ß-Catenin-activated inflammatory hepatocellular adenoma with pigmentation and atypical features: a case report.

Hepatocellular adenomas are rare diseases, defined as benign liver neoplasms composed of cells with hepatocellular differentiation. Differential diagnosis of hepatocellular adenoma from other lesions, including focal nodular hyperplasia and hepatocellular carcinoma, is crucial to determine treatment strategy. We describe a case of ß-catenin-activated inflammatory hepatocellular adenoma with malignant transformation. A 50-year-old man with a suspected liver tumor, based on abdominal ultrasonography findings, was referred to our hospital. Contrast-enhanced computed tomography and magnetic resonance imaging revealed a liver tumor in S2 which was enhanced in the arterial phase to the delayed phase. Based on diagnostic imaging findings, hepatocellular adenoma or focal nodular hyperplasia was suspected. We considered the possibility of malignant potential because of the enlargement of the lesion. Thus, we performed a laparoscopic hepatectomy. Histological examination showed pigment deposition in the hepatocytes, which was determined to be lipofuscin. Mild nuclear swelling and atypia in the tumor area indicated nodular growth. Based on the histological and immunohistochemical findings, the diagnosis was ꞵ-catenin-activated inflammatory hepatocellular adenoma with atypical features. The imaging features of hepatocellular adenoma and focal nodular hyperplasia are similar, but if the tumor tends to grow, surgical treatment should be performed because of the possibility of malignant hepatocellular adenoma.

[A Case of Stage â £ Gastric Cancer Treated with Conversion Surgery after Chemotherapy].

A case is a female of 61-year-old. She visited her local doctor with a chief complaint of frequent burping. She was hospitalized for gastric cancer with pyloric stenosis. Although open gastrectomy was planned the gastric cancer was unresectable due to pancreatic invasion and peritoneal dissemination. Cytology with abdominal lavage was CY0. She underwent gastrojejunostomy. She was treated by 19 courses of chemotherapy with SOX therapy for 2 years. The tumor reduced, and she underwent distal gastrectomy as conversion surgery. Pathological findings were por2>muc>tub2>tub1, ypT2(ypMP), INF c, int, Ly1a, V0, pPM0, pDM0, pN0(0/43), ypStage ⅠB, R0, Grade 2b. Adjuvant chemotherapy(S-1 and docetaxel)was administered after conversion surgery. She is alive without recurrence for 1 year and 6 months after gastrectomy. We report a case of Stage Ⅳ gastric cancer treated with conversion surgery after chemotherapy.

[Three Cases of Conversion Surgery for Unresectable Advanced Gallbladder Cancer with Distant Metastasis Treated with Gemcitabine plus CDDP].

All three patients were female, one in her 50s, and the other two in their 60s. The one in her 50s had liver metastasis and the other two had unresectable advanced cholecystic carcinomas with peritoneal dissemination. All three received 8-12 courses of gemcitabine plus CDDP(GC). After GC, all three were deemed to be candidates for R0 resection and underwent resection of two central liver segments. In addition, the second patient required an extrahepatic cholangiectomy; an extended cholecystectomy, plus an extrahepatic cholangiectomy, plus a complete omental resection; and the third needed an extended cholecystectomy, plus an extrahepatic cholangiectomy with a partial transverse colon resection, plus a partial duodenectomy. The pathologic response to chemotherapy was moderate in the patient with liver metastases, mild in the one who underwent the omental resection, and moderate in the patient who had the partial resection of the digestive tract. All three patients continued with postoperative chemotherapy. The patient with liver metastases and the one with the partial gastrointestinal tract resection have survived without recurrence for 52 months and 43 months, respectively, after the initial treatment. The patient with the omental resection has survived 44 months after the initial treatment with recurrent peritoneal dissemination and is continuing chemotherapy as an outpatient. Although further study is needed to accumulate more cases, the results suggest the usefulness of multidisciplinary treatment including conversion surgery in cases such as these.

