Lengthened Efferent Limb in Braun Enteroenterostomy Reduces Delayed Gastric Emptying After Pancreaticoduodenectomy.

BACKGROUND: Delayed gastric emptying (DGE) is a common complication after pancreaticoduodenectomy (PD), but a method to prevent DGE has not been established. This study aims to demonstrate a novel technique utilizing a lengthened efferent limb in Billroth-II (B-II) reconstruction during PD and to evaluate the impact of the longer efferent limb on DGE occurrence. METHODS: Patients who underwent PD with B-II reconstruction were divided into two groups: PDs with lengthened (50-60 cm) efferent limb (L group) and standard length (0-30 cm) efferent limb (S group). Postoperative outcomes were compared. DGE was defined and graded according to the International Study Group of Pancreatic Surgery criteria. RESULTS: Among 283 consecutive patients who underwent PD from 2002 to 2021, 206 patients were included in this study. Patients who underwent Roux-en-Y reconstruction (n = 77) were excluded. Compared with the S group, the L group included older patients and those who underwent PD after 2016 (p = 0.025, < 0.001, respectively). D2 lymphadenectomy, antecolic route reconstruction, and Braun enteroenterostomy were performed more frequently in the L group (p = 0.040, < 0.001, < 0.001, respectively). The rate of DGE was significantly decreased to 6% in the L group, compared with 16% in the S group (p = 0.027), which might lead to a shorter hospital stay in the L group (p < 0.001). Multivariable analysis identified two factors as independent predictors for DGE: intraabdominal abscess [odds ratio (OR) 5.530, p = 0.008] and standard efferent limb length (OR 2.969, p = 0.047). CONCLUSION: A lengthened efferent limb in Braun enteroenterostomy could reduce DGE after PD.

Modified Intestinal Derotation Procedure with Reversed Kocherization to Facilitate Mesopancreas Excision During Pancreaticoduodenectomy.

BACKGROUND: Although intestinal derotation procedure has advantages of facilitating mesopancreas excision during pancreaticoduodenectomy, the wide mobilization takes time and risks injuring other organs. This article describes a modified intestinal derotation procedure in pancreaticoduodenectomy and its clinical impact on short-term outcomes. METHODS: The modified procedure comprised the pinpoint mobilization of the proximal jejunum following reversed Kocherization. Among 99 consecutive patients who underwent pancreaticoduodenectomy between 2016 and 2022, the short-term outcomes of pancreaticoduodenectomy with the modified procedure were compared with those of conventional pancreaticoduodenectomy. The feasibility of the modified procedure was investigated based on the vascular anatomy of the mesopancreas. RESULTS: Compared with conventional pancreaticoduodenectomy (n = 55), the modified procedure (n = 44) involved less blood loss and shorter operation time (p < 0.001 and 0.017, respectively). Severe morbidity, clinically relevant postoperative pancreatic fistula, and prolonged hospitalization occurred less often with the modified procedure compared with conventional pancreaticoduodenectomy (p = 0.003, 0.008, and < 0.001, respectively). According to preoperative image findings, most (72%) patients had a single inferior pancreaticoduodenal artery sharing a common trunk with the first jejunal artery. The inferior pancreaticoduodenal vein drained into the jejunal vein in 71% of the patients. The first jejunal vein ran behind the superior mesenteric artery in 77% of the patients. CONCLUSIONS: By combining our modified intestinal derotation procedure with preoperative recognition of the vascular anatomy of mesopancreas, mesopancreas excision during pancreaticoduodenectomy can be performed safely and accurately.

Relationship between stromal regulatory T cells and the response to neoadjuvant chemotherapy for locally advanced rectal cancer.

