Laparoscopy-Assisted Restorative Proctocolectomy with Ileal Pouch-Anal Anastomosis in Middle Colic Artery Ligation Immediately before Specimen Removal.

Introduction: Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the surgical procedure for ulcerative colitis (UC). Intestinal ischemia may occur if the main blood vessels are ligated at an early stage of this surgery. Considering that the blood flow in the large intestine can be maintained by preserving the middle colic artery, we have used a new IPAA method: ligating the middle colic artery immediately before removal of the specimens ("M-method"). Here, we evaluated the M-method's clinical outcomes. Methods: Between April 2009 and December 2021, 13 patients underwent a laparoscopy-assisted IPAA procedure at our institution. The conventional method was used for 6 patients, and the M-method was used for the other 7 patients. We retrospectively analyzed the cases' clinical notes. Results: The M-method's rate of postoperative complications (Clavien-Dindo classification grade II or more) was significantly lower than that of the conventional method (14.2% vs. 83.3%). The M-method group's postoperative stay period was also significantly shorter (average 16.4 days vs. 55.5). There were significant differences in the albumin value and the ratio of the modified GPS score 1 or 2 on the 7th postoperative day between the M- and conventional methods (average 3.15 vs. 2.5, average 4/7 vs. 6/6). However, it is necessary to consider the small number of cases and the uncontrolled historical comparison. Conclusion: Late ligation of the middle colic artery may be beneficial for patients' post-surgery recovery and can be recommended for IPAAs in UC patients.

A case of rectal cancer complicated with segmental arterial mediolysis (SAM) safely treated with curative resection - A case report.

INTRODUCTION: Recent advances in diagnostic imaging techniques have led to an increasing number of case reports of segmental arterial mediolysis (SAM). However, reports of abnormalities associated with SAM of abdominal organs, including the bowel, are limited. SAM, a rare vascular disease that causes spontaneous intra-abdominal bleeding, including shock and intestinal ischemia, has been reported to be associated with high mortality, but it has not been reported to coexist with rectal cancer. CASE PRESENTATION: A 74 year-old male was referred to our hospital with a rectal cancer and he was admitted for further examination. Computed tomography angiography (CTA) revealed dissection and aneurysm in the celiac artery, superior mesenteric artery (SMA), and the inferior mesenteric artery were dilated, leading to a diagnosis of SAM. CLINICAL DISCUSSION: Surgery for rectal cancer requires cutting the inferior mesenteric artery. The risk of bleeding during surgery increases when SAM is associated with the inferior mesenteric artery. The radical surgery for rectal cancer was executed without complications, including significant bleeding. This was achieved through careful management of SAM, meticulous control of blood pressure throughout the surgical procedure, and the delicate treatment of the SMA. A pathological diagnosis of the resected inferior mesenteric artery at the time of radical surgery was performed, and a definitive diagnosis of SAM was made. CONCLUSION: We present a first known case in which high anterior resection was successfully performed for rectal cancer complicated by SAM. The relationship between cancer and SAM is unclear and further case accumulation is needed.

Clinical development of a blood biomarker using apolipoprotein-A2 isoforms for early detection of pancreatic cancer.

