Contrasting seasonality of the incidence of incisional surgical site infection after general and gastroenterological surgery: An analysis of 8,436 patients in a single institute.

BACKGROUND: While seasonality of hospital-acquired infections, including incisional SSI after orthopaedic surgery, is recognized, the seasonality of incisional SSI after general and gastroenterological surgeries remains unclear. STUDY DESIGN: This retrospective single-institute observational study analysed the seasonality and risk factors of incisional SSI after general and gastroenterological surgeries using univariate and multivariable analyses. The evaluated variables included age, sex, surgical approach, surgical urgency, operation time, wound classification, and the American Society of Anesthesiologists physical status (ASA-PS). RESULTS: 8,436 patients were enrolled. General surgeries (n=2,241) showed a pronounced SSI incidence in summer (3.9%; odds ratio [OR] 1.87; 95% confidence interval [CI] 1.05-3.27; p=0.025) compared to other seasons (2.1%). Conversely, gastroenterological surgeries (n=6,195) showed a higher incidence in winter (8.3%; OR 1.38; 95% CI 1.10-1.73; p=0.005) than in other seasons (6.1%). Summer for general surgery (OR 1.90; 95% CI 1.12-3.24; p=0.018) and winter for gastroenterological surgery (OR 1.46; 95% CI 1.17-1.82; p=0.001) emerged as independent risk factors for incisional SSI. Open surgery (OR, 2.72; 95% CI 1.73-4.29, p<0.001) and an ASA-PS score ≥3 (OR, 1.64; 95% CI 1.08-2.50, p=0.021) were independent risk factors for incisional SSI in patients undergoing gastroenterological surgery during winter. CONCLUSION: Seasonality exists in the incisional SSI incidence following general and gastroenterological surgeries. Recognizing these trends may help enhance preventive strategies, highlighting the elevated risk in summer for general surgery and in winter for gastroenterological surgery.

Superiority trial for the development of an ideal method for the closure of midline abdominal wall incisions to reduce the incidence of wound complications after elective gastroenterological surgery: study protocol for a randomized controlled trial.

BACKGROUND: The recent guidelines from the European and American Hernia Societies recommend a continuous small-bite suturing technique with slowly absorbable sutures for fascial closure of midline abdominal wall incisions to reduce the incidence of wound complications, especially for incisional hernia. However, this is based on low-certainty evidence. We could not find any recommendations for skin closure. The wound closure technique is an important determinant of the risk of wound complications, and a comprehensive approach to prevent wound complications should be developed. METHODS: We propose a single-institute, prospective, randomized, blinded-endpoint trial to assess the superiority of the combination of continuous suturing of the fascia without peritoneal closure and continuous suturing of the subcuticular tissue (study group) over that of interrupted suturing of the fascia together with the peritoneum and interrupted suturing of the subcuticular tissue (control group) for reducing the incidence of midline abdominal wall incision wound complications after elective gastroenterological surgery with a clean-contaminated wound. Permuted-block randomization with an allocation ratio of 1:1 and blocking will be used. We hypothesize that the study group will show a 50% reduction in the incidence of wound complications. The target number of cases is set at 284. The primary outcome is the incidence of wound complications, including incisional surgical site infection, hemorrhage, seroma, wound dehiscence within 30 days after surgery, and incisional hernia at approximately 1 year after surgery. DISCUSSION: This trial will provide initial evidence on the ideal combination of fascial and skin closure for midline abdominal wall incision to reduce the incidence of overall postoperative wound complications after gastroenterological surgery with a clean-contaminated wound. This trial is expected to generate high-quality evidence that supports the current guidelines for the closure of abdominal wall incisions from the European and American Hernia Societies and to contribute to their next updates. TRIAL REGISTRATION: UMIN-CTR UMIN000048442. Registered on 1 August 2022. https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000055205.

A postoperative body weight increase is a novel risk factor for incisional hernia of midline abdominal incision after elective gastroenterological surgery.

