The impact of the COVID-19 pandemic on colorectal and gastric cancer diagnosis, disease stage and mortality.

Background: Since the outbreak of COVID-19, a significant decline in endoscopic procedures has been observed. Aims: We investigated the change of incidence, clinical characteristics, disease stage and mortality of patients with gastric cancer (GC) or colorectal cancer (CRC) diagnosed in 2020 compared to the pre-pandemic year 2019. Methods: Demographic, clinical and laboratory data on all patients diagnosed with GC or CRC at the Soroka University Medical Center were retrospectively collected and compared. Number of cases, time of diagnosis, clinical presentation, staging at diagnosis and mortality rates were compared. Results: Two hundred sixteen patients were diagnosed with CRC in 2019, whereas only 162 were diagnosed in 2020 (25% reduction), while 36 GC diagnoses were made in 2019 compared to 24 in 2020 (33% reduction). The age-adjusted incidence was calculated to be 24.28 for CRC and 5.0 for GC in 2020 compared to 29.93 and 5.32 in 2019, respectively. CRC patients had a significantly lower rate of rectal bleeding as their presenting symptom in 2020 compared with 2019, 8.1 vs. 19% (p = 0.003), but higher rate of diarrhea as their presenting symptom, 4.3 vs. 1% (p = 0.044). No significant differences regarding other presenting symptoms, comorbidities, surgery or mortality rates were found between the groups diagnosed in 2019 or 2020. Conclusion: A decrease in GC and CRC incidence was observed during the year 2020; lower rate of rectal bleeding and higher rate of diarrhea as presenting symptoms were noted in 2020, but no significant difference was found regarding other presenting symptoms, disease stage, surgery or mortality.

Cell-free deoxyribonucleic acid as a prognostic marker of bowel ischemia in patients with small bowel obstruction.

BACKGROUND: Patients with strangulation small bowel obstruction are at a high risk for serious morbidity and mortality due to ischemic bowel. Measuring serum, cell-free deoxyribonucleic acid levels could help recognize early cell death. Our hypothesis was that small bowel ischemia or necrosis is associated with increases in serum cell-free deoxyribonucleic acid and that recovery is associated with a decrease in cell-free deoxyribonucleic acid levels. METHODS: A prospective cohort study in addition to standard treatment of patients admitted with a diagnosis of small bowel obstruction. The participants were divided into groups depending on the presence of ischemic or necrotic bowel according to operative and clinical outcome. Clinical data and serum-based cell-free deoxyribonucleic acid levels were compared. Cell-free deoxyribonucleic acid levels from these 2 groups also were compared with a third group of healthy controls. RESULTS: In the study, 58 patients were enrolled, and 18 patients (31%) underwent operation. During the operative procedure, ischemic or necrotic bowel was found in 10 cases (17%). Serum levels of cell-free deoxyribonucleic acid at the time of admission in the ischemic/necrotic bowel group were increased compared with patients with well perfused or spontaneously recovered bowel (P = .03). Cell-free deoxyribonucleic acid levels decreased on the day after admission in 88% of the nonoperated patients. No significant differences were found in demographics, medical background, imaging performed, and cause of obstruction nor in clinical admission data. CONCLUSION: Surgeons currently rely on imprecise clinical parameters, including degree of pain, abdominal tenderness, leukocytosis etc to decide when operative intervention is needed. The association of cell-free deoxyribonucleic acid with small bowel obstruction, ischemia, and recovery supports our hypothesis and suggests that this biomarker is a potential surrogate of small bowel perfusion.

Human Colorectal Cancer Stage-dependent Global DNA Hypomethylation of Cancer-associated Fibroblasts.

BACKGROUND/AIM: Cancer-associated fibroblasts (CAFs) play an important role in tumor development and progression. The prevailing consensus favors the view that a specific epigenetic signature underpins the stable CAF phenotype. The aim of the present study was to assess global DNA methylation in CAFs during the adenoma-carcinoma sequence in non-familial sporadic human colorectal cancer (CRC). PATIENTS AND METHODS: Immunohistochemical staining of nuclear 5-methylcytosine (5'-meCyt) was performed in matched samples of colonic tumor tissue and normal colonic mucosa excised from six patients with adenomas and four with adenocarcinomas. The staining intensity was expressed semi-quantitatively as the immunohistochemical staining score (ISS). RESULTS: ISS values of human colonic CAFs and adenomatous samples were 14.00±2.2 and 14.08±1.8, respectively, showing no statistically significant difference. In contrast, a marked trend was found towards global DNA hypomethylation in CAFs from adenocarcinomatous specimens compared to matched normal mucosa: ISS: 9.25±2.44 (range=6-11) vs. 16.17±0.75, respectively, p<0.03. CONCLUSION: Final stages of cancer development in CRC are associated with global DNA hypomethylation in stromal CAFs.

Colectomy for slow transit constipation: effective for patients with coexistent obstructed defecation.

