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Mycobacterium avium subsp. paratuberculosis (MAP) causes a chronic inflammatory intestinal disease, called Johne's disease (JD) in many ruminants. In the dairy industry, JD is responsible for significant economic losses due to decreased milk production and premature culling of infected animals. Test-and-cull strategy in conjunction with risk management is currently recommended for JD control in dairy herds. However, current diagnostic tests are labor-intensive, time-consuming, and/or too difficult to operate on site. In this study, we developed a new method for the detection of anti- M. paratuberculosis antibodies from sera of M. paratuberculosis- infected animals. M. paratuberculosis antigen-coated magnetic beads were sequentially reacted with bovine serum followed by a horseradish peroxidase (HRP)-labeled secondary antibody. The reaction of HRP with its substrate was then quantitatively measured electrochemically using a redox-active probe, ferrocyanide. After optimization of electrochemical conditions and concentration of the redox-active probe, we showed that the new electrochemical detection method could distinguish samples of M. paratuberculosis- infected cattle from those of uninfected cattle with greater separation between the two groups of samples when compared with a conventional colorimetric testing method. Since electrochemical detection can be conducted with an inexpensive, battery-operated portable device, this new method may form a basis for the development of an on-site diagnostic system for JD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Hatate, Rice, Parker, Wu, Turner, Stabel and Eda.)

This study investigated consecutive fluctuations in serum activities of bone-specific alkaline phosphatase (ALP) isoenzyme 3 (ALP3) in 11 clinically healthy Holstein heifers during the first 18 months of life. ALP3 activities at the first sampling time point after weaning (3 months) were significantly lower than those at multiple time points during the pre-weaning period. Those activities increased from a minimum at 3 months to a peak at 6 months during the post-weaning period. In the anthropometric data, daily body weight and wither height gains appeared to be below the public data at 4 months and 4-5 months, respectively. The data suggested that serum ALP3 activity can be used to monitor skeletal growth of heifers at weaning.

This study investigated changes in serum levels of hepatic, bone, and intestinal alkaline phosphatase (ALP) isoenzymes (ALP2, ALP3, and ALP5, respectively) in Holstein cows around parturition. Tartrate-resistant acid phosphatase 5b (TRAP5b) activity and calcium (Ca) concen-trations were also measured. We analyzed blood samples from 11 late-pregnant heifers (primipa-rous group) and 13 multiparous (2-4 lactations; multiparous group) cows at 3 weeks (18-24 days prepartum; -3 weeks), 2 weeks (17-11 days prepartum; -2 weeks), and 1 week (10-4 days prepar-tum; -1 weeks) before parturition; the day of calving (within 12 h post-calving; day 0); and 5 days postpartum (5 days). ALP3 activity was significantly higher in the primiparous group than in the multiparous group, whereas the activities decreased significantly in both groups after 5 days. ALP2 and ALP5 activities did not change, whereas ALP2 activity was significantly higher in the primiparous group than in the multiparous group. TRAP5b activity was significantly higher in the primiparous group than in the multiparous group and showed a transient significant increase at day 0. Ca concentration significantly decreased at day 0 in both groups; the Ca level at day 0 was significantly higher in the primiparous group than in the multiparous group. These data show that ALP3 activity in serum may indicate a change in osteoblastic bone forma-tion after calving, but further study is needed to determine the clinical application for measuring ALP isoenzymes in bovine medicine., (Copyright© by the Polish Academy of Sciences.)