BACKGROUND: In addition to the direct power of anticancer drugs, the effectiveness of anticancer therapy depends on the host immune function. The present study investigated whether or not the reduction rate and histological response of preoperative chemotherapy were related to the immune microenvironment surrounding a primary tumor of the rectum. METHODS: Sixty-five patients received preoperative chemotherapy followed by resection from 2012 to 2014; all of these patients were retrospectively analyzed. CD3, CD8, and FoxP3 were immunohistochemically examined as markers for T lymphocytes, cytotoxic T lymphocytes, and regulatory T lymphocytes (Treg), respectively. The correlation between the tumor-infiltrating lymphocyte composition and the tumor reduction rate and histological response to neoadjuvant chemotherapy was investigated. RESULTS: The average tumor reduction rate was 41.5% ± 18.8%. According to RECIST, 47 patients (72.3%) achieved a partial response (PR), and 1 patient (1.5%) achieved a complete response (CR). Eight patients (12.3%) showed a grade 2 histological response, and 2 (3.1%) showed a grade 3 response. A multivariate analysis demonstrated that a low Treg infiltration in stromal cell areas was significantly associated with the achievement of a PR or CR [odds ratio (OR) 7.69; 95% confidence interval (CI) 1.96-33.33; p < 0.01] and a histological grade 2 or 3 response (OR 11.11; 95% CI 1.37-98.04; p = 0.02). CONCLUSION: A low Treg infiltration in the stromal cell areas may be a marker of a good response to neoadjuvant chemotherapy in patients with locally advanced rectal cancer.

A novel discriminant formula for the prompt diagnosis of strangulated bowel obstruction.

PURPOSES: The diagnosis of strangulated bowel obstruction (SBO) is sometimes difficult. We attempted to create and verify a discriminant formula for use as a diagnostic aid for the early diagnosis of SBO. METHODS: This retrospective study included 97 patients who underwent an operation for SBO from January 2007 to September 2018. First, a discriminant analysis was performed for 73 patients who underwent an operation from January 2007 to December 2015 in order to obtain a formula. Next, we analyzed 34 patients who underwent an operation from January 2016 to September 2018 to verify the formula. RESULTS: The risk factors for SBO included ascites, signs of preperitoneal irritation, and lactate > 1.16 mmol/L. The discriminant formula is as follows: 1.954 × collection of ascites (1 or 0) + 1.239 × peritoneal irritation sign (1 or 0) + 0.378 × lactate - 2.331 (1: positive, 0: negative). The predictive value was as follows: sensitivity, 87.5%; specificity, 64.7%; and predictive accuracy, 73.5%. In patients who presented within 24 h of the onset, the sensitivity was 92.3%, the specificity was 75.0%, and the predictive accuracy was 85.7%. CONCLUSION: Our discriminant formula seems useful for the rapid diagnosis of SBO.

Efficacy and safety of enoxaparin for preventing venous thromboembolic events after laparoscopic colorectal cancer surgery: a randomized-controlled trial (YCOG 1404).

PURPOSE: We conducted a prospective study to evaluate the efficacy and safety of postoperative enoxaparin for the prevention of venous thromboembolism (VTE) after laparoscopic surgery for colorectal cancer (LAC) in Japanese patients. METHODS: The subjects of this multicenter, open-label randomized-controlled trial were 121 patients who underwent LAC between September 2015 and May 2017. The patients were randomly allocated to receive intermittent pneumatic compression (IPC) with enoxaparin (20 mg, twice daily), started 24-36 h after surgery and continued until discharge (Enoxaparin group; n = 61), or IPC alone (IPC group; n = 60). The primary endpoint was the incidence of VTE on day 28 after surgery. The safety outcome was the incidence of any bleeding during treatment and follow-up. RESULTS: The incidence of VTE on day 28 after surgery was 12.3% (7/57 patients) in the enoxaparin group and 11.9% (7/59 patients) in the IPC group ((p = 1.00). One of the 57 patients (1.8%) in the enoxaparin group and none in the IPC group experienced a bleeding event. CONCLUSIONS: It may be unnecessary to give enoxaparin to all Japanese patients for the prevention of VTE after LAC. The UMIN Clinical Trials Registry number was UMIN000018633.

[A Surgical Case of Desmoid Tumor in the Transverse Mesocolon with Pancreatic Invasion].

