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A 53-year-old woman was admitted to another hospital because of a 2-month history of repeated chest pain and breathlessness. Laboratory examinations demonstrated the presence of hypereosinophilia (absolute count of 6,500/mu L). An endomyocardial biopsy confirmed eosinophilic infiltration with myocardial destruction. On cardiac magnetic resonance imaging, late gadolinium enhancement was clearly observed along the visceral pericardium as well as on the endocardial layer. Based on the multimodal imaging and histopathological fmdings, the final diagnosis of "Loffler pancarditis" was made. After the introduction of steroid therapy, the left ventricular contractile function significantly recovered. Furthermore, the late gadolinium enhancement of the visceral pericardium had attenuated.

Both myocardial perfusion scintigraphy andWe retrospectively analyzed 64 patients (65.0 ± 11.2 years, 53% male) with suspected CS who underwent myocardial single-photon emission computed tomography (SPECT) withThe washout score was significantly higher for the CS group than for the non-CS group (3.0 [-1.0-5.0] vs. 0.0 [-0.5-1.0], p = 0.010). Receiver operating characteristic analysis showed that a washout score of ≥ 2 had the best accuracy for detecting CS (88% sensitivity and 56% specificity) and FDG positivity (71% sensitivity and 89% specificity). In the segment-based analysis of 833 segments from 49 patients, excluding 15 patients with diffuse FDG uptake, the median SUVs for FDG uptake for the washout scores of ≤ 0, 1, and 2 were 2.3 (1.8-3.6), 4.2 (2.9-7.8), and 8.3 (6.5-9.4), respectively (p 0.001).The washout of

Background Fluorouracil (5-FU), leucovorin (LV) and oxaliplatin (FOLFOX) plus panitumumab therapy is a commonly used first-line chemotherapy for metastatic colorectal cancer (mCRC). However, the long-term administration of oxaliplatin is associated with peripheral neuropathy (PN). We investigated whether the planned discontinuation of oxaliplatin after FOLFOX plus panitumumab therapy can maintain efficacy and reduce PN incidence. Patients and methods Chemotherapy-naive patients with RAS wild-type mCRC, aged ≥20 years, were enrolled and received six cycles of modified FOLFOX6 (mFOLFOX6) plus panitumumab as induction therapy. Patients who completed induction therapy without progression were randomised to mFOLFOX6 plus panitumumab (group A) or to 5-FU/LV plus panitumumab (group B). The primary end-point was the progression-free survival (PFS) rate at 9 months after randomisation. The secondary end-points were PFS, overall survival (OS), time to treatment failure (TTF), response rate (RR) and safety. Results In total, 164 patients were enrolled; of whom, 113 patients were then randomised (group A, n = 56; group B, n = 57). The median follow-up after randomisation was 19.6 months. The PFS rates at 9 months and median PFS were 46.4% (80% confidence interval [CI], 38.1–54.9) and 9.1 months (95% CI, 8.6–11.1) in group A, compared with 47.4% (80% CI, 39.1–55.8) and 9.3 months (95% CI, 6.0–13.0) in group B, respectively. RR, OS and TTF were also similar in both groups. Grade ≥2 PN incidence was lower in group B (9.3%) than in group A (35.7%). Conclusion Planned discontinuation of oxaliplatin after six cycles of mFOLFOX6 plus panitumumab is a potential treatment option in patients with mCRC, achieving similar efficacy while reducing oxaliplatin-associated PN compared with mFOLFOX6 plus panitumumab. Trial registration number NCT02337946

Background/aim The aim of this study was to investigate the effects of preoperative chemotherapy on the healthy, metastasis-free part of the liver in colorectal cancer patients with liver metastasis, and the relationship between chemotherapy and postoperative complications. Patients and methods Our study included 90 cases of colorectal cancer liver metastasis resected after preoperative chemotherapy. The patients were divided into three groups according to the received chemotherapy regimen: 20 cases received mFOLFOX6, 54 cases a combination of mFOLFOX6 with bevacizumab, and 16 cases a combination of mFOLFOX6 and cetuximab or panitumumab. Results The mean numbers of sinusoidal injuries for each chemotherapy type were compared. The group treated with the combination of mFOLFOX6 and bevacizumab showed a lower extent of sinusoidal injury relative to other groups; this intergroup difference became increasingly remarkable as the number of chemotherapy cycles increased. Complications of various extents were found in all three groups, but no significant differences were observed between the three groups. Conclusion In cases where preoperative chemotherapy was extended over a long period, combined use of bevacizumab was thought to be effective because of stabilization of disturbed liver hemodynamics resulting from sinusoidal injury suppression effects, allowing effective distribution of anti-cancer agents to tumors.

A 70-year-old man was diagnosed with colon cancer with multiple liver metastases.He was administered modified FOLFOX6 plus panitumumab as first-line chemotherapy.He showed consciousness disturbance on the 3rd day during the 8 cycle and was hospitalized urgently.We diagnosed him with 5-FU-induced hyperammonemia.Administration of branchedchain amino acid preparation improved his consciousness disturbance.After changing the regimen of chemotherapy to another one containing oral fluoropyrimidine, the recurrence of hyperammonemic encephalopathy was not found.

Gemcitabine plus nab-paclitaxel (GnP) is widely used in clinical practice, despite a lack of prospective data to validate its efficacy in locally advanced pancreatic cancer (LAPC). We conducted a phase II study of GnP for LAPC to assess its efficacy and safety. We performed a single-arm, single-institution study with GnP in 24 patients with LAPC. The treatment protocol included successive administration of gemcitabine (1000 mg/m2) and nab-paclitaxel (125 mg/m2). The primary endpoint was the tumor overall response rate (ORR), and secondary endpoints were overall survival (OS), progression-free survival (PFS), and adverse events (AEs). The median PFS was 11.0 months, median OS was 21.2 months, ORR was 62.5%, and 37.5% of the patients had stable disease. Four (16.7%) of the patients were converted to surgical resection; 3 of these achieved R0 resection. Grade 3 to 4 AEs included hematological (neutropenia, 64%; thrombocytopenia, 12%), nonhematological (cholangitis, 16%), and sensory neuropathy (4%). These AEs were manageable and tolerable. The GnP treatment in patients with LAPC showed favorable tumor shrinkage, good toxicity profile, and enabled conversion to surgical resection in a subset of patients; therefore, GnP is an option for first-line chemotherapy in patients with LAPC.

