Study on prediction of early adverse events by CapeOX therapy in patients with colorectal cancer.

CapeOX is a regimen used as postoperative adjuvant chemotherapy for the treatment of advanced recurrent colorectal cancer. If early adverse events occur, treatment may not progress as planned and further dose reduction may be necessary. In this study, we investigated whether pre-treatment medical records could be used to predict adverse events in order to prevent adverse events caused by CapeOX treatment. The 178 patients were classified into two groups (97 in the adverse event positive group and 81 in the adverse event-negative group) based on withdrawal or postponement of four or fewer courses. In univariate analysis, age, height, weight, body surface area (BSA), creatinine clearance, muscle mass, and lean body mass were associated with early adverse events (P<0.05). The area under the receiver operating characteristic curve obtained by Stepwise logistic regression analysis using the Akaike information criterion method was 0.832. For nested k-fold cross validation, the accuracy rates of the support vector machine, random forest, and logistic regression algorithms were 0.71, 0.70, and 0.75, respectively. The results of the present study suggest that a logistic regression prediction model may be useful in predicting early adverse events caused by CapeOX therapy in patients with colorectal cancer. J. Med. Invest. 71 : 141-147, February, 2024.

Classifying the destination of right top pulmonary vein in 31 clinical cases.

Disruption in the flow of blood vessels is of great concern during thoracic surgery. Preoperative 3-dimensional computed tomography facilitates visualization of the exact location and course of blood vessels. The right posterior upper lobe segmental vein, known as the right top pulmonary vein (RTPV), is an anomalous vein beginning at the right upper lobe and running through the posterior surface of the intermediate bronchus. We clinically investigated 31 patients with RTPV who underwent lobectomy or total resection of the right lung in our hospital or related institutions. We classified the final destination of RTPV into four types. The RTPV flowed into the left atrium in 35.5% of cases, superior pulmonary vein in 9.7%, inferior pulmonary vein in 41.9%, and independently into V6 in 12.9%. An RTPV with a diameter ≥ 5 mm was considered a main drainage vein in S2. We should pay attention to the RTPV during right lung lobectomy.

Unresectable Advanced Gastric Cancer with Skin Invasion followed by Total Gastrectomy after Second-Line Chemotherapy.

Conversion surgery has been reported but few cases have undergone surgical R0 resection after second-line chemotherapy. We report a case of an unresectable locally advanced gastric cancer in a patient who finally underwent the operation (R0) after second-line chemotherapy. The 77-year-old male was diagnosed with gastric cancer (cT4 [SI; Skin, Liver] N0M0 c Stage IIIA) with invasion to the skin of the abdominal wall, and chemotherapy was initially performed because of his poor performance status and due to the large defect in the abdominal wall that might occur if an operation was performed. Partial response (PR) was observed after S-1+CDDP (SP) therapy, which was then stopped after which progressive disease (PD) was observed. Ramucirumab+Paclitaxel (RAM/PTX) therapy was chosen as second-line therapy, and PR was obtained again, following which total gastrectomy was performed (D2 dissection of lymph nodes, Roux-en-Y reconstruction, and combined resection of the partial skin and the affected region of the liver). At 30 months postoperatively, no recurrence has occurred and the patient is alive after the operation without chemotherapy.

[Effectiveness of Ramucirumab Therapy for Advanced Gastric Cancer after Stent Placement for Esophagogastric Junction Carcinoma Obstruction-A Case Report].

According to the REGARD and RAINBOW trials, ramucirumab(RAM)was introduced as second-line therapy for advanced or metastatic gastric cancer. Endoscopic metallic stent placement and angiogenesis inhibitor administration carry the risk of gastrointestinal perforation. The outcomes of patients who undergo endoscopic placement of metallic stents during RAM treatment have not yet been fully assessed. A 60's man was diagnosed with advanced esophagogastric junction cancer(por) with Virchow's lymph node metastases. His tumor was classified as cT4a(SE), N1(#1), M1, stage Ⅳ. He received chemotherapy, but the size of the primary tumor and metastases increased. After stenting for gastric outlet obstruction, he received a paclitaxel(PTX)plus RAM regimen as third-line treatment. Because of CTCAE Grade 2 peripheral neuropathy, PTX was discontinued after 10 courses. For 11 months, tumor control without adverse events was maintained. The patient was then switched to CPT-11 as fourth-line treatment.

