Genome-wide analysis of DNA methylation in pseudomyxoma peritonei originated from appendiceal neoplasms.

INTRODUCTION: Pseudomyxoma peritonei (PMP) is a disease characterized by progressive accumulation of intraperitoneal mucinous ascites produced by neoplasms in the abdominal cavity. Since the prognosis of patients with PMP remain unsatisfactory, the development of effective therapeutic drug(s) is a matter of pressing concern. Genetic analyses of PMP have clarified the frequent activation of GNAS and/or KRAS. However, the involvement of global epigenetic alterations in PMPs has not been reported. METHODS: To clarify the genetic background of the 15 PMP tumors, we performed genetic analysis using AmpliSeq Cancer HotSpot Panel v2. We further investigated global DNA methylation in the 15 tumors and eight non-cancerous colonic epithelial cells using Methylation EPIC array BeadChip (Infinium 850k) containing a total of 865,918 probes. RESULTS: This is the first report of comprehensive DNA methylation profiles of PMPs in the world. We clarified that the 15 PMPs could be classified into at least two epigenotypes, unique methylation epigenotype (UME) and normal-like methylation epigenotype (NLME), and that genes associated with neuronal development and synaptic signaling may be involved in the development of PMPs. In addition, we identified a set of hypermethylation marker genes such as HOXD1 and TSPYL5 in the 15 PMPs. CONCLUSIONS: These findings may help the understanding of the molecular mechanism(s) of PMP and contribute to the development of therapeutic strategies for this life-threatening disease.

Effect of Biologics on the Risk of Advanced-Stage Inflammatory Bowel Disease-Associated Intestinal Cancer: A Nationwide Study.

INTRODUCTION: The aim of this study was to evaluate the effect of biologics on the risk of advanced-stage inflammatory bowel disease (IBD)-associated intestinal cancer from a nationwide multicenter data set. METHODS: The medical records of patients with Crohn's disease (CD) and ulcerative colitis (UC) diagnosed with IBD-associated intestinal neoplasia (dysplasia or cancer) from 1983 to 2020 were included in this study. Therapeutic agents were classified into 3 types: biologics, 5-aminosalicylic acid, and immunomodulators. The pathological cancer stage was compared based on the drug used in both patients with CD and UC. RESULTS: In total, 1,042 patients (214 CD and 828 UC patients) were included. None of the drugs were significantly associated with cancer stage in the patients with CD. In the patients with UC, an advanced cancer stage was significantly associated with less use of biologics (early stage: 7.7% vs advanced stage: 2.0%, P < 0.001), 5-aminosalicylic acid, and immunomodulators. Biologic use was associated with a lower incidence of advanced-stage cancer in patients diagnosed by regular surveillance (biologics [-] 24.5% vs [+] 9.1%, P = 0.043), but this was not the case for the other drugs. Multivariate analysis showed that biologic use was significantly associated with a lower risk of advanced-stage disease (odds ratio = 0.111 [95% confidence interval, 0.034-0.356], P < 0.001). DISCUSSION: Biologic use was associated with a lower risk of advanced IBD-associated cancer in patients with UC but not with CD. The mechanism of cancer progression between UC and CD may be different and needs to be further investigated.

Immunohistochemical staining as supportive diagnostic tool for pseudomyxoma peritonei arising from intraductal papillary mucinous neoplasm: A report of two cases and literature review.