Patient: Male, 52-year-old Final Diagnosis: Tetralogy of Fallot (TOF) Symptoms: Palpitation Medication: — Clinical Procedure: Computed tomography • echocardiography • magnetic resonance imaging Specialty: Cardiology Objective: Congenital defects/diseases Background: Intracardiac repair of tetralogy of Fallot (TOF) is generally performed during childhood. However, the majority of patients develop the sequelae long after surgical repair, which results in significant right ventricular (RV) dilation, RV myocardial dysfunction, and, ultimately, in right-sided heart failure. Case Report: A 52-year-old man was referred to our institution for the evaluation of sudden-onset ventricular tachycardia. His medical history included RV outflow tract reconstruction at 5 years of age. Auscultation revealed a harsh diastolic regurgitant murmur, widely split first heart sound (S1), and a single second heart sound (S2), indicating a severely dilated RV due to severe pulmonary regurgitation (PR) and the presence of a non-functioning pulmonary valve. Moreover, the right-sided third heart sound (S3) and fourth heart sound (S4) were present, consistent with elevated RV filling pressure and the presence of a non-compliant RV. Eventually, the aforementioned “heart sound quintet” was confirmed using multimodal evaluation as right-sided heart failure with a concomitant severely dilated RV because of complete regression of the pulmonary valve and resultant free PR. Conclusions: We encountered a case with a “heart sound quintet” that was composed of a widely split S1, single S2 with a harsh diastolic regurgitant murmur, and right-sided S3 and S4. The logical interpretation of the findings from physical examination will contribute to understanding the pathophysiology and aid clinical decision-making.

The case involved a 44-year-old man who underwent intersphincteric resection and lateral lymph node dissection for rectal cancer. Pathological diagnosis revealed a well-differentiated adenocarcinoma comprising KRAS wild type, and pT2N0M0 (pathological Stage I). CapeOX (capecitabine plus oxaliplatin[L-OHP]), and bevacizumab therapy was initiated because of local recurrence. Although a partial response (PR) was observed, the therapy was terminated after 6 courses because of the development of hand-foot syndrome. FOLFIRI and cetuximab therapy was initiated after cancer recurrence was observed during a follow up. As the therapeutic efficiency is characterized by stability (stable disease: SD), and the tumor reduction effect observed was not sufficient, we performed an abdominoperineal resection to achieve local control. However, a left hydronephrosis occurred due to the pelvic recurrence, necessitating the emergency hospitalization of the patient. Because resistance to L-OHP was not confirmed, mFOLFOX6 and bevacizumab therapy was introduced in hopes of the effect of the former. As Grade 2 allergy (erythema) appeared immediately after the L-OHP was administered during the 3 courses, treatment was discontinued. We the reinitiated the treatment along with the desensitization therapy from the 4 courses. A total of 27 courses of mFOLFOX6 and bevacizumab therapy were administered until the state of disease progression (progression disease: PD) was determined. PR was defined as the best therapeutic efficiency. In some cases, discontinuation of treatment is necessary as observed in the present case due to the onset of L-OHP allergies, even if the overall effect of the treatment is expected to be good. Our case is essentialas it demonstrates the successfulness of desensitization therapy for L-OHP allergies.

The purpose of this phase II study was to explore the efficacy and safety of an alternating regimen consisting of folinic acid, 5-fluorouracil (5-FU) and oxaliplatin (mFOLFOX6) plus bevacizumab, and folinic acid, 5-FU and irinotecan (FOLFIRI) plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer. Fifty-two patients with metastatic colorectal cancer received an alternating regimen consisting of four cycles of mFOLFOX6 plus bevacizumab followed by four cycles of FOLFIRI plus bevacizumab until disease progression. The primary endpoint was progression-free survival. The median age was 60 years (range 37–75 years). Median progression-free survival was 14.2 months (95 % confidence interval [CI] 10.6–16.3) and median overall survival was 28.4 months (95 % CI 22.6–39.1). The overall response rate was 60.0 % (95 % CI 45.2–73.6). Regarding toxicity, the commonest grade 3–4 hematological adverse events were neutropenia (34.6 %) and leukopenia (7.7 %), and the commonest grade 3–4 non-hematological adverse events were anorexia (13.5 %), fatigue (9.6 %), nausea (9.6 %), and vomiting (9.6 %). Bevacizumab-related grade 3–4 adverse events included hypertension (1.9 %) and thrombosis (1.9 %). An alternating regimen consisting of mFOLFOX6 plus bevacizumab and FOLFIRI plus bevacizumab is an effective and well-tolerated first-line chemotherapy combination for patients with metastatic colorectal cancer.

A 69-year-old man underwent right hemicolectomy for ascending colon cancer with liver metastases. Postoperative systemic chemotherapy did not reduce the metastases, and therefore, hepatic arterial infusion chemotherapy (HAI) was administered. The metastases decreased in size after 26 rounds of therapy, and the patient underwent resection. He is recurrence-free 63 months after the primary operation. A 57-year-old man underwent Hartmann's operation for sigmoid colon cancer with liver metastases. He underwent hepatic left lobe resection after metastases reduction by systemic chemotherapy. However, multiple liver metastases were detected 2 months later. Because the disease progressed despite the administration of systemic chemotherapy, HAI was utilized instead. The metastases decreased in size remarkably, and resection was performed. The patient is surviving 52 months after the primary operation while being continuously treated with HAI, resection, and systemic chemotherapy for re-recurrence. HAI is a potential alternative treatment for patients with colorectal liver metastases resistant to systemic chemotherapy.

