[A case of sarcomatoid intrahepatic cholangiocarcinoma that was difficult to diagnose].

A 70-year-old man presented to our hospital with fever and abdominal pain. A mass was found in the left lobe of his liver. Three months later, disseminated peritoneal nodules and ascites appeared. Liver biopsy and review laparoscopy did not lead to a diagnosis. Approximately five months later, a pathological autopsy was performed, and a final diagnosis of sarcomatoid intrahepatic cholangiocarcinoma was made. Differentiating sarcomatoid cholangiocarcinoma from sarcomatoid malignant peritoneal mesothelioma was difficult due to the similarity of clinical and pathological findings. Because the two diseases are treated differently, being able to differentiate them is a challenge in the future.

[A case of pustular psoriasis preceded by liver dysfunction].

The patient is a female in her thirties. The patient was diagnosed with pustular psoriasis during the treatment course for pneumonia with the appearance of small pustules of the skin and with an increase of serum total bilirubin level. Pustular psoriasis is a designated intractable disease with extremely low prevalence in which the skin of the whole body is flushed with high fever and many sterile pustules occur. This disease has been reported to be accompanied by liver dysfunction. Liver dysfunction appeared 1-2 weeks after the eruption appears in most cases, but this is the rare case in which the liver disorder precedes.

Granulocyte and Monocyte Adsorptive Apheresis for Ulcerative Colitis in a Patient with Low Bone Mineral Density Due to Fanconi-Bickel Syndrome.

Systemic steroid is required for the exacerbation of ulcerative colitis (UC), although its administration should be avoided in patients with a low bone mineral density (BMD) exacerbated by side effects of steroids. We herein report the successful induction of remission in an UC case with a low BMD due to Fanconi-Bickel syndrome-or glycogen storage disease type XI-using granulocyte and monocyte adsorptive apheresis (GMA). For a 43-year-old woman with a BMD of 50% the young adult mean, GMA was performed 2 times a week for a total of 10 times. GMA might be a steroid-free treatment option for UC patients with a low BMD.

Differences in disease status between patients with progression after first-line chemotherapy versus early relapse after adjuvant chemotherapy who undergo second-line chemotherapy for gastric cancer: Exploratory analysis of the randomized phase III TRICS trial.

BACKGROUND: Second-line chemotherapy (SLC) improves survival in advanced gastric cancer (AGC). Patients receiving SLC are categorized into two disease status groups: tumour progression after first-line chemotherapy and early recurrence after adjuvant chemotherapy. Differences between these groups have not yet been clarified. PATIENTS AND METHODS: A total of 163 eligible patients registered in the randomized phase III TRICS trial evaluating SLC for patients with AGC was classified into the progressive disease (PD) group (n = 55) or the early relapse (ER) group (n = 108). We compared overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and safety. Adjusted OS and adjusted PFS were estimated using inverse probability of treatment weighting (IPTW). RESULTS: The ER group had a lower median age than the PD group (66 vs. 72 years; P = 0.016), performance status (PS) 0 was more frequently seen in the ER group (87% vs. 71%; P = 0.012). The adjusted median OS was 13.7 months in the ER group and 13.6 months in the PD group (IPTW hazard ratio [HR]: 1.023; P = 0.854). The adjusted median PFS was 4.9 months in the ER group and 4.4 months in the PD group (IPTW HR: 0.707; P = 0.004). ORR was significantly better in the ER group than the PD group (21.3% vs. 4.9%; P = 0.020). No significant differences were observed in the incidence of adverse events. CONCLUSIONS: ER was associated with improved PFS and better ORR than PD, although no difference in survival was demonstrated. From the viewpoint of treatment outcome, it seems appropriate to treat patients with ER in the same way as patients with PD. CLINICAL TRIAL REGISTRATION: UMIN 000002571.

A study of second-line irinotecan plus cisplatin vs. irinotecan alone in platinum-naïve patients with early relapse of gastric cancer refractory to adjuvant S-1 monotherapy: exploratory subgroup analysis of the randomized phase III TRICS trial.

