BRAF-mutant mismatch repair deficient invasive colon cancer regressing to sessile serrated lesion.

A 69-year-old female was presented with a history of sigmoid colon cancer, uterine cancer, and intrahepatic carcinomas. After computed tomography revealed a disseminated nodule located in the peritoneum, colonoscopy demonstrated a rather flat-to-slightly elevated lesion with a depressed area located in the ascending colon. The flat component showed color similar to its surrounding area, and the depressed area showed redness and an expanded appearance. We obtained a biopsy specimen from the depressed area, and microscopic examination revealed well-differentiated adenocarcinoma, which was immunohistochemically positive for BRAF V600E-mutated and PMS2 proteins, and showed loss of MSH2 and MSH6 protein expressions. These findings suggested the lesion to have transformed from a sessile serrated lesion (SSL) to mismatch repair (MMR) deficient colon cancer. The patient underwent surgical removal of the nodule, which interpreted as metastasis of intrahepatic cholangiocarcinoma histopathologically. After postoperative chemotherapy, the follow-up colonoscopy revealed only the flat portion of the lesion without depressed area. Consequently, we performed an endoscopic resection, and microscopic examination confirmed the existence of BRAF V600E-mutated protein-positive and MMR protein-retained SSL without residual carcinoma. This is the first report of BRAF-mutant and MMR-deficient colon cancer, in association with SSL, showing regression.

Body Composition and Clinical Outcomes in Esophageal Cancer Patients Treated with Immune Checkpoint Inhibitors.

BACKGROUND: Obesity is associated with increased mortality in various cancers, but the relationship between obesity and clinical outcomes in unresectable or recurrent esophageal cancer who receive immune checkpoint inhibitors (ICIs) remains unknown. This study investigated the association between body composition and clinical outcomes in patients with unresectable or recurrent esophageal cancer who received ICIs. METHODS: Utilizing an unbiased database of 111 unresectable or recurrent esophageal cancers, we evaluated the relationships between body composition (body mass index, waist circumference, psoas major muscle volume, and subcutaneous and visceral fat areas) at the initiation of ICI treatment and clinical outcomes including the disease control rate and progression-free survival (PFS). RESULTS: Waist circumference was significantly associated with the disease control rate at the first assessment (P = 0.0008). A high waist circumference was significantly associated with favorable PFS in patients treated with nivolumab. In an univariable model, for 5-cm increase of waist circumference in the outcome category of PFS, univariable hazard ratio (HR) was 0.73 (95% confidence interval [CI], 0.61-0.87; P = 0.0002). A multivariable model controlling for potential confounders yielded a similar finding (multivariable HR, 0.56; 95% CI, 0.33-0.94; P = 0.027). We observed the similar finding in esophageal cancer patients treated with pembrolizumab+CDDP+5-FU (P = 0.048). In addition, waist circumference was significantly associated with the prognostic nutritional index (P = 0.0073). CONCLUSIONS: A high waist circumference was associated with favorable clinical outcomes in ICI-treated patients with unresectable or recurrent esophageal cancer, providing a platform for further investigations on the relationships among body composition, nutrition, and the immune status.

Extracellular water to total body water ratio, a novel predictor of recurrence in patients with colorectal cancer.

