Duodenal gist a single center experience (pdf) paperity postanoxic encephalopathy

See also

Extended adjuvant therapy with imatinib in patients with gastrointestinal … Extended adjuvant therapy with imatinib in patients with gastrointestinal stromal tumors

A large gastrointestinal stromal tumor of the duodenum treated by partial … A large gastrointestinal stromal tumor of the duodenum treated by partial duodenectomy with roux-en-Y duodenojejunostomy: a case report

Gastrointestinal stromal tumour of the duodenum in childhood: a rare case report gastrointestinal stromal tumour of the duodenum in childhood: a rare case report

Histopathological and clinical characteristics of duodenal gastrointestinal …


Histopathological and clinical characteristics of duodenal gastrointestinal stromal tumors as predictors of malignancy

postanoxic encephalopathy

Pancreaticoduodenectomy versus local resection in the treatment of … Pancreaticoduodenectomy versus local resection in the treatment of gastrointestinal stromal tumors of the duodenum

Segmental resection of the duodenum for gastrointestinal stromal tumor (GIST) segmental resection of the duodenum for gastrointestinal stromal tumor (GIST)

Copy-neutral loss of heterozygosity and chromosome gains and losses are … Copy-neutral loss of heterozygosity and chromosome gains and losses are frequent in gastrointestinal stromal tumors

Purpose the duodenum as primary site for gastrointestinal stromal tumors (gists) is rare and mitotic rate, tumor size, type of mutation and number of chromosomal aberrations have prognostic implications.Postanoxic encephalopathy methods we analyzed the outcome of 13 patients with duodenal gists who underwent surgical tumor resection. Either segmental duodenectomy or pylorus-preserving duodenopancreatectomy was performed. The tumors were histopathologically examined and the risk of progression was assessed based on tumor size and mitotic count. Additionally, mutation analysis of the KIT and PDGFRA receptor tyrosine kinase genes and comparative genomic hybridization (CGH) were performed in all cases. Results eight patients underwent segmental duodenectomy and five patients were treated with pylorus-preserving duodenopancreatectomy. None of the five gists with low or no risk for malignancy according to the miettinen classification developed tumor progress.Postanoxic encephalopathy in contrast, five of eight cases (62.5%) with high-risk tumors revealed tumor progress, and four of these patients died (50%). The median overall survival for all patients was 66 months, and the median disease-free survival 41 months. The operative procedure and type of mutation did not correlate with long-term survival. CGH analysis displayed −15q in 12/13 tumors, and −1p in 11/13 cases as characteristic chromosomal aberrations for intestinal origin. Notably, −22q was present in three of four cases with tumor progress. Conclusions both segmental duodenectomy and pylorus-preserving duodenopancreatectomy are appropriate options to treat duodenal GIST and should be implemented depending on resectability and the patient’s performing state.Postanoxic encephalopathy the miettinen classification and CGH findings correlate with the clinical course.

Alexander beham

Inga-marie schaefer

Silke cameron

Katharina von hammerstein

Laszlo fzesi

Giuliano ramadori

Michael B. Ghadimi

Purpose the duodenum as primary site for gastrointestinal stromal tumors (gists) is rare and mitotic rate, tumor size, type of mutation and number of chromosomal aberrations have prognostic implications. Methods we analyzed the outcome of 13 patients with duodenal gists who underwent surgical tumor resection. Either segmental duodenectomy or pylorus-preserving duodenopancreatectomy was performed. The tumors were histopathologically examined and the risk of progression was assessed based on tumor size and mitotic count.Postanoxic encephalopathy additionally, mutation analysis of the KIT and PDGFRA receptor tyrosine kinase genes and comparative genomic hybridization (CGH) were performed in all cases. Results eight patients underwent segmental duodenectomy and five patients were treated with pylorus-preserving duodenopancreatectomy. None of the five gists with low or no risk for malignancy according to the miettinen classification developed tumor progress. In contrast, five of eight cases (62.5%) with high-risk tumors revealed tumor progress, and four of these patients died (50%). The median overall survival for all patients was 66 months, and the median disease-free survival 41 months. The operative procedure and type of mutation did not correlate with long-term survival.Postanoxic encephalopathy CGH analysis displayed 15q in 12/13 tumors, and 1p in 11/13 cases as characteristic chromosomal aberrations for intestinal origin. Notably, 22q was present in three of four cases with tumor progress. Conclusions both segmental duodenectomy and pyloruspreserving duodenopancreatectomy are appropriate options to treat duodenal GIST and should be implemented depending on resectability and the patient’s performing state. The miettinen classification and CGH findings correlate with the clinical course.