BACKGROUND: We have previously reported apolipoprotein A2-isoforms (apoA2-is) as candidate plasma biomarkers for early-stage pancreatic cancer. The aim of this study was the clinical development of apoA2-is. METHODS: We established a new enzyme-linked immunosorbent sandwich assay for apoA2-is under the Japanese medical device Quality Management System requirements and performed in vitro diagnostic tests with prespecified end points using 2732 plasma samples. The clinical equivalence and significance of apoA2-is were compared with CA19-9. RESULTS: The point estimate of the area under the curve to distinguish between pancreatic cancer (n = 106) and healthy controls (n = 106) was higher for apoA2-ATQ/AT [0.879, 95% confidence interval (CI): 0.832-0.925] than for CA19-9 (0.849, 95% CI 0.793-0.905) and achieved the primary end point. The cutoff apoA2-ATQ/AT of 59.5 µg/mL was defined based on a specificity of 95% in 2000 healthy samples, and the reliability of specificities was confirmed in two independent healthy cohorts as 95.3% (n = 106, 95% CI 89.4-98.0%) and 95.8% (n = 400, 95% CI 93.3-97.3%). The sensitivities of apoA2-ATQ/AT for detecting both stage I (47.4%) and I/II (50%) pancreatic cancers were higher than those of CA19-9 (36.8% and 46.7%, respectively). The combination of apoA2-ATQ/AT (cutoff, 59.5 µg/mL) and CA19-9 (37 U/mL) increased the sensitivity for pancreatic cancer to 87.7% compared with 69.8% for CA19-9 alone. The clinical performance of apoA2-is was blindly confirmed by the National Cancer Institute Early Detection Research Network. CONCLUSIONS: The clinical performance of ApoA2-ATQ/AT as a blood biomarker is equivalent to or better than that of CA19-9.

Ceramide synthase CERS4 gene downregulation is associated with KRAS mutation in colorectal cancer.

Ceramide, the central molecule in sphingolipid synthesis, is a bioactive lipid that serves as a regulatory molecule in the anti-inflammatory responses, apoptosis, programmed necrosis, autophagy, and cell motility of cancer cells. In particular, the authors have reported differences in sphingolipid content in colorectal cancer tissues. The associations among genetic mutations, clinicopathological factors, and sphingolipid metabolism in colorectal cancer (CRC) have not been investigated. The objective of this study is to investigate the association between genes associated with sphingolipid metabolism, genetic variations in colorectal cancer (CRC), and clinicopathological factors in CRC patients. We enrolled 82 consecutive patients with stage I-IV CRC who underwent tumor resection at a single institution in 2019-2021. We measured the expression levels of genes related to sphingolipid metabolism and examined the relationships between CRC gene mutations and the clinicopathological data of each individual patient. The relationship between CRC gene mutations and expression levels of ceramide synthase (CERS), N-acylsphingosine amidohydrolase (ASAH), and alkaline ceramidase (ACER) genes involved in sphingolipid metabolism was examined CRES4 expression was significantly lower in the CRC KRAS gene mutation group (p = 0.004); vascular invasion was more common in colorectal cancer patients with high CERS4 expression (p = 0.0057). By examining the correlation between sphingolipid gene expression and clinical factors, we were able to identify cancer types in which sphingolipid metabolism is particularly relevant. CERS4 expression was significantly reduced in KRAS mutant CRC. Moreover, CRC with decreased CERS4 showed significantly more frequent venous invasion.

The first case of laparoscopic surgery for cecal cancer occurring in a blind loop.

Cancer occurrence in a blind loop is extremely rare. An 86-year-old Japanese woman underwent colonoscopy for tarry stools and weight loss; it revealed a bypass of the transverse colon and small intestine, cecal cancer, and a polyp. She had suffered from acute appendicitis and had undergone two surgeries at age 25: an appendectomy and then a bypass surgery between the transverse colon and the small intestine. We performed a laparoscopy-assisted ileocecal resection for the cancer and polyp in the blind loop with an end-to-side instrumental anastomosis. The pathological examination demonstrated that the cancer was medullary carcinoma (T2, N0, M0, Stage I) and the polyp was tubular adenoma. Two months have passed since the patient's discharge, and she is free of abdominal complaints. Our literature search identified 10 cases of cancer in a blind loop. Laparoscopy-assisted surgery may be possible in patients who have undergone blind-loop surgery.

Long-term oncological outcome of reduced-port laparoscopic surgery (single-incision plus one port) as a technical option for rectal cancer.