Adjuvant trastuzumab without chemotherapy for treating early HER2-positive breast cancer in older patients: A propensity score-adjusted analysis of a prospective cohort study.

PURPOSE: To gauge the effects of treatment practices on prognosis for older patients with HER2-positive early breast cancer, particularly to determine whether adjuvant trastuzumab alone can offer benefit over no adjuvant therapy. This is a prospective cohort study which accompanies the RESPECT that is a randomized-controlled trial (RCT). METHODS: Patients who declined the RCT were treated based on the physician's discretion. We studied the 1) trastuzumab-plus-chemotherapy group, 2) trastuzumab-monotherapy group, and 3) non-trastuzumab group (no therapy or anticancer therapy without trastuzumab). The primary endpoint was disease-free survival (DFS), which was compared using the propensity-score method. Relapse-free survival (RFS) and health-related quality of life (HRQoL) were assessed. RESULTS: We enrolled 123 patients aged over 70 years (median: 74.5). Treatment categories were: trastuzumab-plus-chemotherapy group (n = 36, 30%), trastuzumab-monotherapy group (n = 52, 43%), and non-trastuzumab group (n = 32, 27%). The 3-year DFS was 96.7% in trastuzumab-plus-chemotherapy group, 89.2% in trastuzumab-monotherapy group, and 82.5% in non-trastuzumab group. DFS in non-trastuzumab group was lower than in trastuzumab-plus-chemotherapy and trastuzumab-monotherapy groups (propensity-adjusted hazard ratio; HR: 3.29; 95% CI: 1.15-9.39; P = 0.026). The RFS in non-trastuzumab group was lower than in trastuzumab-plus-chemotherapy and trastuzumab-monotherapy groups (propensity-adjusted HR = 7.80; 95% CI: 2.32-26.2, P < 0.0001). There were no significant intergroup differences in the proportions of patients showing HRQoL deterioration at 36 months (P = 0.717). CONCLUSION: Trastuzumab-treated patients had better prognoses than patients not treated with trastuzumab without deterioration of HRQoL. Trastuzumab monotherapy could be considered for older patients who reject chemotherapy.

Conversion surgery following gemcitabine plus cisplatin therapy for initially unresectable gallbladder cancer with peritoneal carcinomatosis: a case report.

BACKGROUND: Conversion surgery, which is defined as chemotherapy or chemoradiotherapy followed by radical surgery, may improve survival of patients with initially unresectable advanced biliary tract cancer, including gallbladder cancer. However, there are few reports on conversion surgery for advanced gallbladder cancer. CASE PRESENTATION: A 69-year-old woman was referred to our hospital with initially unresectable gallbladder cancer with peritoneal carcinomatosis. She underwent gemcitabine plus cisplatin therapy for 9 months. Extended cholecystectomy, resection of the extrahepatic bile duct with regional lymph node dissection, and total omentectomy were then performed as conversion surgery. The patient has survived without recurrence for 19 months postoperatively (31 months after the initial diagnosis) while continuing chemotherapy. CONCLUSIONS: This case suggests that conversion surgery for advanced gallbladder cancer is effective and may be curative for locally advanced disease and distant metastasis such as peritoneal carcinomatosis.

Health-Related Quality of Life With Trastuzumab Monotherapy Versus Trastuzumab Plus Standard Chemotherapy as Adjuvant Therapy in Older Patients With HER2-Positive Breast Cancer.