Gastrointestinal stromal tumors (gists) are supposed to

Arise from the interstitial cells of cajal or their precursors,

Located throughout the muscular wall of the gastrointestinal

Tract. They occur at an incidence of 1020/million per year

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And at a median age of 5560 years [14]. They arise mostly

In the stomach (60%), followed by the small intestine (35%)

And rectum, esophagus, omentum, and mesentery (71 years; P 00.9139) and tumor

Recurrence. The mean tumor size was 7.4 cm (range 1.8

15 cm). There was no significant correlation between

Tumor size and tumor recurrence (10 vs. 10 cm; P0

0.2141). Grossly, the tumors were sharply demarcated

Without infiltrative growth (fig. 1). Histologically, 12

Tumors were of spindle cell differentiation, and one tumor

Was of mixed type differentiation combining spindle cell

And epithelioid areas. There was no significant correlation

Between the histologic subtype (spindle cell vs. Mixed

Type) and tumor recurrence (P 0 0.3618).Postanoxic encephalopathy

Immunohistochemically, all tumors expressed CD117, four tumors

PDGFRA, ten tumors CD34, eight tumors

Smoothmuscle actin, one tumor desmin, and S-100 was positive

Only in the intermixed dendritic cells. The mitotic rate per

50 hpfs ranged from 0 to 100 (mean 16/50 hpfs). The

Risk of malignant behavior according to miettinen resulted

In one case with no risk, four cases of low risk and the

Fig. 4 kaplanmeier estimator demonstrates overall survival for the

13 patients with duodenal GIST comparing low-risk vs. High-risk

Duodenal GIST

T T T T T T T T

W W W W W W W W

K 1 W W W W W

T .23 ;T T T T T T T

W c W W W W W W

T T T T T T T T

K E W W W W W

W W W W W W W W

9 K

(C o 6 3 3 3 0

L 1

0 7 1 2 4 3 9 5

K W W W c W

W W W c W c

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A c 0 1 0 0 1

0 0 0 0 0 0 0 0

G 0 3 2 1 2

0 3 0 0 0 0 1 0

G ah 6 7 5 4 3

C c 1

0 0 1 2 4 3 0 5

1 1

7 V 7 V

C W W c W c c

7 V

7 V

7 V 7 V

T T T T T T T T

W W W W W W W W

Remaining eight cases with high-risk potential [4]. There

Was no significant association of mitotic rate and recurrence

Rate (5 vs. 5 mitoses/50 hpfs; P0 0.8264). There was a

Tendency towards differences in the overall survival for

Patients with high-risk potential compared to patients with

Low-risk potential, however, due to the small patient number

The findings, were not statistically significant (P0 0.0556)

(fig. 4).

Mutation analysis

Mutation analysis of the KIT and PDGFRA gene was

Performed in all cases (table 3). The total number of

Mutations per each examined exon for all patients is

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Summarized in fig. 5. The number of mutations ranged

Between 0 and 2 mutations per tumor. Three tumors

Revealed no mutations (so-called wild-type gists),

And ten tumors displayed one mutation. The

Polymorphism V824V was present in six cases, and a silent KIT

Exon 17 mutation in one case. KIT exon 9 harbored the

A502_Y503 duplication in all four cases, KIT exon 11

Displayed the point mutations W557G, V559D, V560E,

And the deletion W557_K558. KIT exon 13 and PDGFRA

Exon 12 and 14 revealed no mutations.

Comparative genomic hybridization

CGH was performed in all cases (table 3). The

Chromosomal gains and losses of all patients are summarized in fig. 6.