A 40-year-old man with no previous history of abdominal surgery or noteworthy family history presented to our hospital because of a palpable abdominal mass. Abdominal CT revealed a 9 cm diameter mass in the mesocolon. The differential diagnosis included desmoid tumor, and right hemicolectomy with partial resection of the pancreas head and duodenum was performed. Pathologically, the tumor cells were negative for S-100, c-kit, CD34, and desmin but partially positive for a-SMA and slightly for b-catenin. From these findings, desmoid tumor of the mesocolon was diagnosed. Invasion of the pancreas was also found. Desmoid tumor is pathologically benign, but because of its malignant-like characteristics, such as direct invasion and local recurrence, it is treated as a malignant tumor. Desmoid tumors are associated with familial adenomatous polyposis coli and Gardner syndrome, or they arise in patients who have a history of laparotomy or antecedent trauma. In this paper, we report a rare case of resected sporadic desmoid tumor in the mesocolon with pancreatic invasion, together with a review of the literature.

Eribulin regresses a doxorubicin-resistant Ewing's sarcoma with a FUS-ERG fusion and CDKN2A-deletion in a patient-derived orthotopic xenograft (PDOX) nude mouse model.

Ewing's sarcoma is a recalcitrant tumor greatly in need of more effective therapy. The aim of this study was to determine the efficacy of eribulin on a doxorubicin (DOX)-resistant Ewing's sarcoma patient derived orthotopic xenograft (PDOX) model. The Ewing's sarcoma PDOX model was previously established in the right chest wall of nude mice from tumor resected form the patient's right chest wall. In the previous study, the Ewing's sarcoma PDOX was resistant to doxorubicin (DOX) and sensitive to palbociclib and linsitinib. In the present study, the PDOX models were randomized into three groups when the tumor volume reached 60 mm3 : G1, untreated control (n = 6); G2, DOX treated (n = 6), intraperitoneal (i.p.) injection, weekly, for 2 weeks); G3, Eribulin treated (n = 6, intravenous (i.v.) injection, weekly for 2 weeks). All mice were sacrificed on day 15. Changes in body weight and tumor volume were assessed two times per week. Tumor weight was measured after sacrifice. DOX did not suppress tumor growth compared to the control group (P = 0.589), consistent with the previous results in the patient and PDOX. Eribulin regressed tumor size significantly compared to G1 and G2 (P = 0.006, P = 0.017) respectively. No significant difference was observed in body weight among any group. Our results demonstrate that eribulin is a promising novel therapeutic agent for Ewing's sarcoma.

A randomized controlled trial of subcutaneous closed-suction Blake drains for the prevention of incisional surgical site infection after colorectal surgery.

BACKGROUND: The effects of subcutaneous closed-suction Blake drain for preventing incisional surgical site infections (SSIs) after colorectal surgery have never been evaluated in a randomized controlled trial (RCT). Thus, we performed a RCT to evaluate the clinical benefits of using a subcutaneous closed-suction Blake drain in patients undergoing colorectal surgery. METHOD: Consecutive patients who underwent colorectal surgery were enrolled in this study. Patients were randomly assigned to the subcutaneous closed-suction drainage arm or the control (no subcutaneous drainage) arm. The primary endpoint was incidence rate of incisional SSIs. And, we performed logistic regression analysis to detect predictive factors for incisional SSIs after colorectal surgery. RESULTS: From November 2012 to September 2014, a total of 240 patients were enrolled in this study. One-hundred-seventeen patients who were treated by the control arm and 112 patients by the subcutaneous drainage arm were judged to be eligible for analysis. The incidence of incisional SSIs rate was 8.7 % in the overall patients. The incidence of incisional SSIs rate was 12.8 % in the control arm and 4.5 % in the subcutaneous drainage arm. There was significantly reduction of the incidence in the subcutaneous drainage arm than in the control arm (p = 0.025). Logistic regression analysis demonstrated that thickness of subcutaneous fat >3.0 cm, forced expiratory volume in 1 s as percent of forced vital capacity (FEV1.0 %) >70 %, and subcutaneous drain were independent predictors of postoperative incisional SSIs (p = 0.008, p = 0.004, and p = 0.017, respectively). CONCLUSION: The results of our RCT suggest that a subcutaneous Blake drain is beneficial for preventing incisional SSIs in patients undergoing colorectal surgery.