BACKGROUND/OBJECTIVES: Pseudomyxoma peritonei (PMP) arising from an intraductal papillary mucinous neoplasm of the pancreas (IPMN) is a rare condition. The diagnosis of IPMN as the origin of PMP is mainly inferred from the clinical course and the exclusion of PMP from other organs. The pathological diagnosis has not yet been established. To evaluate the usefulness of immunohistochemical staining for the diagnosis of the primary lesion of PMP as IPMN. METHODS: There are 2 cases of PMP arising from IPMN between March 2010 and December 2019 at National Center for Global Health and Medicine. A PubMed search that reported PMP arising from IPMN identified 16 additional cases. Diagnostic methods and clinicopathological features of 18 cases were compared. RESULTS: Four cases including our two cases used immunohistochemical staining for the diagnosis of PMP arising from IPMN. The correspondence of the immunohistochemical staining between PMP and IPMN was shown in the three cases including previously reported two cases and one of our two cases to identify the primary lesion of PMP as IPMN. In addition, we revealed that the comparison of the immunostaining pattern of PMP with the representative immunostaining pattern of the candidate primary lesions is helpful for the diagnosis of the primary lesion of PMP. CONCLUSIONS: Immunohistochemical staining is helpful to identify the primary lesion of PMP as IPMN.

Pseudomyxoma peritonei: visceral scalloping on CT is a predictor of recurrence after complete cytoreductive surgery.

OBJECTIVES: Pseudomyxoma peritonei (PMP) is characterized by peritoneal dissemination of gelatinous ascites following rupture of a mucinous tumor. Treatment by cytoreductive surgery (CRS) has improved its prognosis. Although visceral scalloping, notably liver scalloping, on computed tomography (CT) is a typical feature of PMP, its prognostic value remains unknown. We aimed to investigate the efficacy of liver scalloping in predicting recurrence in PMP patients. METHODS: Among 159 consecutive patients with PMP who had contrast-enhanced CT between September 2012 and December 2018, 64 treatment-naïve patients who subsequently underwent CRS with complete resection (i.e., completeness of cytoreduction score (CC)-0 or CC-1), were included in analysis. Presence of liver scalloping and maximum thickness of mucin deposition at the liver surface were evaluated on CT. Disease-free survival (DFS) was determined based on the combination of postoperative CT features and tumor marker values. RESULTS: Median follow-up was 24.3 months. CT revealed liver scalloping in 40/64 (63.4%) patients. Kaplan-Meier analysis showed significantly shorter DFS in patients with scalloping than in those without (p = 0.001; hazard ratio, 4.3). In patients with scalloping, greater mucin deposition (thickness ≥ 20 mm) significantly correlated with poorer DFS (p = 0.042). In multivariate Cox proportional hazards regression including CC status, pathologic type, and tumor markers, the presence of scalloping independently and significantly correlated with DFS (p = 0.031). CONCLUSIONS: Liver scalloping was an independent predictor even after adjusting for clinical covariates. The presence of liver scalloping can lead to a high recurrence rate after CRS. KEY POINTS: • The presence of liver scalloping is a prognostic factor independent of histological grade and tumor markers. • Greater mucin deposition (thickness ≥ 20 mm at the liver surface) is associated with higher recurrence rates in patients with liver scalloping.

Hepatectomy for metachronous colorectal liver metastases following complete cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal metastases: a report of three cases.

BACKGROUND: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal metastasis (PM) from colorectal cancer (CRC) has been reported to substantially improve the prognosis and the quality of life of patients in comparison to systemic chemotherapy or palliative approaches. This study aimed to demonstrate the safety and feasibility of hepatectomy for metachronous liver metastases from CRC following CRS and HIPEC for PM on the basis of three case reports. CASE PRESENTATION: We describe three cases involving patients who underwent hepatectomy for metachronous liver metastases from CRC after CRS and HIPEC for PM. All patients underwent CRS and HIPEC after primary tumor resection, and hepatectomy was performed for the metachronous liver metastases after CRS and HIPEC. The hepatectomy procedures for cases 1, 2, and 3 were left hemihepatectomy and partial resection of S5, posterior sectionectomy, and left-lateral sectionectomy and partial resection of S5 and S8, respectively. Although adhesion of surrounding organs to the liver surface was observed on a broad level, dissections and hepatectomy could be performed safely. No recurrence was detected in cases 1 and 2 after hepatectomy. In case 3, liver metastases were detected from the time of the initial diagnosis of the primary tumor, and complete remission was achieved once with systemic chemotherapy. Although we performed hepatectomy for the recurrence of liver metastases after complete remission, early re-recurrence was observed after hepatectomy. CONCLUSIONS: Hepatectomy for metachronous liver metastases after CRS and HIPEC for PM could be a multi-modality treatment option for CRC recurrence.