Osteoprotegerin (OPG) inhibits osteoclast (OC) differentiation. TRAP5b (tartrate-resistant acid phosphatase 5b) secreted by OCs reflects the numbers of mature OCs. This study assessed these OC-related markers around parturition in cows of different parities and in cows with milk fever (MF). The blood OPG and TRAP5b concentrations, as well as the ratio of OPG to TRAP5b (O/T), were measured beginning 3 weeks before (-21 d) and over a few days after calving in 49 Holstein Friesian cows at first (n = 8), second (n = 17), third (n = 12), and fourth or greater (n = 12) parities. The ratio of O/T at -21 d to O/T at calving (PreCOT) was also calculated. In the third and greater parities, seven cows developed MF (non-MF, n = 17). Regardless of the development of MF, the serum OPG started to decline in the last week of gestation only in the cows entering the second lactation, while the blood TRAP5b increased at calving in all cows. O/T decreased toward parturition only in multiparous cows. The decrease in O/T at caving was less pronounced in MF cows. PreCOT was negatively correlated with lactation number only in multiparous cows (n = 41, ρ = -0.50, P < .01). This study implied that OC differentiation toward calving was tapered in cows with advanced parities, and these indexes predict the risk of MF., Competing Interests: Declaration of Competing Interest The authors declare no conflicts on interests., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The anthropometric and blood data of an unsuccessfully hand-reared Asian elephant (Elephas maximus) calf were retrospectively compared with the data for calves raised by their real mothers or allomothers, to identify potential reasons for poor outcomes in the hand-reared case. The hand-reared calf grew normally in terms of body weight and withers height. However, blood biochemical data suggested reduced bone metabolism, low immune status, and malnutrition during its life. Blood bone markers were measured to determine whether a skeletal disorder was present in the Asian elephant calf, which was not clear from the anthropometric data. Monitoring these parameters in hand-reared Asian elephant calves, with the aim of keeping them within the normal range, may increase the success rate of hand-rearing of Asian elephant calves.

A recent study found that an agarose gel electrophoresis (AGE) method yielded two distinct major bands corresponding to the hepatic and bone ALP isoenzymes (ALP2 and ALP3, respec-tively) in bovine serum treated with protease and neuraminidase (PN-treatment), although there were concerns that the intestinal ALP isoenzyme (ALP5) often overlapped with ALP3 in human serum treated with neuraminidase. Because ALP5 was separated from ALP3 in bovine serum treated with protease alone (P-treatment), we used a modified method employing both P- and PN-treated bovine sera to measure the activities of the three ALP isoenzymes in 53 lacta-ting Holstein cows: 24 primiparous and 29 multiparous. Upon electrophoresis, 51 of 53 samples (96.2%) subjected to P-treatment yielded a distinct fraction corresponding to ALP5, as did the control serum. All PN-treated sera yielded a definite ALP2 fraction. The ALP3 fraction was calculated as the remainder after excluding ALP2 and ALP5. The activities of total ALP (t-ALP) and ALP3 in primiparous cows were higher than those in multiparous cows (p ⟨ 0.001) at early-to-peak [10-110 days in milk (DIM)] and mid (111-220 DIM) lactation. In the multi-parous cows, the ALP3 activity at late lactation (221-477 DIM) was significantly higher than that at early-to-peak lactation. Thus, the modified AGE method described here is able to discrimi-nate three fractions of ALP isoenzymes in the sera of lactating cows. The AGE pattern of circu-lating ALP isoenzymes will contribute to the understanding of the physiological bone metabolism status in lactating cows., (Copyright© by the Polish Academy of Sciences.)

We measured the bone-specific alkaline phosphatase (ALP) isoenzyme activity in 67 plasma samples from 14 newborn Holstein calves using both a conventional method (featuring heat inactivation) and a commercial agarose gel electrophoresis (AGE) kit; the relevant isoenzymes were termed bone-specific ALP (BAP) and ALP isoenzyme 3 (ALP3). We explored whether the AGE kit afforded reliable data when used to analyze samples from Holstein calves. The blood was collected from the jugular vein of each calf immediately prior to the first colostrum feeding (pre-feeding), 20 and 40 h after pre-feeding, and on days 4 and 7; whereas three samples (from three calves) were not obtained. The total plasma ALP activity varied widely, exceeding the ranges of reference values. On electrophoresis, 52 of 67 plasma samples (77.6 %) clearly contained both ALP isoenzyme 2 and ALP3, as did control human serum. The total ALP activity of the 52 samples ranged from 166-1989 U/L (median: 1013 U/L), whereas the values for the other 15 samples (22.4%) exhibiting abnormal isoenzyme fractionation ranged from 1014-5118 U/L (median: 1780 U/L). In the 52 plasma samples exhibiting clearly separated isoenzymes, ALP3 and BAP activities were strongly positively correlated as revealed by Deming regression (y = 0.93x + 22.6, p⟨0.0001) and Bland-Altman analysis (ALP3/BAP activities limit of agreement: -5.1%). Thus, the AGE kit yields useful information on newborn calves, and can replace the conventional method when the total plasma ALP activity is less than approximately 1000 U/L., (Copyright© by the Polish Academy of Sciences.)

