Impact of Perioperative Immunonutrition on Postoperative Outcomes for Patients Undergoing Head and Neck or Gastrointestinal Cancer Surgeries: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: To clarify whether perioperative immunonutrition is effective in adult patients with or without malnutrition undergoing elective surgery for head and neck (HAN) or gastrointestinal (GI) cancers. BACKGROUND: It is important to avoid postoperative complications in patients with cancer as they can compromise clinical outcomes. There is no consensus on the efficacy of perioperative immunonutrition in patients with or without malnutrition undergoing HAN or GI cancer surgery. MATERIALS AND METHODS: We searched MEDLINE (PubMed), MEDLINE (OVID), EMBASE, Cochrane Central Register of Controlled Trials, Web of Science Core Selection, and Emcare from 1981 to 2022 using search terms related to immunonutrition and HAN or GI cancer. We included randomized controlled trials. Intervention was defined as immunonutritional therapy including arginine, n-3 omega fatty acids, or glutamine during the perioperative period. The control was defined as standard nutritional therapy. The primary outcomes were total postoperative and infectious complications, defined as events with a Clavien-Dindo classification grade ≥ II that occurred within 30 days after surgery. RESULTS: Of the 4825 patients from 48 included studies, 19 had upper GI cancer, 9 had lower, and 8 had mixed cancer, whereas 12 had HAN cancers. Immunonutrition reduced the total postoperative complications (relative risk ratio: 0.78; 95% CI, 0.66-0.93; certainty of evidence: high) and infectious complications (relative risk ratio: 0.71; 95% CI, 0.61-0.82; certainty of evidence: high) compared with standard nutritional therapy. CONCLUSIONS: Nutritional intervention with perioperative immunonutrition in patients with HAN and GI cancers significantly reduced total postoperative complications and infectious complications.

Feasibility of International Proposed Standardized Enteral Connector for Semi-Solid Formula Feeding.

BACKGROUND/AIMS: The current study was undertaken to assess if the semi-solid formulas could be used with a new ENFit connector with similar force to current percutaneous endoscopic gastrostomy (PEG) tubes. METHODS: Experiment 1: We measured the applied pressure (force) needed to compress the syringe containing 7 viscous semi-solid formulas with a 20 Fr PEG tube and low-profile tube through the ENFit connector or the current connector. Experiment 2: This experiment was conducted to evaluate the compression force through 2 connectors in 3 infusion velocity, 7 PEG tube types with 2 semi-solid formulas. RESULTS: Experiment 1: The force needed to compress the syringe through the ENFit connector was higher in 3 semi-solid formulas with a 20 Fr low-profile tube; otherwise, there were no significant differences. Experiment 2: Each formula required a higher force in the ENFit connector in 6 settings out of 21. CONCLUSIONS: The ENFit connector will likely not show any remarkable change in the force to administer the semi-solid formula. However, a higher force was required under some conditions in the prototype ENFit connector. Further investigation of sensory test is needed to confirm the feasibility of the ENFit connector for using the semi-solid formulas.

["Let's become the surgeon" the present status of the medical course beside teaching in Department of surgery, Daisan Hospital the Jikei University School of medicine: based on the experience OF clinical Clark ship for 5 years].

In Department of Surgery, Daisan Hospital, The Jikei University School of Medicine, Clinical Clark ship (C.C.) is positively taken in the bedside teaching of the medical course fifth and sixth grader from April, 2010. We think that the C.C. is a good opportunity to tell the charm of the surgeon to the students. We introduce a bedside teaching going in our Department, based on the experience of the C.C. for 5 years. In the bedside teaching of our department, there are many tasks not to advance before when students do not have discussion with preceptors, about participation in surgery, presentation of the preoperative conference, visiting of outpatient care and night practice. Moreover, students decide the theme about submitting report and research presentation. For our department which built a bedside teaching with on the job training as a concept from 2010, "students in the C.C." is welcome and beneficial for the doctors, the students itself and the patients. When C.C. will be introduced into all Department of our university in earnest from 2016, we have to examine the merits and demerits in future so that C.C. functions going well.

