Evidence of Helicobacter pylori heterogeneity in human stomachs by susceptibility testing and characterization of mutations in drug-resistant isolates.

Heterogeneity of Helicobacter pylori communities contributes to its pathogenicity and diverse clinical outcomes. We conducted drug-susceptibility tests using four antibiotics, clarithromycin (CLR), amoxicillin (AMX), metronidazole and sitafloxacin, to examine H. pylori population diversity. We also analyzed genes associated with resistance to CLR and AMX. We examined multiple isolates from 42 Japanese patients, including 28 patients in whom primary eradication with CLR and AMX had failed, and 14 treatment-naïve patients. We identified some patients with coexistence of drug resistant- and sensitive-isolates (drug-heteroR/S-patients). More than 60% of patients were drug-heteroR/S to all four drugs, indicating extensive heterogeneity. For the four drugs except AMX, the rates of drug-heteroR/S-patients were higher in treatment-naïve patients than in primary eradication-failure patients. In primary eradication-failure patients, isolates multi-resistant to all four drugs existed among other isolates. In primary eradication-failure drug-heteroR/S-patients, CLR- and AMX-resistant isolates were preferentially distributed to the corpus and antrum with different minimum inhibitory concentrations, respectively. We found two mutations in PBP1A, G591K and A480V, and analyzed these in recombinants to directly demonstrate their association with AMX resistance. Assessment of multiple isolates from different stomach regions will improve accurate assessment of H. pylori colonization status in the stomach.

Helicobacter pylori Infection and Chronic Immune Thrombocytopenia.

Approximately half of the world's population is infected with Helicobacter pylori, which causes gastric disease. Recent systematic reviews and meta-analyses have reported that H. pylori may also have extragastric manifestations such as hematologic diseases, including chronic immune thrombocytopenia (cITP). However, the molecular mechanisms by which H. pylori induces cITP remain unclear, and may involve the host immune response, bacterial strain diversity, and delivery of bacterial molecules to the host blood vessels. This review discusses the important pathophysiological mechanisms by which H. pylori potentially contributes to the development of cITP in infected patients.

A Rare Case of Bilateral Pectoralis Major Muscle Defect and Abnormal Muscle.

A 56-year-old female patient with left breast cancer presented at our hospital. Preoperative CT scan showed an isolated bilateral pectoralis major muscle defect and abnormal muscle originating from the entire sternum and inserting in the lower ribs and rectus sheath. Total mastectomy and axillary lymph node dissection were performed. We believe that this case is unique and that others like it have never been reported. If there is a defect in the pectoralis major muscle, reconstructive surgery with a tissue expander is contraindicated. Therefore, preoperative evaluation of the chest wall musculature on imaging is recommended.

Health Effects of Drinking Water Produced from Deep Sea Water: A Randomized Double-Blind Controlled Trial.

Global trends focus on a balanced intake of foods and beverages to maintain health. Drinking water (MIU; hardness = 88) produced from deep sea water (DSW) collected offshore of Muroto, Japan, is considered healthy. We previously reported that the DSW-based drinking water (RDSW; hardness = 1000) improved human gut health. The aim of this randomized double-blind controlled trial was to assess the effects of MIU on human health. Volunteers were assigned to MIU (n = 41) or mineral water (control) groups (n = 41). Participants consumed 1 L of either water type daily for 12 weeks. A self-administered questionnaire was administered, and stool and urine samples were collected throughout the intervention. We measured the fecal biomarkers of nine short-chain fatty acids (SCFAs) and secretory immunoglobulin A (sIgA), as well as urinary isoflavones. In the MIU group, concentrations of three major SCFAs and sIgA increased postintervention. MIU intake significantly affected one SCFA (butyric acid). The metabolic efficiency of daidzein-to-equol conversion was significantly higher in the MIU group than in the control group throughout the intervention. MIU intake reflected the intestinal environment through increased production of three major SCFAs and sIgA, and accelerated daidzein-to-equol metabolic conversion, suggesting the beneficial health effects of MIU.