The aim of this study was to examine the treatment outcomes of tibial fracture using different configurations of transfixation pinning and casting (TPC) in eight cattle. After pins were inserted to stabilize the fracture site, cast material was placed from the level of the stifle to the hoof (full TPC) in six cases and from the stifle to the proximal metatarsus (partial TPC) in two cases. Five cattle (three full TPC and two partial TPC cases) underwent TPC removal 36-86 days after surgery and resumed productivity. The other three cattle which underwent full TPC suffered from irreversible orthopedic complications within 5 weeks of surgery, while a prolonged healing process was observed in the partial TPC cases. Although TPC is an effective method for treating bovine tibial fracture, full TPC may result in a guarded prognosis in some cattle. However, partial TPC can delay healing. Surgeons should choose the optimal TPC configuration while considering the various factors that affect the healing process.

The bone-specific alkaline phosphatase (ALP) isoenzyme activity was measured in 51 serum samples from four captive Asian elephants (Elephas maximus) using a conventional method with wheat germ lectin precipitation and a commercial agarose gel electrophoresis (AGE) kit; the isoenzymes were designated as bone-specific ALP (BAP) and ALP isoenzyme 3 (ALP3), respectively. This study examined the suitability of the AGE kit for analyzing blood biochemistry in Asian elephants. The serum ALP3 and BAP activities were strongly positively correlated and met the evaluation criteria for agreement using Bland-Altman analysis. The results indicate that the AGE kit can be used to examine the blood biochemistry in Asian elephants instead of the conventional method.

The aim of this study was to elucidate the bone metabolic status after taking colostrum in newborn calves. Fourteen neonatal calves were randomly allocated to two groups fed either unheated or heated (60°C, 30 min) colostrum three times on the first day (2 l every 10 hr; 6 l in total). Heat treatment on colostrum was to reduce the bone metabolic markers assumed as heat-sensitive. The concentrations of four bone metabolic markers (the enzymes from bone cells or the bone collagen fragments) and a bone protective protein, osteoprotegerin (OPG), were measured in the blood of calves during a week after the birth and in the colostrum. The colostral concentrations of four bone metabolic markers were reduced by heating. Then those circulatory markers peaked after colostrum intake in the calves fed unheated colostrum; whereas those fed heated colostrum did not show such changes. However, the plasma tartrate resistant acid phosphatase 5b (TRAP5b) activity was transiently increased after taking colostrum in both groups. Meanwhile, heating did not decrease colostral OPG and there was no significant rise in the serum OPG concentrations after the first colostrum intake in both groups. The study revealed that the blood concentrations of studied bone metabolic markers depended on those colostral values except for TRAP5b. Based on the plasma TRAP5b changes, accelerated formation of premature osteoclast cells may be induced by colostrum intake. Meanwhile, colostral OPG absorption is less likely to impact on its circulating levels.

The aim of the present study was to examine the effect of 28 days of dietary difructose anhydride (DFA) III supplementation on calcium (Ca) metabolism in late-lactation dairy cows. Twenty-four multiparous pregnant Holstein cows were divided into two groups. The DFA group was fed total mixed ration (TMR) supplemented with 40 g of DFA III, and the control group was fed TMR only. The replenishment of bone Ca reserves was evaluated by measuring bone mineral density (BMD) and blood biochemical bone markers. Serum Ca concentrations, urinary Ca-to-creatinine (Cre) (Ca/Cre) ratios, and milk Ca concentrations were also analyzed. The BMD of the 4th caudal vertebra in the DFA group was higher than in the control group on day 28. With respect to bone markers, the ratios of undercarboxylated osteocalcin (ucOC) to osteocalcin (OC) in the DFA group were significantly lower than those in the control group on days 21 and 28. Milk Ca concentrations in the DFA group were also higher than those in the control group on days 14, 21, and 28, whereas serum Ca concentrations and urinary Ca/Cre ratios were unchanged in both groups. These results suggest that dietary supplementation with DFA III increased BMD and decreased serum ucOC/OC ratios in late-lactation dairy cows; this indicates that the replenishment of bone Ca reserves may be enhanced by dietary DFA III supplementation.