PURPOSE: Midline abdominal incisions (MAIs) are widely used in both open and minimally invasive surgery. Incisional hernia (IH) accounts for most long-term postoperative wound complications. This study explored the risk factors for IH due to MAI in patients with clean-contaminated wounds after elective gastroenterological surgery. METHODS: The present study targeted patients enrolled in 2 randomized controlled trials to evaluate the efficacy of intraoperative interventions for incisional SSI prevention after gastroenterological surgery for clean-contaminated wounds. The patients were reassessed, and pre- and intraoperative variables and postoperative outcomes were collected. IH was defined as any abdominal wall gap, regardless of bulge, in the area of a postoperative scar that was perceptible or palpable on clinical examination or computed tomography according to the European Hernia Society guidelines. The risk factors for IH were identified using univariate and multivariate analyses. RESULTS: The study population included 1,281 patients, of whom 273 (21.3%) developed IH. Seventy-four (5.8%) patients developed incisional SSI. Multivariate logistic regression analysis revealed that female sex (odds ratio [OR], 1.39; 95% confidence interval [CI] 1.03-1.86, p = 0.031), high preoperative body mass index (OR, 1.81; 95% CI 1.19-2.77, p = 0.006), incisional SSI (OR, 2.29; 95% CI 1.34-3.93, p = 0.003), and postoperative body weight increase (OR, 1.49; 95% CI 1.09-2.04, p = 0.012) were independent risk factors for IH due to MAI in patients who underwent elective gastroenterological surgery. CONCLUSION: We identified postoperative body weight increase at one year as a novel risk factor for IH in patients with MAI after elective gastroenterological surgery.

Update of risk factors for surgical site infection in clean-contaminated wounds after gastroenterological surgery: An analysis of 1,878 participants enrolled in 2 recent randomized control trials for the prevention of surgical site infection.

BACKGROUND: Clean-contaminated wounds should be the main target for reducing the burden of harm caused by surgical site infection after gastroenterological surgery. METHODS: The present study targeted 1,973 patients enrolled in 2 randomized controlled trials to evaluate the efficacy of intraoperative interventions for incisional surgical site infection prevention after gastroenterological surgery with clean-contaminated wounds. Patients were reassessed, and preoperative and postoperative variables were collected. Risk factors for surgical site infection were identified by univariate and multivariate analyses. RESULTS: The study population included 1,878 patients, among whom 213 (11.3%) developed overall surgical site infection and 119 (6.3%) developed incisional surgical site infection. A multivariate analysis revealed that steroid or immunosuppressant use (odds ratio 3.03; 95% confidence interval 1.37-6.73, P = .0064), open surgery (odds ratio 1.77; 95% confidence interval 1.11-2.83, P = .0167), and long operative time (odds ratio 2.31; 95% confidence interval 1.5-3.56, P < .001) were independent risk factors for incisional surgical site infection. Steroid or immunosuppressant use (odds ratio 2.62; 95% confidence interval 1.29-5.33, P = .0078), open surgery (odds ratio 2.13; 95% confidence interval 1.44-3.16, P < .001), and long operative time (odds ratio 2.92; 95% confidence interval 2.08-4.10, P < .001) were also independent risk factors for overall surgical site infection in the multivariate analysis. Furthermore, a multivariate analysis revealed that a long operative time (odds ratio 3.21; 95% confidence interval 1.69-6.1, P = .00378) was an independent risk factor for incisional surgical site infection in patients who underwent laparoscopic surgery. CONCLUSION: Even under current measures for surgical site infection prevention, surgeons should continue to make efforts to appropriately expand the indication of laparoscopic surgery and to reduce operative times even when performing laparoscopic surgery.

Aqueous Povidone-Iodine Versus Normal Saline For Intraoperative Wound Irrigation on The Incidence of Surgical Site Infection in Clean-Contaminated Wounds After Gastroenterological Surgery: A Single-Institute, Prospective, Blinded-Endpoint, Randomized Controlled Trial.