Breast hemangioma with difficulty in preoperative diagnosis: a case report.

We report a rare case of breast hemangioma found in a 70-year-old Japanese female. Before seeking medical attention, the patient noticed a hard mass in her right breast but denied associated symptoms. A mammography revealed a well-circumscribed, highly dense, lobular nodule located in the middle inter portion of the right breast. To verify this finding, we used ultrasonography which revealed an irregular, iso-echoic nodule measuring 10 mm in the same portion. Based on these findings, we suspected a malignancy and performed a core needle biopsy. Unexpectedly, a histological examination of the biopsy displayed normal vasculature, adipose, and mammary tissues. In order to make an accurate diagnosis, the mass was surgically excised under general anesthesia and sent to pathology. Pathological findings of the mass were positive for breast hemangioma, and the patient has had no recurrence of the disease for the past 24 months.

[Administration of low-dose albumin-bound paclitaxel for the treatment of advanced and recurrent breast cancer patients].

A recent foreign clinical trial showed albumin-bound paclitaxel(260mg/m2 tri-weekly)to have a better response for metastatic breast cancer(MBC)than did treatment with paclitaxel alone(175mg/m2 tri-weekly). It was sometimes difficult to control the occurrence of side effects, such as neutropenia and neuropathy, especially after many treatments. The effect of low-dose albumin-bound paclitaxel(180-220mg/m2 tri-weekly)was evaluated in 8 patients with MBC. The overall response rate was 62. 5%(CR 1, PR 4), and 2 cases had Grade 3/4 toxicity(Grade 3 neutropenia); however, all patients were manageable. In addition, there was a good response rate(50%, PR 3)among the patients previously treated with paclitaxel. Because patient's "care" is as important as the "cure" in the treatment of MBC, an effective and well-tolerated regimen is recommended for patients with this disease. Low-dose albumin-bound paclitaxel was effective with reduced side effects, even after PTX treatment. Therefore, albumin-bound paclitaxel may be an optional treatment for MBC after any treatment.

Indications and Strategy for Active Surveillance of Adult Low-Risk Papillary Thyroid Microcarcinoma: Consensus Statements from the Japan Association of Endocrine Surgery Task Force on Management for Papillary Thyroid Microcarcinoma.

Background: The question of how to manage patients with low-risk papillary thyroid microcarcinoma (PTMC; T1aN0M0) has recently become an important clinical issue. Two Japanese centers have conducted prospective clinical trials of active surveillance (AS) for low-risk PTMC since the 1990s, reporting favorable outcomes. This policy has thus seen gradual adoption worldwide to avoid overtreatment. Not all PTMCs are suitable for AS, however, and many physicians still hesitate to apply the management policy in daily clinical practice. A task force on management for PTMC created by the Japan Association of Endocrine Surgery collected and analyzed bibliographic evidence and has produced the present consensus statements regarding indications and concrete strategies for AS to facilitate the management of adult patients diagnosed with low-risk PTMC. Summary: These statements provide indications for AS in adult patients with T1aN0M0 low-risk PTMC. PTMCs with clinical lymph node metastasis, distant metastasis, recurrent laryngeal nerve (RLN) paralysis due to carcinoma invasion, or protrusion into the tracheal lumen warrant immediate surgery. Tumors suspected of aggressive subtypes on cytology are recommended for immediate surgery. Immediate surgery is also recommended for tumors adherent to the trachea or located along the course of the RLN. Practical strategies include diagnosis, decision-making, follow-up, and monitoring related to the implementation of AS. The rate of low-risk PTMC progression is lower in older patients. However, we recommend continuing AS as long as circumstances permit. Future tasks in optimizing management for low-risk PTMC are also described, including molecular markers and patient-reported outcomes. Conclusions: An appropriate multidisciplinary team is necessary to accurately evaluate primary tumors and lymph nodes at the beginning of and during AS, and to adequately reach a shared-decision with individual patients. If appropriately applied, AS of low-risk PTMC is a safe management strategy offering favorable outcomes and preserves quality of life at low cost.