Background: Total body water (TBW) fraction, which accounts for 60% of body weight, is an important indicator of body composition, and the extracellular water to TBW ratio (ECW/TBW) is reportedly useful in predicting clinical outcomes of patients with organ disorders. We aimed to clarify the clinical impact of preoperative ECW/TBW status on survival outcomes in cancer patients. Methods: We used a database of 320 colorectal cancer (CRC) patients who underwent potentially curative resections. Preoperative ECW/TBW was measured using a bioelectrical impedance analysis (BIA), and its correlation with patient survival outcomes, clinicopathological factors, laboratory data, and comorbidities were analyzed. Results: A high preoperative ECW/TBW was significantly associated with poorer relapse-free survival (RFS; p = 0.001) and overall survival (OS; p = 0.003). A high ECW/TBW ratio was significantly associated with older age (p < 0.001), low BMI (p = 0.009), and right-sided tumors (p = 0.03). In a multivariate analysis, a high ECW/TBW significantly predicted a higher RFS mortality (HR: 2.07, 95% CI: 1.10-3.88, p = 0.024) and OS mortality (HR: 3.23, 95% CI: 1.25-8.36, p = 0.016). Furthermore, a high ECW/TBW was significantly associated with lower hemoglobin (p < 0.001) and albumin levels (p < 0.001), but not comorbidities. Conclusions: A high preoperative ECW/TBW was a predictive factor for recurrence and poorer overall survival independent of the tumor, node, and metastasis (TNM) stage. Our data suggest that preoperative evaluation of ECW/TBW using BIA might serve as a novel tool for developing CRC treatment strategies.

Complete pathologic response after laparoscopic hepatectomy following treatment with nivolumab and ipilimumab for anticancer drug-resistant MSI-high colon cancer liver metastasis consisting of poorly differentiated adenocarcinoma with squamous differentiation: A case report.

A 56-year-old man referred to our hospital for cecum cancer. Enhanced computed tomography (CT) found swollen reginal lymph nodes and liver metastasis. Magnetic Resonance Imaging (MRI) revealed a solitary lesion on liver (S2). We performed a laparoscopic ileocolic resection and liver partial resection. Tumor pathology showed that these tumors were moderate-differentiated adenocarcinoma (pT3N2bM1 Stage IVA). Genetic examination revealed MSI-high, KRAS wild type, and BRAF wild type. After surgery, two liver metastases were found in S4 and S7 as new lesion in EOB-MRI. We started chemotherapy with the FOLFOFIRI plus bevacizumab regimen, but two liver metastases were enlarged after six cycles of chemotherapy. As a second-line treatment, nivolumab and ipilimumab combination therapy was started. After three cycles of these therapy, both of these tumors shrinkage were observed. We performed laparoscopic liver resection. In specimens, there were no malignant cells. Pathological study revealed that in the initial surgery specimen, PD-L1 protein was detected in both primary and metastatic lesions, and HLA-DR, CK5/6 in liver. No recurrence was observed at 6 months after the surgery. In conclusion, we reported the case of anticancer drug-resistant MSI-high colon cancer liver metastasis was resected after treatment with immune-checkpoint inhibitors and a pathological complete response was found.

A case of internal hernia in the pararectal fossa.

BACKGROUND: Internal hernias are relatively rare and difficult to diagnose. Diagnostic delays lead to the progression of strangulation. In particular, pararectal fossa hernias are extremely rare. We encountered a case in which internal hernia occurred in the pararectal fossa. CASE PRESENTATION: An 87-year-old woman was referred to our hospital because of persistent lower abdominal pain and vomiting. Contrast-enhanced computed tomography revealed findings of intestinal ischemia, such as closed loop formation with reduced contrast effect on the left side of the rectum in the pelvis. Strangulation small bowel obstruction was diagnosed, and emergency laparotomy was performed. The small intestine was found to invade the peritoneal reflection on the left side of the rectum. The patient was finally diagnosed with pararectal fossa hernia. The incarcerated small intestine was released with no bowel resection. The 4-cm hernia phylum was observed and closed by simple suture. The patient had a good postoperative course without recurrence. CONCLUSIONS: We encountered a very rare case of internal hernia in the left pararectal fossa. Preoperative diagnosis of this disease is difficult, but it should nevertheless be considered in cases in which the cause of the intestinal obstruction is unknown.

Textbook outcome contributes to long-term prognosis in elderly colorectal cancer patients.