Identification of Breast Cancer Stem Cells Using a Newly Developed Long-acting Fluorescence Probe, C5S-A, Targeting ALDH1A1.

BACKGROUND/AIM: Aldehyde dehydrogenase (ALDH) 1A1 is a well-known marker for cancer stem cells (CSCs), characterized by self-renewal capacity and multidrug resistance in breast cancer. We developed a near-infrared turn-on fluorescence probe for ALDH1A1, C5S-A, which is suitable for observing and analyzing viable cells. Here, we demonstrated the utility of C5S-A in CSC research using breast cancer cell lines. MATERIALS AND METHODS: To evaluate concordance between C5S-A and conventional stem cell markers, breast cancer cells sorted for ALDEFLUOR-positive cells and for CD44+/CD24- cell populations were stained with C5S-A. Tumorigenicity of C5S-A-positive cells was examined by mammosphere formation assay and subcutaneous transplantation to immunodeficient mice. Additionally, to determine how long fluorescence from a single staining remained observable, we cultured breast cancer cells for 5 days after C5S-A staining. We then evaluated whether C5S-A-positive cells possessed resistance to cytotoxic drugs by chronological imaging. RESULTS: C5S-A staining showed good concordance with conventional breast CSC markers, and good utility for research into CSC characteristics in breast cancer cell lines, including tumorigenesis. Additionally, C5S-A was observable for more than 3 days with a single staining. Using this property, we then confirmed that C5S-A-positive cells possessed resistance to cytotoxic drugs, which is one of the characteristics of CSCs. CONCLUSION: We showed that C5S-A is suitable for CSC research using breast cancer cell lines, and confirmed its utility in observing cells over time.

[A Case of Metastatic Recurrent Breast Cancer Successfully with Olaparib in Late Line Therapy].

A 44-years-old woman who underwent bilateral mastectomy was treated with chemotherapy after axillary lymph nodes and liver metastases recurrence. She was referred to our hospital for BRCA1/2 germline test and the test revealed BRCA2 pathogenic mutation. Before the administration of olaparib as the fourth-line therapy, liver dysfunction, caused by extensive liver metastasis, was observed. The liver damage improved, and tumor markers decreased immediately as shown in the blood test and CT examination results after 2 months; indicating marked reduction of liver metastasis. In the OlympiAD trial, the patients received olaparib as either the first-, second- or third-line treatment; however, few data on the efficacy of olaparib in the patients, as a late line treatment, were reported. In this article, we report a case of a woman in whom olaparib was used as the fourth-line treatment for metastatic recurrent breast cancer. A high therapeutic effect was obtained and the quality of life has been maintained in her for the past 1 year.

Deep-Red/Near-Infrared Turn-On Fluorescence Probes for Aldehyde Dehydrogenase 1A1 in Cancer Stem Cells.

Accumulating evidence supports that cancer stem cells (CSCs) are responsible for cancer proliferation, metastasis, and therapy resistance; therefore, an effective strategy to identify and isolate CSCs is required urgently. Because of their low invasiveness and high signal/noise ratio, "turn-on" fluorescence probes working in the deep-red/near-infrared (DR/NIR) region are one of the most attractive yet undeveloped tools for CSC detection. Herein, we report DR/NIR turn-on fluorescence probes, CS5-A and CS7-A, targeted to aldehyde dehydrogenase 1A1 as an intracellular CSC marker. In contrast to the conventional "always-on" green-fluorescent ALDEFLUOR, we succeeded in generating high-contrast (signal/noise ratio > 8.3) and wash-free in vitro CSC imaging with the DR probe C5S-A. This probe can facilitate CSC isolation with minimal contamination by autofluorescence from other tissues through fluorescence-activated cell sorting. Furthermore, the NIR absorbance/emission and turn-on properties of C7S-A allow simple and rapid CSC detection in vivo within 15 min.