S-1 plus cisplatin is the standard chemotherapy for recurrent gastric cancer. While depression and delirium are frequent in cancer patients, hypomania during chemotherapy is rare. We describe a rare case of hypomania during S-1 plus cisplatin treatment for recurrent gastric cancer. A 66-year-old woman, with no previous psychiatric disorder, received S-1 plus cisplatin for recurrent gastric cancer. She showed peculiar behavior. Physical examination, urine, blood and imaging findings were normal. There was no gastric cancer progression. During psychiatric consultation, she behaved inappropriately. However, she behaved normally while performing daily activities. She manifested a persistently elevated, expansive or irritable mood, clearly different from her usual non-depressed state, meeting hypomania diagnostic criteria. Her condition did not require chemotherapy discontinuation or additional medication. During the second and subsequent S-1 plus cisplatin cycles, symptoms were stable. Cancer patients often have adjustment disorders, depression and delirium, but rarely hypomania. Our patient showed no significant changes in blood biochemistry and brain and whole body imaging. While S-1 plus cisplatin-induced hypomania cannot be excluded, hypomanic symptoms did not improve during the chemotherapy rest period, nor was there deterioration during subsequent cycles, suggesting drug-induced mania to be unlikely. Possible onset mechanisms include manic defense phenomena, common with stressful life events. There are no reports of recurrent gastric cancer patients experiencing hypomania during S-1 or S-1 plus cisplatin therapy, i.e. our patient represents a rare course. Clinicians should recognize psychosis or mood disorders during gastric cancer treatment. Further accumulation of such rare cases might elucidate pathological mechanisms underlying hypomania in cancer patients.

Patients with cancer often receive chemotherapeutic agents concurrently with other medications to treat comorbidity. The practical effects of concomitant medications, especially polypharmacy, on adverse drug reactions related to irinotecan-based chemotherapy are not well documented. Associations of adverse drug reactions related to irinotecan monotherapy or a combination of irinotecan, 5-fluorouracil, and l-leucovorin (FOLFIRI) with concomitant medicines used to treat comorbidity were retrospectively investigated in Japanese patients with cancer. Of the 172 patients, 118 received concomitant medications. Twenty-one patients had grade 4 neutropenia and/or grade 3 or 4 diarrhea. Univariate and multivariate analyses revealed that concomitant medications were significantly associated with irinotecan-related severe neutropenia and/or diarrhea (P = 0.023 and 0.044). Multiple concomitant medications were significantly related to severe irinotecan-related toxicity in patients given monotherapy or FOLFIRI (P = 0.01). The incidence of severe irinotecan-related toxicities increased in parallel with the number of concomitant medications. We found that multiple concomitant medicines were significantly associated with severe irinotecan-related toxicity, indicating that polypharmacy must be effectively managed to decrease the risk of adverse drug reactions in patients with cancer who received irinotecan-based chemotherapy.

This exploratory retrospective study examined the effects of polymorphisms in transporter genes related to irinotecan pharmacokinetics and those in genes related to irinotecan pharmacodynamics on the efficacy of first-line combination chemotherapy with irinotecan, 5-fluorouracil, and folinic acid (leucovorin) (FOLFIRI) in Japanese patients with advanced colorectal cancer. All patients harbored UDP-glucuronosyltransferase (UGT) 1A1*1/*1, *1/*6, or *1/*28 genotypes, which are associated with similar irinotecan pharmacokinetics and responses to FOLFIRI. Genetic polymorphisms were analyzed by direct sequencing. Overall response rate and median progression-free survival in a total of 61 patients were 43% and 7.5 months, respectively. The overall response rate was higher in patients with the CC genotype at -24 in ATP-binding cassette, subfamily C, and member 2 (ABCC2) than in the others (p = 0.0313). Median progression-free survival was the longest in patients with CC at -24 in ABCC2, followed by those with CT and TT (p = 0.00910). A clear gene-dose effect was seen between -24C>T and median progression-free survival. No other polymorphisms tested were related to the efficacy of FOLFIRI. We thus found that the -24C>T polymorphism in the ABCC2 gene was significantly associated with the efficacy of first-line FOLFIRI in Japanese patients with advanced colorectal cancer.

Differences in efficacy and toxicity between UDP-glucuronosyltransferase (UGT) 1A1*1/*1 and *1/*6 or *1/*28 genotypes remain unclear in Japanese patients. Patients with advanced colorectal cancer who received irinotecan combined with 5-fluorouracil plus l-leucovorin (FOLFIRI) as first-line therapy were divided into two groups: those with UGT1A1*1/*1 genotype and those with UGT1A1*1/*6 or *1/*28 genotype. Efficacy and toxicity were compared between these groups retrospectively. Forty-two patients (24 *1/*1 and 18 *1/*6 or *1/*28) were evaluated. The response rate was 48% in *1/*1 group and 56% in *1/*6 or *1/*28 group (P = 0.847). Median progression-free survival was 8.6 months in *1/*1 group and 8.5 months in *1/*6 or *1/*28 group (P = 0.888). No hematologic or non-hematologic toxic effects were clearly related to UGT1A1*1/*6 or *1/*28 during the first cycle or throughout the entire course of chemotherapy. There were no significant differences in the efficacy or toxicity of FOLFIRI between patients with UGT1A1*1/*1 genotype and those with UGT1A1*1/*6 or *1/*28 genotype. Our results suggest that patients with the latter genotypes can receive FOLFIRI at the same dose of irinotecan as those with the UGT1A1*1/*1 genotype receive.