Impact of Primary Tumor Location on Postoperative Recurrence and Subsequent Prognosis in Nonmetastatic Colon Cancers: A Multicenter Retrospective Study Using a Propensity Score Analysis.

OBJECTIVE: We aimed to clarify the prognostic impact of primary tumor location on recurrence after curative surgery and subsequent survival in patients with nonmetastatic colon cancer. SUMMARY OF BACKGROUND DATA: Right and left colon cancers are suggested to be oncologically different; however, their prognostic differences have been conflictingly reported. METHODS: A total of 5664 patients with curatively resected stage II-III colon cancer were reviewed, retrospectively. Relapse-free survival (RFS) after primary surgery and cancer-specific survival (CSS) after recurrence were compared between patients with right and left colon cancer. Patients' backgrounds were matched using propensity scores. RESULTS: Although patients with right colon cancer had more advanced disease, their 5-year RFS rate was significantly superior compared with that in those with left colon cancer (83.9% vs 81.1%, P = 0.019). However, the 5-year CSS after recurrence rate was significantly inferior in patients with right colon cancer compared with that in those with left colon cancer (30.6% vs 43.6%, P = 0.016). CONCLUSIONS: The primary tumor location of nonmetastatic colon cancer might have different prognostic implications for the rates of recurrence after curative resection and cancer-specific mortality after recurrence.

Nine primary malignant neoplasms-involving the esophagus, stomach, colon, rectum, prostate, and external ear canal-without microsatellite instability: a case report.

BACKGROUND: Although cases of multiple primary malignant neoplasms are increasing, reports of more than three or four primary metachronous malignant neoplasms are extremely rare. Moreover, very few publications have provided a genetic mutational analysis or have evaluated risk factors associated with such neoplasms. We present an extremely rare case of nine primary malignant lesions in a man who was successfully treated. We also report on microsatellite stability status, analyze risk factors, and discuss the relevant literature. CASE PRESENTATION: Between 67 and 73 years of age, a male patient developed nine primary metachronous malignant lesions: Three were located in the esophagus, two in the stomach, two in the colorectum, one in the prostate gland, and one in the external ear canal. The patient's clinical history included hypertension, atrial fibrillation, an acoustic schwannoma, and heavy smoking. The lesions were diagnosed during regular screening over a six-year period. He was successfully treated with surgery (both open surgical and endoscopic resection of lesions) and adjuvant chemotherapy. Immunohistochemistry and mutational analysis showed that the lesions were microsatellite stable, and the KRAS, BRAF, p53, and nuclear ß-catenin status was not uniform among the lesions. CONCLUSIONS: Given that the presence of more than three or four neoplasms is extremely rare, the present case of nine primary malignancies with no associated microsatellite instability and no apparent predisposing hereditary conditions, is extraordinary. Our case study shows that it is possible for up to nine sporadic neoplasms to occur, and efficient disease management requires diligent screening and early detection.

Nomogram Predicting Survival After Recurrence in Patients With Stage I to III Colon Cancer: A Nationwide Multicenter Study.

