Systemic Immune-Inflammation Index Predicts Tumor Recurrence after Radical Resection for Colorectal Cancer.

The systemic inflammatory response is associated with tumor promotion and suppression. Accumulating evidence shows that peripheral blood markers of inflammatory response predict clinical outcomes in various human cancers. The aim of this study was to investigate the prognostic relevance of the inflammation-based biomarkers in colorectal cancer (CRC). We retrospectively analyzed 118 CRC patients who underwent curative resection between 2012 and 2017. The inflammation-based biomarkers were evaluated by using preoperative neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), prognostic nutritional index (PNI), and Glasgow prognostic score (GPS). Prognostic values were assessed by the Kaplan-Meier analysis for cancer-specific recurrence-free survival (RFS) and Cox proportional-hazards model. There were significant differences in the levels of NLR, PLR, SII, and SIRI between recurrence and non-recurrence group. The area under the curve (AUC) for SII was 0.710, which showed the highest value in the inflammation-based biomarkers. Multivariate analysis identified that SII (p = 0.0031) and lymph node metastasis (p = 0.0168) were independent prognostic factors for recurrence. High SII exhibited more dismal RFS than low SII in CRC patients with non-metastatic lymph node (p = 0.0002). Our study suggests that SII and lymph node metastasis could be useful indicators in predicting the recurrence of CRC patients. Additionally, SII could accurately stratify CRC patients with tumor recurrence by combining with lymph node metastasis. This result would be beneficial for determining the optimal therapeutic strategies after surgical resection for CRC.

Genetic alterations of K-ras may reflect prognosis in stage III colon cancer patients below 60 years of age.

PURPOSE: Genetic alterations that are closely associated with patient prognosis can be landmarks of definitive therapeutic targets as well as useful biomarkers in human cancer clinics. METHODS: Three hundred seventy-eight colorectal cancer (CRC) patients were examined for K-ras mutations by single-strand conformation polymorphism (SSCP), with a subsequent 144 young colon cancer (YCC) patients added to validate its prognostic significance. RESULTS: K-ras mutations were identified in 161 (43%) of the 378 CRC patients and were significantly associated with tumor location (colon vs. rectum; 80/218 = 37% vs. 81/160 = 51%; P = 0.0068) and age (≥60 vs. <60; 103/220 = 47% vs. 58/158 = 37%; P = 0.049). The incidence of K-ras mutations was 30% in YCC patients as compared to 55% in elderly rectal cancer patients (P = 0.0004). K-ras mutations significantly correlated with a worse prognosis (P = 0.0014) only in 73 curatively resected YCC with stages I-III, but not in other CRCs, which was further validated in the independent set of the corresponding 144 YCC patients (P = 0.024). Both univariate and multivariate analyses identified K-ras mutations as an independent prognostic factor (HR = 5.5, P = 0.029; HR = 3.6, P = 0.011) in both learning and validation sets of the curatively resected YCC with stages I-III, respectively, and the prognostic relevance was marked in stage III YCC patients (P = 0.002), but not in stages I, II, and IV. CONCLUSION: In curative YCC, K-ras mutations could have excellent prognostic value. Hence, the K-ras mutation status could be a good indicator to predict the clinical outcome in curatively resected stage III YCC patients, and K-ras pathway inhibition may be a relevant therapeutic target in CRC, excluding YCC patients with no K-ras mutation.

Successful laparoscopic resection of a sacrococcygeal teratoma in an adult: report of a case.

Sacrococcygeal teratoma is a relatively rare congenital retroperitoneal tumor in adults. The standard treatment is a complete tumor resection. This report describes the successful laparoscopic resection of a sacrococcygeal teratoma. The patient was a 27-year-old woman with a well-demarcated cystic mass, 6 cm in diameter, in the retroperitoneum overlying the anterior surface of the sacrum. The mass was resected laparoscopically. A histopathological examination showed a mature teratoma. The magnifying function of the laparoscope allowed an en bloc resection in the narrow pelvic cavity, without damaging the tumor. The aesthetic outcome was excellent. The patient remains relapse-free at 1 year 6 months after surgery.