Dairy cows experience hypocalcemia at the onset of lactation; however, the contribution of bone metabolism to circulating Ca concentrations during the periparturient period is not well understood. Osteoprotegerin (OPG) protects against loss of skeletal mass by regulating osteoclastogenesis. We previously reported that the bone resorption increased around parturition in dairy cows from the perspective of bone markers in blood. The aim of this study was to explore osteoclastic bone resorption in periparturient dairy cows by measuring changes in serum OPG concentrations around calving. The OPG concentrations were evaluated in primiparous (n = 9) and multiparous (n = 9) cows at 21 d precalving and over 5 d after calving. Based on mixed model analyses, the multiparous cows had a higher serum OPG concentration than primiparous cows at precalving and exhibited a significant decline in serum OPG and Ca concentrations after calving. In contrast to multiparous cows, primiparous cows did not exhibit these changes. Therefore, we hypothesized that multiparous cows preserve their bone mineral content during late pregnancy and activate the osteoclastic bone resorption after calving. Based on our serum OPG data, we identified the different periparturient osteoclastic bone resorption patterns in healthy primiparous and multiparous dairy cows., (Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

The blood biochemical analysis of bone markers could have a role in the early diagnosis of metabolic bone disease in animals; however, there is limited information on bone markers in captive Asian elephants (Elephas maximus). Serum samples from ten captive Asian elephants were obtained to clarify the relationship between age and the blood bone markers tartrate-resistant acid phosphatase isoform 5b (TRAP5b) and bone specific alkaline phosphatase (BALP). Serum TRAP5b and BALP activities were negatively correlated with age. A positive correlation was observed between TRAP5b activity and BALP activity. These results may contribute to the health management of captive Asian elephants.

Background: Laterality disorders of the abdominal organs include situs inversus totalis that mirrors the arrangements of all internal organs and heterotaxy syndrome (situs ambiguus) in which the thoracic or abdominal organs are abnormally arranged. Heterotaxy is often accompanied by multiple congenital malformations, and it generally comprises asplenia and polysplenia syndromes. To our knowledge, polysplenia syndrome has been reported in only three cattle, and computerized tomographic (CT) images of these animals were not obtained., Case Presentation: A six-month-old Holstein heifer had ruminal tympani and right abdominal distension. CT imaging showed that the rumen occupied the right side of the abdominal cavity, the omasum and abomasum occupied the left ventral side and the liver was positioned on the left. The colon and cecum were located at the left dorsum of the cavity, and the left kidney was located more cranially than the right. Postmortem findings revealed two spleens attached to the rumen. Significantly, the duodenum was too short to be divided into segments, except the cranial and descending parts, or flexures, except the cranial flexure, and the pancreas, which lacked a left lobe, was covered with mesojejunum. The liver comprised a relatively large right lobe and a small left lobe without quadrate and caudate lobes. The caudal vena cava that connected to the left azygous vein passed irregularly through the aortic hiatus of the diaphragm, and the common hepatic vein without the caudal vena cava passed through the caval foramen. Although the lungs and heart were morphologically normal, the right atrium received three major systemic veins. Polysplenia syndrome was diagnosed based on the CT and postmortem findings., Conclusion: We defined the positions of the abdominal organs and morphological abnormalities in various organs of a calf with polysplenia syndrome based on CT and postmortem findings. These findings will improve understanding of the malpositioning and malformations that can occur in the organs of cattle with polysplenia syndrome.

The aim of this study was to show the usefulness of a commercial agarose gel electrophoresis (AGE) kit (QuickGel SP) for separating bovine serum protein fractions in comparison with conventional cellulose acetate electrophoresis (CAE). Serum protein bands were verified using five reference reagents corresponding to albumin and α1-, β1-, β2-, and γ-globulins. AGE clearly revealed six separated fractions of albumin and α1-, α2-, β1-, β2-, and γ-globulin fractions in 100% and 77.8% in serum samples of dairy cows from the healthy (n=27) and diseased groups (n=27), respectively. The α1- and α2-globulins were not separated by CAE in 14.8% and 96.3% of the samples from the healthy and diseased groups, respectively, whereas β2- and γ-globulin were not separated by CAE in 96.3% and 100% of the samples from the healthy and diseased groups, respectively. More than 94% of the points for the α-globulin fractions (α1- and α2-globulins), the β-γ-globulin fractions (β1-, β2-, and γ-globulins), and the albumin/globulin ratio between AGE and CAE were within agreement on the Bland-Altman plots. However, the mean biases were not near zero in the albumin and β-γ-globulin fractions. These results suggest that the high-resolution commercial AGE kit can be utilized to separate bovine serum protein fractions.