Determination of the Optimum Excitation Wavelength for the Parathyroid Gland Using a Near-Infrared Camera.

When performing thyroid/parathyroid surgery, difficulty detecting the parathyroid gland is a common experience because it is frequently mistaken with surrounding structures, including the thyroid gland, lymph nodes, and fat. To obtain successful surgical results, the auto fluorescent property of the parathyroid gland occurring at 820-830 nm has been used. Intraoperative visualization and detection by fluorescence enable protection of the gland from damage and unintended removal. Use of a near-infrared (NIR) camera has been proposed to indicate the parathyroid gland, but the devices and success rates have varied. This study aimed to define optimum excitation wavelength (EWL) by measuring the EWL of the parathyroid gland for its autofluorescence. Glands were exposed to EWL at 10-nm intervals from 670-790 nm with a light-emitting diode monochromator; autofluorescence intensity was recorded with a conventional NIR video camera. Autofluorescence intensity curves of three normal parathyroid glands were depicted; the optimum EWL was measured as 760-770 nm. Also, the illumination of the surrounding structures were compared at the optimum EWL. The auto fluorescent intensity of the parathyroid gland was 2-fold greater than for surrounding structures. This difference in fluorescence intensity should enable distinction of the parathyroid gland from surrounding structures. The clarification of the optimum EWL can guide refinements of the NIR camera for better surgical outcomes by improving detection of the parathyroid glands. Also, an understanding of optimum EWL should lead to developments for microscopic devices to unravel the still unknown mechanisms of the intrinsic autofluorescence of the parathyroid gland.

Complete remission from peritoneal metastasis of late recurrent breast cancer by endocrine therapy: a case report.

BACKGROUND: Peritoneal dissemination associated with the postoperative recurrence of breast cancer is relatively low (3-6%). Although the prognosis of patients with peritoneal metastasis is generally short (7-26 months), we experienced a unique case in which complete remission was achieved for more than 6 years with endocrine therapy alone. CASE PRESENTATION: An 81-year-old woman presented an upper abdominal tumor and loss of appetite. Computer tomography (CT) scan revealed a tumor in the duodenum and the head of pancreas, which malignant lymphoma was suspected. The exploratory laparotomy demonstrated a tumor located in the greater curvature of the pylorus to the transverse colon, and peritoneal dissemination. Because of the previous history of breast cancer 11 years ago and the immunopathological findings, recurrence of breast cancer was diagnosed. Lung metastasis was also detected postoperatively and the endocrine therapy using letrozole was introduced. After a year, CT scan confirmed complete remission from the metastasis. Two years later, tumor markers fell within the normal limit. CONCLUSIONS: A rare case of late-phase metachronous peritoneal metastasis of the breast cancer where complete remission was obtained by a single endocrine agent was presented.

High-Dose Toremifene as a Promising Candidate Therapy for Hormone Receptor-Positive Metastatic Breast Cancer with Secondary Resistance to Aromatase Inhibitors.