BACKGROUND: Patient selection is a crucial step when considering total abdominal colectomy and ileorectal anastomosis (TAC/IRA) for refractory constipation. PURPOSE: This study aimed to evaluate the results of short- and long-term outcomes for patients with pure slow transit constipation (STC) compared to those with slow transit and features of obstructive defecation (STC + OD). METHODS: This study included all patients who underwent TAC/IRA for constipation from 1999-2010. Patients were divided into two groups: group A (STC) and group B (STC + OD) based on abnormal physiology or motility testing in addition to the surgeon's clinical impression of symptomatic obstructive defecation. Demographics, operative variables, and short-term outcomes were collected by retrospective chart review and were compared between groups. Long-term functional outcomes were assessed by telephone survey. This included: number of bowel movements, use of laxatives, antidiarrheal medications, and surgery satisfaction. Validated questionnaires were collected postoperatively. RESULTS: One hundred forty-four patients (143 females; mean age, 40 (18-68) years old) underwent TAC/IRA by either laparoscopic (63 (44 %)) or open (81 (56 %)) techniques. One hundred three patients had pure STC and 41 had STC + OD. Four patients underwent TAC with end ileostomy at first procedure. Seven patients underwent surgery after a trial of diverting ileostomy. One patient died unexpectedly, 2 days after uneventful surgery. Median follow-up was 43 (IQR, 16-75) months. Five (5 %) patients in group A and two (5 %) in group B underwent subsequent ileostomy for poor functional outcomes. Eighty-eight (68 %) patients were available by telephone. Short- and long-term outcomes were equivalent in both groups as well as patient satisfaction (89 vs. 85 %, p = 0.7). CONCLUSIONS: Total abdominal colectomy can be offered to selective patients with slow transit constipation and obstructive defecation with equivalent long-term results.

Factors associated with oncologic outcomes after abdominoperineal resection compared with restorative resection for low rectal cancer: patient- and tumor-related or technical factors only?

BACKGROUND: Previous reports suggest that patients with rectal cancer undergoing abdominoperineal resection have worse oncologic outcomes in comparison with those undergoing restorative rectal resection. OBJECTIVE: This study aimed to assess factors influencing oncologic outcomes for patients undergoing surgery for rectal cancer. DESIGN: This study is a retrospective review of prospectively gathered data. SETTING: Data were gathered from a prospective cancer database. PATIENTS: Patients were included who underwent radical resection for mid and lower third rectal cancer (1991-2006). MAIN OUTCOME MEASURES: The primary outcomes measured were the impact of various factors on perioperative outcomes, local recurrence, and disease-free survival for patients undergoing abdominoperineal resection. RESULTS: Four hundred thirteen (29%) patients underwent abdominoperineal resection and 993 (71%) underwent restorative resection for rectal cancer. Patients with abdominoperineal resection were older (p < 0.0001), had a higher mean ASA score (p < 0.001), worse tumor differentiation (p < 0.001), and higher tumor stage (p = 0.0001). Although overall morbidity was lower in the abdominoperineal resection group (p = 0.001), the length of stay was greater (p < 0.001). After a similar period of follow-up (5.2 ± 3.9 vs 5.3 ± 3.4 y, p = 0.58), local recurrence (7% vs 3%, p = 0.02) was higher after abdominoperineal resection, but overall survival (56% vs 71%, p < 0.001) and disease-free survival (54% vs 70%, p < 0.001) were lower. On multivariate analysis, higher stage, poor tumor differentiation, involved margins, and older age were associated with worse survival, whereas higher stage, poor tumor differentiation, and abdominoperineal resection were associated with greater recurrence. These worse oncologic outcomes persisted even when the groups were stratified based on the location of the cancer in mid or distal rectum and for patients with a clear circumferential margin. LIMITATION: This study was limited by its retrospective nature. CONCLUSION: Technical factors alone are unlikely to be responsible for the worse outcomes after abdominoperineal resection in comparison with restorative resection. A combination of patient- and tumor-related factors that may have indicated the choice of the procedure also probably contribute to the worse outcomes. Because patients undergoing abdominoperineal resection represent a high risk for poor outcomes, management strategies need to consider all these factors during treatment.

Interactions of carboplatin with fibrin(ogen), implications for local slow release chemotherapy.

The effect of carboplatin (CPt) on fibrin(ogen) clot formation and the possible use of this combination for local slow release chemotherapy were examined. CPt significantly reduced thrombin-induced fibrin clotting time (CT) and increased clot turbidity in a concentration-dependent manner. When CPt was mixed with physiological levels of fibrinogen (>1 mg/ml), electron-dense nanoparticles (3 nm) were formed, as demonstrated by both optical particle counter and transmission electron microscopy (TEM). Upon thrombin-induced coagulation, the CPt nanoparticles were trapped within the fibrin mesh. At higher fibrinogen levels (>5 mg/ml), the 3-nm CPt nanoparticles aggregated, so that approximately 2% and approximately 0.5% of the CPt on the fibrinogen appeared as larger particles of 10 and 50 nm, respectively. Dialysis experiments showed that 60-70% of the CPt was released from the fibrin clot within one hour as a non-particulate soluble form, while approximately 30% of particulate CPt were retained. Up to 5 mg/ml this portion of firmly attached CPt was dependent of the initial drug level. CPt released from the fibrin by either diffusion or by fibrinolysis exhibited cytotoxic activity towards retinoblastoma (RB) cell lines (Y-79 and Weri RB1) equivalent to free drug. Our study indicates that CPt enhances fibrin clot formation and suggests the use of fibrin with high dose CPt for slow release chemotherapy against localized tumors such as retinoblastoma.