendiğinde diffüz tipteki hastaların yaşları mix tipteki hastaların yaşlarına göre
anlamlı olarak daha düşüktür (p=0,015). Gastrin düzeyi >400 olan hastalarda intestinal
metaplazi, displazi, polip ve tümör varlığı daha sık bulunmuştur (p<0,001). Gastrin düzeyi ve
NEHH alt tiplerine göre sigara kullanımı, alkol kullanımı, obezite, kronik ppi kullanımı,
otoimmun hastalıklar gibi faktörler incelendiğinde istatistiksel olarak anlamlı sonuç
bulunamamıştır
Anahtar Kelimeler: Nöroendokrin hücre hiperplazisi, Gastrin, Nöroendokrin Tümör

Abstract:
Objective: In our study, patients with neuroendocrine cell hyperplasia (NEHH) were diagnosed
with hypergastrinemia; We aimed to investigate whether there is a relationship between the
accompanying endoscopic findings and NEHH subtypes and to contribute to the literature.
Materials and Methods: The study was conducted in 511 patients, who were followed up in
Akdeniz University Hospital Gastroenterology Department, underwent upper GIS endoscopy
between 01.07.2021 and 01.07.2022 and were found to have NEHH in the pathological
examination of gastric biopsy materials, and gave consent, including age, gender, Hashimoto's
thyroiditis and Type 1 DM. Histological subtypes of neuroendocrine cell hyperplasia were
examined, including other accompanying autoimmune diseases, chronic ppi use, smoking and
alcohol use, presence of obesity, gastrin level, endoscopic accompanying findings.
Statistical method: Data IBM SPSS Statistics 18 © Copyright SPSS Inc. It was analyzed using
1989, 2010 software. The conformity of continuous variables to the normal distribution was
examined using the Shapiro-Wilk test. Categorical variables in the study were presented with
frequency (n) and percentage (%), and continuous variables with mean±standard deviation
(SD), median (IQR: 25th-75th percentile) values. Pearson Chi-square, Yates correction, FisherExact Test, Monte Carlo test and Bonferroni corrections were used in the analysis of categorical
variables. One Way ANOVA and post hoc LSD test were used in cases where parametric test
assumptions were met, and Kruskal Wallis H test and post hoc Bonferroni correction were used
when they were not provided in the mean comparisons of more than two independent groups.
The statistical significance level was accepted as 0.05 in the study.
vi
Results: 64.4% of 511 patients with NEHH were women, and the frequency of NEHH was
found to be higher in women. The mean age of patients with NEHH was calculated as
54.59±14.46 years. In our study, gastric atrophy was not found in 81.6% of the patients with
NEHH. Helicobacter pylori was detected in 50.9% of the patients. NEHH subtypes were found
13.9% diffuse, 39.5% linear, 15.5% micronodular, 3.3% adenomatoid, 27.8% mixed
(Linear+Nodular) and the most common subtype was linear. The mean age was lower in those
with normal gastrin level, and it was calculated as 47.73±13.66 years, 56.5±13.33 years in those
between 115-400, and 56.1±11.94 years in those with 400 and over (p=0.001). ). 55.2% of the
group with a normal gastrin level, 72.7% of the group with a gastrin level of 115-400, and
79.5% of the group with a gastrin level of 400 and above consisted of female patients, which is
statistically significant (p=0.019). There was no significant relationship between gastrin levels
and the presence of atrophic gastritis and helicobacter pylori. Intestinal metaplasia, dysplasia,
presence of tumor and presence of polyps were found to be significantly lower in patients with
normal gastrin levels compared to other patients (p<0.001). Linear type gastrin levels of NEHH
subtypes were higher in patients with normal, while it was higher in patients with adenomotide
and mixed type gastrin levels of 400 and above (p<0.001). No statistically significant results
were found with factors such as gastrin level and NEHH subtypes, smoking, alcohol use,
obesity, chronic ppi use, autoimmune diseases. When the NEHH subtypes and the median age
were examined, the age of the diffuse type patients was significantly lower than the age of the
mixed type patients (p=0.015). The median age was 49 (38-62) in the diffuse NEHH subtype,
57 (45-67) in the linear group, 53 (45-64) in the micronodular group, 53 (45-61) in the
adenomotide group, and 58 in the mixed group. It is calculated as (49-67) years. There was no
significant difference between NEHH subtypes and the presence of atrophic gastritis (p=0.576),
helicobacter pylori (p=0.674) and polyps. Intestinal metaplasia and dysplasia were found to be
significantly lower in linear type compared to adenomotide and mixed type (p=0.001). Tumor
presence was found to be lowest in linear type and highest in adenomotide type compared to all
other groups (p<0.001).
Conclusion: Neuroendocrine cell hyperplasia was found to be more common in women over
50 years of age. The mean age was higher in patients with high gastrin levels, and it was more
likely to be seen in women. The most common linear type was found among the NEHH
subtypes. When the subtypes were examined, the age of the patients with the diffuse type was
significantly lower than the age of the patients with the mixed type (p=0.015). Intestinal
metaplasia, dysplasia, polyps and tumors were found more frequently in patients with a gastrin
level >400 (p<0.001). When factors such as smoking, alcohol use, obesity, chronic ppi use,
autoimmune diseases were examined according to gastrin level and NEHH subtypes, no
statistically significant results were found.
Keywords: Neuroendocrine cell hyperplasia, Gastrin, Neuroendocrine Tumor