Midterm follow-up of a randomized trial of open surgery versus laparoscopic surgery in elderly patients with colorectal cancer.

BACKGROUND: Laparoscopic surgery has been widely accepted for the treatment of colorectal cancer; however, long-term outcomes in elderly patients remain controversial. The midterm results of a randomized trial comparing open surgery with laparoscopic surgery in elderly patients with colorectal cancer are presented. METHODS: This was a randomized trial comparing open surgery with laparoscopic surgery in elderly patients with colorectal cancer. The primary outcome was complication rate, and secondary outcomes included 3-year recurrence-free survival and overall survival. A total of 200 patients were randomly assigned to open surgery or laparoscopic surgery between 2008 and 2012. The main study objective was to compare the midterm outcomes of open surgery with those of laparoscopic surgery in elderly patients with colorectal cancer. This trial is registered with Clinical Trials.gov (NCT01862562). RESULTS: There were no differences between the laparoscopic surgery group and open surgery group in the 3-year overall survival rate (91.5% for laparoscopic surgery vs. 90.6% for open surgery, p = 0.638) or the 3-year recurrence-free survival rate (84.8% for laparoscopic surgery vs. 88.2% for open surgery, p = 0.324). The local recurrence rate was significantly higher in the laparoscopic surgery group than in the open surgery group in rectal cancer (13.8% for laparoscopic surgery vs. 0% for open surgery, p = 0.038). In subgroup analysis according to tumor location, there were no significant differences in the 3-year overall survival rate or 3-year recurrence-free survival rate between the two treatment groups. CONCLUSION: The midterm outcomes of laparoscopic surgery are similar to those of open surgery in elderly patients with colorectal cancer.

[A Case of Rhabdomyolysis Related to SOX Therapy for Liver Metastasis of Gastric Cancer].

We report a case of rhabdomyolysis related to S-1 plus oxaliplatin(SOX)therapy for liver metastasis of gastric cancer. A 76- year-old man who had received SOX therapy for metastatic gastric cancer was admitted to our hospital for a chief complaint of fatigue and weakness. He diagnosed with rhabdomyolysis related to SOX therapy because of his symptoms and because his laboratory studies showed significant elevation of his serum creatine kinase(CK)level. The symptoms disappeared and the CK level normalized following large-volume transfusions. Rhabdomyolysis following SOX therapy is a very rare, but severe adverse event. This is the first detailed case report of rhabdomyolysis related to SOX therapy.

Color-Coded Imaging of Breast Cancer Metastatic Niche Formation in Nude Mice.

We report here a color-coded imaging model in which metastatic niches in the lung and liver of breast cancer can be identified. The transgenic green fluorescent protein (GFP)-expressing nude mouse was used as the host. The GFP nude mouse expresses GFP in all organs. However, GFP expression is dim in the liver parenchymal cells. Mouse mammary tumor cells (MMT 060562) (MMT), expressing red fluorescent protein (RFP), were injected in the tail vein of GFP nude mice to produce experimental lung metastasis and in the spleen of GFP nude mice to establish a liver metastasis model. Niche formation in the lung and liver metastasis was observed using very high resolution imaging systems. In the lung, GFP host-mouse cells accumulated around as few as a single MMT-RFP cell. In addition, GFP host cells were observed to form circle-shaped niches in the lung even without RFP cancer cells, which was possibly a niche in which future metastasis could be formed. In the liver, as with the lung, GFP host cells could form circle-shaped niches. Liver and lung metastases were removed surgically and cultured in vitro. MMT-RFP cells and GFP host cells resembling cancer-associated fibroblasts (CAFs) were observed interacting, suggesting that CAFs could serve as a metastatic niche.

Role of connexins in metastatic breast cancer and melanoma brain colonization.