A middle-aged man who underwent a thorough examination for epigastric pain was diagnosed with unresectable pancreatic cancer and referred to our department. A circumaortic left renal vein1 was incidentally detected on abdominal CT (figures 1 and 2). The ventral branch of the left renal vein (red arrow) ran between the aorta and the superior mesenteric artery, and …

A middle aged man underwent sigmoidectomy and hepatic metastasis resection for sigmoid cancer and hepatic metastases, respectively. Subsequently, hepatic arterial infusion therapy was performed for recurrence after the hepatic metastasis resection. However, no local control was obtained, and metastasis occurred at a site other than the liver, namely, the diaphragm. Therefore, the patient was referred to our department for systemic chemotherapy. Abdominal …

Pulmonary resection for colorectal metastases is well accepted. However, the main cause of death after pulmonary resection is recurrence in the lung. The aim of this study was to clarify whether a repeat pulmonary resection was warranted in patients with recurrent lung metastases. The records of 76 patients undergoing initial pulmonary resection, including 14 patients undergoing a repeat operation for lung metastases, were reviewed for survival, operative morbidity, and mortality. Overall, pulmonary resection was performed 96 times in this group of patients. The operative mortality was 0%, morbidity involved only one case of major postoperative hemorrhage associated with the first operation. The cumulative 5-year survival rate for the 76 patients was 32%. After the second pulmonary operation, recurrence was identified in 79% (11 of 14) of the patients. In 10 patients with isolated lung recurrence after a first pulmonary resection, who showed no extrapulmonary disease before or at the time of first thoracotomy, the 3-year, and 5-year-survival rate after the second pulmonary resection was 67%, and 33%, respectively, comparing favorably with the survival rate in those who underwent primary pulmonary resection. In contrast, all 4 patients with extrapulmonary disease before or at the time of thoracotomy had poor prognosis. Repeat pulmonary operation for isolated recurrent colorectal metastases to the lung yielded results comparable to those after the first pulmonary resection in terms of operative mortality and survival in the absence of hilar/mediastinal lymph node or extrathoracic involvement.

A giant bulla of the lung is suggested as a risk factor for lung cancer. Here we report a case with lung cancer in a giant bulla, which showed rapid progression. A 57-year-old man, who had a history of heavy smoking, was admitted to our hospital due to hemoptysis. A chest X-ray revealed a giant bulla with a ground glass shadow and a high fluid level in the right upper lung. Sputum cytology was negative for malignant cells. A chest X-ray a month later showed increases of the size of the radio-opaque shadow and of the air-fluid retention, suggesting pulmonary hemorrhage from the giant bulla. Limited resection or lobectomy was indicated, but pneumonectomy was performed due to the severe air-leak. Macroscopically, a multiple nodular tumor arose from the bulla wall, which might be related to blood flow and necrotic tissue. The postoperative pathological diagnosis was papillary adenocarcinoma. Unfortunately, the patient developed a recurrence of carcinoma in the pleuroperitoneal cavity and died at 2.5 months after the operation. Based on this report and review of other cases in the literature, we should keep in mind the rapid progression of lung cancer in association with an emphysematous bulla.

Objective: Optimal tracheobronchial stenosis treatment in esophageal cancer remains a clinical challenge.Methods: Subjects were 26 patients with tracheobronchial stenosis due to esophageal cancer treated by modalities such as expandable metallic stent emplacement, laser therapy, radiotherapy, and/or chemotherapy. We assessed patient outcome and modality efficacy, and determined prognostic factors for survival using multivariate analysis.Results: Of the 26, 16 (61%) had improved respiration after treatment. Average post-treatment survival was 140 days (10–1550 days). Multivariate analysis indicated that a Karnofsky performance score of ≥70% was the most significant prognostic factor, with chemotherapy and laser therapy also significant factors.Conclusions: Although individual modalities were effective in ameliorating respiratory symptoms, patients with good performance status survived the longest. After a tracheobronchial stenosis diagnosis in esophageal cancer patients, chemotherapy and laser therapy are recommended if the patient is in good general condition.

Silicone stents are widely used to treat benign or malignant airway stenosis. However, since straight silicone stents placed into the subglottic trachea to treat stenosis display a high risk of migration, novel approaches are required. The present report outlines our method of external fixation for silicone stents in the subglottic trachea. This technique utilizes a fixation apparatus, is readily performed, and may help to overcome the hesitation seen in placing silicone stents for subglottic tracheal stenosis.

A 33-year-old woman being treated for rheumatoid arthritis was referred to our hospital for investigation of a mediastinal mass. A chest computed tomography scan showed an anterior mediastinal mass, 8.5 x 7.0 cm in size, with a cystic lesion and calcification. These findings were suggestive of either a noninvasive thymoma or a mature teratoma. Therefore, we performed tumor resection and thymectomy. Histologically, the tumor consisted of diffuse deposits of massive eosinophilic amorphous material. The tumor was stained red-orange by Congo red, and the staining disappeared following potassium permanganate digestion. Based on these findings, a diagnosis of reactive amyloidosis of the amyloid A-protein-derived type was made. Amyloidosis in the mediastinum has rarely been described.

A 74-year-old woman who had undergone surgery for rectal cancer and also had lung metastases developed abdominal pain, diarrhoea and bloody stools 5 days after receiving her 22nd dose of S-1, oxaliplatin and bevacizumab therapy.1 She was admitted to the hospital with a suspected adverse reaction to chemotherapy and infectious enteritis. CT imaging …

BACKGROUND: The biological basis for cancer of unknown primary (CUP) at the molecular level remains largely unknown, with no evidence of whether a common biological entity exists. Here, we assessed the possibility of identifying a common diagnostic biomarker for CUP using a microarray gene expression analysis. METHODS: Tumor mRNA samples from 60 patients with CUP were analyzed using the Affymetrix U133A Plus 2.0 GeneChip and were normalized by asinh (hyperbolic arc sine) transformation to construct a mean gene-expression profile specific to CUP. A gene-expression profile specific to non-CUP group was constructed using publicly available raw microarray datasets. The t-tests were performed to compare the CUP with non-CUP groups and the top 59 CUP specific genes with the highest fold change were selected (p-value