PURPOSE: Textbook outcome (TO) has been used to define achievement of multiple "ideal" or "optimal" surgical and postoperative quality measures from the patient's perspective. However, TO has not been reported for their impact on survival in elderly, including CRC surgery. This study determined whether TO is associated with long-term outcomes after curative colorectomy in patients with colorectal cancer (CRC). METHODS: Patient who underwent curative surgery over 75 years old for CRC between March 2005 and December 2016. TO included five separate parameters: surgery within 6 weeks, radical resection, Lymph node (LN) yield ≥ 12, no stoma, and no adverse outcome. When all 5 short-term quality of care parameters were realized, TO was achieved (TO). If any one of the 5 parameters was not met, the treatment was not considered TO (nTO). RESULTS: TO was realized in 80 patients (43.0%). Differences in surgical-related characteristics and pathological characteristics according to TO had no statistically significant differences in baseline characteristics, except for Lymph node dissection. The Kaplan-Meier curves for OS and RFS association between TO and nTO had significantly poor 5-year OS and 5-year RFS compared with the TO groups (OS, 77.8% vs. 60.8%, P < 0.01; RFS, 69.6% vs. 50.8%, P = 0.01). In the multivariate analysis, nTO was an independent predictive factor for worse OS (HR, 2.04; 95% confidence interval (CI), 1.175-3.557; P = 0.01) and RFS (HR, 1.72; 95% CI, 1.043-2.842; P = 0.03). CONCLUSIONS: TO can be a useful predictor for postoperative morbidity and prognosis after curative colorectomy for CRC.

Repeated intestinal perforations in vascular Ehlers-Danlos syndrome: a case report of a novel mutation in the COL3A1 gene.

BACKGROUND: Ehlers-Danlos syndrome is an inherited connective-tissue disorder characterized by skin hyperextensibility, joint hypermobility, and tissue fragility. Intestinal perforation is one of the fatal manifestations of this syndrome, and its management is complicated. CASE PRESENTATION: A 58-year-old woman with a familial history of Ehlers-Danlos syndrome visited the emergency department due to a sudden onset of lower abdominal pain. Plain abdominal computed tomography showed abdominal free air. We found a perforated descending colon and subsequently resected this lesion and performed ileostomy. Fifty-one days after this first operation, the patient had transverse colon perforation and thus underwent the Hartmann procedure as the second operation. In addition, she was diagnosed with small bowel perforation 53 days after the first operation and consequently underwent a third operation-partial resection of the jejunum with functional end-to-end anastomosis. Fifty-eight days after the first operation, she complained of acute abdominal pain. Plain abdominal computed tomography showed fluid collection near the jejunojejunal anastomosis. We detected dehiscence at the entry hole of the linear stapler during the operation and thus performed partial resection of the affected jejunum, followed by jejunostomy. The postoperative course of the fourth operation was uneventful. Genetic testing revealed a novel missense mutation (c.2095G>T, p.Gly699Cys) in the COL3A1 gene, which is presumed to be a pathogenic variant of vascular Ehlers-Danlos syndrome. CONCLUSION: Vascular Ehlers-Danlos syndrome should be considered in the case of repeated intestinal perforation. The identified missense mutation in the COL3A1 gene (c.2095G>T, p.Gly699Cys) might be a novel pathogenic variation causing vascular Ehlers-Danlos syndrome. Careful postoperative screening and multidisciplinary management are required.

Emerging evidence of immunotherapy for colorectal cancer.

Since the advent of immune checkpoint inhibitors, which modulate the interplay between the tumor cell and immune system, immunotherapy has become widely recognized as a new standard treatment for cancers including microsatellite instability-high (MSI-H) colorectal cancer. Immune checkpoint inhibitors such as pembrolizumab and nivolumab (anti-PD-1 antibodies) that act in the effector phase of T cells and ipilimumab (anti-CTLA-4 antibody) that acts mainly in the priming phase are now in clinical use. These antibodies have shown therapeutic efficacy in MSI colorectal cancer patients who have failed to respond to existing standard therapies. Pembrolizumab is also strongly recommended as first-line therapy for MSI-H metastatic colorectal cancer. Therefore, the MSI status and tumor mutation burden of the tumor should be clarified before starting treatment. Because many patients do not respond to immune checkpoint inhibitors, combination therapies with immune checkpoint inhibitors, including chemotherapy, radiotherapy, or molecularly targeted agents, are being investigated. Furthermore, treatment methods for preoperative adjuvant therapy for rectal cancer are being developed.