OBJECTIVE: This trial evaluated the superiority of intraoperative wound irrigation (IOWI) with aqueous povidone-iodine (PVP-I) compared with that with saline for reducing the incidence of surgical site infection (SSI). BACKGROUND: IOWI with aqueous PVP-I is recommended for the prevention of SSI by the World Health Organization and the Centers for Disease Control and Prevention, although the evidence level is low. METHODS: This single institute in Japan, prospective, randomized, blinded-endpoint trial was conducted to assess the superiority of IOWI with aqueous PVP-I in comparison with IOWI with saline for reducing the incidence of SSI in clean-contaminated wounds after gastroenterological surgery. Patients 20 years or older were assessed for eligibility, and the eligible participants were randomized at a 1:1 ratio using a computer-generated block randomization. In the study group, IOWI was performed for 1 minute with 40 mL of aqueous 10% PVP-I before skin closure. In the control group, the procedure was performed with 100 mL of saline. Participants, assessors, and analysts were masked to the treatment allocation. The primary outcome was the incidence of incisional SSI in the intention-to-treat set. RESULTS: Between June 2019 and March 2022, 941 patients were randomized to the study group (473 patients) or the control group (468 patients). The incidence of incisional SSI was 7.6% in the study group and 5.1% in the control group (risk difference 0.025, 95% CI -0.006 to 0.056; risk ratio 1.484, 95% CI 0.9 to 2.448; P =0.154). CONCLUSION: The current recommendation of IOWI with aqueous PVP-I should be reconsidered.

Enhancement of DNA hypomethylation alterations by gastric and bile acids promotes chromosomal instability in Barrett's epithelial cell line.

Gastric and bile acid reflux leads to chronic inflammation, resulting in methylation alterations in Barrett's esophagus (BE) together with chromosomal instability (CIN). We investigated DNA hypomethylation following acid exposure and confirmed its significance in BE-related carcinogenesis by inducing CIN in vitro. OACP4C, an esophageal cancer cell line, and CP-A, a non-dysplastic cell line originating from BE, were exposed to acidic conditions using deoxycholic acid. CP-A exhibited substantially increased DNA hypomethylation of alpha satellite sequences in the centromere region, as well as increased levels of alpha satellite transcripts, but no changes were observed in the long interspersed nucleotide element-1 sequences distributed throughout the entire genome. These changes were not clearly found in OACP4C. Copy number changes at specific chromosomes were identified in CP-A, along with an increased number of cells exhibiting abnormal segregations, whereas these changes were rarely observed in OACP4C. The changes were maintained after several cell divisions. These findings suggest that alpha satellites are likely targets of DNA hypomethylation induced by acid exposure. CP-A was more sensitive to acid exposure than OACP4C, indicating that acid-induced DNA hypomethylation is involved in cancer development rather than progression, which could be involved in the underlying mechanism of esophagogastric junction carcinoma development.

Minimally invasive esophagectomy in the semi-prone position for corrosive esophagitis: a case report.

Treatment strategies for corrosive esophagitis include conservative treatment, such as balloon dilatation at the stenosis site, and surgical treatment. Esophagectomy for corrosive esophagitis is usually performed through the transthoracic or transhiatal approaches. Herein, we report a case of corrosive esophagitis treated with thoracoscopic esophagectomy with the patient in the semi-prone position. The patient was a 48-year-old woman who developed corrosive esophagitis due to accidental ingestion of an alkaline agent. Surgical intervention was required for esophageal stenosis. Therefore, thoracoscopic esophagectomy was performed with the patient in the semi-prone position with bilateral pulmonary ventilation. In our hospital, good operative outcomes have been obtained using thoracoscopic esophagectomy for esophageal cancer with the patient in the semi-prone position with bilateral pulmonary ventilation. This technique is also considered effective for the treatment of corrosive esophagitis.

Indications and Outcomes of a Hybrid Method Combining Laparoscopic and Anterior Approaches for Inguinal Hernia Repair.