The mean number of aberrations was 5.4 (range 013)

Fig. 5 results of KIT exon 9,

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11, 13, and 17 and PDGFRA

Exon 12, 14, and 18 mutation

Analyses in 13 duodenal

Gastrointestinal stromal tumors

Including a mean of 1 gain (range, 03), 4.3 losses (range,

010), and 0.16 amplifications (range, 01). Patient 6

Displayed no chromosomal imbalances. The most frequently

Observed aberrations comprised losses at 1p (11/13 cases,

84.6%), losses at 15q (12/13 cases, 92.3%), and losses at

22q (5/13 cases, 38.4%). Less than or five losses were not

Associated with a better survival rate as compared to 5

Losses (P0 0.0799) (fig. 7).

Only 45% of all gists are located in the duodenum [4, 6,

13]. As reported, abdominal pain, anemia, and

Gastrointestinal bleeding are usually the most common symptoms [13].

Due to the absence of lymph node metastases or infiltrative

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Growth of gists, local excision is usually sufficient, but

When the tumor is located close to important anatomical

Structures, pylorus-preserving duodenopancreatectomy

May become necessary [6].

We reviewed the outcome of 13 patients, who underwent

Surgery for duodenal GIST by segmental duodenectomy and

Pylorus-preserving duodenopancreatectomy.

Based on the criteria proposed by miettinen et al. [4] for

The estimation of the risk of progression, the tumors in the

Present study were classified as no risk in one case (7.7%),

Low risk in four cases (30.8%), and high risk in nine cases

(69.2%). Six tumors displayed more than five mitoses/50

HPF, thus automatically qualifying as high-risk tumors. Of

The seven patients with 5 mitoses/50 HPF, two were

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Fig. 6 chromosomal

Imbalances in 13 duodenal

Gastrointestinal stromal tumors

As detected by comparative

Genomic hybridization are

Shown as bright gray (gains),

Black (losses), and dark gray

Bars (amplifications) for each

Chromosome. Losses at 1p, 15q,

And 22q are among the most

Frequently observed aberrations

Classified as high risk due to the large tumor size of 5 cm.

The mean tumor size of 7.4 cm in the present study is in

Accordance with previous findings in 90 primary and

Metastatic duodenal gists in which the mean tumor size was

6 cm (range 1.531 cm) [13]. The reported prevalence of

High-risk cases ranges from 23 to 44% in gists of all

Locations [1517]. The large number of high-risk tumors in

The present study may be explained by both, the location, as

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No intermediate stage is defined for duodenal gists and

Because of the high mitotic rate in some of our cases. As

Expected, only the high-risk cases developed recurrence (5/

Fig. 7 kaplanmeier estimator demonstrates overall survival for the

13 patients with duodenal GIST comparing the cases with 5 and 5

Chromosomal losses as detected by comparative genomic hybridization

8 cases) as compared to none of the patients with low-risk

GIST (0/5). In the present study, 38.5% of the patients

Developed localized or distant tumor progress. These

Findings are similar to previous findings in duodenal gists, in

Which recurrence was reported to occur in 35% [13].

Furthermore, four of eight patients with high-risk GIST died

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Compared to none of the patients with low-risk tumors (0/5),

Indicating an impact of the miettinen classification on

Longterm survival, even though it was not statistically significant

(P0 0.0556) in our cohort due to the small number of cases.

Our findings are in accordance with a previous study on

Duodenal gists [11], in which the authors identified the

Classification as high-risk GIST as the only predictor for

Disease recurrence [11]. In a study on 90 duodenal gists,

However, only the mitotic rate predicted relapse in

Multivariate analysis [13]. Furthermore, in univariate analyses, age

And ECOG performance state had an impact on overall

Survival, and necrosis, spindle cell morphology, tumor size,

And mitotic rate were predictors for relapse [13].Postanoxic encephalopathy in the

Present study, the ECOG state and necrosis were not

Assessed. Age, spindle cell differentiation, tumor size, and

Mitotic rate were not associated with a higher rate of

Recurrence.