PURPOSE: We report findings on quality of life (QoL) in the RESPECT trial, which compared adjuvant trastuzumab monotherapy with trastuzumab plus chemotherapy in older patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC). PATIENTS AND METHODS: Patients age 70-80 years with human epidermal growth factor receptor 2-positive surgically treated breast cancer were randomly assigned to receive trastuzumab (T) or trastuzumab plus chemotherapy (T + C). QoL was assessed using the Functional Assessment of Cancer Therapy-General (FACT-G), Philadelphia Geriatric Center Morale Scale, Hospital Anxiety and Depression Scale, Patient Neurotoxicity Questionnaire, and Tokyo Metropolitan Institute of Gerontology Index of Competence at baseline and after 2, 12, and 36 months. Comparisons were based on individual changes from baseline and were performed by Fisher's test or mixed-model repeated-measures. RESULTS: Among 275 patients in the parent study, 231 (84%) (average age: 74 years) were included in the analysis. At 2, 12, and 36 months, 198, 177, and 178 patients completed surveys, and the mean FACT-G scores at each survey point were 78.9, 80.4, 82.7, and 79.1 in group T and 79.5, 74.5, 78.4, and 78.5 in group T + C. Compared with group T + C, the proportion of patients showing QoL deterioration (≥ 5 points decrease from baseline in FACT-G) was significantly lower at 2 months (31% v 48%; P = .016) and 12 months (19% v 38%; P = .009). In group T, the Hospital Anxiety and Depression Scale score (P = .003) and the proportion of severe sensory peripheral neuropathy (P = .001) were significantly lower at 2 months, and Philadelphia Geriatric Center Morale Scale and Tokyo Metropolitan Institute of Gerontology Index of Competence scores were significantly higher (P = .024, .042) at 12 months. At 36 months, there were no significant differences in any QoL items. CONCLUSION: Detrimental effects of adjuvant chemotherapy on global QoL, morale, and activity capacity lasted for at least 12 months but were not observed at 36 months.

Randomized Controlled Trial of Trastuzumab With or Without Chemotherapy for HER2-Positive Early Breast Cancer in Older Patients.

PURPOSE: Adjuvant trastuzumab monotherapy has not been compared with trastuzumab + chemotherapy. We investigated the relative value of trastuzumab monotherapy for older patients with breast cancer. METHODS: This study was an open-label, randomized controlled study with a treatment selection design in which a noninferiority criterion was predefined. Patients aged 70-80 years with surgically treated human epidermal growth factor receptor 2-positive invasive breast cancer received trastuzumab monotherapy or trastuzumab + chemotherapy. The primary end point was disease-free survival (DFS) with assessment of prespecified hazard ratio (HR), relapse-free survival (RFS), adverse events (AEs), health-related quality of life (HRQoL), and restricted mean survival time (RMST). RESULTS: The study involved 275 patients (mean age, 73.5 years) who were followed up for a mean of 4.1 years (range, 0.3-8.0 years). The percentages of patients by cancer stage were as follows: I (pT > 0.5 cm), 43.6%; IIA, 41.7%; IIB, 13.5%; and IIIA, 1.1%. Three-year DFS was 89.5% with trastuzumab monotherapy versus 93.8% with trastuzumab + chemotherapy (HR, 1.36; 95% CI, 0.72 to 2.58; P = .51). At 3 years, RMST differed by -0.39 months between arms (95% CI, -1.71 to 0.93; P = .56). Three-year RFS was 92.4% with trastuzumab monotherapy versus 95.3% with trastuzumab + chemotherapy (HR, 1.33; 95% CI, 0.63 to 2.79; P = .53). Common AEs were anorexia (7.4% v 44.3%; P < .0001) and alopecia (2.2% v 71.7%; P < .0001), and grade 3/4 nonhematologic AEs occurred in 11.9% versus 29.8% (P = .0003) for trastuzumab monotherapy versus trastuzumab + chemotherapy, respectively. Clinically meaningful HRQoL deterioration rate showed significant differences at 2 months (31% for trastuzumab monotherapy v 48% for trastuzumab + chemotherapy; P = .016) and at 1 year (19% v 38%; P = .009). CONCLUSION: The primary objective of noninferiority for trastuzumab monotherapy was not met. However, the observed loss of survival without chemotherapy was < 1 month at 3 years. Therefore, and in light of the lower toxicity and more favorable HRQoL profile, trastuzumab monotherapy can be considered an adjuvant therapy option for selected older patients.

[Gallbladder Cancer with Multiple Liver Metastases Completely Responding to Gemcitabile plus Cisplatin Chemotherapy-A Case Report].