A healthy 71-day-old female Japanese Black calf was evaluated for fracture of the left humerus. The left humeral fracture was treated by closed repair and unilateral external skeletal fixation (ESF) with an epoxy putty fixator. The calf was active, and eight days after surgery slipped and fell, resulting in breakage of the ESF. The calf underwent repair by transfixation pinning and casting (TPC), which is an alternative to the ESF method. The TPC was removed 37 days after the first surgery, and the calf could bear weight on the left forelimb while walking. This case suggests that recovery after closed repair with TPC for a humeral fracture in an active calf can be successfully managed on the farm.

The fluctuations in the plasma levels of several bone markers were investigated in newborn calves. Experiment 1 monitored the postnatal changes in the plasma levels of tartrate-resistant acid phosphatase isoform 5b (TRAP5b), total alkaline phosphatase (t-ALP) and bone-specific alkaline phosphatase (BAP) in four calves. These markers increased significantly from 9-20 hr after the first colostrum-suckling compared with the values immediately after birth. Experiment 2 evaluated changes in the plasma TRAP5b, t-ALP, BAP and type I collagen cross-linked N-telopeptide (NTx) levels within 2 days post-birth in five calves with successful passive immunization via colostrum (non-deficient group) and five others with poor colostrum intake (deficient group). The non-deficient group had significantly higher plasma levels of the four parameters around 12 hr of life compared with the deficient group. The results suggest that the increase in plasma bone markers in calves in the first day of life is related to the colostrum intake.

The patient was a 66-year-old woman with left breast cancer who underwent left segmental mastectomy with sentinel lymph node biopsy. The histopathological diagnosis was estrogen receptor-positive (ER+), progesterone receptor-positive( PgR+), human epidermal growth factor receptor-2-equivocal( HER2()2+)( with no HER2 gene amplification by fluorescence in-situ hybridization analysis) invasive ductal carcinoma (scirrhous carcinoma) with Ki-67 expression of less than 10% (pathological T1c, N0, M0, stage I). The patient requested chemotherapy, and 4 cycles of docetaxel plus cyclophosphamide (TC) were scheduled. Fever and epigastric pain developed on day 13 of cycle 2. On day 22, the patient was examined before the third cycle of TC, and right lower abdominal pain was reported. Computed tomography revealed appendicitis and an intraperitoneal abscess. She was admitted to the hospital and underwent partial ileocecal resection. The patient was discharged on the 12th postoperative day with no further complications. Acute abdomen during chemotherapy for malignant tumors has been reported sporadically in patients with leukemia. A diagnosis of acute abdomen in patients undergoing cancer treatment requires careful assessment of gastrointestinal symptoms such as nausea and vomiting during chemotherapy, fever associated with granulocytopenia, and findings indicative of local inflammation. The patient in this case recovered uneventfully because imaging studies and surgery were performed promptly after presentation.

We describe a case of a 69-year-old woman who underwent left breast-preserving surgery and axillary dissection for left-sided breast cancer at 60 years of age. The histopathological diagnosis was papillotubular carcinoma, luminal A (pathological T1N0M0).In the eighth year after surgery, computed tomography (CT) revealed recurrence in the liver and cervical lymph node metastasis. The patient did not respond to 3 months of treatment with letrozole (progressive disease [PD]). Six courses of chemotherapy with epirubicin and cyclophosphamide (EC) were administered. Subsequently, the attending physician was replaced while the patient was receiving paclitaxel( PTX).After 4 courses of treatment with PTX, the liver metastasis disappeared (complete response [CR]).However, the cervical lymph nodes did not shrink (PD).The cytological diagnosis was papillary thyroid cancer with associated cervical lymph node metastasis. Total thyroidectomy and D3b cervical lymph node dissection were performed. The pathological diagnosis was pEx0T1bN1Mx, pStage IVA disease. Replacement of the attending physician is a critical turning point for patients. During chemotherapy or hormone therapy for breast cancer, each organ should be evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST).In the case of our patient, thyroid cancer was diagnosed according to RECIST. Cancer specialists should bear in mind that the treatment policy may change dramatically depending on the results of RECIST assessment.