Breast cancer and melanoma cells commonly metastasize to the brain using homing mechanisms that are poorly understood. Cancer patients with brain metastases display poor prognosis and survival due to the lack of effective therapeutics and treatment strategies. Recent work using intravital microscopy and preclinical animal models indicates that metastatic cells colonize the brain, specifically in close contact with the existing brain vasculature. However, it is not known how contact with the vascular niche promotes microtumor formation. Here, we investigate the role of connexins in mediating early events in brain colonization using transparent zebrafish and chicken embryo models of brain metastasis. We provide evidence that breast cancer and melanoma cells utilize connexin gap junction proteins (Cx43, Cx26) to initiate brain metastatic lesion formation in association with the vasculature. RNAi depletion of connexins or pharmacological blocking of connexin-mediated cell-cell communication with carbenoxolone inhibited brain colonization by blocking tumor cell extravasation and blood vessel co-option. Activation of the metastatic gene twist in breast cancer cells increased Cx43 protein expression and gap junction communication, leading to increased extravasation, blood vessel co-option and brain colonization. Conversely, inhibiting twist activity reduced Cx43-mediated gap junction coupling and brain colonization. Database analyses of patient histories revealed increased expression of Cx26 and Cx43 in primary melanoma and breast cancer tumors, respectively, which correlated with increased cancer recurrence and metastasis. Together, our data indicate that Cx43 and Cx26 mediate cancer cell metastasis to the brain and suggest that connexins might be exploited therapeutically to benefit cancer patients with metastatic disease.

Fluorescence-guided surgery, but not bright-light surgery, prevents local recurrence in a pancreatic cancer patient derived orthotopic xenograft (PDOX) model resistant to neoadjuvant chemotherapy (NAC).

BACKGROUND: The aim of this study is to determine the efficacy of neoadjuvant chemotherapy (NAC) with gemcitabine (GEM) in combination with fluorescence-guided surgery (FGS) on a pancreatic cancer patient derived orthotopic xenograft (PDOX) model. METHODS: A PDOX model was established from a CEA-positive tumor from a patient who had undergone a pancreaticoduodenectomy for pancreatic adenocarcinoma. Mice were randomized to 4 groups: bright light surgery (BLS) only; BLS + NAC; FGS only; and FGS + NAC. An anti-CEA antibody conjugated to DyLight 650 was administered intravenously via the tail vein of mice with a pancreatic cancer PDOX 24 h before surgery. RESULTS: The PDOX was clearly labeled with fluorophore-conjugated anti-CEA antibody. Only one out of 8 mice had local recurrence in the FGS only group and zero out of 8 mice had local recurrence in the FGS + NAC which was significantly lower than BLS only or BLS + NAC mice, where local disease recurred in 6 out of 8 mice in each treatment group (p = 0.041 and p = 0.007, respectively). NAC did not significantly reduce recurrence rates when combined with either FGS or BLS. CONCLUSION: These results indicate that FGS can significantly reduce local recurrence compared to BLS in pancreatic cancer resistant to NAC.

Efficacy of Salmonella typhimurium A1-R versus chemotherapy on a pancreatic cancer patient-derived orthotopic xenograft (PDOX).

The aim of this study is to determine the efficacy of tumor-targeting Salmonella typhimurium A1-R (A1-R) on pancreatic cancer patient-derived orthotopic xenografts (PDOX). The PDOX model was originally established from a pancreatic cancer patient in SCID-NOD mice. The pancreatic cancer PDOX was subsequently transplanted by surgical orthotopic implantation (SOI) in transgenic nude red fluorescent protein (RFP) mice in order that the PDOX stably acquired red fluorescent protein (RFP)-expressing stroma for the purpose of imaging the tumor after passage to non-transgenic nude mice in order to visualize tumor growth and drug efficacy. The nude mice with human pancreatic PDOX were treated with A1-R or standard chemotherapy, including gemcitabine (GEM), which is first-line therapy for pancreatic cancer, for comparison of efficacy. A1-R treatment significantly reduced tumor weight, as well as tumor fluorescence area, compared to untreated control (P = 0.011), with comparable efficacy of GEM, CDDP, and 5-FU. Histopathological response to treatment was defined according to Evans's criteria and A1-R had increased efficacy compared to standard chemotherapy. The present report is the first to show that A1-R is effective against a very low-passage patient tumor, in this case, pancreatic cancer. The data of the present report suggest A1-1 will have clinical activity in pancreatic cancer, a highly lethal and treatment-resistant disease and may be most effectively used in combination with other agents.