A case of familial adenomatous polyposis with protein-losing enteropathy treated by laparoscopic total colorectal resection: A literature review.

Familial adenomatous polyposis (FAP) with protein-losing enteropathy is a rare disorder and is difficult to treat medically. A 74-year-old female patient was referred to our hospital with a chief complaint of anorexia. Lower gastrointestinal endoscopy showed multiple adenomas from the ascending colon to the rectum and adenocarcinoma in the sigmoid colon and descending colon. Laboratory findings showed hypoalbuminemia (albumin 1.6 mg/dl). Protein leak scintigraphy using 99mTc-HSAD found a protein leak from the colon. Although hypercaloric infusion was administered, the nutritional status was not improved and albumin transfusion was required. The patient underwent laparoscopic total proctocolectomy, ileal pouch-anal anastomosis, and temporary ileostomy. She had a good postoperative course and the hypoalbuminemia normalized in a few weeks. The patient underwent temporary ileostomy reversal. Here we report a case of FAP with protein-losing enteropathy who underwent laparoscopic total proctocolectomy, which resulted in improvement of the protein leak as well as cancer treatment.

C-Reactive Protein Levels After Esophagectomy are Associated with Increased Surgical Complications and Poor Prognosis in Esophageal Squamous Cell Carcinoma Patients.

BACKGROUND: C-reactive protein (CRP) levels are reported to predict complications and survival after surgery in various cancers. However, the relationship between postoperative CRP levels and short- and long-term outcomes of esophageal squamous cell carcinoma (ESCC) patients after esophagectomy is unclear. METHOD: We reviewed the records of 543 ESCC patients who underwent subtotal esophagectomy with gastric conduit reconstruction at Kumamoto University Hospital between August 2010 and July 2021. Blood tests for CRP were done on postoperative days (PODs) 1, 3, 5 or 6, and 7 or 8. RESULTS: The mean CRP levels on day 1, day 3, day 5/6, and day 7/8 were 6.68 ± 0.13 mg/dL, 11.49 ± 0.27 mg/dL, 7.48 ± 0.26 mg/dL, and 5.38 ± 0.22 mg/dL, respectively. Mean CRP levels were highest on day 3, and CRP levels after day 3 correlated with grade >2 complications based on the Clavien-Dindo classification. Receiver operating characteristic curve analysis established the optimal cut-off value for CRP day 3 levels to be 12.19 mg/dL. Multivariate logistic regression analyses found that high CRP day 3 levels significantly correlated with grade >2 complications (odds ratio [OR] 3.77, 95% confidence interval [CI] 2.56-5.35; p < 0.001). Moreover, high day 7/8 CRP levels (>3.52) correlated with postoperative survival, and based on multivariate logistic regression analyses, were significantly associated with poor prognosis (hazard ratio 1.67, 95% CI 1.14-2.43; p = 0.008). CONCLUSION: Our findings suggest CRP day 3 levels as a potential biomarker for predicting postoperative complications and that CRP day 7/8 levels have potential prognostic value for ESCC patients after esophagectomy.

Pathologic complete response after laparoscopic surgery following treatment with nivolumab and ipilimumab for anticancer drug-resistant MSI-high descending colon cancer: a case report and literature review.