BACKGROUND: Although a number of studies have been conducted to investigate factors affecting colon cancer recurrence and patient overall survival after surgical treatment, no prognostic risk models have been proposed for predicting survival specifically after postsurgical recurrence. OBJECTIVE: We aimed to identify factors affecting the survival of the patients with recurrent colon cancer and to construct a nomogram for predicting their survival. DESIGN: This was a retrospective study. SETTINGS: This study used the Japanese Study Group for Postoperative Follow-Up of Colorectal Cancer database, which contains retrospectively collected data of all consecutive patients with stage I to III colorectal cancer who underwent surgical curative resection between 1997 and 2008 at 23 referral institutions. PATIENTS: A total of 2563 patients with stage I to III colon cancer who experienced recurrence after surgery were included in the present study. MAIN OUTCOME MEASURES: A nomogram predicting survival was constructed using a training cohort composed of patients from 15 hospitals (n = 1721) using a Cox regression hazard model analysis. The clinical applicability of this nomogram was validated in patients from the 8 remaining hospitals (the validation cohort; n = 842). RESULTS: Eight factors (age, location of the primary tumor, histopathological type, positive lymph node status, presence of peritoneal metastasis, number of organs involved in the first recurrence, treatment for recurrence, and the interval between initial surgery and recurrence) were identified as nomogram variables. Our nomogram showed good calibration, with concordance indexes of 0.744 in the training cohort and 0.730 in the validation cohort. The survival curves stratified by the risk score calculated by the nomogram were almost identical for the training and validation cohorts. LIMITATIONS: The study was conducted using the data until 2008, and more advanced chemotherapeutic agents and multidisciplinary therapies that might have improved the outcomes predicted by our nomogram were not available. In addition, treatment strategies for recurrence might differ between countries. CONCLUSIONS: Our nomogram, which is based on a nationwide multicenter study, is the first statistical model predicting survival after recurrence in patients with stage I to III colon cancer. It promises to be of use in postoperative colon cancer surveillance. See Video Abstract at http://links.lww.com/DCR/A687.

LMR predicts outcome in patients after preoperative chemoradiotherapy for stage II-III rectal cancer.

BACKGROUND: Recently, lymphocyte-to-monocyte ratio (LMR) has attracted attention as a new marker of the chronic systemic inflammatory response and has been associated with patient prognosis in those who underwent chemoradiotherapy (CRT) for several solid cancers. This study aimed to evaluate the association between LMR and the prognosis of patients with rectal cancer. METHODS: A total of 183 stage II-III rectal cancer patients who underwent preoperative CRT followed by surgical R0 resection were retrospectively reviewed. The LMR was calculated from pre- and post-CRT blood samples. To determine the optimal cutoff value for pre- and post-CRT LMR for predicting relapse-free survival (RFS) and overall survival (OS), a receiver operator characteristic curve was used. Cox's proportional hazard models were applied to identify risk factors for recurrence and overall mortality. RESULTS: Low LMR was observed in 54 patients (pre-CRT <4.0) and 29 patients (post-CRT <1.5). Although pre-CRT LMR correlated with tumor size and ypT stage, post-CRT LMR showed no correlation to any pathologic features. Median follow-up term was 66.3 months; the 5-year RFS and OS of all patients were 72.5% and 88.7%, respectively. We found that a low pre-CRT LMR was an independent risk factor for OS (hazard ratio, 2.83; 95% confidence interval 1.03-8.13; P = 0.043). CONCLUSIONS: In rectal cancer patients who have undergone preoperative CRT, a low pre-CRT LMR is a poor prognostic factor for OS.

The short-term outcomes of robotic sphincter-preserving surgery for rectal cancer: comparison with open and laparoscopic surgery using a propensity score analysis.

PURPOSE: The aim of this study is to clarify the short-term outcomes of robotic sphincter-preserving surgery for rectal cancer in a retrospective study. METHODS: The short-term outcomes of robotic sphincter-preserving surgery (n = 130) were retrospectively compared to open (n = 234) and laparoscopic surgery (n = 318) by a propensity score analysis. RESULTS: Robotic surgery was performed more frequently for patients with lower rectal cancer (55%) than open (30%, p < 0.0001) or laparoscopic surgery (36%, p < 0.0001). None of the robotic surgery cases were converted to open surgery. After propensity score matching, robotic surgery was found to be associated with a longer operation time (342 vs. 230 min, p < 0.0001) and less blood loss (7 vs. 420 mL, p < 0.0001) than open surgery. The overall complication rate of robotic surgery was lower than that of open surgery (13 vs. 28%, p = 0.032). Robotic surgery was associated with a lower incidence of surgical site infections (SSIs) than laparoscopic surgery (0 vs. 7%, p = 0.028). There were no cases of anastomotic leakage after robotic surgery. The circumferential resection margin was involved in 0.8% of the patients who underwent robotic surgery; the incidence did not differ among the treatment groups. CONCLUSIONS: Although robotic surgery for rectal cancer was associated with a longer operation time, it was associated with a very low incidence of SSIs. The degree of safety was comparable to both open and laparoscopic surgery.

