McKittrick Wheelock syndrome secondary to adenocarcinoma of the rectum: case report and diagnostic considerations

Introduction: McKittrick-Wheelock syndrome is a rare entity characterized by chronic diarrhea, acute kidney injury, and hydroelectrolytic imbalance associated with a large rectal tumor, frequently a villous adenoma. Case report: A 69-year-old male with chronic diarrhea with mucus. He underwent a colonoscopy with biopsies, reporting adenocarcinoma of the rectum in situ, and underwent a robot assisted intersphincteric resection with colo-anal anastomosis and a protecitive ileostomy. Discussion: Described in 1954, this syndrome is manifested by electrolyte imbalance and acute renal injury secondary to diarrhea associated with a rectal villous adenoma, often with long lasting symptoms. The most frequent symptom being watery diarrhea with mucus. The definitive treatment consists of surgical resection. Conclusion: Although this is a rare pathology, it should be considered as a differential diagnosis in cases of chronic diarrhea associated with water and electrolyte disorders. (AU)

Whole lesion histogram analysis of apparent diffusion coefficient predicts therapy response in locally advanced rectal cancer.

BACKGROUND: Whole-tumor apparent diffusion coefficient (ADC) histogram analysis is relevant to predicting the neoadjuvant chemoradiation therapy (nCRT) response in patients with locally advanced rectal cancer (LARC). AIM: To evaluate the performance of ADC histogram-derived parameters for predicting the outcomes of patients with LARC. METHODS: This is a single-center, retrospective study, which included 48 patients with LARC. All patients underwent a pre-treatment magnetic resonance imaging (MRI) scan for primary tumor staging and a second restaging MRI for response evaluation. The sample was distributed as follows: 18 responder patients (R) and 30 non-responders (non-R). Eight parameters derived from the whole-lesion histogram analysis (ADCmean, skewness, kurtosis, and ADC10th, 25th, 50th, 75th, 90th percentiles), as well as the ADCmean from the hot spot region of interest (ROI), were calculated for each patient before and after treatment. Then all data were compared between R and non-R using the Mann-Whitney U test. Two measures of diagnostic accuracy were applied: the receiver operating characteristic curve and the diagnostic odds ratio (DOR). We also reported intra- and interobserver variability by calculating the intraclass correlation coefficient (ICC). RESULTS: Post-nCRT kurtosis, as well as post-nCRT skewness, were significantly lower in R than in non-R (both P < 0.001, respectively). We also found that, after treatment, R had a larger loss of both kurtosis and skewness than non-R (∆%kurtosis and ∆skewness, P < 0.001). Other parameters that demonstrated changes between groups were post-nCRT ADC10th, ∆%ADC10th, ∆%ADCmean, and ROI ∆%ADCmean. However, the best diagnostic performance was achieved by ∆%kurtosis at a threshold of 11.85% (Area under the receiver operating characteristic curve [AUC] = 0.991, DOR = 376), followed by post-nCRT kurtosis = 0.78 × 10-3 mm2/s (AUC = 0.985, DOR = 375.3), ∆skewness = 0.16 (AUC = 0.885, DOR = 192.2) and post-nCRT skewness = 1.59 × 10-3 mm2/s (AUC = 0.815, DOR = 168.6). Finally, intraclass correlation coefficient analysis showed excellent intraobserver and interobserver agreement, ensuring the implementation of histogram analysis into routine clinical practice. CONCLUSION: Whole-tumor ADC histogram parameters, particularly kurtosis and skewness, are relevant biomarkers for predicting the nCRT response in LARC. Both parameters appear to be more reliable than ADCmean from one-slice ROI.

SOX9 is associated with advanced T-stages of clinical stage II colon cancer in young Mexican patients.

Colorectal cancer (CRC) is one of the most common malignancies worldwide and includes colon cancer (CC) and rectal cancer (RC). Regarding CC, the development of novel molecular biomarkers for the accurate diagnosis and prognosis, as well as the identification of novel targets for therapeutic intervention, are urgently needed. SRY-related high-mobility group box 9 (SOX9), a transcription factor, is involved in development, and has been associated with the progression of human cancer. However, its underlying clinical and functional effects in CRC have not been fully understood. Therefore, the present study aimed to evaluate the clinical and functional relevance of SOX9 expression in CC. The expression of SOX9 in tumor tissues was evaluated in 97 biopsies from Mexican patients with CC with early-stage I and II disease by immunohistochemistry (IHC). In addition, SOX9 silencing in the HCT116 cell line was performed using specific small interfering RNAs, while downregulation efficiency was verified by reverse transcription-quantitative PCR and immunofluorescence. Spheroid-formation assay was carried out using ultra-low attachment plates. The IHC results showed that SOX9 was upregulated in patients with stage II (91%) and advanced T3 stage (67%) CC. Interestingly, higher SOX9 expression was associated with clinical stage, tumor size and tumor location. Furthermore, increased SOX9 expression was found in relapsed cases with local tumors; however, it was not associated with increased survival probability. Additionally, functional analysis indicated that SOX9 silencing significantly attenuated the sphere-formation capability of HCT116 cells. The present study was the first to evaluate the expression levels of SOX9 in Mexican patients diagnosed with early-stage CC. The aforementioned findings indicated that high SOX9 expression could play an important role in tumorigenesis and be associated with advanced T-stages of clinical-stage II patients, but not with relapse-free survival.