Mutations of the KIT or PDGFRA gene have been

Identified as primary steps in tumorigenesis of gists [7]. In this

Study, ten tumors (76.9%) showed mutations of the KIT

Gene, and two tumors (15.4%) were wild-type gists.

Four patients had an exon 9 mutation (30.8%) and six

Patients an exon 11 mutation (46.2%) [3, 18, 19]. KIT exon

9 mutations are reported to occur in 1315%, exon 11

Mutations in 66.170% (76% in duodenal gists), and

Wild-type gists making up approximately 1015% [3, 13,

18, 20]. Thus, in the present study, KIT exon 9 mutations

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Were observed slightly more frequent and exon 11 mutations

Less frequent than reported previously in the literature for

GISTs. KIT exon 11 mutations are known to harbor a less

Favorable prognosis than KIT exon 9 mutations and are at

High metastatic risk [20]. Also, point mutations are generally

Associated with a clinically more favorable course as

Compared to deletions [21]. However, exon 11 mutations show a

Better response to targeted treatment with imatinib mesylate

Than do exon 9 mutations [20].

Losses at 1p, 15q and 22q, as detected by CGH, are

Imbalances typical of small intestinal gists, being observed

In 88%, 59%, and 82% of cases, respectively [22].

Especially, combined losses at 1p and 15q are described to occur

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In 75% of intestinal gists [22]. As reported previously,

Losses at 22q being present in 75% of our cases with tumor

Progress, are associated with an unfavorable cytogenetic

Sub-pathway and significantly more additional imbalances

Than tumors without 22q, reflecting an increased capacity

For cytogenetic complexity [7]. GISTs with 22q are

Significantly more often high-risk tumors, behave clinically

Malignant, and have a poorer disease-free survival [7].

In a previous study, gists classified as probably benign

Or of low malignant potential had a smaller mean number of

Aberrations than those evaluated as probably malignant (4.6

Versus 7.4) [22]. In our study, the mean number of 5.4

Aberrations per tumor indicates that the tumors display a

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Moderate degree of genetic instability and thus range

Between benign and malignant risk potential. Of all 13 tumors,

6 displayed 5 aberrations, thus tending towards a rather

Instable karyotype with genetic progression. CGH can be

Used as helpful additional method to assess the risk of

Malignancy or progression in duodenal gists and might

Help in deciding for or against (neo-) adjuvant treatment.

Concerning the operative procedure, the authors of

Previous studies preferred segmental duodenectomy to

Duodenopancreatectomy since this procedure has a lower

Operative morbidity while providing comparable

Oncological results [5, 6, 9, 1113, 23]. However, in one of these

Studies, only tumors with 5 cm are already classified

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As high-risk tumors according to the miettinen

Classification, irrespective of the mitotic count. In these cases and in

Locally advanced tumors neoadjuvant treatment is an option

To reduce tumor size [13]. Adjuvant therapy should follow.

However, in our study, four high-risk patients did not

Receive adjuvant therapyas at the time, adjuvant therapy (i.E.,

Therapy within the first weeks after operation) was not

Generally performed after complete resection of the tumor. To our

Knowledge, two of these four patients died of tumor

Progression. In our study, one of the patients, who underwent

Segmental duodenectomy, died within 30 days after the

Operation in contrast to none of the patients with

Duodenopancreatectomy, but no significant advantage of one or the other

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Operative method was detectable.

In conclusion, complete surgical resection is the only

Curative treatment for duodenal gists. Since both, limited

And extended surgery yield comparable survival rates, tumor

Size and location in regard to the papilla of vater [11],

Associated diseases and the patient’s performing state should

Be considered when deciding between segmental

Duodenectomy and pylorus-preserving duodenopancreatectomy. If

Duodenopancreatectomy is necessary, it has no impact on

Overall survival and recurrence rates in experiences centers.

Neoadjuvant imatinib treatment might be an option and is

Tested in clinical studies. The risk stratification according to

The miettinen criteria and the assessment of genomic

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Aberrations by CGH are helpful in predicting the biological

Behavior and clinical course of duodenal gists.

Acknowledgements the authors thank PD dr. Bastian gunawan for

His diagnostic and scientific support.

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