Hand-held high-resolution fluorescence imaging system for fluorescence-guided surgery of patient and cell-line pancreatic tumors growing orthotopically in nude mice.

BACKGROUND: In this study, we investigated the advantages of fluorescence-guided surgery (FGS) in mice of a portable hand-sized imaging system compared with a large fluorescence imaging system or a long-working-distance fluorescence microscope. METHODS: Mouse models of human pancreatic cancer for FGS included the following: (1) MiaPaCa-2-expressing green fluorescent protein, (2) BxPC3 labeled with Alexa Fluor 488-conjucated anti-carcinoembryonic antigen (CEA) antibody, and (3) patient-derived orthotopic xenograft (PDOX) labeled with Alexa Fluor 488-conjugated anti-carbohydrate antigen 19-9 antibody. RESULTS: Each device could clearly detect the primary MiaPaCa-2-green fluorescent protein tumor and any residual tumor after FGS. In the BxPC3 model labeled with Alexa Fluor 488-conjugated anti-CEA, each device could detect the primary tumor, but the MVX10 could not clearly detect the residual tumor remaining after FGS whereas the other devices could. In the PDOX model labeled with Alexa Fluor 488-conjugated anti-carbohydrate antigen 19-9, only the portable hand-held device could distinguish the residual tumor from the background, and complete resection of the residual tumor was achieved under fluorescence navigation. CONCLUSIONS: The results described in the present report suggest that the hand-held mobile imaging system can be applied to the clinic for FGS because of its convenient size and high sensitivity which should help make FGS widely used.

Pathologic Complete Response and Long-Term Survival After Preoperative Chemotherapy for Transverse Colon Cancer With Para-Aortic Lymph Node Metastases.

A 52-year-old male patient was diagnosed with transverse colon cancer and synchronous stage IVA para-aortic lymph node (PALN) metastases (cT3N1bM1a of the lymph node). Six courses of mFOLFOX6 plus bevacizumab were administered as neoadjuvant chemotherapy. Computed tomography showed shrinkage of the primary tumor and PALN metastases. Extended right hemicolectomy, D3 lymph node dissection, and PALN dissection were performed. A pathologic examination indicated that the tumor had completely changed and comprised necrotic tissue with no viable cells. Therefore, it was considered that mFOLFOX6 plus bevacizumab resulted in a pathologic complete response. Postoperatively, six courses of mFOLFOX6 were administered. Six years postoperatively, the patient did not exhibit any signs of recurrence. There have been few reports of pathologic complete response after neoadjuvant therapy and resection for colon cancer with synchronous PALN metastases. This report describes a unique case involving a pathologic complete response with long-term survival after mFOLFOX6 plus bevacizumab and radical resection, including PALN dissection. Preoperative mFOLFOX6 plus bevacizumab followed by radical resection and adjuvant mFOLFOX6 therapy was safe and resulted in a good outcome. This regimen should be considered for advanced colon cancer with PALN metastases.

Effects of neoadjuvant chemotherapy for patients with obstructive colon cancer: A multicenter propensity score-matched analysis (YCOG2101).

Aim: Obstructive colon cancer is locally advanced colon cancer with poor prognosis. However, the effect of neoadjuvant chemotherapy (NAC) on obstructive colon cancer remains unclear. Therefore, this study aimed to investigate the safety and efficacy of NAC in patients with obstructive colon cancer. Methods: From January 2012 to December 2017, we collected patient data for clinical stage II/III obstructive colon cancer at seven Yokohama Clinical Oncology Group (YCOG) institutions. The long-term outcomes of the NAC and non-NAC groups were analyzed retrospectively after adjusting for patients' background characteristics using propensity score matching. Results: Among the 202 eligible patients, propensity score matching extracted 51 patients each for the NAC and non-NAC groups. After matching, the groups showed no marked differences in the background factors. All the patients in the NAC group underwent diverting stoma construction. Nineteen patients (37.3%) experienced grade 3-4 adverse events during NAC. The incidence of postoperative complications was similar between groups. The 5-year progression-free survival rates were 75.8% in the NAC group and 63.0% in the non-NAC group (p = 0.22, log-rank test). The 5-year overall survival rates were 88.5% in the NAC group and 78.8% in the non-NAC group (p = 0.09, log-rank test). Conclusion: Although NAC was feasible for obstructive colon cancer after diverting stoma construction, its effects on long-term outcomes could not be proven.