There are currently no established second- and later-line therapies for postmenopausal women with hormone receptor-positive advanced or metastatic breast cancer. We examined the efficacy of high-dose toremifene (HD-TOR) for this patient group and whether aromatase inhibitor (AI) resistance influences HD-TOR treatment outcome. This retrospective analysis investigated the outcomes of 19 women with postmenopausal hormone-sensitive recurrent or metastatic breast cancer who received HD-TOR, defined as 120 mg daily from 2012 to 2016. The median follow-up duration was 9.67 months. The overall response rate (ORR) and clinical benefit rate (CBR) were compared between various clinical subgroups, including patients exhibiting primary or secondary AI resistance as defined by the timing of recurrence or progression. Time to treatment failure (TTF) was estimated by the Kaplan-Meier method and compared between subgroups by the log-rank test. The overall ORR was 21.1%, and the CBR was 31.6%. CBR was significantly higher for patients without liver metastasis (50% vs. 0%, p = 0.044). Nine cases exhibited primary and eight cases secondary AI resistance. Both ORR and CBR were higher in patients with secondary AI resistance (25% vs. 0%, p = 0.087; 38% vs. 11%, p = 0.29). The median TTF was 6.2 months in the entire AI-resistant group (n = 17) and was longer in the secondary resistance subgroup than in the primary resistance subgroup (8.40 vs. 4.87 months; log-rank: p = 0.159). High-dose TOR appears to be most effective for postmenopausal breast cancer cases with secondary resistance to AIs, cases without prior AI treatment, and cases without liver metastasis. The detailed mechanisms of AI resistance and the clinical features of responsive cases need to be further clarified to identify the best candidates for HD-TOR.

Male breast metastasis of ureteral cancer: a case report.

BACKGROUND: Breast metastasis from extra-mammary primary tumors is extremely rare. We recently experienced a rare case of a male breast metastasis of ureteral cancer and will provide a case report. CASE PRESENTATION: A 74-year-old man developed a ureteral cancer and underwent left nephroureterectomy with lymph node dissection. Although enlarged abdominal lymph nodes did not disappear completely after chemoradiotherapy, further extensive therapy was not performed. A mass just below the nipple of his right breast was acknowledged and he visited our department. Histological diagnosis was invasive carcinoma. It was initially diagnosed as a primary breast cancer, and he underwent a mastectomy and a sentinel lymph node biopsy. There was no intraductal lesion and the border of the tumor was clear. It was very similar to that of the previous ureteral cancer. The final diagnosis was breast metastasis of ureteral cancer rather than primary breast cancer. The postoperative course was good, but multiple lung metastases appeared 2 months after surgery. He eventually died of cancerous lymphangiopathy. CONCLUSION: It is important to accurately diagnose primary breast cancer or breast metastasis so as not to cause extra-invasion, but it was considered difficult to make a complete preoperative diagnosis.

Characterization and comparative DNA methylation profiling of four adipogenic genes in adipose-derived stem cells and dedifferentiated fat cells from aging subjects.

Adipose-derived stem cells (ASCs) and dedifferentiated fat (DFAT) cells are alternative cell sources in tissue engineering and regeneration because they are easily obtained and exhibit multilineage differentiation. However, aging may attenuate their regenerative potential and metabolic functions. Reports characterizing DFAT cells derived from aging donors are rare, and comparisons of DNA methylation profiles between aging ASCs and DFAT cells are poorly understood. Therefore, this study aimed to characterize DFAT cells relative to ASCs derived from aging subjects and compare the DNA methylation profiles of four adipogenic genes in these cells. ASCs and DFAT cells from aging donors exhibited characteristics similar to those of stem cells, including colony formation, proliferation, and multilineage differentiation abilities. However, compared with ASCs, DFAT cells exhibited increased proliferation, smooth muscle actin alpha (SMA-α) expression and decreased cellular senescence. DNA methylation profiling of ASCs and DFAT cells by combined bisulfite restriction analysis (COBRA) demonstrated hypermethylation patterns in three potent adipogenic genes-peroxisome proliferator-activated receptor gamma 2 (PPARγ2), fatty acid-binding protein 4 (FABP4), and lipoprotein lipase (LPL)-but hypomethylation of CCAAT/enhancer binding protein alpha (C/EBPα) in the aging group. Statistically significant differences were observed between the aging group and the young group. Epigenetic regulation maintains the stability of ASCs and DFAT cells in an age-dependent manner. Our findings suggested that although the DNA methylation patterns of three adipogenic genes correlated with hypermethylation and aging, ASCs and DFAT cells exhibited cellular stability and several stem cell characteristics, offering further opportunities for personalized regeneration and energy maintenance by adipogenesis during aging.