BACKGROUNDS: Many patients with gastric cancer relapse during or early after adjuvant chemotherapy. The standard treatment for early relapse patients is a second-line chemotherapy (SLC) based on irinotecan, taxanes, or a platinum-based chemotherapy. The platinum-containing biweekly irinotecan plus cisplatin (IRI/CDDP) combination was assumed to be promising in several reports of clinical trials as SLC. TRICS trial, a randomized phase III study of IRI/CDDP vs. IRI in platinum-naïve gastric cancers refractory to S-1 monotherapy, revealed that both irinotecan-based chemotherapies were effective and well tolerated. METHODS: This study analyzed 108 patients in the TRICS trial who experienced early relapse. Patients receiving IRI/CDDP (IRI, 60 mg/m2; CDDP, 30 mg/m2, q2w) versus IRI (150 mg/m2, q2w) were compared regarding overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and safety. RESULTS: The OS was 14.0 (95% confidence interval [CI]: 11.0-21.2) and 14.0 (95% CI: 10.7-16.5) months for IRI/CDDP and IRI, respectively (hazard ratio [HR]: 0.782; 95% CI: 0.515-1.188, P = 0.249). No significant differences were observed for PFS (5.0 vs. 4.5 months, respectively; HR: 0.802; 95% CI: 0.543-1.185, P = 0.268) or ORR (19.6% [95% CI: 9.4-33.9%] vs. 23.3% [95% CI: 11.8-38.6%], respectively). The incidence of grade 3-4 anemia was higher for IRI/CDDP than for IRI (20% vs. 0%, respectively; P = 0.0006). CONCLUSION: Our study showed no significant survival differences between IRI/CDDP and IRI in platinum-naïve patients who relapsed during or within 6 months after S-1 adjuvant therapy; therefore, IRI may be a good option in this population. CLINICAL TRIAL INFORMATION: UMIN 000002571.

Immunoglobulin G4-related sclerosing cholangitis diagnosed by liver biopsy: a case report.

Patients with immunoglobulin (Ig) G4-related sclerosing cholangitis typically have a high serum IgG4 level. However, here we describe our experience of a patient with a normal serum IgG4 level for whom the cholangitis was diagnosed by liver biopsy. A 61-year-old male presented with elevated liver enzymes and a normal serum IgG4 level. The hilar, intrahepatic, and upper extrahepatic bile ducts were stenotic, with no evidence of a pancreatic lesion. We therefore performed a liver biopsy to differentiate between cholangiocarcinoma and primary sclerosing cholangitis. Pathological examination revealed lymphoplasmacytic infiltrates around the bile ducts with a storiform fibrosis. IgG4-positive plasma cells were also observed. These results fulfilled the Japanese diagnostic criteria for IgG4-related sclerosing cholangitis. When this condition is suspected, liver biopsy should be performed even when serum IgG4 levels are normal.

[Locally Advanced Gastric Cancer Treated with Curative Gastrectomy and Showing Pathological Complete Response after Chemotherapy with S-1].

A 77-year-old man presented with epigastralgia. Gastrointestinal endoscopic examination showed advanced gastric cancer, type 3, in the distal antrum. The patient refused surgery and preferred chemotherapy. The regimen consisted of 80 mg/body/day of S-1, continuously administered from day 1-14, followed by discontinuation for 2 weeks. After 2 courses, the patient experienced fatigue and recurrent vomiting. Laboratory studies revealed severe anemia; the hemoglobin level was 5.5 g/dL. An upper gastrointestinal endoscopy revealed pyloric stenosis and significant tumor reduction. Therefore, distal gastrectomy was performed. Histological examination did not reveal any viable cancer cells in the stomach and lymph nodes. Thus, a Grade 3 postchemotherapeutic effect was revealed.

Randomised phase III trial of second-line irinotecan plus cisplatin versus irinotecan alone in patients with advanced gastric cancer refractory to S-1 monotherapy: TRICS trial.