Fiber-based, hybrid terahertz spectrometer using dual fiber combs.

We constructed a fiber-based, hybrid terahertz (THz) spectrometer having two working modes, asynchronous-optical-sampling THz time-domain spectroscopy (AOS-THz-TDS) and multiple-frequency-heterodyning THz comb spectroscopy (MFH-THz-CS), by use of dual fiber-laser-based frequency combs. A spectral range of 2THz and dynamic range of 100 was achieved at the single sweep measurement of 200ms in the AOS-THz-TDS mode, whereas the detailed structure of the THz frequency comb was clearly observed in the MFH-THz-CS mode. The spectrometer features compactness, robustness, flexibility, and cost effectiveness, in addition to high spectral resolution in rapid data acquisition, and has the potential to become a powerful tool for practical applications.

Real-time monitoring of continuous-wave terahertz radiation using a fiber-based, terahertz-comb-referenced spectrum analyzer.

We propose a fiber-based, terahertz-comb-referenced spectrum analyzer which has the advantages of being a portable, alignment-free, robust, and flexible apparatus suitable for practical use. To this end, we constructed a 1550-nm mode-locked Er-doped fiber laser whose mode-locked frequency was stabilized precisely by referring to a rubidium frequency standard, and used it to generate a highly stable terahertz (THz) frequency comb in a photoconductive antenna or an electro-optic crystal. By standardizing the THz comb, we determined the frequency accuracy of an active-frequency-multiplier-chain (AFMC) source to be 2.4 x 10(-11). Furthermore, the potential of the THz spectrum analyzer was effectively demonstrated by real-time monitoring of the spectral behavior of the AFMC source and a photomixing source of two free-running CW lasers at adjacent wavelengths.

Analysis of the risk factors for wound infection after surgical treatment of colorectal cancer: a matched case control study.

BACKGROUND/AIMS: The present study, with a matched case-control study design, was undertaken to evaluate the usefulness of high-pressure washing for preventing postoperative wound infection by comparing the outcomes in cases in which the high-pressure washing was performed with those in which the procedure was not adopted. METHODOLOGY: A total of 100 of the above-mentioned 264 patients were selected for this study and divided into two groups (the high- pressure washing group (n=50) and the non-high pressure washing group (n=50)) in such as manner as to obtain good matching of the following 6 parameters between the two groups. RESULTS: Postoperative wound infection was noted in 11% of all cases (11/100). Univariate analysis revealed that postoperative wound infection was significantly more frequent in cases where the tumor site was the rectum (p = 0.011), the surgical approach was open abdominal surgery (p = 0.032) and high- pressure washing of the wound was not adopted (p = 0.021). CONCLUSION: The results of this study suggest that in order to prevent wound infection after surgery for colorectal cancer, it is advisable to select, as far as possible, the laparoscopic surgical approach and to undertake high- pressure washing of the wound immediately before closure of the abdomen.

Retrospective, matched case-control study comparing the oncologic outcomes between laparoscopic surgery and open surgery in patients with right-sided colon cancer.

PURPOSE: The short- and long-term outcomes of laparoscopic surgery for right-sided colon cancer remain largely uninvestigated. This study was undertaken to compare the morbidity and mortality after either a laparoscopic right hemicolectomy (LRHC) or an open right hemicolectomy (ORHC) for this type of tumor. METHODS: The study group included 100 patients who underwent an LRHC and 100 patients who underwent an ORHC for right-sided colon cancer from 1990 through 2004. The two groups were retrospectively well matched with respect to sex, age (+/-5 years), and pathological tumor-node-metastasis (TNM) stage. RESULTS: The median follow-up period was 83 months in the LRHC group and 105 months in the ORHC group. The LRHC group had a lower volume of intraoperative bleeding (P < 0.001), a lower rate of wound infection (P = 0.019) or postoperative intestinal obstruction (P = 0.013), and a shorter hospital stay (P < 0.001) than the ORHC group. The rate of recurrence did not differ significantly between the LRHC group (19%) and the ORHC group (22%). In patients with TNM stage I or II, the disease-free survival (DFS) rate (94.9% vs 95.1%) and overall survival (OS) rate (95.8% vs 95.0%) did not differ significantly between the two groups. A similar tendency was observed in patients with stage III with the rates for DFS (71.3% vs 60.4%) and OS (73.6% vs 64.1%), respectively. CONCLUSIONS: An LRHC for right-sided colon cancer has the advantage over an ORHC of better short-term outcomes, and both groups have similar long-term oncologic outcomes. An LRHC is thus an acceptable alternative to an ORHC for the treatment of this type cancer.