Multicenter randomized phase II study on S-1 and oxaliplatin therapy as an adjuvant after hepatectomy for colorectal liver metastases (YCOG1001).

PURPOSE: The high recurrence rate of colorectal cancer liver metastasis (CRCLM) after surgery remains a crucial problem. However, adjuvant chemotherapy after hepatectomy for CRCLM has not yet been established. This study evaluated the efficacy of adjuvant therapy with S-1 and oxaliplatin (SOX). METHODS: In a multicenter, randomized, phase II study, patients undergoing curative resection of CRCLM were randomly enrolled in a 1:1 ratio to either the low- or high-dose group. S-1 and oxaliplatin were administered from days 1 to 14 of a 3-week cycle as a 2-h infusion every 3 weeks. The dose of S-1 was fixed at 80 mg/m2. The doses in the low- and high-dose oxaliplatin groups were 100 mg/m2 (low-dose group) and 130 mg/m2 (high-dose group), respectively. This treatment was repeated eight times. The primary endpoint was the rate of discontinuation owing to toxicity. The secondary endpoints were the relapse-free survival (RFS) and frequency of adverse events (AEs). RESULTS: Between August 2010 and March 2015, 44 patients (low-dose group: 31 patients and high-dose group: 13 patients) were enrolled in the study. Of these, one patient was excluded from the efficacy analysis. In the high-dose group, five of nine patients were unable to continue the study due to toxicity in February 2013. At that time, recruitment to the high-dose group was stopped from the protocol. The relative dose intensity (RDI) for S-1 in the low- and high-dose groups were 49.8 and 48.7% (p = 0.712), and that for oxaliplatin was 75.9 and 73.0% (p = 0.528), respectively. The rates of discontinuation due to toxicity were 60 and 53.8% in the low- and high-dose groups, respectively, with no marked difference noted between the groups (p = 0.747). The frequency of grade ≥ 3 common adverse events was neutropenia (23.3%/23.1%), diarrhea (13.3%/15.4%), and peripheral sensory neuropathy (6.7%/7.7%). The disease-free survival (DFS) at 3 years was 52.9% in the low-dose group, which was not significantly different from that in the high-dose group (46.2%; p = 0.705). CONCLUSIONS: SOX regimens as adjuvant therapy after hepatectomy for CRCLM had high rates of discontinuation due to toxicity in both groups. In particular, the RDI of S-1 was < 50%. Therefore, the SOX regimen is not recommended as adjuvant chemotherapy after hepatectomy for CRCLM.

Imaging the efficacy of UVC irradiation on superficial brain tumors and metastasis in live mice at the subcellular level.

The effect of UVC irradiation was investigated on a model of brain cancer and a model of experimental brain metastasis. For the brain cancer model, brain cancer cells were injected stereotactically into the brain. For the brain metastasis model, lung cancer cells were injected intra-carotidally or stereotactically. The U87 human glioma cell line was used for the brain cancer model, and the Lewis lung carcinoma (LLC) was used for the experimental brain metastasis model. Both cancer cell types were labeled with GFP in the nucleus and RFP in the cytoplasm. A craniotomy open window was used to image single cancer cells in the brain. This double labeling of the cancer cells with GFP and RFP enabled apoptosis of single cells to be imaged at the subcellular level through the craniotomy open window. UVC irradiation, beamed through the craniotomy open window, induced apoptosis in the cancer cells. UVC irradiation was effective on LLC and significantly extended survival of the mice with experimental brain metastasis. In contrast, the U87 glioma was relatively resistant to UVC irradiation. The results of this study suggest the use of UVC for treatment of superficial brain cancer or metastasis.