AIM: The optimal second-line regimen for treating advanced gastric cancer (AGC) remains unclear. While irinotecan (CPT-11) plus cisplatin (CDDP) combination therapy and CPT-11 monotherapy have been explored in the second-line setting, the superiority of second-line platinum-based therapies for AGC patients initially treated with S-1 monotherapy has not yet been evaluated; therefore, we aimed to examine the survival benefit of CPT-11/CDDP combination over CPT-11 monotherapy. METHODS: AGC patients showing progression after S-1 monotherapy for advanced cancer or recurrence within 6 months after completion of S-1 adjuvant therapy were randomly allocated to CPT-11/CDDP (CPT-11, 60 mg/m(2); CDDP, 30 mg/m(2), q2w) or CPT-11 (150 mg/m(2), q2w). RESULTS: Sixty-eight advanced and 95 recurrent cases were evaluated. The median overall survivals were 13.9 (95% confidence interval [CI]: 10.8-17.6) and 12.7 (95% CI: 10.3-17.2) months for CPT-11/CDDP and CPT-11, respectively (hazard ratio: 0.834; 95% CI: 0.596-1.167, P = 0.288). No significant differences were observed in the secondary end-points, including progression-free survival (4.6 [95% CI: 3.4-5.9] versus 4.1 [95% CI: 3.3-4.9]months) and response rate (16.9% [95% CI: 8.8-28.3] versus 15.4% [95% CI: 7.6-26.5]). The incidences of grade 3-4 anaemia (16% versus 4%) and elevated serum lactate dehydrogenase levels (5% versus 0%) were higher for CPT-11/CDDP than for CPT-11. Exploratory subgroup analysis revealed that CPT-11/CDDP was significantly more effective for intestinal-type AGC, compared with CPT-11 (overall survival: 15.8 versus 14.0 months; P = 0.019). CONCLUSION: No survival benefit was observed upon adding CDDP to CPT-11 after S-1 monotherapy failure.

[Assessment of hand-foot syndrome in cancer patients treated with capecitabine-containing chemotherapy].

Capecitabine is one of the most effective oral chemotherapeutic drugs for advanced or recurrent colorectal cancer and gastric cancer. Capecitabine-containing chemotherapy is recommended as a first-line option for gastrointestinal tract cancer. The incidence of hand-foot syndrome (HFS), an adverse event of chemotherapy with capecitabine, is high. Moreover, once the symptoms of HFS are identified, they can significantly impair the quality of life (QOL) of patients. HFS should be managed by dose interruption and, if necessary, by dose reduction. Pharmacists and oncology nurses play an increasingly important role in the early identification and prevention of HFS through patient education and close clinical assessment. The aim of this study was to evaluate the efficacy of support tools for the early identification, prevention, and management of HFS and to assess the effectiveness of "patient self-check sheets". The patient was detected as having HFS of mild severity and had used a moisturizer at the time of initiation of therapy. Maintaining moisture retention is important in the management of HFS. The ambulatory team plays a key role by using self-check sheets to educate patients on how to recognize HFS, when to interrupt treatment, and how to adjust the dose so as to maintain effective therapy with capecitabine. For the continuation and completion of treatment and for maintaining an improved QOL in the home environment, supportive measures for adverse effects such as HFS and an ambulatory team are indispensable.

[Assessment of hand-foot syndrome in cancer outpatients undergoing chemotherapy].

Capecitabine, an oral prodrug of 5 -fluorouracil, is a promising treatment for colorectal, breast, and gastric cancers, but often causes hand-foot syndrome(HFS), which is the most common dose-limiting toxicity. The aim of this study was to evaluate of the efficacy of the pharmacist in providing support at ambulatory therapy centers, especially for HFS. The HFS is a higher-incidence adverse event that may develop during chemotherapy with capecitabine. Once developed, the symptoms significantly impair quality of life(QOL), leading to a reduction in the dosage or discontinuation of the treatment. Patient symptoms may therefore increase in severity. This study was performed to analyze the treatment adherence and adverse events resulting from capecitabine therapy provided by pharmacists to cancer outpatients. All patients were prescribed vitamin B6(pyridoxine), which can help to reduce or prevent HFS. A lesser or milder extent of HFS was detected in patients who had used a moisturizer at the same time as the introduction of capecitabine therapy. Adherence to this approach will benefit the patients' selfcare in maintaining moisture retention, which is an important countermeasure for HFS. Additionally, early introduction of effective countermeasures for skin care, dose reduction, and rest periods is important for HFS management; in addition, team care support is dispensable. Our support system may be useful for management strategies for HFS. We suggest that improved quality of lif e is needed in cancer outpatients being treated with chemotherapy.