Dihydropyridine- and voltage-sensitive Ca2+ entry in human parathyroid cells.

Patch-clamp and fluorescence measurements of cytoplasmic Ca(2+) concentration ([Ca(2+)](i)) were performed to directly detect extracellular Ca(2+) entry into cultured parathyroid cells from patients with secondary hyperparathyroidism. Cells loaded with fluo-3 AM or fluo-4 AM showed a transient increase in fluorescence (Ca(2+) transient) following 10 s exposure to 150 mm K(+) solution in the presence of millimolar concentrations of external Ca(2+). The Ca(2+) transient was completely inactivated after 30-40 s exposure to the high-K(+) solution, was reduced by dihydropyridine antagonists and was enhanced by FPL-64176, an L-type Ca(2+) channel agonist. The electrophysiological and pharmacological properties of the whole-cell Ca(2+) and Ba(2+) currents were similar to those of L-type Ca(2+) channels. The Ca(2+) transients induced by 10 s exposure to 3.0 mm extracellular Ca(2+) concentration ([Ca(2+)](o)) were inhibited by dihydropyridine antagonists and were partly inactivated following 30-40 s exposure to the high-K(+) solution. These results demonstrate, for the first time, that human parathyroid cells express L-type-like Ca(2+) channels that are possibly involved in the [Ca(2+)](o)-induced change in [Ca(2+)](i). This Ca(2+) entry system might provide a compensatory pathway for the negative feedback regulation of parathyroid hormone secretion, especially in hyperplastic conditions in which the Ca(2+)-sensing receptor is poorly expressed.

EGFR as paradoxical predictor of chemosensitivity and outcome among triple-negative breast cancer.

We retrospectively analyzed the expression of epidermal growth factor receptor (EGFR) as a prognostic marker to predict neoadjuvant chemotherapy response and survival among breast cancer subtypes. We used immunohistochemical profiles to subtype the patients. EGFR expression was determined using immunohistochemistry. All patients received an anthracycline-based regimen preoperatively. Ninety-three patients also received docetaxel. Of the 117 patients tested, 28 (24%) were triple-negative breast cancer (TNBC) and 73 (62%) were hormone receptor-positive (luminal) subtype. Among the TNBC patients, a significantly higher incidence of EGFR expression (50%) was observed (P=0.002), and EGFR expression was related to a less favorable response to chemotherapy (P=0.03) and poorer survival (P=0.17); in contrast, among the luminal subtype patients, positive EGFR expression was related to a favorable clinical response (P=0.06) and better survival (P=0.11). This retrospective analysis demonstrated that EGFR expression may represent an adverse prognostic marker in patients with TNBC and may provide a valuable tool for selecting appropriate treatment regimens for patients with TNBC.

Establishment and characterization of HER2-positive cell line derived from pleural effusion of human breast scirrhous carcinoma.

We have established a cell line derived from a pleural effusion of breast scirrhous carcinoma. This cell line presented immunohistochemically negative for estrogen receptor and slightly positive for progesterone receptor, and positive for c-erbB/HER2/neu. However the original tumor was found to be positive for estrogen receptor and progesterone receptor and slightly positive for c-erbB/HER2/neu expression. Enzyme and electrochemiluminescence immunoassays of tumor markers in the conditioned medium by the cell line revealed they secrete CA15-3, NCC-ST-439 and HER2 protein. We believe the cell line will contribute to the therapeutic study of malignant breast cancer.

Effects of a novel method for enteral nutrition infusion involving a viscosity-regulating pectin solution: A multicenter randomized controlled trial.