Introduction Surgery for complex inguinal hernia (IH) (recurrent IH or IH after radical prostatectomy (RP)) may be difficult because of the presumed scar or adhesion in the retropubic space. A hybrid method combining the laparoscopic and anterior approaches (HLAA) in a bidirectional surgical technique may be an option in complex IH cases. Methods Patients at our institution who underwent IH repair for complex IH using HLAA from April 2018 to November 2019 were included. We retrospectively evaluated the patient characteristics, IH diagnosis, intraoperative variables, complications, and hernia recurrence during the follow-up period. Results Twenty patients were involved in this study. Seven patients underwent hLAA for recurrent IH, whereas the remaining 13 underwent hLAA for IH after RP. Five patients had bilateral IH, all of whom had IH after RP. The type of IH was lateral in 21 patients, medial in six patients, and lateral and medial in two patients. Hernia repair was performed using a patch alone in two patients and a plug and patch in 18 patients. Seroma or hematoma was observed in five patients, and one patient experienced chronic pain. No hernia recurrence was observed during the median follow-up period of 24 months. Conclusion hLAA could facilitate precise diagnosis and intraoperative confirmation of repair for recurrent IH and IH after RP. The intraoperative findings and the cause of recurrence can be easily shared among surgeons in hLAA. Further investigations are necessary to determine the long-term efficacy of hLAA in a larger cohort.

Superiority trial comparing intraoperative wound irrigation with aqueous 10% povidone-iodine to saline for the purpose of reducing surgical site infection after elective gastrointestinal surgery: study protocol for a randomised controlled trial.

INTRODUCTION: Surgical site infection (SSI) is one of the most common complications after gastrointestinal surgery, with a reported incidence of approximately 10%-25%, which is higher than the rates after other types of surgery. Intraoperative wound irrigation (IOWI) is a simple intervention for SSI prevention, and recent studies have reported that IOWI with aqueous povidone-iodine (PVP-I) is significantly more effective at reducing the incidence of SSI than saline. However, the evidence level of previous trials evaluating the efficacy of aqueous PVP-I solution for preventing SSI has been low. METHODS AND ANALYSES: We propose a single-institute, prospective, randomised, blinded-endpoint trial to assess the superiority of IOWI with aqueous 10% PVP-I solution compared with normal saline for reducing SSI in clean-contaminated wounds after elective gastrointestinal surgery. In the study group, IOWI with 40 mL of aqueous 10% PVP-I solution is performed for 1 min before skin suture, and in the control group, IOWI with 100 mL of saline is performed for 1 min before skin suture. We hypothesise that IOWI with aqueous 10% PVP-I solution will achieve a 50% reduction in the incidence of SSIs. The target number of cases is set at 950. The primary outcome is the incidence of incisional SSI up to postoperative day 30 and will be analysed in the modified intention-to-treat set. ETHICS AND DISSEMINATION: This trial was designed and is being conducted by Saitama Medical Center, Jichi Medical University, with approval from the Bioethics Committee for Clinical Research, Saitama Medical Center, Jichi Medical University. Participant recruitment began in June 2019. The final results will be reported in international peer-reviewed journals immediately after trial completion. TRIAL REGISTRATION NUMBER: UMIN000036889.

Intestinal perforation secondary to intestinal Burkitt lymphoma.

INTRODUCTION AND IMPORTANCE: Small intestinal perforation in patients with Burkitt lymphoma is extremely rare. We present the first report of such a case. CASE PRESENTATION: A 53-year-old woman was admitted with abdominal pain and vomiting. Abdominal examination revealed rigidity and tenderness in the upper abdomen. Computed tomography scan showed thickening of the wall of the jejunum, intra-abdominal free gas, and ascites; the patient was diagnosed with small intestinal perforation, and underwent emergency surgery on the same day. Laparoscopic findings were a 50 mm jejunal perforation and perforation in the transverse mesocolon. A partial jejunal resection of the perforated area, partial transverse colectomy, temporary colostomy, and intra-abdominal drainage were performed. Histological examination showed diffuse infiltration of medium-sized atypical lymphocytes in the perforated area, exhibiting a "starry sky" appearance. Immunostaining results showed that the atypical lymphocytes were CD20 and virtually 100% Ki-67 positive, and CD56, CD30, and EBER negative. The lesion was identified as Burkitt lymphoma (BL). The postoperative course was favorable. On postoperative day 18 the patient began chemotherapy through the hematology department. Currently, the patient is in remission. CLINICAL DISCUSSION: The majority of the malignant lymphomas occurring in the digestive tract are identified in the stomach; over 90% are B-cell lymphomas and mucosa-associated lymphoid tissue lymphoma Nakamura et al. BL originating from the small intestine accounts for only about 9%. CONCLUSION: The incidence of BL in the small intestine is low. Pretreatment BL can lead to bowel perforation. Prompt involvement of the hemato-oncologist after definitive diagnosis, and commencing chemotherapy as early as possible after surgery, are thought to improve prognosis.