[Role of Cancer Chemotherapy Is Expected to Improve PS and QOL].

We report three cases of advanced lung cancer with poor PS treated with molecular-targeted drugs and consider the role of cancer chemotherapy to improve quality of life(QOL). Case 1: A 67-year-old woman(PS 3)with multiple liver, bone, and lymph node metastases from lung cancer received gefitinib and radiation therapy for bone metastasis. Abdominal CT then showed shrinkage of the liver metastasis, and daily life activities became possible after 2 months. Case 2: A 76-year-old woman with SVC syndrome from Stage ⅢA of lung cancer received gefitinib and radiation therapy. After that, edema and cough disappeared, and the PS improved from 3 to 0. Case 3: A 41-year-old woman with pleural dissemination from Stage Ⅳ lung cancer received ALK inhibitors and anticancer drug therapy for 5 years. Subsequently, a decrease in QOL was noted due to symptoms such as bloody sputum and persistence of cough. ALK inhibitors were administered as a re-challenge. A dramatic improvement in symptoms was observed in a few days. Even if the general condition is poor, PS can be improved by administering drugs such as molecular-targeted drugs.

Clinical outcomes after initial treatment of methicillin-resistant Staphylococcus aureus infections.

OBJECTIVE: To evaluate the clinical outcomes associated with anti-methicillin-resistant Staphylococcus aureus (MRSA) antimicrobials. METHODS: We reviewed a prospective database of 247 consecutive patients with clinically and microbiologically confirmed MRSA infections, hospitalized in 7 Japanese hospitals between April 2014 and March 2015, and treated with anti-MRSA pharmaceuticals. Survival was measured at 30 days. We examined the relationships between initial antimicrobial administered and survival and organ toxicity. HR and 95% CIs were calculated. RESULTS: Overall 30-day mortality was 12%. The lungs were infected in 105 (41%), skin and soft tissue in 73 (30%), and bones and joints in 21 (9%) patients. Bacteremia complicated the illness in 69 patients (28%). Among 5 pharmaceuticals, vancomycin was prescribed to 174 (71%), linezolid to 38 (16%), teicoplanin to 22 (9%), and daptomycin to 11 (5%) patients. Vancomycin tended to be associated with the lowest survival (HR=2.47; 95% CI=0.93-6.51; P=0.067), particularly in the lung-infected subgroup (HR=4.85; 95% CI=1.12-20.94; P=0.034) after adjustments for baseline illness severity. The incidence of renal dysfunction tended to be higher in patients with trough serum concentrations of vancomycin >15 mg/dL. CONCLUSION: In this observational study reflecting real-world conditions, vancomycin was associated with higher 30-day mortality and incidence of kidney dysfunction than other anti-MRSA agents. The significance of the differences observed among antimicrobials other than vancomycin is uncertain.

Progressive renal insufficiency related to ALK inhibitor, alectinib.

Alectinib is a second generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor and is generally effective and tolerated in patients who have demonstrated disease progression or adverse effects while on the first generation inhibitor, crizotinib. ALK inhibitors can cause a reversible chronic increase of serum creatinine concentration; however, they rarely induce progressive renal insufficiency. We herein report a case of a 68-year-old woman diagnosed with ALK-positive advanced non-small cell lung cancer and who received ALK inhibitors. Due to dysgeusia and transaminitis, her medication was switched from crizotinib to alectinib. Rapid progressive glomerulonephritis developed 1 year after the initiation of alectinib treatment. A renal biopsy revealed unique kidney lesions in both tubules and glomeruli. Glucocorticoid therapy partially reversed kidney impairment. However, re-administration of alectinib caused kidney dysfunction, which was improved by the cessation of alectinib. Our case suggests that much attention should be paid to kidney function when using ALK inhibitors.

A feasibility study of postoperative adjuvant chemotherapy with fluoropyrimidine S-1 in patients with stage II-IIIA non-small cell lung cancer.