We report here a case of reversible posterior leukoencephalopathy syndrome(RPLS)induced by modified FOLFOX6(mFOLFOX6). The patient was a 43-year-old woman who had sigmoid colon cancer with multiple liver metastases. Treatment with mFOLFOX6 was started. Early in the morning of day 11, the patient was transported by ambulance to the hospital due to nausea with headache, disturbed consciousness, and visual disturbance. The patient experienced sudden, severe nausea and subsequently presented generalized tonic-chronic seizures. The seizures subsided after treatment. On the evening of day 11, another episode of generalized tonic-chronic seizures occurred. Status epilepticus developed and tracheal intubation was performed for airway protection. Cranial MRI showed increased signal intensity in both occipital lobes, centered on the boundary between the gray and white matter on FLAIR images. Her condition stabilized with no seizure recurrence following intubation. Although hypertension was present on admission to the emergency room, blood pressure gradually fell to within the normal range without antihypertensive treatment. She was extubated on day 18. There were no neurologic sequelae. Cranial MRI on day 40 showed that the increased intensity in both occipital lobes had almost disappeared. Because the patient's condition was characterized by a reversible central nervous system disorder, RPLS was diagnosed.

Small cell carcinoma of the gastrointestinal tract is rare, and no effective strategy has yet been established. On the basis of regimens reportedly effective for small cell lung cancer, we performed chemotherapy with cisplatin plus etoposide in combination with radiotherapy to relieve obstruction, in a patient with small cell carcinoma of the gastro-oesophageal junction. Chemotherapy was switched to carboplatin plus etoposide due to renal toxicity. No distant metastases were detected and lesion spread was limited. A complete response, with no evidence of recurrence to date, was achieved. Curative resection was suggested but refused by the patient. He has been closely followed up in our outpatient clinic for more than a year and has shown no evidence of recurrence since the completion of treatment. Although cisplatin plus etoposide is a standard chemotherapy regimen for small cell carcinoma, carboplatin plus etoposide may be effective in cases in which cisplatin is contraindicated due to renal toxicity.

A 74-year-old man, who had been receiving S-1 plus cisplatin combination chemotherapy for gastric cancer and metastatic disease of the liver,1 developed disorientation, amnesia and anorexia on day 13 of the fourth cycle of the chemotherapy regime. On day 16, he was reviewed in the outpatients department and was admitted as an emergency. MRI of the brain obtained on his admission showed no metastatic …

To evaluate the safety and efficacy of combination chemotherapy with 5-fluorouracil (5-FU), leucovorin, irinotecan and oxaliplatin (FOLFOXIRI) in Japanese patients with advanced colorectal cancer.This phase I dose-finding study was designed to determine the maximum tolerated dose (MTD), recommended dose (RD) or both of FOLFOXIRI. Patients with UDP-glucuronosyltransferase (UGT) 1A1*6/*6, *28/*28 and *6/*28 genotypes were excluded, because these UGT1A1 genotypes are linked to severe neutropenia in Japanese.A total of 10 Japanese patients with advanced colorectal cancer were studied. The MTD of FOLFOXIRI in these Japanese patients was 165 mg/m(2) irinotecan, 85 mg/m(2) oxaliplatin and 2,400 mg/m(2) 5-FU. Accordingly, the RD of FOLFOXIRI was determined to be 150 mg/m(2) irinotecan, 85 mg/m(2) oxaliplatin and 2,400 mg/m(2) 5-FU. Toxic effects, evaluated until the completion of 4 cycles, were manageable. Grade 3-4 neutropenia occurred in 27% of cycles, but there was no febrile neutropenia. Among the 9 assessable patients, the objective response rate was 89%.We thus determined the RD of FOLFOXIRI in Japanese patients with advanced colorectal cancer who do not have UGT1A1*28/*28, *6/*6 or *6/*28 genotypes. Our results indicate that FOLFOXIRI is a well-tolerated regimen for these Japanese patients.

Objective: We examined the feasibility of regimen selection for first-line irinotecan, 5-fluorouracil and leucovorin or oxaliplatin, 5-fluorouracil and leucovorin in Japanese patients with advanced colorectal cancer based on UDP-glucuronosyltransferase 1A1 genotype as well as physical status of patients related to diarrhea. Methods: As first-line irinotecan, 5-fluorouracil and leucovorin is a little bit superior to oxaliplatin, 5-fluorouracil and leucovorin with respect to efficacy and toxicity, patients without risk factors of irinotecan-induced toxicity were first assigned to irinotecan, 5-fluorouracil and leucovorin. Patients with UDP-glucuronosyltransferase 1A1*28/*28, *6/*6, *28/*6 or *28/*27 and those with ascites, peritoneal dissemination or diarrhea first received oxaliplatin, 5-fluorouracil and leucovorin to avoid the irinotecan-induced neutropenia and diarrhea, respectively. We retrospectively evaluated the feasibility of this strategy by assessing toxicity and total progression-free survival in first- and subsequent second-line therapies in all patients studied. Results: In the first-line irinotecan, 5-fluorouracil and leucovorin (n ¼ 61), Grade 4 neutropenia, febrile neutropenia and Grade 3 diarrhea occurred in 8.2, 3.3 and 3.3% of patients, respectively. In the first-line oxaliplatin, 5-fluorouracil and leucovorin (n ¼ 26), Grade 4 neutropenia, febrile neutropenia, Grade 3 thrombocytopenia and Grade 3 neuropathy were observed in 11.5, 3.8, 3.8 and 7.7% of patients, respectively. In the second-line oxaliplatin, 5fluorouracil and leucovorin (n ¼ 38), Grade 3 diarrhea occurred in 2.6% of patients. In the second-line irinotecan monotherapy (n ¼ 11), Grade 4 or febrile neutropenia occurred in 18% of patients and Grade 3 diarrhea in 9.1% of patients. In second-line S-1 (n ¼ 9), Grade 3 anemia occurred in 2 patients. Median total progression-free survival in all 87 patients was 11.5 months. Conclusions: Present regimen selection strategy would be feasible, since it causes less toxicity and similar efficacy comparing to previous studies. Determination of appropriate reduced dose in the second-line irinotecan monotherapy or other standard second-line therapy for patients with high-risk to irinotecan-induced toxicity might make this strategy more effective.