The patient was a 73-year-old woman with diabetes mellitus who was receiving insulin therapy. A poorly demarcated mass of 2 cm in diameter was palpated in the C region of the left breast. Mammography showed a dense locally asymmetric shadow. Ultrasonography revealed an irregular, poorly demarcated, hypoechoic mass measuring 14×21×10 mm accompanied by an attenuated posterior echo. Needle biopsy showed no evidence of malignancy, and the patient was kept under observation. An ultrasonographic examination performed 6 months later showed no change, but the possibility of cancer could not be ruled out on contrast-enhanced computed tomography and magnetic resonance imaging. Tumor resection at the patient's request was therefore performed. Histopathological examination of the breast revealed interstitial fibrosis with superimposed ground-glass opacities and lymphocyte infiltration around the ducts, leading to a diagnosis of diabetic mastopathy. Diabetic mastopathy occurs primarily in patients with a prolonged history of diabetes mellitus. It is difficult to distinguish diabetic mastopathy from breast cancer by palpation and imaging studies. Most cases are conclusively diagnosed by needle biopsy. Clinicians should be aware of diabetic mastopathy to avoid overdiagnosis and overtreatment. In our patient, diabetic mastopathy could be diagnosed on the basis of clinical characteristics and needle biopsy.

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., (Copyright © 2011 Elsevier Inc. All rights reserved.)

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.

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.

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.

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).

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.

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.

Background/aims: The long-term outcome of laparoscopic resection (Lap-R) of rectal cancer is still unclear. The purpose of this study was to elucidate the validity of Lap-R by comparing the short-term and mid-term outcome of Lap-R performed in our hospital to treat T1 and T2 rectal cancer patients with that of patients with the same clinicopathological background treated for rectal cancer by open surgery (O-R)., Methodology: We conducted a matched case-control study of the oncologic outcome of T1 and T2 rectal cancer patients who had undergone Lap-R between 1996 and 2002 by matching them for sex, age, location, and TNM classification with patients who underwent O-R during the same period, and the total number of subjects in both groups combined was 76., Results: The median follow-up period in the Lap-R group was 36 months, as opposed to 58 months in the O-R group. There were no operative deaths in either group. Comparison of the postoperative complications showed that intraoperative blood loss was significantly less in the Lap-R group than in the O-R group (P < 0.0001), and there were fewer cases of intestinal obstruction (p = 0.0312). The number of postoperative hospital days was also significantly shorter (p = 0.00046). The overall survival rate was 91.6% in the Lap-R group and 92.7% in the O-R groups, and the difference was not significant (p = 0.5306). The recurrence-free survival rate was 96.7% in the Lap-R group and 82.4% in the O-R group, and the difference was not significant (p = 0.4587). The difference in recurrence rate between the groups was not significant (p = 0.446), and there were no differences in modes of recurrence, but local recurrence was the most common mode in both groups. No recurrences were observed at the site of the port in the Lap-R group., Conclusions: When we performed our matched case-control study of Lap-R and O-R as surgical procedures for T1 and T2 rectal cancer, Lap-R was less invasive based on the short-term outcome. Moreover, there were no significant differences in mode of recurrence or recurrence rate, and no significant difference between the two groups was observed in oncologic outcome. It will be necessary to await the results of both Japanese and international randomized controlled trials (RCT). However, short- and mid-term follow-up of identical patients at a single institution as in the present study also appeared to have sufficient significance.

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.

More so than with other types of colon cancer, rectal cancer is associated with a range of laparoscopic surgical techniques. Treatment of cancer of the lower rectum requires favorable operative fields, minimal contact with the tumor during dissection, and delicate surgical procedures to avoid nerve damage. Such surgery thus requires immobilizing the trunk so the patient can be repositioned as needed, placing ports at appropriate locations, as well as careful handling of surgical equipment. To minimize the risk of disseminating cancer cells during the procedure, the surgery should be restricted to patients with early-stage cancer. The most difficult surgical procedure is resection of the lower rectum. While safe resection of the intestinal tract was difficult using previously available surgical equipment, newly developed equipment makes today's resections much safer and easier. Indications for surgical intervention should be broadened carefully, based on a deeper understanding of the surgical anatomy within the pelvis and on various relevant oncological and technical factors.