BACKGROUND: Adjuvant chemotherapy with uracil tegafur (UFT) improved survival among patients with completely resected stage I lung adenocarcinoma. S-1, an oral dihydropyrimidine dehydrogenase (DPD)-inhibitory 5-fluorouracil, is a more potent DPD inhibitor than UFT;therefore, we hypothesized that postoperative adjuvant chemotherapy with S-1 would be effective for advanced non-small cell lung cancer (NSCLC). We conducted a feasibility study of S-1 as postoperative adjuvant chemotherapy in patients with curatively resected pathological stage bold I back 10 bold I and bold I back 10 bold I back 20 bold I A NSCLC. METHODS: Adjuvant chemotherapy consisted of 9 courses (4-week administration, 2-week withdrawal) of S-1 at 80-120 mg/body per day. Twenty-four patients with completely resected NSCLC were enrolled in this study from November 2007 through December 2010. The primary endpoint was the rate of completion of the scheduled adjuvant chemotherapy. The secondary endpoints were safety, overall survival, and relapse-free survival. RESULTS: Five patients were censored because of disease recurrence. The planned 9 courses of S-1 were administered to completion in 8 patients. Twelve patients completed more than 70% of the planned courses. Grade 3 adverse reactions, such as elevated total bilirubin (4.2%) and pneumonitis (4.2%), were observed, but there were no Grade 4 adverse reactions. Patients who completed more than 70% of the 9 courses demonstrated better overall survival than those who completed less than 70%. CONCLUSION: Postoperative administration of S-1 may be possible with few severe adverse events as adjuvant chemotherapy for patients with curatively resected pathological stage bold I back 10 bold I -bold I back 10 bold I back 20 bold I A NSCLC. J. Med. Invest. 65:90-95, February, 2018.

[Clinical experience of the use of pemetrexed (PEM) combined with cisplatin (CDDP)/Carboplatin (CBDCA) followed by long-term maintenance PEM in patients with non-squamous non-small cell lung cancer].

This study evaluated the efficacy and safety of pemetrexed and carboplatin (CBDCA) or cisplatin (CDDP) followed by maintenance pemetrexed for cases of advanced non-squamous non-small cell lung cancer (NSCLC) that were treated in our hospital. Patients received pemetrexed (PEM 500mg/m²) and CBDCA(area under the curve, 5 mg/[mL/min]) or CDDP (75 mg/m²) every 21 days. For patients without disease progression after 4-6 courses, pemetrexed was continued until disease progression or unacceptable toxicity. Fourteen patients received maintenance pemetrexed(median, 11.5 courses; range, 4- 43 courses). Among the 14 patients, the median progression-free survival time from the beginning of the induction treatment was 13 months. Continuation maintenance with pemetrexed after cisplatin plus pemetrexed induction is recommended as a first-line treatment for patients who have advanced non-squamous NSCLC and as a maintenance strategy.

Resection of an azygos vein aneurysm with thrombosis.

Aneurysm of the azygos vein is rare. We describe the case of a 51-year-old nonsmoking woman with a posterior mediastinal mass caused by a giant azygos vein aneurysm with subtotal thrombosis. Surgical resection of the azygos vein was offered to our patient as a treatment option owing to theoretical risks of rupture and pulmonary embolism. After taping the azygos vein proximally and distally, the aneurysm was resected with video-assisted thoracoscopy. Approximately 30 cases have been reported in the literature to date. Dynamic computed tomography and a videoassisted approach were useful for the diagnosis and treatment for this abnormality.

Lymphoepithelial cyst of the pancreas that was difficult to distinguish from branch duct-type intraductal papillary mucinous neoplasm: report of a case.

A 58-year-old woman was admitted to our hospital to optimize the management of her diabetes mellitus. A computed tomography (CT) scan showed a 30-mmdiameter, multilocular cyst in the head of the pancreas. The tumor markers, including DUPAN 2, SPAN-1, and carbohydrate antigen 19-9, were within the normal ranges. A contrast-enhanced CT scan showed a nonenhanced, multilocular cyst. Abdominal magnetic resonance imaging showed a multilocular cyst. Endoscopic retrograde cholangiopancreatography showed that the main pancreatic duct was normal. Based on these findings, we suspected a branch duct type intraductal papillary mucinous neoplasm. A distal pancreatectomy with a splenectomy was performed, since more of the mass was located on the dorsolateral side, inconsistent with the preoperative imaging results. On the resected specimen, a 4-cm-diameter, multilocular cyst containing serous fluid was found. Pathologically, the cyst wall was lined with squamous epithelium surrounded by abundant lymphoid tissue with follicles, consistent with a lymphoepithelial cyst of the pancreas, which is an unusual benign cyst.