[A Case of Primary Lymphoma of the Breast with Hepatic Cirrhosis].

We report a case of primary lymphoma of the breast complicated by heart failure and alcoholic-decompensated hepatic cirrhosis. The patient was a woman in her 60s who noticed a right breast tumor growing 3 months previously. The size of the tumor was approximately 5 cm, and the tumor had infiltrated the skin. There was no metastasis to the axillary lymph node or other organs by CT. We performed right breast mastectomy. Pathology indicated diffuse large B cell lymphoma(DLBCL). We considered chemotherapy, but her general condition was not good because of hepatic cirrhosis, so we administered palliative care. Although chemotherapy is the first choice of treatment for DLBCL, it is necessary to individually consider each patient's circumstances.

[Bone Marrow Metastases of Breast Cancer Treated with Endocrine Therapy-A Case Report].

We report a case of bone marrowmetastases of breast cancer treated with endocrine therapy. A 54-year-old woman underwent right partial mastectomy and sentinel lymph node biopsy, followed by adjuvant chemotherapy and radiotherapy. She declined the endocrine therapy and was lost to follow-up after 3 postoperative years. After 9 postoperative years, she visited our hospital because of backache and an axillary lump. FDG-PET scan, incisional biopsy of the axillary lump, and bone marrowbiopsy revealed multiple bone and bone marrowmetastases of the breast cancer. She was treated with endocrine therapy(fulvestrant: FUL), which effectively decreased the FDG uptake in the metastatic lesions after 6 months. However, tumor markers elevated after 1 year and 6 months, and she is currently under combination therapy with aromatase inhibitors and CDK4/6 inhibitors.

[A Case of Hyperammonemia Induced by Chemotherapy with 5-Fluorouracil for Metastatic Colon Cancer].

Systemic chemotherapy based on 5-fluorouracil(5-FU)is a standard treatment for unresectable or recurrent colon cancers. Here, we report a case of hyperammonemia induced by chemotherapy using 5-FU for metastatic colon cancer. An 84-yearold male patient with past histories of liver cirrhosis related to hepatitis C virus and renal dysfunction underwent an operation for the rectosigmoid colon cancer 8 years ago. Three years after that operation, a local recurrence of the colon cancer was diagnosed, and chemotherapy using sLV5FU2 was initiated. The recurrence lesion reduced markedly by this chemotherapy, which was ceased 2 years ago. Two years after the cessation the recurrent tumor had been enlarged, and the chemotherapy using the same drugs at the same dose was performed. On the treatment day 3, he was emergently transported to our hospital due to the disturbance of consciousness. Since laboratory tests showed the high concentration of plasma ammonia and the progressed renal dysfunction with no other definite cause of obnubilation, he was diagnosed as the hyperammonemia induced by 5-FU. He was treated by administrating the branched-chain amino acids solutions combined with fluid therapy, which quickly recovered him from the encephalopathy. He is followed up without any chemotherapy because of his high age. When a patient treated with the chemotherapy using 5-FU is sent with the disturbance of consciousness, we should take hyperammonemia into consideration, especially when he or she has the hepatic or renal dysfunction.

[A Case of Chemotherapy with FOLFOXIRI plus Cetuximab for Liver Metastasis of Sigmoid Colon Cancer].

We report a case of chemotherapy with FOLFOXIRI plus cetuximab for liver metastasis of sigmoid colon cancer. The patient was a 40's man who was diagnosed with sigmoid colon cancer with liver metastasis. Colonoscopy revealed a type 2 tumor with stenosis in the sigmoid colon. He underwent sigmoidectomy under laparotomy, and after the operation, received 7 courses of chemotherapy with FOLFOXIRI plus cetuximab. The liver tumor was sufficiently reduced, and laparotomy and liver right lobectomy were performed. Histopathology revealed a modified, Grade 2 tumor regression. He has been followed for 1 year 4months after the operation.

