Ficus pumila L. improves the prognosis of patients infected with HTLV-1, an RNA virus.

Human T-cell leukemia virus type 1 was isolated as the retrovirus to be identified in humans. Here, we focused on Ficus pumila L. as a factor that be effective against human T-cell leukemia virus type 1. The significant and novel findings is that symptoms of patients with drinking Ficus pumila L. extracts did not worsen despite a lack of aggressive pharmacotherapy against adult T-cell leukemia, a human T-cell leukemia virus type 1-associated myelopathy, or T-cell leukemia virus type 1 uveitis. Twenty-eight of the 194 inpatients who underwent showed high levels of human T-cell leukemia virus type 1.Among human T-cell leukemia virus type 1-infected patients, those who were administered Ficus pumila L. extracts had no human T-cell leukemia virus type 1-related symptoms, while those who were not administered Ficus pumila L. extracts had human T-cell leukemia virus type 1-related diseases and a significantly poorer prognosis. This suggests that the Ficus pumila L. extracts may show some utility against virus infection.

MLH1 germline mutation associated with Lynch syndrome in a family followed for more than 45 years.

BACKGROUND: Lynch syndrome, is an autosomal dominantly inherited disease that predisposes individuals to a high risk of colorectal cancers, and some mismatch-repair genes have been identified as causative genes. The purpose of this study was to investigate the genomic rearrangement of the gene in a family with Lynch syndrome followed for more than 45 years. CASE PRESENTATION: The family with Lynch syndrome is family N, who received colorectal cancer treatment for 45 years. The proband of family N had multiple colorectal and uterine cancers. Because the proband met the diagnostic Amsterdam criteria and was Microsatellite instability (MSI) - positive, we performed genetic testing several times. However, germline mutations in MLH1 and MSH2 genes were not found by long-distance PCR or RT-PCR/direct sequencing analysis within the 45-year follow-up. MLPA analysis showed that the genomes of the proband and proband's daughter contained a deletion from exon 4 through exon 19 in the MLH1 gene. Her son's son and her daughter's son were found to be carriers of the mutation. CONCLUSIONS: For carriers of mismatch-repair gene mutation among families with Lynch syndrome, the onset risk of associated cancers such as uterine cancer is particularly high, including colorectal cancer. The diagnosis of carriers among non-onset relatives is important for disease surveillance.

Prognostic impact of elevated preoperative C-reactive protein on patients with differentiated thyroid carcinoma.

BACKGROUND: C-reactive protein (CRP) has been reported to be associated with poorer prognosis in various malignancies. However, the relationship between CRP and differentiated thyroid carcinoma (DTC) remains to be elucidated. METHODS: A total of 45 patients, including 32 patients with preoperative DTC and 13 DTC patients with metastatic disease, were included in the study. The relationships between CRP levels and clinicopathological features were retrospectively analyzed. RESULTS: Analysis using a receiver operating characteristic curve revealed a preoperative CRP cutoff value of 0.155 mg/dL. Patients with preoperative CRP ≥ 0.155 mg/dL, those with T3 + T4, those with extrathyroidal invasion, or those with stage II, showed a statistically shorter recurrent-free survival than those with preoperative CRP < 0.155 mg/dL, those with T1 + T2, those without extrathyroidal invasion, or those with stage I (P = 0.001, P = 0.004, P = 0.024, and P = 0.025, respectively). Preoperative CRP ≥ 0.155 mg/dL was an independent prognostic factor for recurrent-free survival in the DTC patients (hazard ratio = 6.334, 95% confidence interval: 1.023-39.234, P = 0.037). The proportion of patients aged ≥55 y, and those with T3 + T4, was statistically higher in those with preoperative CRP ≥ 0.155 mg/dL than in those with preoperative CRP < 0.155 mg/dL (P = 0.037 and P = 0.038, respectively). CONCLUSIONS: Higher preoperative CRP levels have a robust prognostic impact on recurrence-free survival in DTC patients. In addition, higher preoperative CRP levels were associated with age ≥ 55 y and T3 + T4.

Serum transthyretin level is associated with prognosis of patients with gastric cancer.