BACKGROUND: Preoperative treatment is performed for locally advanced colon cancer with extensive tumor proximity or suspected invasion of skeletal muscles, major organs, and blood vessels. Oxaliplatin-based regimens are often used in preoperative chemotherapy. However, microsatellite instability (MSI)-high colorectal cancer is often resistant to cytotoxic anticancer agents. Herein, we describe a case of treatment of anticancer drug-resistant MSI-high locally advanced colon cancer and review cases of complete response to immune checkpoint inhibitor therapy for colorectal cancer. CASE PRESENTATION: A 57-year-old woman was referred to our hospital with a large tumor in the descending colon and extensive thoracic and abdominal wall involvement, including the ribs and diaphragm. No distant metastasis was observed. The tumor had perforated the abdominal wall and formed an abscess. Upon visiting our hospital, emergency surgery was performed. An abdominal wall incision was made to drain the abscess and laparoscopic colostomy was performed. Histopathological examination of biopsy specimens revealed an adenocarcinoma with positive immunohistochemical expressions of both CDX2 and CK20. The patient was diagnosed with a descending colon cancer. Genetic examination found MSI-high, Kras mutation (F12G), and wild-type BRAF. After the inflammation improved, chemotherapy with the FOLFIRI regimen was initiated, but the tumor grew rapidly. As a second-line treatment, nivolumab and ipilimumab combination therapy was initiated. After four cycles of these therapies, the patient was administered nivolumab alone for five cycles. Tumor shrinkage was observed and radical surgery was performed. The patient underwent laparoscopic descending colon and partial thoracic and abdominal wall resection. The abdominal wall muscle was dissected from the abdominal cavity, and subcutaneous tissues, diaphragm, ribs were dissected from the body surface. Pathological examination revealed mucus components, fibrous tissues, and no malignant cells, indicating a complete pathological response (pCR). The patient had a good postoperative course and returned to work after being discharged. No recurrence was observed six months postoperatively. CONCLUSIONS: Herein, we report a case of anticancer drug-resistant MSI-high colon cancer that was resected after treatment with immune checkpoint inhibitors, and a pCR was achieved. This new treatment strategy can be used for the treatment of cases that are not responsive to conventional therapies.

Index of estimated benefit from lymph node dissection for stage I-III transverse colon cancer: an analysis of the JSCCR database.

PURPOSE: Main lymph node metastasis (LNM) dissection of transverse colon (TC) cancer is a difficult surgical procedure. Nonetheless, the main LNM ratio and the benefit of main lymph node (LN) dissection in TC cancer were unclear. This study aimed to identify high-risk patients for LNM and to evaluate the benefit of LN dissection in TC cancer. METHODS: Data for 26,552 colorectal cancer patients between 2007 and 2011 were obtained from the JSCCR database. Of these, 871 stage I-III TC cancer patients underwent surgery with radical LN dissection. These patients were evaluated using the index of estimated benefit from lymph node dissection (IEBLD), where IEBLD = (LNM ratio of each LN station) × (5-year overall survival (OS) rate of the patients with LNM) × 100. RESULTS: None of the patients with depth of invasion pT1-2 had main LNM. The presence of main LNM was associated with depth of invasion pT4, CEA-4H (carcinoembryonic antigen 4 times higher than preoperative cutoff value), or type 3, and 323 patients (37.1%) who had these factors were high-risk patients for main LNM. In these high-risk patients, the LNM ratio, 5-year OS rate of patients with LNM and IEBLD values, respectively, were 43.9%, 70.3%, and 30.5 for the pericolic LN; 20.3%, 66.0%, and 15.1 for the intermediate LN; and 9.6%, 58.5%, and 5.6 for the main LN. CONCLUSION: Main LNM is associated with depth of invasion pT4, CEA-4H, or type 3. The IEBLD for the main LN of high-risk TC cancer patients was over 5.

Appendiceal bleeding in an elderly male: a case report and a review of the literature.

