Background
The most recent Chicago Classification expanded the criteria for diagnosis of jackhammer esophagus (JHE) to include the distal contractile integral (DCI) of the lower esophageal sphincter (LES). The clinical impact of the manometric inclusion of LES hypercontractility remains unclear. We aimed to analyze the clinical features and long‐term outcomes of measured LES‐dependent (LD‐JHE) and LES‐independent (LI‐JHE) jackhammer esophagus.
Methods
Patients meeting diagnostic criteria for JHE were identified at two academic medical centers. High‐resolution esophageal manometry data were re‐analyzed with inclusion and exclusion of the LES DCI. LD‐JHE was defined by falling outside JHE diagnostic criteria with exclusion of the LES. A telephone survey was conducted for follow‐up utilizing the impact dysphagia (IDQ‐10) questionnaire.
Key Results
Eighty‐one patients met study inclusion criteria, with 12 (14.8%) classified as LD‐JHE. LD‐JHE patients had a significantly lower mean DCI and fewer swallows with DCI >8000 mm Hg‐s‐cm. Basal LES pressure was higher in patients with dysphagia to solids than those with dysphagia to solids and liquids. Clinical and manometric parameters were otherwise similar between groups. Sixty‐six patients had clinical or phone follow‐up at a median of 46.6 months. Forty‐one patients (62.1%) received therapies directed at JHE. There was no difference in symptom improvement for treated vs untreated patients or for JHE subtype.
Conclusions and Inferences
Our findings suggest that LD‐JHE and LI‐JHE are clinically indistinguishable and thus support existing diagnostic criteria. Furthermore, our long‐term follow‐up data suggest that JHE, irrespective of LES involvement, may improve without treatment. Further study is needed to clarify which patients merit therapeutic intervention.
DCLK1 expression is critically required for maintaining growth of human colon cancer cells (hCCCs). Human colorectal tumors (CRCs) and hCCCs express a novel short isoform of DCLK1 (DCLK1-S) (isoform2) from β-promoter of hDCLK1-gene, while normal-colons express long-isoform (DCLK1-L) (isoform1) from 5′(α)-promoter, suggesting that DCLK1-S, and not DCLK1-L, marks cancer stem cells (CSCs). Even though DCLK1-S differs from DCLK1-L by only six amino-acids, we succeeded in generating a mono-specific DCLK1-S-Antibody (PS41014), which does not cross-react with DCLK1-L, and specifically detects CSCs. Sub-cellular localization of S/L isoforms was examined by immune-electron-microscopy (IEM). Surprisingly, besides plasma membrane and cytosolic fractions, S/L also localized to nuclear/mitochondrial fractions, with pronounced localization of S-isoform in the nuclei and mitochondria. Sporadic CRCs develop from adenomas. Screening colonoscopy is used for detection/resection of growths, and morphological/pathological criteria are used for risk assessment and recommendations for follow-up colonoscopy. But, these features are not precise and majority of the patients will never develop cancer. We hypothesized that antibody-based assay(s), which identify CSCs, will significantly improve prognostic value of morphological/pathological criteria. We conducted a pilot retrospective study with PS41014-Ab, by staining archived Adenoma specimens from patients who developed (High-risk) or did not develop (Low-risk) adenocarcinomas within 10–15 years. PS41014-Ab stained Adenomas from initial and follow-up colonoscopies of high-risk patients, at significantly higher levels (3–5 fold) than Adenomas from low-risk patients, suggesting that PS41014-Ab could be used as an additional tool for assessing CRC risk. CRC patients, with high DCLK1-S expressing tumors (by qRT-PCR), were reported to have worse overall survival than low-expressers. We now report that DCLK1-S specific Ab may help to identify high-risk patients at the time of index/screening colonoscopy.
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