We report here the case of a 64-year-old man with sternal osteomyelitis after pneumonectomy through a median sternotomy who was successfully treated using a pedicled omental flap. This is the first report in the literature to describe sternal osteomyelitis and mediastinitis after pneumonectomy. In this case, the visceral pleura of the remnant right lung was located just under the infected sternum. Careful management is recommended because empyema pleurae can be a fatal complication.

This prospective study is designed to examine the effects of severe renal failure on the pharmacokinetics of irinotecan. The pharmacokinetics of irinotecan, 7-ethyl-10-hydroxycamptothecin (SN-38), and SN-38 glucuronide (SN-38G) in three cancer patients with severe renal failure [creatinine clearance (Ccr) ≤ 20 ml/min] who were undergoing dialysis and received 100 mg/m(2) irinotecan as monotherapy were prospectively compared with those in five cancer patients with normal renal function (Ccr ≥ 60 ml/min). To ensure that the subjects had similar genetic backgrounds of UDP-glucuronosyltransferase (UGT) 1A1, patients with UGT1A1*1/*1, *1/*6, or *1/*28 were enrolled. The estimated terminal elimination rate constant of SN-38 in patients undergoing dialysis was approximately one tenth of that in patients with normal renal function (P = 0.025). Approximately 50% of SN-38 was dialyzed with a 2.1-m(2) dialysis membrane, whereas 27% was dialyzed with a 1.5-m(2) membrane. Our results showed that the elimination of SN-38 was significantly delayed in patients with severe renal failure compared with patients with normal renal function. We demonstrated that SN-38 was partly dialyzed.

We developed a population pharmacokinetic (PPK) model of S-1 including the cytochrome P450 (CYP) 2A6 genotype and then used this PPK model to assess the influence of the CYP2A6 genotype on PK parameters of S-1 and the relationship between toxicity and the individual maximum concentrations (Cmax) or the area under the concentration-time curve (AUC) of 5-fluorouracil (5-FU) in Japanese patients with advanced cancer. Fifty-eight patients with advanced cancer were assessed. A dose of 80 mg/m(2)/day of S-1 was given orally. On the basis of the CYP2A6 genotypes (*1, *4, *7 and *9), all patients were classified as having the wild-type, 1 variant allele or 2 variant alleles. The PPK model was established with plasma concentration data for tegafur (FT), 5-chloro-2,4-performed dihydroxypyridine (CDHP) and 5-FU. In patients with 2 variant alleles of CYP2A6, the clearance of FT was 58% less than in patients with the wild-type or 1 variant allele. The AUC of 5-FU correlated with the AUC of CDHP, but not with the AUC of FT. Therefore, the CYP2A6 genotype did not affect the AUC of 5-FU. The individual AUC or Cmax of 5-FU did not differ significantly between patients with grade 3 or 4 toxicities and patients with grade 0-2 toxicities. In conclusion, the CYP2A6 genotype did not affect the AUC of 5-FU, although the clearance of FT was lower in patients with 2 variant alleles of CYP2A6 than in patients with the wild-type or 1 variant allele.

S-1 is an oral anticancer agent that combines tegafur, a prodrug of 5-fluorouracil (5-FU), and 5-chloro-2,4-dihydroxypyridine (CDHP), an inhibitor of dihydropyrimidine dehydrogenase. We examined the effects of aging on the pharmacokinetics of the components of S-1. The median area under the concentration-time curve (AUC) of active 5-FU did not significantly differ between 10 patients 75 years or older and 53 patients younger than 75 years (P = 0.598, Mann-Whitney U test). It is interesting to note that the median oral clearance of tegafur in patients 75 years or older was significantly lower than that in patients younger than 75 years (P = 0.011). Furthermore, the median AUC of CDHP was significantly higher in patients 75 years or older than in those younger than 75 years (P = 0.004). This effect was caused by reduced renal function in the elderly, because CDHP is excreted in the urine by glomerular filtration. The opposing effects of aging on the oral clearance of tegafur and the AUC of CDHP may offset each other, leading to unchanged systemic exposure of 5-FU.

BACKGROUND S-1 is an oral anticancer agent that combines tegafur (FT) with 5-chloro-2,4-dihydroxypyridine (CDHP) and potassium oxonate. The recommended initial dose of S-1 is 120 mg/day for patients with a body surface area (BSA) of > or =1.5 m(2) in Japan. METHODS We examined the effects of using this fixed dose on the pharmacokinetics of FT, CDHP, and active 5-fluorouracil (5-FU) on the basis of actual BSA. The pharmacokinetics was compared between patients with a BSA of 1.5-1.75 m(2) and those with a BSA of > or =1.75 m(2). RESULTS The median areas under the time-concentration curves (AUCs) of 5-FU and CDHP were significantly lower in patients with a BSA of > or =1.75 m(2) than in those with a BSA of 1.5-1.75 m(2) (P = 0.005 and 0.006, respectively; Mann-Whitney U-test). There was no difference between the groups in the median AUC of FT. CONCLUSION Systemic exposure to 5-FU is significantly lower in Japanese cancer patients with a large BSA of >1.75 m(2) who received the recommended fixed dose of S-1.