Successful Management of a Positive Air Leak Test during Laparoscopic Colorectal Surgery.

BACKGROUND/AIMS: Anastomotic leakage remains the most serious complications of colorectal surgery. To prevent colorectal anastomotic leakage (CAL), an air leak test (ALT) with intraoperative colonoscopy (IOCS) is performed to detect mechanically insufficient colorectal anastomoses. The approaches to an intraoperative anastomotic air leak (IOAL) have not been fully investigated. This study aimed to clarify the safe management of an IOAL in laparoscopic colorectal surgery. METHODS: One hundred forty-eight consecutive patients who underwent laparoscopic resection with double-stapling technique (DST) anastomosis for left-sided colorectal cancer between April 2015 and June 2016 were included and retrospectively reviewed. RESULTS: Intraoperative anastomotic ALT yielded positive results in 7 patients. In all 7 patients, reanastomoses were performed, and diverting stomas were constructed to protect the anastomosis in 2 patients whose reanastomosis sites were close to the anus. Three of the revised DST anastomoses showed air leakage on the repeat ALT; these sites underwent suturing repair and were confirmed to be airtight. None of the patients with a positive intraoperative ALT had postoperative CAL. The overall CAL rate was 1.4%. CONCLUSIONS: Combination management using DST revision, direct suturing repair, and a diverting stoma is recommended for intraoperative repair of anastomotic defects detected by IOCS.

Different Impacts of Preoperative Radiotherapy and Chemoradiotherapy on Oncological Outcomes in Patients with Stages II and III Lower Rectal Cancer: A Propensity Score Analysis.

BACKGROUND/AIMS: The neoadjuvant therapy for locally advanced rectal cancer has been changed from radiotherapy (RT) to chemoradiotherapy (CRT). This study is aimed at evaluating the benefit of CRT in patients with stage II or III lower rectal cancer, with regard to the impact on recurrence. METHODS: A total of 474 patients with clinical stage II or III lower rectal cancer who received either preoperative RT (n = 221) or CRT (n = 253) followed by total mesorectal excision were identified from our institutional database. Propensity score analysis was performed to mitigate selection biases. RESULTS: Among stage II patients, the CRT group showed a significantly lower 5-year local recurrence rate than the RT group (3.0 vs. 14.8%, p = 0.002). In contrast, among stage III patients, the CRT group showed a significantly lower 5-year distant recurrence rate than the RT group (27.8 vs. 42.6%, p = 0.04) and also a better 5-year recurrence-free survival (64.2 vs. 48.3%, p = 0.03). CONCLUSIONS: Addition of concurrent chemotherapy to preoperative RT significantly enhanced the local control in stage II patients and decreased distant recurrence in stage III patients. The oncological benefit of CRT may differ between patients with stage II or III rectal cancer.

Results of a 36-year surveillance program for ulcerative colitis-associated neoplasia in the Japanese population.

BACKGROUND AND AIM: Surveillance colonoscopy has been carried out for patients with long-standing ulcerative colitis who have an increased risk for colorectal cancer. The aim of the present study was to determine the incidence of and the risk factors for neoplasia. METHODS: We evaluated 289 ulcerative colitis patients who underwent surveillance colonoscopy between January1979 and December 2014. Cumulative incidence of neoplasia and its risk factors were investigated. Clinical stage and overall survival were compared between the surveillance and non-surveillance groups. RESULTS: Cumulative risk of dysplasia was 3.3%, 12.1%, 21.8%, and 29.1% at 10, 20, 30 and 40 years after the onset of ulcerative colitis, respectively. Cumulative risk of colorectal cancer was 0.7%, 3.2%, 5.2%, and 5.2% at 10, 20, 30 and 40 years from the onset of ulcerative colitis, respectively. Total colitis was a risk factor for neoplasia (P = 0.015; hazard ratio, 2.96). CONCLUSIONS: Our surveillance colonoscopy program revealed the incidence and risk factors of ulcerative colitis-associated neoplasias in the Japanese population. Total colitis is a risk factor for neoplasia.

