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.

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.

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.

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.

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.

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.

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 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.

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.

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.

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.

Treatment of advanced or recurrent colorectal cancer with irinotecan in Japan and elsewhere.

BACKGROUND: Dramatic prolongation of the survival of patients with advanced or recurrent colorectal cancer has been achieved by multi-drug chemotherapy using agents such as continuous 5-fluorouracil and leucovorin, irinotecan (CPT-11), L-OHP, bevacizumab and cetuximab. OBJECTIVE: To explain the background of CPT-11 and to discuss its role in the treatment of advanced or recurrent colorectal cancer in Japan and elsewhere together with the authors' own experience.

Surgical resection of stage IV colorectal cancer and prognosis.

BACKGROUND: Colorectal cancer (CRC) harbors accumulated genetic alterations with cancer progression, which results in uncontrollable disease. To regulate the most malignant CRC, we have to know the most dismal phenotype of stage IV disease. METHODS: A retrospective review of the Kitasato University Hospital was performed (from 1990 to 2001) to extract the 162 resected stage IV CRC. Clinical variables were tested for their relationship to survival in a multivariate prognostic analysis and revealed the interaction of the prognostic factors. RESULTS: In stage IV CRC with noncurable resection, the most robust univariate predictors for poor prognosis were preoperative high value of CA19-9, peritoneal dissemination, depth of invasion, age, extent of liver metastases, pathologic lymph node metastasis status, and gender as tumor factors, and postoperative therapy, perioperative transfusion, and lymph node dissection extent as treatment factors. Among these factors, postoperative therapy (p < 0.0001), perioperative transfusion (0.0002), CA19-9 (0.001), extent of liver metastases (0.004), and peritoneal dissemination (0.02) were identified as independent prognostic factors by multivariate analysis. Interestingly, among the independent prognostic factors, treatment factors did not depend upon tumor factors and the combination of the three tumor factors (CA19-9, extent of liver metastases, and peritoneal dissemination) can clearly classify the patients into the definite prognostic groups. CONCLUSION: Our results suggested that the most dismal CRC harbors three definite vectors that may represent the strongest phenotype of putative systemic immune (CA19-9), distant metastasis (extent of liver metastases), and local progression (peritoneal dissemination).

[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.

Gastrointestinal stromal tumor of the rectum resected by laparoscopic surgery: report of a case.

A 53-year-old man visited our hospital with the chief complaint of pain on urination. On digital rectal examination, a rigid immobile tumor mass with a smooth surface was palpated on the anterior wall on the right side of the rectum near the anal canal. Computed tomography (CT) and magnetic resonance imaging (MRI) of the pelvis revealed a heterogeneous tumor mass measuring 6.5 cm in diameter, which occupied the cavity of the lesser pelvis. This rectal tumor was diagnosed to be a gastrointestinal stromal tumor (GIST) based on the results of a transrectal needle biopsy. A laparoscopic abdominoperineal resection of the rectum was performed to remove the mass. The intraoperative findings showed an ambiguous boundary between the tumor and the rectum but clear boundaries between the tumor and the peripheral organs, and the use of a laparoscope allowed for a good separation by providing a good visual field. The bleeding volume was approximately 80 ml and the operative time was 320 min. The macroscopic findings of excised specimens of the mass showed the tumor, measuring 6.5 x 5.5 x 5.0 cm, to be growing extrinsically from the anterior wall on the right side of the rectum. A histological examination of the excised specimens revealed at most 5 mitoses per 50 high-power fields (x 400). The tumor mass was diagnosed to be a GIST of low-grade malignancy based on these findings. The postoperative course was favorable, and there were no postoperative complications. The patient was discharged on the 8th hospital day. Laparoscopic surgery is a minimally invasive surgical procedure for rectal GIST, which is excellent in terms of esthetics. Laparoscopic surgery is therefore considered to be useful for a resection of the rectum, because the magnifying effect allows surgical maneuvers with a favorable visual field within the pelvis.

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.

[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.