The apparent diffusion coefficient is a useful biomarker in predicting treatment response in patients with locally advanced rectal cancer.

BACKGROUND: Apparent diffusion coefficient (ADC) values achieve promising results in treatment response prediction in patients with several types of cancers. PURPOSE: To determine whether ADC values predict neoadjuvant chemoradiation treatment (nCRT) response in patients with locally advanced rectal cancer (LARC). MATERIAL AND METHODS: Forty-four patients with LARC who underwent magnetic resonance imaging scans before and after nCRT followed by delayed surgery were enrolled retrospectively. The sample was distributed as follows: responders (R), n = 8; and non-responders (Non-R), n = 36. Three markers of treatment response were considered: post-nCRT measures; ΔADC; and Δ%ADC. Statistical analysis included a Wilcoxon test, a Mann-Whitney U test, and a receiver operating characteristic (ROC) analysis in order to evaluate the diagnostic accuracy for each ADC value marker to differentiate between R and Non-R. RESULTS: Both minimum and mean ADC values were significantly higher after nCRT in the R group, while non-significant differences between basal and control ADC values were found in the non-R group. In addition, ΔADC and Δ%ADC exhibited increased values after nCRT in R when compared with non-R. ROC analysis revealed the following diagnostic performance parameters: post-nCRT: ADCmin = 1.05 × 10-3 mm2/s (sensitivity 61.1% and specificity 66.7%), ADCmean = 1.50 × 10-3 mm2/s (sensitivity 72.2% and specificity 83.3%), ΔADC: ADCmin = 0.35 (sensitivity 66.7% and specificity 83.3%), ADCmean = 0.50 (sensitivity 72% and specificity 83%); and Δ%ADC: ADCmin = 44% (sensitivity 66.7% and specificity 83.3%) and ADCmean = 60% (sensitivity 83% and specificity 99%). CONCLUSION: Our findings suggest that post-treatment rectal tumor ADC values, as well changes between pre- and post-treatment values, may be biomarkers for predicting treatment response in patients with LARC who underwent nCRT.

Mesorectal Invasion Depth in Rectal Carcinoma Is Associated With Low Survival.

BACKGROUND: Most cases of rectal cancer (RC) in our institution are in pathologic stage T3. They are a heterogeneous group but have been classified in a single-stage category. We performed the present study to validate the prognostic significance of the mesorectal extension depth (MED) in T3 RC measured in millimeters beyond the muscularis propria plane. MATERIALS AND METHODS: We performed a retrospective analysis of 104 patients with T3 RC who had undergone curative surgery after a course of preoperative chemoradiotherapy at a tertiary referral cancer hospital. The patients were grouped by MED (T3a, < 1 mm; T3b, 1-5 mm; T3c > 5-10 mm; and T3d > 10 mm). The clinicopathologic data and disease-free survival were analyzed. RESULTS: The 5-year disease-free survival rate according to the T3 subclassification was 87.5% for those with T3a, 57.9% for T3b, 38.7% for T3c, and 40.3% for those with T3d tumors (P = .050). On univariate and multivariate analysis, the prognostic factors affecting survival were overall recurrence (hazard ratio [HR], 3.670; 95% confidence interval [CI], 1.710-7.837; P = .001), histologic grade (HR, 2.204; 95% CI, 1.156-4.199; P = .016), mesorectal invasion depth (HR, 1.885; 95% CI, 1.164-3.052; P = .010), and lymph node metastasis (HR, 1.211; 95% CI, 1.015-1.444; P = .033). CONCLUSION: MED is a significant prognostic factor in patients with T3 RC who have undergone neoadjuvant chemoradiotherapy, especially when the MED is > 5 mm. The MED could be as important as other clinicopathologic factors in predicting disease-specific survival.

Gastric cancer in young people under 30 years of age: worse prognosis, or delay in diagnosis?

BACKGROUND: Gastric cancer is an aggressive disease with nonspecific early symptoms. Its incidence and prognosis in young patients has shown considerable variability. PURPOSE OF THE STUDY: Our objective was to retrospectively study patients from our institution aged <30 years with gastric carcinoma. The study was undertaken to describe the experience of gastric cancer in this population, and to demonstrate its specific clinical and pathological characteristics. MATERIALS AND METHODS: We reviewed the cases of histologically confirmed gastric cancer between 1985 and 2006 at the Instituto Nacional de Cancerología of Mexico (INCan); emphasis in our review was placed on clinical presentation, diagnostic and therapeutic intervention, pathology, and the results. RESULTS: Thirty cases of gastric carcinoma were reviewed. The patients' median age was 27 years (range, 18-30 years) and the male:female ratio was 1:1. CONCLUSION: Gastric cancer exhibits different behavior in patients aged, 30 years, but delay in diagnosis and the tumor's behavior appear to be the most important factors in prognosis of the disease.