Survival and Prognostic Factors for Metachronous Peritoneal Metastasis in Patients with Colon Cancer.

BACKGROUND: The clinical course of metachronous peritoneal metastasis of colorectal origin is poorly understood. In this retrospective study, we aimed to elucidate survival and prognostic factors for metachronous peritoneal metastasis. METHODS: Patients with metachronous peritoneal metastasis after curative resection for stage I-III colon cancer were retrospectively reviewed, and the incidence and prognosis of metachronous peritoneal metastasis were investigated. Prognostic factors were identified by univariate and multivariate analyses. RESULTS: Among 1582 surgically resected stage I-III colon cancer patients, 65 developed metachronous peritoneal metastasis. The 5-year cumulative incidence rate was 4.5%, and the median survival after diagnosis of peritoneal metastasis was 29.6 months. None of the patients underwent peritonectomy or intraperitoneal chemotherapy. Independent prognostic factors included right colon cancer [hazard ratio (HR) 2.69, 95% confidence interval (CI) 1.26-5.64; p = 0.011], time to metachronous peritoneal metastasis of <1 year (HR 2.02, 95% CI 1.04-3.87; p = 0.040), Peritoneal Cancer Index (PCI) >10 (HR 3.68, 95% CI 1.37-8.99; p = 0.012), concurrent metastases (HR 4.09, 95% CI 2.02-8.23; p < 0.001), and peritoneal nodule resection (HR 0.31, 95% CI 0.13-0.65; p = 0.002). CONCLUSIONS: A proportion of colon cancer patients with metachronous peritoneal metastasis may benefit from combined peritoneal nodule resection and systemic chemotherapy. Right colon cancer, early peritoneal metastasis, a high PCI, and concurrent metastases negatively affected prognosis in patients with metachronous peritoneal metastasis.

Characterization of Conversion Chemotherapy for Secondary Surgical Resection in Colorectal Cancer Patients with Lung Metastases.

OBJECTIVE: Clinical trials demonstrated that 6-37% of the patients with colorectal liver-limited metastases underwent surgical resection after first-line chemotherapy. However, limited information is available on the conversion of colorectal cancer patients with lung metastases to resection by systemic chemotherapy. METHODS: We retrospectively investigated 156 patients with unresectable colorectal cancer who received oxaliplatin- or irinotecan-based first-line systemic chemotherapy with or without antibodies in our department between January 2007 and December 2015. The conversion rate to surgery and chemotherapeutic regimens and periods were analyzed with respect to the target organ. RESULTS: In addition to 4 patients who achieved complete response, 73 exhibited tumor shrinkage of any extent. Twenty patients underwent secondary surgery, all of whom received targeting antibodies. In 75 patients with liver metastases, 18 (24%) were converted to resection after chemotherapy for a median of 110 days. In contrast, 4 (7%) out of 56 patients with lung metastases underwent resection after chemotherapy for a median of 449 days. Conversion was an independent prognostic factor in patients with lung metastases. CONCLUSION: The conversion rate to resection was lower for colorectal cancer patients with lung metastasis by systemic chemotherapy, which required a longer duration than for those with liver metastases.

Brain Metastasis from Colorectal Cancer: Predictors and Treatment Outcomes.