Real-time terahertz color scanner for moving objects.

Terahertz time-domain spectroscopic (THz-TDS) imaging is an interesting new tool for nondestructive testing and other applications. However, the current speed of image acquisition is relatively low, making it difficult to use for moving objects. In this paper, we propose a real-time THz-TDS line scanner based on electro-optical time-to-space conversion and line focusing of a THz beam. The proposed system functions as a color scanner in the terahertz spectral region with fast line-scanning and has been successfully used to image objects, which are moved on a translation stage. The achieved THz-TDS imaging rate is 23,200 pixels per second. This proposed THz-TDS line scanner has the potential to become a powerful tool for monitoring moving objects in various real-world applications.

Liver metastasis of colorectal cancer by protein-tyrosine phosphatase type 4A, 3 (PRL-3) is mediated through lymph node metastasis and elevated serum tumor markers such as CEA and CA19-9.

Phosphatase of regenerating liver (PRL)-3 was identified as a molecule associated with liver metastasis in colorectal cancer (CRC), although its precise causative role in distant metastasis remains elusive from a clinical point of view. The aim of this study was to promote the mechanistic insight of PRL-3 involvement in liver metastasis in CRC. One hundred and seven CRC patients with resection of the primary lesions were studied for clinicopathological and prognostic association with PRL-3 and were evaluated by immunohistochemistry in univariate and multivariate analyses. Intense immunostaining of PRL-3 was found in Dukes' A (0/26), Dukes' B (0/30), Dukes' C (18/30) and Duke's D (20/21) although the PRL-3 expression could not predict metachronous liver metastasis (MLM) in Dukes' C patients. PRL-3 expression showed an inverse correlation of prognosis in a univariate prognostic analysis (P<0.0001), though a multivariate assay failed to demonstrate PRL-3 relevance as an independent prognostic factor. PRL-3 expression was closely associated with classic prognostic factors such as the pN factor (P<0.0001), H factor-synchronous liver metastasis (SLM) (P<0.0001), pT factor (P=0.0002), preoperative CEA (P<0.0001) and preoperative CA19-9 (P<0.0001). Multivariate logistic regression analysis of PRL-3 expression revealed that the pN factor (P<0.0001), CEA (P<0.0001) and CA19-9 (P<0.0001) were finally remnant as an independent association with PRL-3. However, the H factor (SLM) was eliminated. Our data suggested that liver metastasis by PRL-3 is putatively mediated through lymph node metastasis and elevated tumor markers in the serum and the PRL-3 expression may not represent a direct causative mechanism of liver metastasis.

Diminishing impact of preoperative carcinoembryonic antigen (CEA) in prognosis of Dukes' C colorectal cancer.

BACKGROUND: In curable colorectal cancer (CRC), preoperative serum carcinoembryonic antigen (CEA) (preCEA) has been reported to have predictive prognostic value. However, data remains insufficient to support its clinical use. The aim of the current study was to validate the prognostic impact of preCEA in Dukes' C CRC. PATIENTS AND METHODS: The prognostic significance of preCEA for 237 Dukes' C CRC patients assessed retrospectively (between 1990 and 2000: previous cases) and the prospective relevance for 197 counterparts (between 2001 and 2004: recent cases) according to preCEA, were both examined. RESULTS: The previous cases showed the most potent impact of preCEA as an independent prognostic factor (hazard ratio=2.0, p=0.003) among the clinicopathological factors using a multivariate proportional hazard model, while the recent cases did not even show a univariate prognostic impact. A significant difference in the prognosis between the two periods was only found in the patients with elevated preCEA administered adjuvant chemotherapy (ADT) (p=0.03). Between the two terms, a dramatic change of ADT regimens from 5FU alone (p<0.001) to 5FU in combination with leucovorin (p<0.001) and/or irinotecan (p-0.0009/0.005) was introduced, and N2 patient survival was dramatically improved. However, a significant prognostic difference for the elevated preCEA patients with ADT could not be demonstrated by sub-analysis of N1 and N2 disease due to diminished correlation of preCEA and the N factor (p=0.02 to 0.5), indicating that preCEA did not predict chemosensitivity. CONCLUSION: The preCEA is no longer useful in predicting prognosis with Dukes' C CRC patients, because of the loss of preCEA association with the N factor, putatively through undefined diagnostic or therapeutic advancement.