BACKGROUND: The prevalence of acute lower gastrointestinal bleeding has been increased including colonic diverticulitis and angioplasty. However, appendiceal bleeding is extremely rare. CASE PRESENTATION: We present a case of lower gastrointestinal bleeding from the appendix in an elderly male who presented with melena. Appendiceal bleeding was diagnosed using lower gastrointestinal endoscopy, and laparoscopic appendectomy was performed. The patient did not have melena postoperatively, and was discharged 6 days after the surgery. CONCLUSION: It is important to distinguish appendiceal bleeding from lower gastrointestinal bleeding and to treat it as soon as possible with less invasiveness.

Increased EZH2 expression during the adenoma-carcinoma sequence in colorectal cancer.

The adenoma-carcinoma sequence, the sequential mutation and deletion of various genes by which colorectal cancer progresses, is a well-established and accepted concept of colorectal cancer carcinogenesis. Proteins of the polycomb repressive complex 2 (PRC2) function as transcriptional repressors by trimethylating histone H3 at lysine 27; the activity of this complex is essential for cell proliferation and differentiation. The histone methyltransferase enhancer of zeste homolog 2 (EZH2), an essential component of PRC2, is associated with the transcriptional repression of tumor suppressor genes. EZH2 expression has previously been reported to increase with the progression of pancreatic intraductal papillary mucinous neoplasm. Thus, we hypothesized that EZH2 expression also increases during the adenoma-carcinoma sequence of colorectal cancer. The present study investigated changes in EZH2 expression during the colorectal adenoma-carcinoma sequence. A total of 47 patients with colorectal adenoma, 20 patients with carcinoma in adenoma and 43 patients with colorectal carcinoma who underwent surgical or endoscopic resection were enrolled in this study. Non-cancerous tissue from the clinical specimens was also examined. The association between EZH2 expression, pathology and expression of tumor suppressor genes during colorectal carcinogenesis were analyzed. Each specimen was immunohistochemically stained for EZH2, proliferation marker protein Ki-67 (Ki-67), cyclin-dependent kinase inhibitor (CDKN) 1A (p21), CDKN1B (p27) and CDKN2A (p16). Total RNA was extracted from formalin-fixed paraffin-embedded blocks and reverse transcription-quantitative polymerase chain reaction analysis of these genes was performed. Ki-67 and EZH2 expression scores increased significantly during the progression of normal mucosa to adenoma and carcinoma (P=0.009), and EZH2 expression score was positively associated with Ki-67 expression score (P=0.02). Conversely, p21 mRNA and protein expression decreased significantly, whereas expression of p27 and p16 did not change significantly. During the carcinogenesis sequence from normal mucosa to adenoma and carcinoma, EZH2 expression increased and p21 expression decreased significantly. EZH2 may therefore contribute to the development of colorectal cancer from adenoma via suppression of p21.

Risk factors for pulmonary morbidities after minimally invasive esophagectomy for esophageal cancer.

BACKGROUND: Pulmonary morbidities after esophagectomy are still common and are a major cause of surgery-related mortality. The relationship between minimally invasive esophagectomy (MIE) and pulmonary morbidities is not clear. The current study aimed to examine the incidence of pulmonary morbidities after MIE and to clarify the associated risk factors. METHODS: Between May 2011 and December 2016, 184 patients underwent MIE for esophageal cancer. Clinical data were prospectively collected and analyzed. Patient- and surgery-related factors, relating to pulmonary complications, were compared between the complicated and uncomplicated cases. RESULTS: The incidence of any pulmonary morbidity following MIE was 17.9%. Univariate analysis showed that past heavy smoking [Brinkman index (BI) ≥ 1000], presence of neoadjuvant therapy, advanced clinical stage (stage III, IV), and intraoperative bleeding ≥ 600 g were candidates for being postoperative pulmonary morbidity risk factors. Multivariate analysis suggested that BI ≥ 1000 and advanced clinical stage were independent risk factors for causing pulmonary morbidities. CONCLUSIONS: Past heavy smoking and advanced stage are independent risk factors for pulmonary morbidities after MIE. When performing MIE for such cases, various preoperative precautions and careful postoperative monitoring are necessary.