OBJECTIVE: Difficulties are associated with the management of brain metastasis (BM), which portends a poor prognosis in the treatment of colorectal cancer (CRC). The aim of the present study was to identify risk factors for BM in CRC and evaluate the outcomes of various treatment modalities. METHODS: We retrospectively reviewed data on a total of 2,238 patients with primary CRC who underwent surgical resection at our hospital between 1999 and 2014. Predictive factors for BM and prognostic factors after the diagnosis of BM were examined by univariate and multivariate analyses using Cox proportional hazards models. RESULTS: Three patients (0.1%) had BM at the initial diagnosis, and 23 patients (1.2%) developed metachronous BM during the median follow-up period of 44.6 months. Lung and bone metastases were identified as independent predictive factors for BM. Median survival after the diagnosis of BM was 7.4 months. Stereotactic radiosurgery, administered to 41% of the patients with BM, was associated with a better postdiagnostic survival. CONCLUSION: CRC patients with metastasis to the lung or bone were at a higher risk of BM. Because the survival is still limited, it is crucial to determine the treatment strategy in consideration of the characteristics of each therapy and quality of life in CRC patients with BM.

Prognostic Value of Pre- and Postoperative Anti-p53 Antibody Levels in Colorectal Cancer Patients: A Retrospective Study.

OBJECTIVE: To determine the utility of the post-/preoperative anti-p53 antibody (p53 Ab) ratio as a prognostic factor for colorectal cancer (CRC) recurrence. METHODS: A total of 737 nonmetastatic CRC patients who had undergone R0 resection were retrospectively analyzed. p53 Ab levels were measured within 1 month prior to and at least every 3 months after surgery. Post-/preoperative p53 Ab ratios were calculated, and the optimal ratio cutoff values for predicting recurrence were determined using the Kaplan-Meier method and the log-rank test. RESULTS: Preoperative p53 Ab elevation was observed in 194 patients (pre-p53 high). Preoperative p53 Ab levels correlated with TNM stage. Re-elevation of p53 Ab levels occurred on recurrence in the pre-p53 high group, but not in the pre-p53 low group (n = 543). In the pre-p53 high group, patients who experienced tumor recurrence exhibited a slow postoperative reduction of p53 Ab levels, and a post-/preoperative p53 Ab ratio >0.4 at postoperative 3 months predicted relapse-free survival. In other words, a p53 Ab level remaining higher than 40% of the preoperative level was an independent and strong risk factor for recurrence in multivariate analyses. CONCLUSION: In CRC patients with preoperative p53 Ab elevation, the rate of p53 Ab reduction in the early postsurgical period is a promising prognostic factor for recurrence.

Diagnosis, Assessment, and Therapeutic Strategy for Colorectal Mixed Adenoneuroendocrine Carcinoma.

Colorectal mixed adenoneuroendocrine carcinoma (MANEC), which acts like an aggressive tumor, is a rare clinical manifestation on which only a limited amount of literature exists. Surgical resection by regional lymphadenectomy is considered as the only curative treatment for colorectal MANEC, and adjuvant chemotherapy or radiotherapy is recommended because of its high recurrence rate. Colorectal MANEC is frequently diagnosed at an advanced stage, when it is unresectable, and chemotherapy plays a central role in its treatment. Pathological confirmation of the target lesion component is critical for regimen selection. If the lesion comprises an adenocarcinomatous component, a regimen for colorectal adenocarcinoma should be administered. For lesions comprising mainly a neuroendocrine carcinomatous component, cisplatin combined with etoposide or irinotecan has proven to be clinically appropriate. Everolimus, a mechanistic target of rapamycin pathway inhibitor, also improves survival. Sunitinib malate, another molecular targeting agent, is effective for treating neuroendocrine carcinoma; however, the evidence on its effectiveness for treating gastrointestinal neuroendocrine carcinoma is insufficient.

Prediction of Pathological Complete Response Using Endoscopic Findings and Outcomes of Patients Who Underwent Watchful Waiting After Chemoradiotherapy for Rectal Cancer.