A case of corrosive esophagitis causing extensive cicatricial esophageal stenosis treated by esophageal bypass with supercharged pedicled jejunal pull-up.

INTRODUCTION: Swallowing a corrosive substance causes delayed gastrointestinal stenosis due to scar formation. Here, we report on our use of esophageal bypass using a supercharged pedicled jejunal flap to treat cicatricial esophageal stenosis caused by corrosive esophagitis. PRESENTATION OF CASE: Nineteen years before presentation, a 57-year-old man had swallowed a chemical cleaning agent, which caused extensive corrosive cicatricial stenosis from the thoracic upper esophagus to the gastric fornix. An enterostomy had been created, and the patient had since been subsisting on enteral nutrition. However, he wanted to be able to eat through his mouth again and was referred to our department for treatment. With the exception of the cervical esophagus, circumferential cicatricial stenosis was present throughout the esophagus and gastric fornix, with severe adhesions to the surrounding tissue. It was decided not to perform esophagectomy but to perform esophageal bypass surgery using a supercharged pedicled jejunal flap. DISCUSSION: Despite the extremely high risk of cancer in the stenotic esophagus due by corrosive esophagitis, indicating that esophagectomy should be performed if possible, we chose to perform bypass surgery because the severe adhesions posed a high risk of early injury to the surrounding organs. CONCLUSION: We suggest that esophageal bypass using pedicled jejunal pull-up "supercharging" by creating anastomoses between the jejunal and internal thoracic vessels is the optimal procedure for patients with extensive cicatricial esophageal stenosis caused by corrosive esophagitis.

Multiple primary malignancies of six organs in a Japanese male patient: A case report.

As a result of recent advances in diagnostic techniques and treatment modalities, the number of patients diagnosed with multiple primary malignancies has been increasing. We report the case of a 79-year-old male with multiple primary malignancies of three histological types in six different organs: Stomach, prostate, colon, urinary bladder, facial skin and pancreas, in chronological order. The first malignancy was upper gastric cancer diagnosed in 1998. The second and third malignancies were prostate cancer and ascending colon cancer, which were diagnosed in 2010. The fourth malignancy was bladder cancer diagnosed in 2011. The fifth and sixth malignancies were squamous cell skin cancer of the right cheek and intraductal papillary mucinous carcinoma (IPMC), respectively, diagnosed in 2014. The gastric cancer, colon cancer, bladder cancer, skin cancer and IPMC were surgically resected. The prostate cancer was treated by anti-androgen therapy. The patient died of local recurrence of IPMC in August 2016. Although multiple primary malignancies are not uncommon, diagnosis of six primary malignancies in a single patient, as reported in the present study, is extremely rare. It is important to understand the characteristics of multiple primary malignancies in order to administer suitable treatment and determine relevant follow-up plans for patients with cancer.

Monitoring circulating tumor DNA revealed dynamic changes in KRAS status in patients with metastatic colorectal cancer.

KRAS mutated circulating tumor DNA (MctDNA) can be monitored in the blood of patients with metastatic colorectal cancer (mCRC), but dynamic changes have not been determined. Four hundred and fifty-seven plasma samples were collected prospectively from 85 mCRC patients who underwent chemotherapy. MctDNA in plasma was detected by droplet digital PCR, and the percentage of MctDNA in total circulating cell-free DNA was calculated. KRAS assessment in tumor tissues showed 29 patients with the mutant-type (MT) and 56 patients with the wild-type (WT). Twenty-three of 29 MT patients (79.3%) and 28 of 56 WT patients (50.0%) showed MctDNA. Emergence of MctDNA was recognized during treatments with various drugs. Regardless of KRAS status in tumor tissues, patients with MctDNA in blood showed poor progression-free survival with first-line treatment. Median percentage of MctDNA accounted for 10.10% in MT patients and 0.22% in WT patients. These differences between MT and WT likely affected patterns of changes in MctDNA. KRAS monitoring identified dynamic changes in MctDNA, such as continuous, intermittent, and transient changes (quick elevation and disappearance). Emergence of MctDNA involved drug resistance, except for transient changes, which were seen in WT patients and likely corresponded with the drug response. Transient changes could be involved in recovery of sensitivity to anti-EGFR antibody in WT patients. Monitoring MctDNA during various treatments showed dynamic changes in KRAS status and could provide useful information for determining treatments for patients with mCRC.