S-1 is an oral anticancer agent composed of tegafur (FT), 5-chloro-2,4-dihydroxypyridine (CDHP), and potassium oxonate. CDHP is added to prevent degradation of 5-fluorouracil (5-FU) by inhibiting dihydropyrimidine dehydrogenase. CYP2A6 is involved in the biotransformation of FT to 5-FU. Thus, we prospectively analyzed the effects of the CYP2A6 genotype, plasma level of CDHP, and patient characteristics on the pharmacokinetic (PK) variability of FT and 5-FU. Fifty-four Japanese patients with metastatic or recurrent cancers who received S-1 were enrolled. The CYP2A6 polymorphisms (*4A, *7, and *9) with deficient or reduced activity were analyzed. All subjects were classified into three groups according to their CYP2A6 genotype: wild type (*1/*1), one-variant allele (*1/any), or two-variant alleles (combination other than *1). The PK of FT, 5-FU, and CDHP were measured on day 1 of treatment. Multivariate regression analysis revealed that oral clearance of FT was associated with the CYP2A6 genotype (analysis of variance [ANOVA], P = 0.000838). The oral clearance of FT seen in patients with the two-variant alleles was significantly lower than those in wild type and the one-variant allele (95% confidence intervals 0.75-2.41 and 0.41-1.82, respectively; Tukey-Kramer test). The area under the time-concentration curve (AUC) of 5-FU was significantly correlated with the AUC of CDHP (ANOVA, P = 0.00126). The AUC of 5-FU and CDHP were inversely correlated with creatinine clearance (ANOVA, P = 0.0164 and P = 0.000762, respectively). Although the CYP2A6 variants are the cause of the PK variability of FT, the AUC of CDHP affected by renal function is the key determinant of the variability in the PK of 5-FU.

We report two patients with refractory recurrent breast cancer (HER2/neu: +) postoperatively, who had failed response to the available conventional chemotherapy of CAF (cyclophosphamide, adriamycin, 5-fluorouracil) and docetaxel, etc. They markedly responded to the combination immunotherapy using intraperitumoral injections of autologous tumor cell-stimulated T lymphocyte (AuTL) and trastuzumab (Herceptin), an anti-HER2 monoclonal antibody.AuTLs were administrated directly into the recurrent tumor by intraperitumoral injections biweekly and trastuzumab was infused systemically every week. The treatments were repeated for 6 and 11 injections in the patients, respectively. The total administered T cells had reached to 3.8 x 10(9) and 6.4 x 10(9), respectively. The dosage of trastuzumab was 2 mg/kg in each patient.The carcinomatous pleural effusion had disappeared and was well controlled in patient 1 and a marked regression in injected fields in comparison to the size of the recurrent tumor before treatment was observed in patient 2. The tumor marker proteins (CEA, CA15-3, TPA) had also decreased significantly. The adverse effects of the immunotherapy were tolerable with grades 1-2 infusion reaction of fever, tachycardia and hypotension, but no cardiac dysfunction was observed.Clinical responses of recurrent breast cancer were observed in two patients after receiving the intra-peritumoral AuTL injection plus trastuzumab immunotherapy. These results showed that refractory recurrent breast cancer may be controlled effectively and safely by repeating the cellular immunotherapy combined with trastuzumab and suggested utility of combining these agents in clinical trial.

Antineoplastons such as A10 include naturally occurring peptides and amino acid derivatives that control the neoplastic growth of cells. The mechanism underlying this antitumor effect was investigated using the breast cancer cell line, SKRB-3. Cells treated with A10 were monitored for any changes in cell cycle, expression of protein kinase C (PKC), or intracellular signal transduction, particularly phos-phorylation of mitogen-activated protein kinase (MAPK). The A10 markedly inhibited SKBR-3 proliferation due to arrest in the G(1) phase. A10 down-regulated the expression of PKCalpha protein, resulting in inhibition of extracellular signal-regulated kinase (ERK) MAPK phosphorylation. This increased the expression of p16 and p21 protein, with resultant inhibition of Rb phosphorylation, leading to G(1) arrest. This study has defined a pathway in which A10 arrested SKBR-3 cells in the G(1) phase via PKCalpha and MAPK. Our findings indicate that the antineoplaston A10 antitumor effect could be utilized as an effective therapy for breast cancer patients.

We present a case of a 78-year-old man with a synchronous double cancer of the lung and Vater's papilla. A pancreaticoduodenectomy was performed for Vater's papilla cancer and a partial lung resection for lung cancer. The pathological diagnosis of the tumors was a well differentiated tubular adenocarcinoma and well differentiated bronchioloalveolar carcinoma, respectively. Although most cases of synchronous double cancers involve lung and gastric cancers, a combination of lung and Vater's papilla is extremely rare. This patient is still alive with no recurrence for 5 years after the last operation.

A 65-year-old man was admitted to our hospital for treatment of a squamous cell carcinoma in his right lung. Respiratory function testing showed an extremely reduced forced expiratory volume in 1 second (FEV1) of 1.0 l (29.9% of predicted), and a reduced FEV1/FVC ratio of 24.1%. Arterial blood gases on room air showed a pH of 7.41, a PaCO(2) of 36.7 mmHg, and a PaO(2) of 79.3 mmHg. To assess the predictive postoperative cardiopulmonary function, unilateral pulmonary artery occlusion (UPAO) testing was performed. In the condition of right main PA occlusion, the mean pulmonary artery pressure (mPAP), cardiac index (CI) and total pulmonary vessel resistance index (TPVRI) was 18 mmHg, 3.2 l/min/m(2) and 443.37 dyne.sec.cm(-5)/m(2), respectively. He underwent a middle lobectomy with combined partial resection of both the upper and lower lobes. He also underwent simultaneous resection of a giant bulla arising from the right upper lobe as lung volume reduction surgery. At 80 days after the operation, his FEV1 rose to 1.88 l, and the PaO(2) on room air was improved to 88.9 mmHg. UPAO testing was suggested to be more useful than routine pulmonary function test to determine the accurate predictive postoperative cardiopulmonary function and to decide indication for a radical operation.

We present the case of a 55-year-old man with advanced esophageal cancer who was successfully treated using a self-expandable metallic stent (S-EMS) for 6 months and subsequently was treated for an esophagobronchial fistula as a complication of the initial S-EMS using a silicone airway stent for an additional 4 months. This is the first report in the literature concerning penetration into the airway of an S-EMS implanted in the esophagus. The present case suggests that airway stenting using a silicone stent as treatment for an esophagobronchial fistula may represent a useful modality.