Hepatobiliary cystadenoma exhibiting morphologic changes from simple hepatic cyst shown by 11-year follow up imagings.

BACKGROUND: A long-term follow up case of hepatobiliary cystadenoma originating from simple hepatic cyst is rare. CASE PRESENTATION: We report a case of progressive morphologic changes from simple hepatic cyst to hepatobiliary cystadenoma by 11 - year follow up imaging. A 25-year-old man visited our hospital in 1993 for a simple hepatic cyst. The cyst was located in the left lobe of the liver, was 6 cm in diameter, and did not exhibit calcification, septa or papillary projections. No surgical treatment was performed, although the cyst was observed to gradually enlarge upon subsequent examination. The patient was admitted to our hospital in 2004 due to epigastralgia. Re-examination of the simple hepatic cyst revealed mounting calcification and septa. Abdominal CT on admission revealed a hepatic cyst over 10 cm in diameter and a high-density area within the thickened wall. MRI revealed a mass of low intensity and partly high intensity on a T1-weighted image. Abdominal angiography revealed hypovascular tumor. The serum levels of AST and ALT were elevated slightly, but tumor markers were within normal ranges. Left lobectomy of the liver was performed with diagnosis of hepatobiliary cystadenoma or hepatobiliary cystadenocarcinoma. The resected specimen had a solid component with papillary projections and the cyst was filled with liquid-like muddy bile. Histologically, the inner layer of the cyst was lined with columnar epithelium showing mild grade dysplasia. On the basis of these findings, hepatobiliary cystadenoma was diagnosed. CONCLUSION: We believe this case provides evidence of a simple hepatic cyst gradually changing into hepatobiliary cystadenoma.

Giant pulmonary cyst associated with congenital pericardial defect.

Congenital defects of the pericardium are rare. This report describes a young woman with a congenital complete pericardial defect who developed a giant pulmonary cyst. After operation the patient experienced chest pain caused by myocardial ischemia due to cardiac displacement. It is important to note that heart lability in patients with congenital pericardial defects may cause grave complications after thoracotomy associated with volume loss of the residual lung.

The use of flexible silastic drains after chest surgery: novel thoracic drainage.

PURPOSE: We report a new strategy for drainage with silicon thoracic tube (Blake drain) after chest surgery. DESCRIPTION: To confirm the effect of Blake drain, we have performed a three-part study including in vitro and clinical investigations compared with those of conventional chest tubes. We carried out an in vitro analysis to achieve the best possible drainage; in the second part, we used this drain in a cohort of 30 patients to establish safety and efficacy; and in a third substudy, we carried out a nonrandomized comparison with an earlier cohort between the Blake drain group and standard, rigid drain group. EVALUATION: In vitro tests demonstrate that the drainage capability of the Blake drain depends on sufficient length in the fluted part of the structure. Clinical outcome demonstrates no significant differences. The Silastic drain (Ethicon, Inc, Somerville, NJ) group had a significantly shorter period of tube drainage compared with the conventional drain group. CONCLUSIONS: From this small study the Blake drains seem to be safe and effective. Therefore, a prospective, randomized comparison should be carried out.

[A case of rectal cancer treated by preoperative chemoradiation].

Fifty-one-year-old male visited our hospital suffering from anal pain and subileus. Further examination revealed that advanced rectal cancer which invaded to presacral space (Ai, N 0, P 0, H 0, M(-), stage IIIa) caused such symptom. We administered neo-adjuvant chemoradiotherapy for fear of non curative resection of the rectum. The regimen was once weekly administration of intravenous CPT-11 40 mg, plus daily oral administration of UFT-E 600 mg/day and Uzel 75 mg/day for 4 weeks. In addition we underwent radiation 2.4 Gy/day and intravenous low-dose cisplatin (CDDP) 5 mg/day, 5 days/week for 3 weeks. Four weeks after the first administration, a partial response was confirmed on CT, and so we carried out an abdominoperineal resection. The postoperative course is almost uneventful without a little perineal infection. The specimen revealed that no malignant lesion remained, which changed to necrotic tissue. The side effects were not so severe. For example, diarrhea, nausea, and mucosal dysfunction were each less than grade 2, and there was much tolerate for renal, liver, and bone marrow function. This combination chemoradiotherapy is considered to be effective for locally advanced rectal cancer.