BACKGROUND: The purpose of this study was to clarify the oncological safety of reduced-port laparoscopic surgery (single-incision plus one port) (RPS) for patients with rectal cancer. METHODS: The clinicopathological data of 63 selected patients with clinical Stage I-III (T1-3 and N0-2) rectal cancer who underwent RPS of radical anterior resection between 2012 and 2017 were retrospectively analyzed. The median distance of tumor from anal verge was 11 cm. Ordinarily, a multiport platform with three channels was placed in the 3-cm umbilical incision, and another 5- or 12-mm port was placed in the right lower abdomen. RESULTS: The median operative time, amount of intraoperative bleeding, number of harvested lymph nodes, and length of distal margin were 272 min, 10 mL, 22 nodes, and 4.0 cm, respectively, and there was one (2%) patient with involvement of the radial margin. There were eight patients (13%) who required additional ports, and one patient (2%) who converted to open surgery. Intra- and postoperative complications occurred in one (2%) and 12 patients (19%), respectively. The median length of postoperative hospital stay was 8 days. The median follow-up period was 79 months, and incisional hernia was observed in 3 (5%) patients at the platform site not the port site, and cancer recurrence occurred in four patients (6%). The 5-year relapse-free and overall survival rates were 100% and 100% in the patients with pathological Stage I disease, 94% and 100% in the patients with pathological Stage II disease, and 83% and 89% in the patients with pathological Stage III disease, respectively. CONCLUSION: RPS in the selected patients with rectal cancer, performed by an expert laparoscopic surgeon, may be technically safe and oncologically acceptable as well as multiport laparoscopic surgery.

Development of fluorogenic substrates for colorectal tumor-related neuropeptidases for activity-based diagnosis.

The M3 metalloproteases, neurolysin and THOP1, are neuropeptidases that are expressed in various tissues and metabolize neuropeptides, such as neurotensin. The biological roles of these enzymes are not well characterized, partially because the chemical tools to analyse their activities are not well developed. Here, we developed a fluorogenic substrate probe for neurolysin and thimet oligopeptidase 1 (THOP1), which enabled the analysis of enzymatic activity changes in tissue and plasma samples. In particular, the probe was useful for studying enzyme activities in a single-molecule enzyme assay platform, which can detect enzyme activity with high sensitivity. We detected the activity of neurolysin in plasma samples and revealed higher enzyme activity in the blood samples of patients with colorectal tumor. The result indicated that single-molecule neurolysin activity is a promising candidate for a blood biomarker for colorectal cancer diagnosis.

Inhibition of CXCR4 Enhances the Efficacy of Radiotherapy in Metastatic Prostate Cancer Models.

Radiotherapy (RT) is a standard treatment for patients with advanced prostate cancer (PCa). Previous preclinical studies showed that SDF1α/CXCR4 axis could mediate PCa metastasis (most often to the bones) and cancer resistance to RT. We found high levels of expression for both SDF1α and its receptor CXCR4 in primary and metastatic PCa tissue samples. In vitro analyses using PCa cells revealed an important role of CXCR4 in cell invasion but not radiotolerance. Pharmacologic inhibition of CXCR4 using AMD3100 showed no efficacy in orthotopic primary and bone metastatic PCa models. However, when combined with RT, AMD3100 potentiated the effect of local single-dose RT (12 Gy) in both models. Moreover, CXCR4 inhibition also reduced lymph node metastasis from primary PCa. Notably, CXCR4 inhibition promoted the normalization of bone metastatic PCa vasculature and reduced tissue hypoxia. In conclusion, the SDF1α/CXCR4 axis is a potential therapeutic target in metastatic PCa patients treated with RT.

Prediction of tissue-of-origin of early stage cancers using serum miRNomes.