We report a case of minute lung carcinoma that developed in a focal honeycombed lesion in the right lung. A 70-year-old man presented hemosputum, and a cytological examination result was at class IV. A right lower lobectomy of the lung was performed. Microscopically, the thickened alveolar wall revealed tumor cells indicating a minute carcinoma, and showed squamous hyperplasia, metaplasia, and dysplasia, with the carcinoma in the distal airway epithelium. This peripheral lung carcinoma in a focal honeycombed lesion demonstrated the various stages of multistep carcinogenesis, which is recognized in hilar type squamous cell carcinoma. To date, the association between a honeycombed lesion and lung cancer has been poorly described. Here we have presented clear evidence of the association of this carcinoma with the honeycombed lesion.

We present a case of a 56-year-old male with esophageal cancer who underwent successful temporary tracheal stenting followed by a surgical procedure. The trachea was obstructed owing to endotracheal metastasis and the patient had severe dyspnea. A silicone Y-stent was initially inserted into the tracheal stenosis to secure the airway, and then tumor-specific chemo-radiotherapy was applied. The tumor was reduced, the stent was removed and a pathological study indicated that the tracheal metastasis had disappeared. The patient then underwent esophagectomy and tumor-specific chemo-radiotherapy was continued after the surgery. The patient has remained alive and free of esophageal cancer for 18 months after the airway stent emplacement. These findings suggested that the silicone stent was suitable as a temporary measure and that temporary stenting combined with tumor-specific therapy was effective as part of the aggressive therapeutic strategy with which to treat the malignant airway stenosis due to esophageal cancer.

Thoracoscopic lung biopsy is becoming the procedure of first choice for the diagnosis of many localized and diffuse lung diseases. We have performed thoracoscopic lung biopsy for 17 patients with diffuse infiltrative lung disease, in Kurume University Hospital. There were 13 females and 4 males with a mean age of 48 years (range: 19-71 years). Thoracoscopic surgical biopsy was performed in the right lung in 12 and in the left lung in 5. Adequate lung tissue from each case was obtained for pathological examination. The mean surgical biopsy time was 49 min (range: 25-72 min) and bleeding was negligible. The mean duration for chest tube drainage was 2.6 days. No postoperative complication such as prolonged air leakage occurred. A specific diagnosis from the biopsy was achieved in 13 (76.4%) of the 17 cases. In only 6 (35.2%) of the 17 cases, the pathological diagnosis was the same as that from the thoracoscopic biopsy. In these 6 cases, the same diagnosis was obtained only in those with idiopathic interstitial pneumonitis or diffuse panbronchitis. Thoracoscopic lung biopsy was safe and useful for diagnosis for diffuse infiltrative lung disease.

Postoperative bilateral chylothorax after cervical surgery has been rarely reported, whereas unilateral chylothorax has been occasionally reported after thoracic surgery. Here, we report a rare case of bilateral pleural effusion that developed after cervical abscess drainage. On the second day after the drainage, the patient felt dyspnea, and bilateral pleural effusion was found on a chest X-ray. The effusion was thought to be chyle and was successfully treated with conservative management. Additionally here, we have suggested that non-traumatic chylothorax was caused by increasing intraluminal pressure occurring inside the thoracic duct after its ligation. Careful follow up of any respiratory symptoms and of chest X-rays is recommended after cervical intervention.

We present the case of a 79-year-old woman with partial anomalous pulmonary venous connection (PAPVC), discovered incidentally during upper left division segmentectomy for primary lung cancer. The left superior pulmonary vein originated from the hilum of the upper left lobe and flowed into the left brachiocephalic vein. The left inferior pulmonary vein was connected normally, and neither atrial septal defect nor other anomalous condition was present. Upper left lobectomy with ligation of the anomalous connected vein was performed, as the lingual segment was anatomically difficult to retain. Although this type of PAPVC is extremely rare, it is advisable to exercise caution when performing lung resection with the potential for PAPVC in mind.

A 71-year-old man with esophageal cancer received esophagectomy with stomach reconstruction. He presented with dyspnea on postoperative day 42. Chest computed tomography and bronchoscopy revealed an elevated lesion at the orifice of the left main bronchus (Fig. 1). Gastrobronchial fistula was diagnosed on histological examination. Silicone stent placement resulted in resolution of symptoms. European Journal of Cardio-thoracic Surgery 25 (2004) 460 www.elsevier.com/locate/ejcts

SummaryFarletuzumab is a humanized monoclonal antibody against folate receptor α (FRA). The purpose of the study is to assess safety and tolerability, the pharmacokinetic (PK) profile, and preliminary antitumor effect. Patients with ovarian cancer (OC) or FRA-expressing solid tumors who are resistant to standard treatments were eligible for the study. After single-dose administration for PK assessment, farletuzumab was administered by intravenous injection, repeating every week until disease progression. Dose-limiting toxicities (DLTs) were defined as grade 4 hematological and grade 3/4 nonhematological toxicities. Dose escalation was planned in 4 cohorts (50, 100, 200, and 400 mg/m2). Fourteen patients with OC and two patients with gastric cancer (GC) received farletuzumab infusion. Neither DLTs nor grade 3/4 toxicities were reported in all cohorts. Major adverse events, including grade 1/2 infusion related reaction (15 patients, 93.8 %), headache (seven patients, 43.8 %), and nausea and decreased appetite (five patients each, 31.3 %), were observed and medically managed. AUC and Cmax increased dose-dependently and linear PK profiles were observed. No tumor shrinkage was recorded, but long-term disease stabilization for 25 and 20 months was observed in one patient with clear cell OC (100 mg/m2) and one patient with GC (400 mg/m2), respectively. No cumulative toxicity occurred in any patient. Farletuzumab was well tolerated in Japanese patients with a similar PK profile as compared with the US population. Long-term disease stabilization was observed in a subpopulation of clear cell OC and GC; both of them were resistant and progressive after standard chemotherapies (ClinicalTrials.gov Identifier: NCT01049061).