Matrix metalloproteinase inhibitor MMI-166 inhibits lymphogenous metastasis in an orthotopically implanted model of lung cancer.

Matrix metalloproteinases (MMP) are considered to be critically involved in tumor invasion and the metastasis of various cancers. MMI-166 is a selective inhibitor of matrix metalloproteinase (MMP-2, MMP-9, and MMP-14). The purpose of this study was to evaluate the effects of MMI-166 on both the growth of the implanted tumor and the lymph node metastasis of the mediastinum and prolonging the life span, using an orthotopic implantation model of the Ma44-3 cancer cell line. We examined the anti-invasive effect of MMI-166 in lung cancer cell lines using an in vitro invasion assay. Next, we examined the anticancer effect of MMI-166 in vivo. MMI-166 (200 mg/kg body weight) or a vehicle was administered orally to the orthotopically implanted lung cancer model. MMI-166 dose-dependently inhibited the invasion of cancer cell lines with expressions of MMP-2 and/or MMP-9 in vitro. In vivo, MMI-166 significantly inhibited mediastinal lymph node metastasis in this orthotopic model (weight of the mediastinum: control, 0.089 +/- 0.009 versus MMI-166, 0.069 +/- 0.008 mg; P = 0.005; metastatic area: control, 93,495 +/- 55,747 versus MMI-166, 22,747 +/- 17,478 pixels; P = 0.045). MMI-166 prolonged the life span by 6 days in median survival time in the orthotopically implanted model (P = 0.039). These results showed that MMI-166 could possibly inhibit lymph node metastasis and prolong the life span in lung cancer patients.

Orthotopically implanted SCID mouse model of human lung cancer suitable for investigating metastatic potential and anticancer drug effects.

To evaluate the effects of drugs in clinical settings, an animal model of lung cancer similar to clinical cancer is necessary. Our previous studies described an SCID mouse model using orthotopic implantation of the human lung cancer cell line which mimicked the lymph node metastasis of patients with lung cancer. In this study, we made animal models that reflected various metastatic forms of lung cancer in humans. We applied our procedure to 6 lung cancer cell lines. Suspensions of 2.0 x 10(4) cancer cells were injected into the left lung of SCID mice. We evaluated the mRNA expressions of 52 proteins related to the metabolism of and resistance to anticancer drugs of each tumor cell line and its orthotopically implanted tumor using a customized cDNA array. Three lung cancer cell lines had the potential of lymphogenous metastasis and 3 cell lines had the potential of hematogenous metastasis in this model system. The A549 line showed multiple metastases, and Ma2 line showed solitary metastasis. The expression of 52 genes in each implanted tumor was closely correlated with that in each cell lines (correlation coefficients: 0.8883-0.9533), and the gradient of the regression line was more than 0.9. This model was similar to the metastatic form in patients with lung cancer. The similar expression of proteins in each tumor cell line in vitro and implanted tumor in vivo gives an advantage in evaluating the effects of molecular-targeted drugs and the relationship between specific genes and tumor potential in preclinical studies.

Green fluorescent protein expression and visualization of mediastinal lymph node metastasis of human lung cancer cell line using orthotopic implantation.

BACKGROUND: Suppression of lymphatic metastasis improves survival in lung cancer patients. We have reported a patient-like model of lung cancer metastasis based on orthotopic implantation in severe combined immunodeficiency (SCID) mice and demonstrated the lymphogenous spread histologically using human NSCLC cell lines. MATERIALS AND METHODS: To visualize micrometastases, we transfected the Aequorea Victoria jellyfish green fluorescent protein (GFP) gene to the cancer cell line. RESULTS: The tumor cell lines were able to stably express GFP at high levels both in vitro and in vivo. Fluorescent tumors and metastasis of the mediastinum could be visualized at microscopic levels after transplantation. CONCLUSION: This model demonstrated that GFP gene-transfected tumor cells represent a new tool for evaluating the metastatic process and are very useful for developing chemotherapy to inhibit metastasis.