Preoperative controlling nutritional status (CONUT) is useful to estimate the prognosis after esophagectomy for esophageal cancer.

PURPOSE: The aim of this study is to confirm the predictive value of controlling nutritional status (CONUT), as a postoperative prognostic marker for esophageal cancer patients undergoing esophagectomy. METHODS: We retrospectively analyzed 373 patients who underwent three-incision esophagectomy with 2- or 3-field lymphadenectomy for esophageal cancer between April 2005 and March 2016. The patients were divided into three groups based on the degree of preoperative malnutrition as assessed by CONUT: normal, light malnutrition, and moderate or severe malnutrition. RESULTS: The patients with moderate or severe malnutrition experienced a significantly higher frequency of reoperation (normal or light malnutrition, 6.3%; moderate or severe malnutrition, 18.2%; P = 0.033) and a higher tendency for respiratory morbidities (normal or light malnutrition, 14.0%; moderate or severe malnutrition, 27.3%; P = 0.088). Cox regression analysis identified a significantly poor prognosis, in both overall survival (hazard ratio (HR), 3.56; 95% confidence interval (CI), 1.714-7.390; P < 0.001) and cancer-specific survival (HR, 3.41; 95% CI, 1.790-6.516; P = 0.046). CONCLUSIONS: CONUT is convenient and useful for preoperatively assessing malnutrition and prognosis of esophageal cancer patients who underwent surgery.

Elevated preoperative neutrophil-to-lymphocytes ratio predicts poor prognosis after esophagectomy in T1 esophageal cancer.

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) has been reported to predict the prognosis of various malignant tumors, including esophageal cancer. However, no previous reports have supported the use of the preoperative NLR as an independent prognostic marker focused on superficial (T1) esophageal cancer. The aim of this study was to elucidate the prognostic impact of the preoperative NLR in T1 esophageal cancer. METHODS: This retrospective study recruited 245 consecutive patients with T1 esophageal cancer who underwent subtotal esophagectomy between 2005 and 2016. The relationship between the preoperative NLR and clinicopathological characteristics was analyzed. RESULTS: The preoperative NLR was significantly higher in male patients (p = 0.029), patients with T1b esophageal cancer (p = 0.0274), and patients with venous vessel invasion (p = 0.0082). In the Kaplan-Meier analysis, the elevated preoperative NLR was significantly associated with a poorer disease-free survival (p < 0.0001) and overall survival (p = 0.0004). In the multivariate Cox model, the elevated preoperative NLR was an independent prognostic marker for both disease-free survival (p = 0.0013) and overall survival (p = 0.0027). CONCLUSION: An elevated preoperative NLR predicts poor prognosis in T1 esophageal cancer, suggesting the utility of the NLR as an easily measurable and generally available independent prognostic marker.

CONUT: a novel independent predictive score for colorectal cancer patients undergoing potentially curative resection.

BACKGROUND: Controlling nutritional status (CONUT) score, calculated from serum albumin and total cholesterol concentrations and total lymphocyte count, is reportedly valuable for nutritional assessment. This study investigated whether CONUT score was predictive of outcomes in colorectal cancer (CRC) patients undergoing surgical resection. METHODS: Preoperative CONUT scores were retrospectively evaluated in 417 CRC patients who underwent potentially curative resection at Kumamoto University Hospital from March 2005 to August 2014. Patients were divided into four groups based on preoperative CONUT scores: normal, light, moderate, and severe. The associations of CONUT score with clinicopathological factors, patient survival, and postoperative complications were examined. RESULTS: CONUT score correlated significantly with age (P < 0.001), body mass index (P = 0.005), carcinoembryonic antigen (P = 0.002), and carbohydrate antigen 19-9 (P = 0.005) concentrations. Overall survival (OS) rate was significantly lower in patients with moderate/severe than light or normal CONUT scores. CONUT score was independently prognostic of OS [moderate/severe vs. normal, hazard ratio = 5.92, 95 % confidence interval (CI) 2.30-14.92; P < 0.001)]. Patients with moderate/severe CONUT scores were at greater risk for complications, especially for severe complications. Multivariate analysis showed that CONUT score was independently predictive of severe complications (moderate/severe vs. normal, odds ratio = 4.51, 95 % CI 1.89-10.74; P < 0.001). CONCLUSIONS: CONUT score may predict survival and postoperative severe complications in CRC patients undergoing potentially curative resection. Management of CRC patients may need consideration of host nutritional status.