Overexpression of satellite alpha transcripts leads to chromosomal instability via segregation errors at specific chromosomes.

The impairment of the stability of the chromosomal structure facilitates the abnormal segregation of chromosomes, thus increasing the risk of carcinogenesis. Chromosomal stability during segregation is managed by appropriate methylation at the centromere of chromosomes. Insufficient methylation, or hypomethylation, results in chromosomal instability. The centromere consists of satellite alpha repetitive sequences, which are ideal targets for DNA hypomethylation, resulting in the overexpression of satellite alpha transcript (SAT). The overexpression of SAT has been reported to induce the abnormal segregation of chromosomes. In this study, we verified the oncogenic pathway via chromosomal instability involving DNA hypomethylation and the overexpression of SAT. For this purpose, we constructed lentiviral vectors expressing SAT and control viruses and then infected human mammary epithelial cells with these vectors. The copy number alterations and segregation errors of chromosomes were evaluated by microarray-based comparative genomic hybridization (array CGH) and immunocytochemistry, respectively. The levels of hypomethylation of satellite alpha sequences were determined by MethyLight polymerase chain reaction. Clinical specimens from 45 patients with breast cancer were recruited to verify the data in vitro. The results of immunocytochemistry revealed that the incidence of segregation errors was significantly higher in the cells overexpressing SAT than in the controls. An array CGH identified the specific chromosomes of 8q and 20q as frequent sites of copy number alterations in cells with SAT overexpression, although no such sites were noted in the controls, which was consistent with the data from clinical specimens. A regression analysis revealed that the expression of SAT was significantly associated with the levels of hypomethylation of satellite alpha sequences. On the whole, the overexpression of SAT led to chromosomal instability via segregation errors at specific chromosomes in connection with DNA hypomethylation, which was also recognized in clinical specimens of patients with breast cancer. Thus, this oncogenic pathway may be involved in the development of breast cancer.

[An Elderly Patient with Metastatic Colon Cancer Achieved Long-Term Survival Following Single-Agent Chemotherapy with S-1].

Colorectal cancer is a common malignancy and a major health issue in geriatrics. Systemic chemotherapy should be considered for elderly patients. We report an 85-year-old man with metastatic cecal cancer who has achieved long-term survival following single-agent chemotherapy with S-1. His fecal occult blood test results were positive; he then underwent colonoscopy and was diagnosed with cecal cancer. Chest CT revealed multiple metastases in both lungs. Since radical excision was infeasible, we performed right hemicolectomy to prevent bowel obstruction. Histological examination revealed a T3, N0, M1a (PUL2), Stage IV tumor. After discharge from the hospital, the patient preferred receiving chemotherapy that would have fewer side effects. S-1 monotherapy was administered. Despite increased progression of the pulmonary metastases, he experienced no subjective symptoms, his QOL remained consistent, and he completed 42 cycles of chemotherapy in total. The patient is currently being managed on an outpatient basis. In conclusion, elderly patients with cancer should be carefully evaluated according to both disease control and individual circumstances, such as patient's tolerability, QOL, and preference.

Spatial variations of tritium concentrations in groundwater collected in the southern coastal region of Fukushima, Japan, after the nuclear accident.