Irinotecan and S-1 neoadjuvant chemoradiation therapy in patients with advanced rectal cancer.

We performed preoperative chemoradiotherapy in locally advanced cases of rectal cancer without distant metastasis. The methods for drug administration and irradiation were as follows: oral administration of S-1 at 80 mg/m2/day on days 1-5, 8-12, 22-26, and 29-33, with periods of 5 days on drug and 2 days off drug and intravascular administration of CPT-11 for 120 minutes on days 1, 8, 22, and 29, at doses of 60 mg/m2/day in Case 1 and 70 mg/m2/day in Case 2. The radiation dosage was a fractionated exposure of 1.8 Gy/day x 5 days/week for 5 weeks, for a total of 45 Gy. No major adverse events were observed in either case, and the treatment was performed as per the protocol. No postoperative complications were observed in either case. Both patients showed complete pathological remission with no evidence of tumor cells in the primary focus and no lymph node metastases. Preoperative chemoradiotherapy with a combination of S-1 and CPT-11 may be a new treatment for rectal cancer.

[Neoadjuvant chemoradiation therapy for locally advanced rectal cancer].

Not only the improvement of overall survival, but also the control of local recurrence, a unique type of recurrence, is an important issue in the treatment of advanced local rectal cancer. Total mesorectal excision is internationally accepted to be a standard procedure that lowers the rate of local recurrence. In 1999, the National Institutes of Health in the United States recommended "resection plus postoperative chemoradiotherapy" as the standard treatment for pathological stage II and III rectal cancer. In Japan, however, few large clinical trials of adjuvant radiotherapy have been performed because the rate of local recurrence in patients undergoing surgery alone is lower than that in Western countries. Multicenter, randomized, controlled studies with total mesorectal excision as a control are ongoing in Japan, and the results are awaited. We describe the current status of adjuvant chemoradiotherapy for advanced local rectal cancer in Japan and other countries, along with a review of the literature.

[Outpatient chemotherapy of an advanced or metastatic colorectal cancer].

We report the outpatient chemotherapy of an advanced or metastatic colorectal cancer. From April 2005 to May 2006, 50 patients were treated with FOLFIRI or FOLFOX in our hospital. Forty five patients (90%) had an intravenous catheter and a port for the chemotherapy, 23 patients (46%) were treated at the outpatient booths. We used the clinical pathway in chemotherapy for patients and co-medical roles. We were not experiencing emergency admission of side effects. Outpatient chemotherapy utilizing FOLFIRI or FOLFOX for advanced or metastatic colorectal cancer can be enforced safely by using the clinical pathway.

Venous invasion and down-regulation of p21(WAF1/CIP1) are associated with metastasis in colorectal carcinomas.