[Continued Chemotherapy for Advanced Gastric Cancer and Seven Year Survival after Operation].

The patient was a 66-year-old man. Total abdominal gastrectomy and D2 dissection were performed for gastric cancer (cT3N0M0P0CYXH0, cStage II A). Pathological examination confirmed a diagnosis of Stage III C mucinous adenocarcinoma (pT4pN3pM0, pStage III C). He underwent adjuvant chemotherapy with TS-1(120mg/body). One year after adjuvant chemotherapy, anastomotic stricture was caused. Although it was not possible to point out recurrent lesions on the CT image, we strongly suspected that extrinsic compression around the anastomotic portion was due to peritoneal dissemination recurrence because of symptoms and marked tumor elevation. Therefore, TS-1(120mg/body)plus cisplatin(CDDP 60mg/m2)were administered as first-line therapy for advanced gastric cancer. TS-1 plus CDDP(SP)chemotherapy resulted in marked tumor reduction and improved symptoms. However, after 33 courses of SP chemotherapy, renal function was worse due to cisplatin; thus, docetaxel(DTX 70mg/m2)was administered as second line therapy. After 8 courses of DTX, peritoneal dissemination recurrence was diagnosed, and the patient was treated with irinotecan(CPT-11 150mg/m / 2), ramucirumab(RAM 8 mg/kg) plus paclitaxel(PTX 80mg/m2 day 1, 8, 15). However, the disease worsened. The side effect of SP therapy was renal dysfunction. Nonetheless, we experienced that long-term disease control could be achieved by administering chemotherapy under strict follow-up.

[A Case of a Single Incisional Laparoscopic Assisted Partial Jejunectomy Performed to Treat a Primary Small Intestine Cancer in a Young Woman].

A 35-year-old woman was followed by epilepsy therapy. She was admitted to our hospital because of a 15 kg decrease in weight, bilious vomit, and frequent epileptic seizures because she could not take oral antiepileptic drugs. A primary small intestinal cancer was suspected in the jejunum about 100 cm from the incisor by single-balloon enteroscopy. A single incisional laparoscopic assisted partial jejunectomy that was minimally invasive was performed to improve the symptoms of intestinal obstruction. The histopathological diagnosis was moderately differentiated adenocarcinoma, ly0, v1, pT4(SE), pN0, pM0, pStage II B. A primary small intestinal cancer is a relatively rare disease, accounting for 0.3-1.0%ofall cancers ofthe digestive tract. The primary method oftreatment is surgery, and understanding the positional relationship ofthe tumor is important when performing surgery because most primary small intestinal cancers are located in the vicinity ofthe ligaments ofTreitz. We present a case in which safe and minimally invasive surgery was performed to treat a primary small intestinal cancer in a young woman with intractable epilepsy and a significant decrease in ADL for intestinal obstruction, along with a review of the literature.

[A Case of Long-Term Survival of Resected Pancreatic Metastasis from Colon Cancer].

Pancreatic metastasis of colorectal cancer is uncommon and is often identified in later stages of cancer, thereby making resection more uncommon. We report a case oflong -term survival after resection of metachronous metastasis to the pancreas from primary sigmoid colon cancer. A 50-year-old female patient underwent a sigmoid colon resection and bilateral salpingo-oophorectomy for sigmoid colon cancer and metastatic ovarian cancer in 2007. She underwent partial lung resection for metastatic lung cancer twice. Four years and 11 months after the first operation, an isolated mass was identified in the pancreatic tail, and a distal pancreatectomy, splenectomy, left adrenal gland removal, and regional lymph node dissection were performed. The tumor stained negatively for cytokeratin 7 and positively for cytokeratin 20, resulting in a diagnosis of pancreatic metastatic cancer from sigmoid colon cancer. The patient is alive 3 years and 4 months after distal pancreatectomy. This suggests that curative resection is effective for metastasis of colorectal cancer to the pancreas, similarly to metastases to the liver and lung.