Spatial variations in tritium concentrations in groundwater were identified in the southern part of the coastal region in Fukushima Prefecture, Japan. Higher tritium concentrations were measured at wells near the Fukushima Daiichi Nuclear Power Station (F1NPS). Mean tritium concentrations in precipitation in the 5 weeks after the F1NPS accident were estimated to be 433 and 139 TU at a distance of 25 and 50 km, respectively, from the F1NPS. The elevations of tritium concentrations in groundwater were calculated using a simple mixing model of the precipitation and groundwater. By assuming that these precipitation was mixed into groundwater with a background tritium concentration in a hypothetical well, concentrations of 13 and 7 TU at distances of 25 and 50 km from the F1NPS, respectively, were obtained. The calculated concentrations are consistent with those measured at the studied wells. Therefore, the spatial variation in tritium concentrations in groundwater was probably caused by precipitation with high tritium concentrations as a result of the F1NPS accident. However, the highest estimated tritium concentrations in precipitation for the study site were much lower than the WHO limits for drinking water, and the concentrations decreased to almost background level at the wells by mixing with groundwater.

Morphological response contributes to patient selection for rescue liver resection in chemotherapy patients with initially un-resectable colorectal liver metastasis.

Morphological response is considered an improved surrogate to the Response Evaluation Criteria in Solid Tumors (RECIST) model with regard to predicting the prognosis for patients with colorectal liver metastases. However, its use as a decision-making tool for surgical intervention has not been examined. The present study assessed the morphological response in 50 patients who underwent chemotherapy with or without bevacizumab for initially un-resectable colorectal liver metastases. Changes in tumor morphology between heterogeneous with uncertain borders and homogeneous with clear borders were defined as an optimal response (OR). Patients were also assessed as having an incomplete response (IR), and an absence of marked changes was assessed as no response (NR). No significant difference was observed in progression-free survival (PFS) between complete response/partial response (CR/PR) and stable disease/progressive disease (SD/PD), according to RECIST. By contrast, PFS for OR/IR patients was significantly improved compared with that for NR patients (13.2 vs. 8.7 months; P=0.0426). Exclusion of PD enhanced the difference in PFS between OR/IR and NR patients (15.1 vs. 9.3 months; P<0.0001), whereas no difference was observed between CR/PR and SD. The rate of OR and IR in patients treated with bevacizumab was 47.4% (9/19), but only 19.4% (6/31) for patients that were not administered bevacizumab. Comparison of the survival curves between OR/IR and NR patients revealed similar survival rates at 6 months after chemotherapy, but the groups exhibited different survival rates subsequent to this period of time. Patients showing OR/IR within 6 months appeared to be oncologically stable and could be considered as candidates for surgical intervention, including rescue liver resection. Comparing the pathological and morphological features of the tumor with representative optimal response, living tumor cells were revealed to be distributed within the area of vascular reconstruction induced by bevacizumab, resulting in a predictive value for prognosis in the patients treated with bevacizumab. The present findings provided the evidence for physicians to consider patients with previously un-resectable metastatic colorectal cancer as candidates for surgical treatment. Morphological response is a useful decision-making tool for evaluating these patients for rescue liver resection following chemotherapy.

Sequential administration of XELOX and XELIRI is effective, feasible and well tolerated by patients with metastatic colorectal cancer.

Sequential administration of the chemotherapy regimes capecitabine and oxaliplatin (XELOX) and capecitabine and irinotecan (XELIRI) in the first- to second-line treatment setting would allow patients to be managed more easily in an outpatient unit. However, a small number of studies have raised concerns of cumulative adverse events as a consequence of the continuous use of capecitabine. To investigate this, the present study conducted a retrospective review of 81 consecutive metastatic colorectal cancer (mCRC) patients treated with the oxaliplatin, fluorouracil and leucovorin-irinotecan, fluorouracil and leucovorin (FOLFOX-FOFIRI/F-F) regimen (n=40) or the XELOX-XELIRI (X-X) regimen (n=41) in first- to second-line chemotherapy in Saitama Medical Center between 2006 and 2012. The disease control rate (DCR), the progression free survival (PFS), the overall survival (OS) and the time to failure of strategy (TFS) from first to second-line chemotherapy, as well as adverse events, were assessed and compared between patients receiving X-X or F-F. A total of 10 and 20 patients were additionally treated with bevacizumab in the F-F and X-X regimens, respectively, during first or second-line chemotherapy. There was no significant difference in DCR and the median PFS between the two regimens for first or second-line chemotherapy. There was no significant difference in the median OS and TFS between the two regimens (OS=24.5 and TFS=14 months in the F-F vs. 23.2 and 12.0 months in the X-X). Regarding adverse events, 45.0% of patients (18/40) exhibited grade 3-4 neutropenia throughout treatment with F-F. Whilst, 15.0% of patients (6/41) exhibited grade 3 hypertension throughout treatment with X-X, which was effectively controlled by a single antihypertensive drug. The results show that sequential administration of X-X is as effective and feasible as F-F treatment, while additionally reducing the frequency of infusion visits and eliminating the need for a central venous access device or home infusion pump, thereby offering a more convenient treatment option to patients with mCRC.

