Prognostic Role of the Platelet-to-Lymphocyte Ratio for Patients With Metastatic Colorectal Cancer Treated With Aflibercept.

BACKGROUND/AIM: The efficacy of aflibercept plus 5-fluorouracil, leucovorin and irinotecan (FOLFIRI) therapy has been demonstrated in patients with metastatic colorectal cancer (mCRC) in global and Japanese clinical trials. However, a practical biomarker to predict its efficacy is lacking. PATIENTS AND METHODS: This was a single-institution retrospective study of 21 patients with mCRC consecutively treated with aflibercept plus FOLFIRI from March 2018 to July 2019. We investigated the association and predictive value of pretreatment blood inflammation and immune-based scores, including the neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio (PLR), and lymphocyte-monocyte ratio, using their median values as cut-offs, in regard to disease control (DC), progression-free (PFS), and overall (OS) survival. RESULTS: The number of patients in each treatment line of aflibercept was as follows: Second, 14 (66.7%); third, four (19.0%); fourth, two (9.5%); eighth, one (4.8%). The median number of aflibercept treatment courses was seven (range=2-17). The median follow-up time was 391 days. In univariate analysis, patients with DC had a significantly lower PLR than those without DC. Only the PLR was significantly negatively associated with PFS, but not with OS. Multivariate analysis showed a significantly poor prognostic impact of a high PLR on PFS (hazard ratio=10.28; p=0.003). CONCLUSION: A low pretreatment PLR might be a predictor of aflibercept efficacy in patients with mCRC and may be clinically useful for selecting patient responders.

Pretreatment Neutrophil-to-Lymphocyte Ratio Predicts Survival After TAS-102 Treatment of Patients With Metastatic Colorectal Cancer.

BACKGROUND/AIM: TAS-102 is recommended as salvage-line therapy for metastatic colorectal cancer (mCRC), but practical predictors for its efficacy are lacking. PATIENTS AND METHODS: In a single-institutional retrospective study of 33 patients treated with TAS-102, we investigated the predictive value of the pretreatment neutrophil-to-lymphocyte (NLR), platelet-to-lymphocyte (PLR), and lymphocyte-monocyte (LMR) ratios for progression-free (PFS) and overall (OS) survival. Predictive ability using cut-offs of the median value (3.14) and 5 for NLR were compared. RESULTS: In univariate analysis, Eastern Cooperative Oncology Group performance score, NLR, and PLR were negatively significantly associated with PFS and OS. The number of treatment lines was negatively associated with PFS. The NLR cut-off of 5 was superior to the median value. Multivariate analyses showed a significant prognostic impact for NLR at cut-off 5 (hazard ratio(HR)=6.26, p=0.02 for PFS; HR=6.97, p=0.07 for OS). CONCLUSION: The pretreatment NLR is a prognostic biomarker for patients with mCRC who receive TAS-102 treatment.

Phlegmonous gastritis associated with advanced esophageal cancer.

Phlegmonous gastritis is a rapidly progressive bacterial infection of the stomach wall. It has a high mortality rate and aggressive treatment, either with antibiotics or surgical resection, is required. Here, we report an extremely rare case of phlegmonous gastritis associated with advanced esophageal cancer. A 65-year-old Japanese man was urgently admitted to the hospital due to pyrexia and gastrointestinal symptoms. Abdominal computed tomography revealed widespread diffuse thickening of the gastric wall. On endoscopic examination, an ulcerative mass was detected at the lower thoracic esophagus, and a markedly elevated submucosal lesion was present in the middle of the stomach body. Biopsy specimens taken endoscopically from the esophageal tumor confirmed a diagnosis of squamous cell carcinoma. Gastric biopsy cultures were positive for Streptococcus viridans, leading to a diagnosis of phlegmonous gastritis associated with esophageal cancer. After the patient's condition improved with preoperative antibiotic administration, we performed a thoracoscopic esophagectomy, a total gastrectomy and a reconstruction of the gastrointestinal tract using a pedicled right colon. Histological examination of the resected specimen confirmed that the gastric mass was compatible with a phlegmon.

A case of repeated small bowel perforations in a short period in a patient with cholesterol crystal embolism.

We report a case of jejunal perforation related to cholesterol crystal embolism (CCE) in a woman in her seventies. The jejunum was partially resected;histological examination of the resected tissue revealed that the perforation was caused by CCE. On postoperative day 12, computed tomography (CT) showed free air in the abdomen. We then performed a second operation to alleviate the anastomotic leakage. Subsequently, 26 days after the second surgery, CT again showed free air in the abdomen. A third operation was performed, and multiple perforations of the jejunum were detected. She died of multiple organ failure 43 days after the first surgery. The prognosis of CCE with gastrointestinal perforation is reported to beextremely poor, and there is a high rate of anastomotic leakage. Partial resection of the intestine and ileostomy might be useful for removing the intestinal perforations caused by a CCE. Steroid administration should be continued, however, because discontinuation may worsen the problem.

SnoN/SKIL modulates proliferation through control of hsa-miR-720 transcription in esophageal cancer cells.

It is now evident that changes in microRNA are involved in cancer progression, but the mechanisms of transcriptional regulation of miRNAs remain unknown. Ski-related novel gene (SnoN/SKIL), a transcription co-factor, acts as a potential key regulator within a complex network of p53 transcriptional repressors. SnoN has pro- and anti-oncogenic functions in the regulation of cell proliferation, senescence, apoptosis, and differentiation. We characterized the roles of SnoN in miRNA transcriptional regulation and its effects on cell proliferation using esophageal squamous cell carcinoma (ESCC) cells. Silencing of SnoN altered a set of miRNA expression profiles in TE-1cells, and the expression levels of miR-720, miR-1274A, and miR-1274B were modulated by SnoN. The expression of these miRNAs resulted in changes to the target protein p63 and a disintegrin and metalloproteinase domain 9 (ADAM9). Furthermore, silencing of SnoN significantly upregulated cell proliferation in TE-1 cells, indicating a potential anti-oncogenic function. These results support our observation that cancer tissues have lower expression levels of SnoN, miR-720, and miR-1274A compared to adjacent normal tissues from ESCC patients. These data demonstrate a novel mechanism of miRNA regulation, leading to changes in cell proliferation.

Successful treatment of a spontaneous esophageal rupture in an elderly patient: a case report.

An 80-year-old woman was admitted to our hospital with severe chest and back pains after vomiting. Computed tomography (CT) of the chest revealed left-sided pneumothorax and pleural effusion. Some food was drained from an inserted chest tube, and we diagnosed spontaneous esophageal rupture (Boerhaave's syndrome). A left thoracotomy was performed 7 hours after the onset of symptoms. A 3-cm perforation was discovered in the lateral wall of the distal esophagus. The perforation was repaired with a primary two-layered closure and covered with pericardial fat. The patient had a good postoperative course and was discharged 1 month after surgery. This case suggests the importance of early surgical treatment, even in elderly patients with spontaneous esophageal rupture.