UHRF1 regulates global DNA hypomethylation and is associated with poor prognosis in esophageal squamous cell carcinoma.

BACKGROUND: Global DNA hypomethylation contributes to oncogenesis through various mechanisms. The level of long interspersed nucleotide element-1 (LINE- 1) methylation is considered a surrogate marker of global DNA methylation, and is attracting interest as a good predictor of cancer prognosis. However, the mechanism how LINE-1 (global DNA) methylation is controlled in cancer cells remains to be fully elucidated. Ubiquitin-like with PHD and RING finger domain 1 (UHRF1) plays a crucial role in DNA methylation. UHRF1 is overexpressed in many cancers, and UHRF1 overexpression may be a mechanism underlying DNA hypomethylation in cancer cells. Nonetheless, the relationship between UHRF1, LINE-1 methylation level, and clinical outcome in esophageal squamous cell carcinoma (ESCC) remains unclear. RESULTS: In ESCC cell lines, vector-mediated UHRF1 overexpression caused global DNA (LINE-1) hypomethylation and, conversely, UHRF1 knockdown using siRNA increased the global DNA methylation level. In ESCC tissues, UHRF1 expression was significantly associated with LINE-1 methylation levels. Furthermore, UHRF1 overexpression correlated with poor prognosis in our cohort of 160 ESCC patients. MATERIALS AND METHODS: The relationships between UHRF1 expression and LINE-1 methylation level (i.e., global DNA methylation level) were investigated using ESCC tissues and cell lines. In addition, we examined the correlation between UHRF1 expression, LINE-1 methylation, and clinical outcome in patients with ESCC. CONCLUSIONS: Our results suggest that UHRF1 is a key epigenetic regulator of DNA methylation and might be a potential target for cancer treatment.

Prognostic and clinical impact of PIK3CA mutation in gastric cancer: pyrosequencing technology and literature review.

BACKGROUND: Phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) mutations that activate the PI3K/AKT signaling pathway have been observed in several types of carcinoma and have been associated with patient prognosis. However, the significance of PIK3CA mutations in gastric cancer remains unclear. This retrospective study investigated the relationship between PIK3CA mutations and clinical outcomes in patients with gastric cancer. Additionally, we reviewed the rate of PIK3CA mutations in gastric cancer and the association between PIK3CA mutations and prognosis in human cancers. METHODS: The study included 208 patients with gastric cancer who underwent surgical resection at Kumamoto University Hospital, Japan, between January 2001 and August 2010. Mutations in PIK3CA exons 9 and 20 were quantified by pyrosequencing assays. RESULTS: PIK3CA mutations were detected in 25 (12 %) of the 208 patients. Ten patients had c.1634A > G (p.E545G), 10 had c.1624G > A (p.E542K), 13 had c.1633G > A (p.E545K), nine had c.3139C > T (p.H1047R), and 1 had c.3140A > G (p.H1047Y) mutations. PIK3CA mutations were not significantly associated with any clinical, epidemiologic, or pathologic characteristic. Kaplan-Meier analysis showed no significant differences in disease-free survival (log rank P = 0.84) and overall survival (log rank P = 0.74) between patients with and without PIK3CA mutations. CONCLUSIONS: Mutations in PIK3CA did not correlate with prognosis in patients with gastric cancer, providing additional evidence for the lack of relationship between the two.