Clinical and molecular assessment of regorafenib monotherapy.

Regorafenib has shown survival benefits in metastatic colorectal cancer patients who were exacerbated after all standard therapies. Some patients, however, exhibit severe adverse events (AEs) resulting in treatment discontinuation. Therefore, the selection of patients likely to benefit from regorafenib is crucial. Twenty patients were treated with regorafenib for metastatic colorectal cancer; 122 plasma samples were taken from 16 of these patients for monitoring of circulating tumor DNA (ctDNA) in the blood. The treatment response, AEs, overall survival (OS), progression-free survival (PFS) and tumor morphologic changes on CT images were evaluated. KRAS mutant ctDNA was determined using digital PCR. Median PFS and OS were 2.5 and 5.9 months, respectively. Treatment was discontinued because of disease progression (PD) in 10 patients, and AEs in another 10 patients. AEs included hyperbilirubinemia, severe fatigue and skin rash. Hyperbilirubinemia was seen in two patients with multiple bilateral liver metastases, and severe fatigue in another 2 patients with poor performance status (PS). These severe AEs resulted in treatment discontinuation. Ten patients had a median PFS of 2.1 months with AE related discontinuation; PD occurred at 3.5 months (p=0.00334). Four patients exhibited a morphologic response, achieving better PFS times of 3.5, 5.3, 5.6 and 14.2 months. Emergence of the KRAS mutation in ctDNA was observed during anti-EGFR antibody treatment in 3 patients among 11 with KRAS wild-type tumors; it was detectable in the blood prior to radiographic detection of PD. Moreover, the KRAS mutation declined in two patients during regorafenib monotherapy. These patients were re-challenged with anti-EGFR antibody. Patients with extensive multiple liver metastases or poor PS are unlikely to benefit from regorafenib. Patients with a morphologic response will probably benefit from regorafenib with adequate management of other AEs. KRAS monitoring in ctDNA could be useful regarding treatment response and in determining treatment strategy.

Clinical characteristics of synchronous colorectal cancers in Japan.

BACKGROUND: Incidence and clinical characteristics of synchronous colorectal cancer (sCRC) patients significantly vary among studies, likely due to differences in surveillance methodology. If remain undetected, sCRC can progress to more advanced stages seriously aggravating patient prognosis. We studied the incidence and clinicopathological characteristics of Japanese patients with sCRCs who underwent surgery for primary CRC and received exhaustive perioperative surveillance. METHODS: We recruited 1005 patients with surgically resected CRCs between January 2007 and December 2011. The associations of clinical and pathological factors with sCRC development were assessed by univariate and multivariate logistic regression. RESULTS: Eighty-four patients (8.4 %) developed sCRCs, 16 of them (19.0 %) harboring three or more cancers. Companion sCRCs were smaller and earlier stage than the index lesion (P < 0.0001). In multivariate analysis, advanced age (odds ratio (OR) 1.03 per year; P = 0.009) and left colon tumor location (OR 1.78; P = 0.013) are associated with higher risk of sCRCs, particularly in females. Overall survival did not differ between solitary CRC and sCRC (P = 0.62). CONCLUSIONS: Our results highlight the importance of perioperative colonoscopy examination to ensure the absence of sCRCs that, being small and early staged, are more difficult to detect. The incidence of sCRC, and notably of triple or more sCRCs, was higher than previously recognized. Because they are also significantly higher than expected by merely stochastic accumulation of individual cancerous lesions, we suggest that the occurrence of many sCRC reflects a hitherto uncharacterized predisposition condition.