BACKGROUND: Nonoperative management for patients with rectal cancer who have achieved a clinical complete response after chemoradiotherapy is becoming increasingly important in recent years. However, the definition of and modality used for patients with clinical complete response differ greatly between institutions, and the role of endoscopic assessment as a nonoperative approach has not been fully investigated. OBJECTIVE: This study aimed to investigate the ability of endoscopic assessments to predict pathological regression of rectal cancer after chemoradiotherapy and the applicability of these assessments for the watchful waiting approach. DESIGN: This was a retrospective comparative study. SETTINGS: This study was conducted at a single referral hospital. PATIENTS: A total of 198 patients with rectal cancer underwent preoperative endoscopic assessments after chemoradiotherapy. Of them, 186 patients underwent radical surgery with lymph node dissection. MAIN OUTCOME MEASURES: The histopathological findings of resected tissues were compared with the preoperative endoscopic findings. Twelve patients refused radical surgery and chose watchful waiting; their outcomes were compared with the outcomes of patients who underwent radical surgery. RESULTS: The endoscopic criteria correlated well with tumor regression grading. The sensitivity and specificity for a pathological complete response were 65.0% to 87.1% and 39.1% to 78.3%. However, endoscopic assessment could not fully discriminate pathological complete responses, and the outcomes of patients who underwent watchful waiting were considerably poorer than the patients who underwent radical surgery. Eventually, 41.7% of the patients who underwent watchful waiting experienced uncontrollable local failure, and many of these occurrences were observed more than 3 years after chemoradiotherapy. LIMITATIONS: The number of the patients treated with the watchful waiting strategy was limited, and the selection was not randomized. CONCLUSIONS: Although endoscopic assessment after chemoradiotherapy correlated with pathological response, it is unsuitable for surveillance of patients treated via a nonoperative approach. Incorporation of a "watchful waiting" strategy without establishing proper surveillance protocols and salvage strategies might result in poor local control.

Oncological Outcomes of Lateral Pelvic Lymph Node Metastasis in Rectal Cancer Treated With Preoperative Chemoradiotherapy.

BACKGROUND: Oncological outcomes of lateral pelvic lymph node metastasis in rectal cancer treated with preoperative chemoradiotherapy remain to be elucidated. OBJECTIVE: The purpose of this study was to clarify the therapeutic effect of chemoradiotherapy on lateral pelvic lymph node metastasis, the risk factors of lateral pelvic lymph node metastasis, and oncological outcomes of lateral pelvic lymph node dissection after chemoradiotherapy. DESIGN: This was a nonrandomized, retrospective study. SETTINGS: The study was conducted at a tertiary referral university hospital. PATIENTS: Patients with rectal cancer treated with chemoradiotherapy and radical surgery from 2003 to 2015 (N = 222) were included. INTERVENTIONS: Radiation (total, 50.4 Gy in 28 fractions) with concomitant fluorouracil-based chemotherapy was administered. Lateral pelvic lymph nodes with a diameter of ≥8 mm before chemoradiotherapy were selectively dissected. MAIN OUTCOME MEASURES: Frequency and risk factors of lateral pelvic lymph node metastasis were examined. RESULTS: Lateral pelvic lymph node dissection was performed in 31 patients (14.0%), and 16 (51.6%) of these patients were pathologically diagnosed as positive for metastasis. Among the patients treated with total mesorectal excision alone (n = 191), 2 (0.9%) had recurrence in the lateral pelvic lymph node area, which was pathologically confirmed after salvage R0 resection. T category downstaging (73.3% vs 12.5%; p < 0.01) and high histological regression of the primary lesion (73.3% vs 18.8%; p < 0.01) were more frequent in patients with pathologically negative lateral pelvic lymph nodes than in those with positive lateral pelvic lymph nodes. Young age, short distance from the anal verge, and enlarged lateral pelvic lymph node before chemoradiotherapy were associated with lateral pelvic lymph node metastasis. LIMITATIONS: The study was limited by its retrospective nature and small study population. CONCLUSIONS: The incidence of lateral pelvic lymph node metastasis after chemoradiotherapy was estimated to be 8.1% (18/222). Young age, short distance from the anal verge, and enlarged lateral pelvic lymph node before chemoradiotherapy were risk factors of lateral pelvic lymph node metastasis after chemoradiotherapy.