BACKGROUND & AIMS: The initial complications associated with infusion of enteral nutrition (EN) for clinical and nutritional care are vomiting, aspiration pneumonia, and diarrhea. There are many recommendations to prevent these complications. A novel method involving a viscosity-regulating pectin solution has been demonstrated. In Japan, this method along with the other so-called "semi-solid EN" approaches has been widely used in practice. However, there has been no randomized clinical trial to prove the efficiency and safety of a viscosity-regulating pectin solution in EN management. Therefore, we planned and initiated a multicenter randomized controlled trial to determine the efficiency and safety. METHODS: This study included 34 patients from 7 medical institutions who participated. Institutional review board (IRB) approval was obtained from all participating institutions. Patients who required EN management were enrolled and randomly assigned to the viscosity regulation of enteral feeding (VREF) group and control group. The VREF group (n = 15) was managed with the addition of a viscosity-regulating pectin solution. The control group (n = 12) was managed with conventional EN administration, usually in a gradual step-up method. Daily clinical symptoms of pneumonia, fever, vomiting, and diarrhea; defecation frequency; and stool form were observed in the 2 week trial period. The dose of EN and duration of infusion were also examined. RESULTS: A favorable trend for clinical symptoms was noticed in the VREF group. No significant differences were observed in episodes of pneumonia, fever, vomiting, and diarrhea between the 2 groups. An apparent reduction in infusion duration and hardening of stool form were noted in the VREF group. CONCLUSIONS: The novel method involving a viscosity-regulating pectin solution with EN administration can be clinically performed safely and efficiently, similar to the conventional method. Moreover, there were benefits, such as improvement in stool form, a short time for EN infusion, and a reduction in vomiting episodes, with the use of the novel method. This indicates some potential advantages in the quality of life among patients receiving this novel method.

Establishment and characterization of a cell line (BTIC) including HER-2-positive cells derived from pleural effusion of recurrent breast invasive ductal carcinoma, scirrhous type.

Human epidermal growth factor receptor-2 (HER-2) overexpression in breast cancer occurs in 20% to 30% of patients with breast cancer. Trastuzumab (Herceptin) targets HER-2 tyrosine kinase receptors expressed on tumor cells and mediates anti-proliferative effects against HER-2-positive tumor cells. Adjuvant chemotherapy with trastuzumab has improved the prognosis of patients with HER-2 positive high-grade breast cancer. However, patients often experience appearance and proliferation of recurrent tumor cells after trastuzumab treatment. In this study, we report the successful establishment and characterization of a cell line (BTIC) derived from a patient with recurrent breast cancer after adjuvant chemotherapy with trastuzumab. Characteristics of the BTIC cell line were investigated by phase contrast or electron microscopic observations, chromosome analysis, xenotransplantation, immunohistochemistry and radioimmunoassay for tumor markers. We confirmed that the BTIC cell line grown as multilayered culture in culture dishes, has a poorly developed endoplasmic reticulum in the cytoplasm and some desmosomes. The population doubling time was approximately 44 hr. A graft in nude mouse after xenotransplantation was diagnosed as scirrhous carcinoma. Immunohistochemistry on cultured BTIC cells revealed that the BTIC cells were negative for estrogen receptor and progesterone receptor, and 30% positive for HER-2. Radioimmunoassay indicated secretion of HER-2 protein, NCC-ST-439 and CA15-3.

Percutaneous endoscopy-guided biopsy of an intracystic tumor with a mammary ductoscopy.

BACKGROUND: Intracystic abnormalities of the breast may result from debris, intracystic papilloma, or rarely breast cancer. Intracystic tumors cannot be diagnosed based on imaging examinations or fine needle aspiration alone, and therefore excisional biopsy must be performed. We have treated many cases who had nipple discharge with mammary ductoscopy since 1992, and we have used this method to diagnose intracystic tumors. METHODS: An endoscope was inserted into the cyst percutaneously, and the intracystic tumor was biopsied using forceps. RESULTS: Six intracystic tumors were biopsied with the endoscope. Four of six cases were cancer, and two were benign papillomas. CONCLUSION: We were able to visualize and accurately biopsy intracystic tumors of the breast using mammary ductoscopy.