BACKGROUND: Noninvasive detection of early stage cancers with accurate prediction of tumor tissue-of-origin could improve patient prognosis. Because miRNA profiles differ between organs, circulating miRNomics represent a promising method for early detection of cancers, but this has not been shown conclusively. METHODS: A serum miRNA profile (miRNomes)-based classifier was evaluated for its ability to discriminate cancer types using advanced machine learning. The training set comprised 7931 serum samples from patients with 13 types of solid cancers and 5013 noncancer samples. The validation set consisted of 1990 cancer and 1256 noncancer samples. The contribution of each miRNA to the cancer-type classification was evaluated, and those with a high contribution were identified. RESULTS: Cancer type was predicted with an accuracy of 0.88 (95% confidence interval [CI] = 0.87 to 0.90) in all stages and an accuracy of 0.90 (95% CI = 0.88 to 0.91) in resectable stages (stages 0-II). The F1 score for the discrimination of the 13 cancer types was 0.93. Optimal classification performance was achieved with at least 100 miRNAs that contributed the strongest to accurate prediction of cancer type. Assessment of tissue expression patterns of these miRNAs suggested that miRNAs secreted from the tumor environment could be used to establish cancer type-specific serum miRNomes. CONCLUSIONS: This study demonstrates that large-scale serum miRNomics in combination with machine learning could lead to the development of a blood-based cancer classification system. Further investigations of the regulating mechanisms of the miRNAs that contributed strongly to accurate prediction of cancer type could pave the way for the clinical use of circulating miRNA diagnostics.

Easy preparation of a liposome-mediated protein delivery system by freeze-thawing a liposome-protein complex.

Homeostasis can be achieved by adding a protein supplement; however, an appropriate vector is required to deliver the protein into the cell because of the low stability of proteins in the blood and low cell membrane permeability. Here we report an easy one-step method of encapsulating proteins into liposomes for delivery. We used negatively charged superoxide dismutase (SOD) and a polycation liposome as protein and liposome models, respectively. Liposome-encapsulated SOD was prepared by freeze-thawing the SOD-liposome complex (lipoplexes). The amount of immobilized SOD within the lipoplex significantly increased on freeze-thawing. Surprisingly, subjecting the single-layered lipoplexes to freeze-thawing produced multilayered liposomes with SOD localized between the lipid layers. The amount of SOD delivered intracellularly significantly increased by freeze-thawing compared with that delivered by lipoplexes without freeze-thawing. SOD, liposomes, and endosomes were separately localized in the cells. The freeze-thawed lipoplex-encapsulated SOD samples were intravenously injected in mice. The SOD biodistribution was dramatically changed compared with the injection of free SOD or lipoplex. SOD was detached from the lipoplex in the bloodstream after the injection of non-freeze-thawed lipoplex, whereas the encapsulation of SOD in the liposomes upon freeze-thawing enabled the stable circulation of SOD with the liposomes in the bloodstream. This work paves the way for the application of the freeze-thawing technology for the easy one-step encapsulation of proteins into liposomes for protein delivery.

Endoscopic Resection Before Surgery Does Not Affect the Recurrence Rate in Patients With High-Risk T1 Colorectal Cancer.

INTRODUCTION: Patients with high-risk T1 colorectal cancer (CRC) after endoscopic resection (ER) should undergo surgery in view of the risk of lymph node metastasis. Although additional surgery can potentially prevent recurrence, there is a paucity of data and longitudinal studies exploring this potential. Hence, this study aimed to evaluate the prolonged influence of ER before additional surgery on recurrence in T1 CRC. METHODS: Between January 2004 and October 2015, 162 patients who underwent secondary surgery (SS) after ER ([ER + SS] group) and 392 consecutive patients with T1 CRC who underwent primary surgery at our institution were retrospectively analyzed. Recurrence was analyzed in these 2 groups. High-risk CRC patients were histologically defined according to the Japanese Society for Cancer of the Colon and Rectum guidelines (2016) for the treatment of CRC. Data were analyzed based on clinical and histological features, including lymph node metastasis, and the number of lymph nodes evaluated. RESULTS: The recurrence rate was comparable between the ER + SS and primary surgery groups, with no significant difference (P = 0.625, log-rank test). There was no significant difference in the recurrence in patients receiving adjuvant chemotherapy in both groups (7.4% vs 10.4%, P = 0.27). The difference in the mean number of lymph nodes dissected between both groups was also not significant (24.3 vs 25.3, P = 0.43). DISCUSSION: There was no significant difference in recurrence rates between patients undergoing ER before surgery and those undergoing primary surgery for high-risk T1 CRC. Hence, ER may be acceptable for high-risk T1 CRC.