A 59-year-old man was diagnosed with cholecystolithiasis and cholecystitis and underwent cholecystectomy. The pathological findings were moderately differentiated adenocarcinoma(pT2)in the gallbladder fundus. Sixteen days after surgery, he visited our hospital due to jaundice. Abdominal enhanced CT and EOB-MRI revealed multiple liver metastases and lymph node metastases in the hepatoduodenal ligament that we deemed to be unresectable. A metallic stent was inserted for bile duct obstruction, and he underwent chemotherapy with gemcitabine plus cisplatin(GC). After 12 courses of GC, the metastatic lesions disappeared, and the patient showed complete response. FDG-PET/CT showed FDG uptake in the hepatoduodenal ligament and we subsequently decided to perform surgery. He underwent resection of the extrahepatic bile duct and regional lymphadenectomy. The pathological findings revealed no residual carcinomas in the bile duct or lymph nodes. We are continuing chemotherapy at present, and the patient is alive with no signs of recurrence at 1 year and 3 months following the diagnosis of multiple liver metastases.

[A Case of Liver Recurrence of Choriocarcinoma and AFP-Producing Carcinoma of the Stomach Showing a Complete Histological Response after Chemotherapy].

A 65-year-old man was hospitalized for gastric cancer. Abdominal computed tomography detected lower gastric cancer and invasion of the liver. Initial laboratory data showed high levels of serum AFP(2,688.6 ng/mL). He underwent distal gastrectomy with left lobectomy of the liver and cholecystectomy. Histology confirmed that the tumor consisted of 2 components: primary gastric choriocarcinoma and AFP-producing carcinoma. The pathological staging was pT4b(liver), N3aM0, Stage ⅢC. After surgery, AFP levels decreased to within the normal limits. Adjuvant chemotherapy(S-1)was administered for 1 year after the operation. Fourteen months later, PET-CT and EOB-MRI detected liver recurrence. He was treated with weekly paclitaxel(PTX)chemotherapy for the liver recurrence. After 12 courses, the tumor had disappeared. The patient was continuously treated with weekly PTX and is doing well without recurrence 24 months after the resection of the liver tumor. Co-existence of primary gastric choriocarcinoma and AFP-producing carcinoma is very rare. We report a case of liver recurrence of choriocarcinoma and AFP-producing carcinoma of the stomach showing a complete histological response after chemotherapy.

[A Case of Multiple Lymph Node Metastases Treated with Nivolumab after an Adrenalectomy for Solitary Adrenal Metastasis of Gastric Cancer after a Gastrectomy].

A 69-year-old man was hospitalized for gastric cancer. He underwent total gastrectomy with distal pancreatectomy, splenectomy, and cholecystectomy. Pathological staging was pT3N3aM0 and Stage ⅢB. Adjuvant chemotherapy(S-1)was administered postoperatively. Ten months later, left adrenal metastasis was detected on computed tomography(CT)scans. He was then treated with 4 courses of chemotherapy with SOX therapy and 2 courses of PTX plus RAM therapy for the left adrenal metastasis. However, the tumor size increased. He underwent adrenalectomy with left nephrectomy and partial resection of the transverse colon for the solitary adrenal metastasis. His pathological diagnosis was metastatic carcinoma of the left adrenal gland and lymph nodes, which invaded the left renal vein and originated from gastric carcinoma. Three months after the adrenalectomy, CT scans identified paraaortic, porta hepatis, and left supraclavicular lymph node metastases. The patient was continuously treated with nivolumab, for 20 courses, and is doing well with good PS. Adrenalectomy for solitary adrenal metastasis of gastric cancer very rarely occurs. We report a case of multiple lymph node metastases treated with nivolumab after an adrenalectomy for solitary adrenal metastasis of gastric cancer after a gastrectomy.

[Successful Treatment of Necrotizing Fasciitis Due to Ascending Colon Cancer-A Case Report].