Subareolar breast abscess in male patients: a report of two patients with a literature review.

BACKGROUND: Subareolar breast abscess (SBA) is a rare infectious disease of the breast in male patients. CASE PRESENTATION: Herein, we report two male patients with SBA. Patient 1 was initially diagnosed with a malignant tumor based on imaging findings; ultrasonography revealed a hypoechoic mass with blood flow. Patient 2 was diagnosed with inflammatory changes to his nipple; ultrasonography findings supported the diagnosis with an irregular hypoechoic mass with blood flow. Both patients received a cytological or histological biopsy preoperatively, which showed an abscess without malignant cells. CONCLUSION: These cases serve as an important reminder to consider complete resection of the tumor including the responsible mammary duct (tumor and duct resection (TDR)) for curative therapy of SBA.

Establishment and characterization of a cell line (NABCA) derived from metastatic lymph nodes of breast scirrhous carcinoma.

We successfully established a breast scirrhous carcinoma cell line (designated as NABCA) derived from metastatic tumors of the lymph node. The cells grew as multi-layered cultures without contact inhibition. The population doubling time was approximately 66 h. G-band karyotype of NABCA revealed 66% diploid, XX. Surprisingly, the cells had a number of secretory granules and straight microvilli as a brash border. In heterotransplantation, the cells produced a tumor resembling the original tumor. The NABCA is sensitive to Adriamycin (doxorubicin; KYOWA HAKKO KOGYO, Tokyo, Japan) and Taxol (paclitaxel; Bristol-Myers KK, Tokyo, Japan). This cell line is useful for studying the mechanism of lymphatic metastasis and susceptibility of anticancer drugs in human breast scirrhous cancer.

Establishment and characterization of EB virus-free normal B-lymphocyte and interleukin-6-producing poorly differentiated adenocarcinoma cell lines derived from gastric tumor tissue.

We successfully established two cell lines, an adenocarcinoma cell line (designated as HIGS) and Epstein-Barr virus-free normal B-lymphocyte cell line (designated as HIGS-BL), derived from a moderately to poorly differentiated adenocarcinoma of the stomach, and examined their characteristics. The tumor delivered to our laboratory from an operating room was cut into small pieces and cultured on the dishes. HIGS and HIGS-BL were established from each individual dish after the onset of primary culture. Although their culture methods were the same, the HIGS cell line was not established from the dishes growing HIGS-BL cells. In addition, HIGS-BL cells were scarcely observed in the HIGS cell dishes. Because of these factors, we have considered until now that HIGS-BL cells may inhibit the growth of HIGS cells or cause damage to HIGS cells by unknown mechanisms. Injection of HIGS-BL cells, other B-lymphocyte cell lines, or the conditioned media of HIGS-BL cells into nude mice bearing HIGS-grafted tumors was performed individually. When HIGS and HIGS-BL cells were co-cultured in the same dishes, HIGS-BL cells inhibited the proliferation of HIGS cells. The inhibition of grafted tumor growth was confirmed by the injection of not only the HIGS-BL cells but also the B-lymphocytes. Furthermore, this inhibition was only observed when the conditioned medium of B-lymphocytes was injected into the nude mice. These results suggested that the secretory products by general B-lymphocytes (including HIGS-BL) have some ability to inhibit the proliferation of HIGS cells. In addition, susceptibility tests to anti-cancer drugs suggested that HIGS cells were sensitive to CDDP, ADM and MMC, and HIGS-BL cells were sensitive to CDDP. If CDDP was used for chemotherapy in the patient, the drug produced atrophy of HIGS-BL cells. The study about HIGS and HIGS-BL cells reported the necessity for novel therapeutic approaches in oncotherapy.