Enhancement of target toxin neutralization effect in vivo by PEGylation of multifunctionalized lipid nanoparticles.

Protein-protein (e.g., antibody-antigen) interactions comprise multiple weak interactions. We have previously reported that lipid nanoparticles (LNPs) bind to and neutralize target toxic peptides after multifunctionalization of the LNP surface (MF-LNPs) with amino acid derivatives that induce weak interactions; however, the MF-LNPs aggregated after target capture and showed short blood circulation times. Here we optimized polyethylene glycol (PEG)-modified MF-LNPs (PEG-MF-LNPs) to inhibit the aggregation and increase the blood circulation time. Melittin was used as a target toxin, and MF-LNPs were prepared with negatively charged, hydrophobic, and neutral amino-acid-derivative-conjugated functional lipids. In this study, MF-LNPs modified with only PEG5k (PEG5k-MF-LNPs) and with both PEG5k and PEG2k (PEGmix-MF-LNPs) were prepared, where PEG5k and PEG2k represent PEG with a molecular weight of 5000 and 2000, respectively. PEGylation of the MF-LNPs did not decrease the melittin neutralization ability of nonPEGylated MF-LNPs, as tested by hemolysis assay. The PEGmix-MF-LNPs showed better blood circulation characteristics than the PEG5k-MF-LNPs. Although the nonPEGylated MF-LNPs immediately aggregated when mixed with melittin, the PEGmix-MF-LNPs did not aggregate. The PEGmix-MF-LNPs dramatically increased the survival rate of melittin-treated mice, whereas the nonPEGylated MF-LNPs increased slightly. These results provide a fundamental strategy to improve the in vivo toxin neutralization ability of MF-LNPs.

Usefulness of laparoscopic surgery and preoperative examinations for chronic recurrent small bowel obstruction.

PURPOSE: The aim of this study was to investigate the usefulness of laparoscopic surgery for patients with postoperative abdominal symptoms, including chronic recurrent small-bowel obstruction (SBO), and preoperative examinations of barium follow-through and computed tomography (CT) to predict the postoperative outcomes of laparoscopic surgery. METHODS: Between 2016 and 2018, 49 patients with postoperative symptoms were treated by laparoscopic surgery at our institute. The data from two preoperative examinations were available for 42 patients. The patients were divided into 4 groups: CT-positive (CP, n = 18), barium follow-through-positive (BP, n = 1), both positive (AP [all positive] n = 13), and both negative (AN [all negative], n = 10). RESULTS: Among the 49 patients, 41 received pure laparoscopic surgery, 7 received laparoscopic-assisted surgery with mini-laparotomy, and 1 required conversion. Intra- and postoperative complications occurred in two and seven patients, respectively. Improvement of abdominal symptoms was observed in 40 patients. In terms of the medium-term outcomes, the rate of improvement of symptoms was poorer in the AN group than in the other three groups, but not to a significant degree. CONCLUSION: Laparoscopic surgery was safe and feasible for patients with chronic recurrent abdominal symptoms, including SBO. Furthermore, in patients with negative results on both preoperative examinations, laparoscopic surgery may yield only poor improvement of symptoms.

Dual Programmed Death Receptor-1 and Vascular Endothelial Growth Factor Receptor-2 Blockade Promotes Vascular Normalization and Enhances Antitumor Immune Responses in Hepatocellular Carcinoma.