A 70-year-old woman was brought to our hospital by ambulance because of severe groin pain on the right side. Computed tomography scan revealed a tumor in the ascending colon, intraperitoneal abscess spread to the subcutaneous tissues, and a large amount of pneumoderma. She was diagnosed with necrotizing fasciitis caused by penetration of ascending colon cancer and underwent lavage and drainage, right hemicolectomy, end ileostomy, and debridement of necrotic tissues on emergency. Postoperatively, she underwent debridement and irrigation at the bedside every day, but the necrotizing tissues spread. Debridement under general anesthesia was repeated on postoperative day 8. On postoperative day 20, negative pressure wound therapy(NPWT)was initiated to manage the exudates and wound condition, and healthy granulation tissues formed gradually. After 4 weeks, she underwent split-thickness skin graft implantation. The postoperative course was uneventful, and she was discharged from the hospital. She is currently on chemotherapy and has been alive for 1 year and 3 months after the first operation.

[Is the LHRH Agonist Recommended for Fertility Preservation ?].

The POEMS reportedan effect of goserelin for fertility preservation. The Clinical Practice Guideline for Breast Cancer by The Japanese Breast Cancer Society indicates that the use of the LHRH agonist (LHRHa) for preventing chemotherapy-induced early menopause is a grade C-1 recommendation, and its use for fertility preservation is a grade C-2 recommendation. Results from previous studies on the effects of LHRHa for fertility preservation have varied owing to differences in chemotherapy regimens, definitions of ovarian failure, and dosages of tamoxifen. In the POEMS, the primary endpoint of ovarian failure at 2 years was significantly lower, and the secondary endpoint of pregnancy outcomes was better in the combination group; however, precise interpretation is difficult because many cases were excluded. Currently, it is not necessary to revise The Clinical Practice Guideline; however, desirable results from future studies may allow the recommendation of a specific dosage of LHRHa for fertility preservation.

[A case of sigmoid colon cancer with a sigmoidovesical fistula treated with preoperative XELOX+bevacizumab therapy and urinary bladder-conserving surgery].

A 64-year-old man presented with abdominal pain, diarrhea, urinary pain, and frequent urination.He was diagnosed with locally advanced sigmoid colon cancer accompanied by a sigmoidovesical fistula, which was determined to require total cystectomy for curative resection.Expecting tumor shrinkage and conservation of the urinary bladder, we performed loop ileostomy followed by preoperative mFOLFOX6+bevacizumab therapy.After 1 course of administration, the implanted port became infected.Therefore, the regimen was changed to 4 courses of XELOX+bevacizumab therapy.After the treatment, there was no longer any evidence of sigmoidovesical fistula.We performed a urinary bladder-conserving sigmoidectomy and finally achieved pathological curative resection.After adjuvant chemotherapy, no findings suggestive of recurrence were noted during 10 postoperative months.Preoperative XELOX+bevacizumab therapy may be worth considering as a therapeutic option for conserving the urinary bladder in cases of locally advanced colon cancer.

[Pharmacological and clinical properties of didanosine (VIDEX), a nucleoside reverse transcriptase inhibitor].

An active metabolite, ddATP, of didanosine that is an analogue of purine-nucleoside (a component of nucleic acid) was known to inhibit the activity of DNA polymerase for E. coli. In 1985, Dr. Michiya et al. of NCI reported that didanosine and ddA inhibited replication of the human immunodeficiency virus (HIV). This discovery led to the clinical application of both the compounds. Didanosine, after being uptaken into a cell, becomes an active metabolite, ddATP, to inhibit a reverse transcriptase of HIV. Compared with zidovudine, didanosine has weak cytotoxicity both in vitro and in vivo. Didanosine, which is recommended as a first-line therapy drug in the Japanese Guideline on an anti-HIV Infection Therapy, was approved as twice-daily Videx Tablet and Dry Syrup formulations for launch in June 1992. In March 2001, a once-daily Videx EC Capsule formulation was approved and launched, having expected adherence improvements in HIV/AIDS patients.