BACKGROUND/AIMS: Liver and lymph node metastasis the major prognostic factor in patients with colorectal carcinoma. The aim of this work was to search for tumor parameters which can be employed to predict whether this has occurred. METHODOLOGY: A total of 211 patients with a colorectal carcinoma (Dukes' B group, 83; Dukes' C, 94; Dukes' D, 34) were investigated for 10 clinicopathological variables, as well as apoptotic activity, expression of Ki-67, p21(WAF1/CIP1), p53, bcl-2 and DCC proteins, and the c-Ki-ras mutations. Data were analyzed by univariate and multivariate statistics. RESULTS: Lymph node metastasis-predictive models were developed using the venous involvement index (the number of vascular involvements per elastica van Gieson-stained slide; Odds ratio [OR], 2.38; 95% confidence interval [CI], 1.52-3.71; p=0.0001), tumor size (OR, 0.82; 95% CI, 0.70-0.97; p=0.0179), and p21(WAF1/CIP1) immunolabeled index (the percentages of positive tumor cells; OR, 0.76; 95% CI, 0.64-0.90; p=0.0011). Liver metastasis-predictive models were developed using the venous involvement index (OR, 2.40; 95% CI, 1.71-3.37; p=0.0000) and tumor location (rectum vs. colon; OR, 9.31; 95% CI, 2.41-36.01; p=0.0012). CONCLUSIONS: Down-regulation of p21(WAF1/CIP1) as well as marked venous involvement, small tumor size and colonic tumor are associated with lymph node and/or liver metastasis. Criteria for assessment of metastasis risk provide a basis for additional treatment guidelines.

Clinicopathologic differences among subtypes of serrated adenomas of the colorectum.

BACKGROUND/AIMS: Serrated adenomas (SAs) of the colorectum can be broadly divided into two subtypes: type I more closely mimicking hyperplastic polyps, and type II unequivocal traditional adenomas. The aim of this study was to clarify their differential clinicopathologic and colonoscopic features. METHODOLOGY: A total of 127 SAs (53 type I, 52 type II and 22 admixed type I+II) were investigated and colonoscopic surface patterns were divided into three categories: speckled, granular and cerebriform. RESULTS: The cerebriform pattern was most frequently observed in all SA types. Types I+II (median size, 7.5 mm) or type II SAs (median size, 10 mm) were generally sessile or pedunculated polyps in the rectosigmoid colon whereas some type I lesions (median size, 5 mm) demonstrated a flat-elevated morphology and were found in the ascending colon and cecum. Co-existing (2/127: 1.6%) invasive carcinomas were only detected with type II SAs. In contrast, synchronous invasive carcinomas distant from SAs were more frequently observed with type I (31%) than types I+II (5%) or II (12%). CONCLUSIONS: Clinicopathologic differences are apparent among the types of SAs. A type II SA-invasive carcinoma sequence might exist. We stress recognition of type I SA as a neoplastic, rather than a hyperplastic lesion, often accompanying invasive carcinomas at a distance from the SA.

[Colorectal cancer].

The current status of laparoscopic surgery for colorectal cancer is herein described. After cholecystectomy, laparoscopic colorectomy, minimally invasive surgery for an infection of the rectum, prepares a patient for endoscopic surgery. Opinion is still divided on the procedure, but it is likely to be recognized as a standard operation at least for early cancer. In recent years, randomized controlled trials have been compared to laparoscopic surgery and open surgery, and the results were almost the same. However, it will be possible for laparoscopic surgery to be performed on advanced cancer patients regularly hereafter. Thus, it is important to consider the technical background evidence and suitable cases.

Different apoptotic activity and p21(WAF1/CIP1), but not p27(Kip1), expression in serrated adenomas as compared with traditional adenomas and hyperplastic polyps of the colorectum.

PURPOSE: Serrated adenomas (SAs), which include a wide spectrum of lesions, can be broadly divided into two subtypes: type I, closely mimicking hyperplastic polyps (HPs), and type II, unequivocal adenomatous tumor. Our preliminary findings showed clinicopathologic differences between them. The present study was conducted to investigate apoptotic activity and expression of the cell cycle regulator proteins p21(WAF1/CIP1) and p27(Kip1) in type I and II SAs, as compared with traditional adenomas (TAs) and HPs. METHODS: Apoptotic activity was estimated in hematoxylin-eosin stained specimens, and p21(WAF1/CIP1) or p27(Kip1) immunoreactivity was determined in 62 SAs (19 type I and 43 type II), 50 TAs and 19 HPs. The numbers (percentages) of apoptotic or immunoreactive cells were counted per 1,000 epithelial cells in equally separated crypt zones (upper, middle, and lower thirds). RESULTS: The apoptotic activity in the middle, but not the upper or lower crypt zone was higher in type II SAs (median 0.2%, interquartile range 0.1-0.5%) than in HPs (0.1%, 0.1-0.2%, P<0.01), whereas it was lower in type I SAs (0.2%, 0.1-0.3%) than in TAs (0.5%, 0.2-0.6%, P<0.001). P21(WAF1/CIP1) expression in the lower crypt zone was higher in both type I and type II SAs (19.8%, 7.0-33.2% and 20.4%, 3.9-47.8%, P<0.0001) than in TAs (1.2%, 0.6-5.2%), and a similar tendency was also observed for the middle crypt zone. p27(Kip1) expression did not vary among the groups. CONCLUSIONS: The differences in apoptotic activity and p21(WAF1/CIP1) expression between SAs and TAs or HPs indicate that SA should be considered as a distinct subtype of colorectal neoplasm. The two subtypes of SA do not differ in these parameters despite specific clinicopathological features.