[Complete histological response in advanced gastric cancer with Virchow's node metastasis after chemotherapy including S-1/CDDP--report of a case].

A 63-year-old male complaining of jaundice was examined and diagnosed with advanced gastric cancer (type 3, tub 2, cT3, cN3, cH0, cM1, cStage IV), and obstructive jaundice due to lymph node metastasis. Since curative surgery was deemed not possible, we started chemotherapy with S-1+CDDP. S-1 (120 mg/day) was administered orally for 21 days, followed by CDDP (60 mg/m2) div on day 8. After the 9th course, a significant tumor reduction was obtained. Total gastrectomy and lymph node resection (D1) were performed. The histological diagnosis revealed complete disappearance of cancer cells in both the main tumor and lymph nodes. Herein we report this rare case with a view of the literature.

[A case of adenosquamous gastric carcinoma successfully treated with TS-1, low-dose CDDP and docetaxel as neoadjuvant chemotherapy].

The patient was a 66-year-old male with extremely advanced gastric cancer type 3 and diagnosed with adenocarcinoma by endoscopic biopsies specimens. Combined chemotherapy of TS-1, CDDP and docetaxel was prescribed in order for tumor reduction and downstaging. TS-1 (80 mg/m(2)) was administered 28 days followed by 14 days rest as one course. CDDP (8 mg/m(2)) was administered on days 1, 2, 14 and 15 and docetaxel (40 mg/m(2)) was administered on day 1 and 14, followed by 4 weeks rest as one course. After 2 courses of treatment, a CT scan revealed a minor response of tumor reduction. Therefore, total gastrectomy, partial pancreas body and tail resection, and D 2 lymph node dissection were performed. The patient had undergone adjuvant chemotherapy of TS-1 and biweekly docetaxel after surgery with no recurrence for 13 months. Adverse reactions were grade 3 neutropenia and grade 2 diarrhea. Combined chemotherapy of TS-1, low-dose CDDP and docetaxel were intensive and required constant patient monitoring. However, it proved effective and feasible as a neoadjuvant chemotherapy regimen for advanced gastric cancer.

[The team medical support in out-patient chemotherapy: a role of nurses].

The number of cancer patients and families desiring home-based care and out-patient chemotherapy has been increasing. Hence, a support system for home-based care is urgently needed for a patient with recurrent and/or advanced unresectable cancer who recieved cancer chemotherapy. The cancer therapy especially in patients with colorectal cancer could have expected an improvement of the prognosis utilizing FOLFOX/FOLFIRI, a standard therapy established in Europe and America. Thereby, it was well recognized that the department of out-patient chemotherapy is very important for continuous venous infusion using a central venous port. Since May 2005, we started an out-patient department for patients receiving cancer chemotherapy and a risk management in order to establish a patient care team. The important thing we should recognize about the out-patient treatment is that there are many cases of cancer patients who are in the state of poor nourishment caused by plural factors such as protein-calorie malnutrition (PCM) by an intake disturbance, and the poor absorption in glucose, protein and fat which are necessary for a good metabolism. The poor nutritional status causes a deterioration of immune function and complications such as infectious diseases. Thereby, a good management of nourishment to the patient who received cancer chemotherapy is an important supportive therapy. It appears that a good management of nourishment prevented and/or alleviated the complication that caused by the treatment of cancer chemotherapy. Because of the out-patient treatment is to treat a patient in a short period of time without thorough evaluation about the same for in hospitalized patient, a team medical support, a prudent policy of chemotherapy by the medical team members consisting of nurses, pharmacists, dietitian, chemotherapist and the self-care guidance of the patient are strongly required.

Hepatic angiomyolipoma associated with splenic hamartoma.

A 52-year-old woman was admitted to our hospital with thrombophlebitis of the internal jugular vein. Abdominal ultrasonography demonstrated a high echogenic mass measuring 4.5 cm in diameter in the liver, and abdominal CT revealed another liver tumor and an isodensity mass in the spleen. Abdominal MRI and angiography were performed and we presumed the tumors to be two hepatic angiomyolipoma and a splenic hamartoma. As an abdominal CT 21 months later revealed that all tumors were growing, these tomors were surgically resected. The histological diagnoses were hepatic angiomyolipoma and splenic hamartoma.