BACKGROUND AND AIMS: Activation of the antitumor immune response using programmed death receptor-1 (PD-1) blockade showed benefit only in a fraction of patients with hepatocellular carcinoma (HCC). Combining PD-1 blockade with antiangiogenesis has shown promise in substantially increasing the fraction of patients with HCC who respond to treatment, but the mechanism of this interaction is unknown. APPROACH AND RESULTS: We recapitulated these clinical outcomes using orthotopic-grafted or induced-murine models of HCC. Specific blockade of vascular endothelial receptor 2 (VEGFR-2) using a murine antibody significantly delayed primary tumor growth but failed to prolong survival, while anti-PD-1 antibody treatment alone conferred a minor survival advantage in one model. However, dual anti-PD-1/VEGFR-2 therapy significantly inhibited primary tumor growth and doubled survival in both models. Combination therapy reprogrammed the immune microenvironment by increasing cluster of differentiation 8-positive (CD8+ ) cytotoxic T cell infiltration and activation, shifting the M1/M2 ratio of tumor-associated macrophages and reducing T regulatory cell (Treg) and chemokine (C-C motif) receptor 2-positive monocyte infiltration in HCC tissue. In these models, VEGFR-2 was selectively expressed in tumor endothelial cells. Using spheroid cultures of HCC tissue, we found that PD-ligand 1 expression in HCC cells was induced in a paracrine manner upon anti-VEGFR-2 blockade in endothelial cells in part through interferon-gamma expression. Moreover, we found that VEGFR-2 blockade increased PD-1 expression in tumor-infiltrating CD4+ cells. We also found that under anti-PD-1 therapy, CD4+ cells promote normalized vessel formation in the face of antiangiogenic therapy with anti-VEGFR-2 antibody. CONCLUSIONS: We show that dual anti-PD-1/VEGFR-2 therapy has a durable vessel fortification effect in HCC and can overcome treatment resistance to either treatment alone and increase overall survival in both anti-PD-1 therapy-resistant and anti-PD-1 therapy-responsive HCC models.

Improving Selection for Resection of Synchronous Para-Aortic Lymph Node Metastases in Colorectal Cancer.

INTRODUCTION: The clinical benefit of extended lymphadenectomy for synchronous extraregional lymph node metastasis, such as para-aortic lymph node (PALN) metastasis in colorectal cancer, remains highly controversial. AIM: To evaluate the clinical benefit of PALN dissection in colorectal cancer patients with synchronous PALN metastasis with or without multiorgan metastases. METHODS: Thirty-six patients with pathologically positive PALN metastasis below the renal veins who underwent concurrent PALN dissection and primary colorectal cancer resection from January 1984 through September 2011 at the National Cancer Center Hospital in Tokyo, Japan, were included in this retrospective cohort study. We examined 5-year recurrence-free survival (RFS) rates in patient groups depending on the number of nodes involved (≤2 and ≥3 nodes) and on the presence or absence of other organ involvement (M1a and M1b,c categories in TNM staging). RESULTS: The 5-year RFS rate was significantly different depending on the number of metastatic PALNs (42.1 and 0.6% for PALN ≤2 and ≥3, respectively, p = 0.01). The 5-year RFS rate was significantly better in patients in the M1a category than in patients in the M1b and M1c categories (27.6 and 0.0%, respectively, p < 0.01). Twenty-nine patients (80.6%) experienced recurrence after PALN dissection. Postoperative complications were seen in 14 (38.9%) patients. CONCLUSION: PALN dissection below the renal veins for patients with isolated PALN metastasis with 2 or fewer involved PALNs may be effective in improving prognosis in colorectal cancer.

Short-term and midterm outcomes of single-incision laparoscopic surgery for right-sided colon cancer.