Late-Onset Bowel Strangulation due to Reduction En Masse of Inguinal Hernia.

Incarcerated inguinal hernia is often encountered by surgeons in daily practice. Although rare, hernial reduction en masse is a potential complication of manual reduction of an incarcerated hernia. Manual reduction was performed in a case of Zollinger classification type VII (combined type) hernia in which the indirect hernia portion included an incarcerated small intestine. This procedure caused hernial reduction en masse, but this went unnoticed, and the remaining portion of the direct hernia in the inguinal region was treated surgically by the anterior approach. Because the incarcerated small bowel that had been reduced en masse was not completely obstructed, the patient's general condition was not greatly affected, and he was able to resume eating. Twenty days after surgery, he developed sudden abdominal pain as a result of gastrointestinal perforation. When performing manual reduction of an incarcerated hernia in cases after self-reduction over a long period, the clinician should always be aware of the possibility of reduction en masse.

A Phase II trial of neoadjuvant preoperative chemoradiotherapy with S-1 plus irinotecan and radiation in patients with locally advanced rectal cancer: clinical feasibility and response rate.

PURPOSE: We aimed to validate our hypothesis that a preoperative chemoradiotherapy regimen with S-1 plus irinotecan is feasible, safe, and active for the management of locally advanced rectal cancer in a single-arm Phase II setting. METHODS AND MATERIALS: Eligible patients had previously untreated, locally advanced rectal adenocarcinoma. Radiotherapy was administered in fractions of 1.8 Gy/d for 25 days. S-1 was administered orally in a fixed daily dose of 80 mg/m2 on Days 1 to 5, 8 to 12, 22 to 26, and 29 to 33. Irinotecan (80 mg/m2) was infused on Days 1, 8, 22, and 29. Four or more weeks after the completion of the treatment, total mesorectal excision with lateral lymph node dissection was performed. The primary endpoint was the rate of completing treatment in terms of feasibility. The secondary endpoints were the response rate and safety. RESULTS: We enrolled 43 men and 24 women in the study. The number of patients who completed treatment was 58 (86.6%). Overall, 46 patients (68.7%) responded to treatment and 24 (34.7%) had a complete histopathologic response. Three patients had Grade 3 leukopenia, and another three patients had Grade 3 neutropenia. Diarrhea was the most common type of nonhematologic toxicity: 3 patients had Grade 3 diarrhea. CONCLUSIONS: A preoperative regimen of S-1, irinotecan, and radiotherapy to the rectum was feasible, and it appeared safe and effective in this nonrandomized Phase II setting. It exhibited a low incidence of adverse events, a high rate of completion of treatment, and an extremely high rate of pathologic complete response.

Risk factors for wound infection after surgery for colorectal cancer.

BACKGROUND: Among complications after surgery for colorectal cancer, wound infections may prolong hospitalization and increase healthcare costs. This study was designed to clarify the incidence, risk factors, and pathogens responsible for wound infections after surgery for colorectal cancer. METHODS: The study group comprised 144 patients (94 men and 50 women) with colorectal cancer in whom the same surgeon at Kitasato University Hospital performed resection from January 2004 through December 2005. Their mean age was 67.1 years (range = 38-90). To identify risk factors for surgical wound infections, we examined the following 11 variables: gender, age (>65 vs. 25 vs. 180 vs. 120 vs.