INTRODUCTION: The purpose of this study was to clarify the usefulness of SILS for right-sided colon cancer by evaluating the short-term and midterm outcomes. METHODS: Between 2012 and 2017, 65 selected patients with right-sided colon cancer underwent ileocecal resection, right hemicolectomy, or transverse colectomy; all were enrolled in the study. The same well-trained surgeon performed each procedure by using a multi-instrument access port with three channels, which was placed at the umbilicus via an approximately 3-cm skin incision. RESULTS: The pathological disease stage distribution was stage 0, 4 cases; stage I, 23 cases; stage II, 19 cases; stage III, 17 cases; and stage IV, 2 cases. The surgical procedures performed were ileocecal resection, 23 cases; right hemicolectomy, 35 cases; and transverse colectomy, 7 cases. The median operative time and intraoperative blood loss were 216 min and 10 mL, respectively. Although 18 cases needed additional ports, none required conversion to open surgery. The median number of harvested lymph nodes was 24. No major perioperative morbidities occurred in this patient series. The median postoperative hospital stay was 7 days. The median follow-up period was 30 months, and the 3-year relapse-free and overall survival rates were 100% and 100%, respectively, in the stage 0-I cases and 89% and 96% in the stage II-III cases, respectively. CONCLUSION: We concluded that SILS is as feasible as multiport laparoscopic surgery and a reliable surgical option in selected cases of right-sided colon cancer.

ROK study-C (Rainbow of KIBOU study-colorectum): a colorectal cancer survivor cohort study on food, nutrition, physical activity, psychosocial factors and its influences on colorectal cancer recurrence, survival and quality of life in Japan.

BACKGROUND: Many studies have shown that lifestyle factors such as diet, physical activity are related to the incidence of cancer. However, there are few studies on the association between lifestyle factors and cancer prognosis. To investigate the influence of lifestyle factors and psychosocial factors on prognosis, we started a prospective study of women with breast cancer, the Rainbow of KIBOU study-Breast (ROK Study-B) in 2007. As of February 2018, more than 6300 women have been enrolled, thus making this one of the world's largest cancer patient cohort studies. Based on the know-how obtained from this study, we started another new cohort study for colorectal cancer patient (ROK Study-C). METHODS: The ROK Study-C is a prospective observational study for colorectal cancer survivors at the National Cancer Center Hospital. Participants fill in several self-administrated questionnaires about lifestyle, psychosocial factors (including posttraumatic growth and benefit finding, support), and quality of life (QOL) 5 times in total: at diagnosis, 3 and 6 months, 1 and 5 years after surgery. CT-scans will be collected to assess body composition and obesity. We also use blood and cancer tissue from the Biobank. The primary endpoint is disease-free survival. The secondary endpoints are overall survival and health-related QOL. The planned sample size is 2000 and the follow-up period is 5 years after the last enrollment. DISCUSSION: Recruitment began in December 2015 and the study is still ongoing. The ROK Study-C will contribute to improvements in patient prognosis and yield important evidence for colorectal cancer survivorship.

Intersphincteric Resection Has Similar Long-term Oncologic Outcomes Compared With Abdominoperineal Resection for Low Rectal Cancer Without Preoperative Therapy: Results of Propensity Score Analyses.

BACKGROUND: Intersphincteric resection has been performed for very low rectal cancer in place of abdominoperineal resection to avoid permanent colostomy. OBJECTIVE: This study aimed to evaluate long-term oncologic outcomes of intersphincteric resection compared with abdominoperineal resection. DESIGN: In this retrospective study, propensity score matching and stratification analyses were performed to reduce the effects of confounding factors between groups, including age, sex, BMI, CEA value, tumor height, tumor depth, lymph node enlargement, and circumferential resection margin measured by MRI. SETTING: A database maintained at our institute was used to identify patients during the period between 2000 and 2014. PATIENTS: A total of 285 patients who underwent curative intersphincteric resection (n = 112) or abdominoperineal resection (n = 173) for stage I to III low rectal cancer without preoperative chemoradiotherapy were enrolled in this study. MAIN OUTCOME MEASURE: The main outcome was recurrence-free survival. RESULTS: Patients in the abdominoperineal resection group were more likely to have a preoperative diagnosis of advanced cancer before case matching. After case matching, clinical outcomes were similar between intersphincteric resection and abdominoperineal resection groups. Five-year relapse-free survival rates were 69.9% for the intersphincteric resection group and 67.9% for abdominoperineal resection group (p = 0.64), and were similar in the propensity score-matched cohorts (89 matched pairs). Three-year cumulative local recurrence rates were 7.3% for intersphincteric resection and 3.9% for abdominoperineal resection (p = 0.13). In the propensity score-matched model, the hazard ratio for recurrence after intersphincteric resection in comparison with abdominoperineal resection was 0.90. Stratification analysis revealed similar recurrence rates (HR, 0.75-1.68) for intersphincteric resection in comparison with abdominoperineal resection. LIMITATION: Eight covariates were incorporated into the model, but other covariates were not included. CONCLUSIONS: Our findings suggest similar oncologic outcomes for intersphincteric resection and abdominoperineal resection without preoperative chemoradiotherapy in patients with low rectal cancer adjusted for background variables. See Video Abstract at http://links.lww.com/DCR/A661.

Long-term survival with extended lateral lymphadenectomy for lateral lymph node recurrence after laparoscopic abdominoperineal resection for rectal adenosquamous carcinoma: a case report.

The patient was a 54-year-old female who presented with the chief complaint of melena. Lower gastrointestinal endoscopy detected a type 1 tumor extending from the anal canal to the rectum. CT did not detect any distant metastasis. Proximal D3 lymphadenectomy with laparoscopic abdominoperineal resection was performed for stage IA rectal cancer. In the histopathological examination, the tumor was identified as stage IIIa adenosquamous carcinoma. Although the patient underwent postoperative adjuvant chemotherapy with S-1, a recurrent left lateral lymph node tumor was detected on CT and PET 12 months later. The patient underwent the treatment with mFOLFOX + bevacizumab for 6 months. However, the tumor continued to progress, and therefore, extended lateral lymphadenectomy was performed 21 months after the first surgery. The patient did not undergo postoperative adjuvant therapy and is alive without recurrence 90 months after the first surgery and 70 months after the reoperation. Adenosquamous carcinoma of the rectum is a rare histological type of colorectal cancer for which there is no effective treatment besides surgical resection, and its prognosis is known to be worse than that of adenocarcinoma. Since there has been no report of long-term survival after extended lateral lymphadenectomy for recurrent lateral lymph node tumors following surgery for adenosquamous carcinoma of the rectum, herein, we report the case with a review of the literature.

Long-term outcomes of laparoscopic versus open D3 dissection for stage II/III colon cancer: Results of propensity score analyses.

BACKGROUND: Non-inferiority of the laparoscopic approach for stage II/III colon cancer has not been clearly established. This study aimed to evaluate the long-term outcomes of laparoscopic versus open D3 surgery. METHODS: Subjects were 1230 consecutive patients with stage II/III colon cancer, who were referred to the National Cancer Center Hospital from 2004 to 2013. Open surgery was performed in 821 (67%) patients, and laparoscopic surgery was performed in 409 (33%). Propensity score analyses with overall survival as the primary endpoint were performed in three different propensity score methods. RESULTS: Regression adjustment using the propensity score as a linear predictor in the model showed similar overall survival between laparoscopic and open surgeries [hazard ratio (HR), 0.98 (95% CI [0.64-1.46]; p = 0.916)]. Stratification analysis of the entire cohort revealed that, among five strata, only the highest stratum (clinical T2/T3, clinical N0/N1, tumor size <6 cm, and body mass index (BMI) < 28) had an HR of <1 (0.37). In the other four strata, open surgery was favored as reflected by HRs of >1 (1.13-1.26). The propensity score-matched cohort (365 matched pairs), from which patients with advanced disease and high BMI were excluded, yielded an HR of 0.93 (95% CI [0.57-1.52]; p = 0.772). CONCLUSIONS: Laparoscopic surgery appeared to be a safe and reasonable option for patients with stage II/III colon cancer in general. Patients with high BMI, clinical N2 and T4 disease, and tumor size ≥6 cm might require prudent selection of surgical approach.