BACKGROUND: The goal of the present study was to determine whether serum transthyretin level can be used as a novel prognostic biomarker for patients with gastric cancer. PATIENTS AND METHODS: Serum levels of transthyretin were examined before treatment in 42 patients with gastric cancer, 30 of whom underwent curative operation and had their prognostic factors analyzed. RESULTS: In an analysis using a receiver operating characteristic curve, transthyretin was evaluated as a useful biomarker to predict the overall survival of the patients (P = 0.033), and a level of 22.8 mg/dL was determined as the cut off value. The transthyretin levels exhibited statistically significant correlations with total protein (r = 0.598, P < 0.001), albumin (r = 0.626, P < 0.001), and retinol binding protein (r = 0.753, P < 0.001). On the other hand, the transthyretin levels showed statistically significant inverse correlations with tumor size (r = -0.753, P < 0.001) and the numbers of involved lymph nodes (r = -0.453, P = 0.012). The patients with serum transthyretin levels of <22.8 mg/dL showed poorer prognosis than those with levels of ≥22.8 mg/dL (P = 0.033); therefore, serum transthyretin level was an independent prognostic factor for the gastric cancer patients (hazard ratio: 0.420, 95% confidence interval: 0.180-0.985, P = 0.042). CONCLUSIONS: Anthropometric measurement of serum transthyretin can be useful for predicting the prognosis of patients with gastric cancer.

[A Case of Recurrent Colon Cancer with Peritoneal Dissemination Treated with Aflibercept Showing Partial Response for One Year].

We report a case of recurrent colon cancer that achieved partial response with chemotherapy of combined 5-fluorouracil (5-FU), irinotecan, Leucovorin(FOLFIRI), and aflibercept. A 65-year-old man was diagnosed with colon cancer with lymph node metastasis. He underwent surgery, but after 1 year, he had a recurrence of peritoneal dissemination, nodal enlargement, and liver metastases. He received chemotherapy(mFOLFOX plus bevacizumab), but suffered progressive disease. Thereafter, FOLFIRI plus aflibercept was administered, and CT revealed a decrease in peritoneal dissemination after 2 cycles of chemotherapy. After 23 cycles, a PET-CT showed no evidence of the disease. We also examined 9 recent cases treated with aflibercept in terms of Grade 3 and 4 adverse effects, leukopenia, neutropenia, thrombocytopenia, hypertension, and sweating. Placentalderived growth factor(PIGF)has been reported to stimulate macrophages and induce production of IL-6, and thus it promotes inflammation and growth of extant cancer. Among the responses to chemotherapy based on the RECIST criteria, a partial response was significantly higher in patients with a low neutrophil-to-lymphocyte ratio(NLR)(p≤0.05)compared to those with high NLR. As regards the relationship between NLR and OS in patients treated with FOLFIRI plus aflibercept, OS was significantly worse in patients with high NLR than those with low NLR(p≤0.05). NLR may be a useful marker in conjunction with aflibercept treatment.

[A Case of Rectal Colon Cancer with Paraneoplastic Cerebellar Degeneration].

A case complicated with colorectal and prostate cancers in paraneoplastic(subacute)cerebellar degeneration(PCD)is extremely rare. We report a retrospective case of rectal carcinoma with paraneoplastic cerebellar degeneration. A 79-year-old man with Parkinson's disease was unable to walk because of paralysis. Brain MRI showed cerebellar atrophy. He was admitted to our hospital for anal bleeding and was diagnosed with colon cancer. An associated diagnosis of PCD was made. After resection, his paralysis and dysarthria were resolved to the extent of beingable to walk and speak fluently. Brain MP-RAGE showed no findings suggestive of metastasis or atrophy. He was treated surgically, which resulted in a transient improvement in PCD symptoms. Per blood testing, cytokines IL-6 and IL-10 were lower postoperatively. Immunosuppressive levels of myeloid- derived suppressor cells(MDSCs)were lower compared with the preoperative values. Thus, innate immunocompetence and resolution of paralysis followed the surgical intervention.

[A Case of Esophageal Cancer with Cervical Lymph Node Recurrence Six Years after Complete Response to Definitive Chemoradiotherapy].

Neoadjuvant chemotherapy plus surgery is recommended for clinical StageⅡ and Ⅲ esophageal cancer treatment by the JCOG9906. In contrast, definitive chemoradiotherapy(dCRT)is also a curative treatment. We encountered a case of recurrence in the cervical lymph nodes that was confirmed 6 years later, although thoracic esophageal cancer had completely disappeared following dCRT. Since there was no recurrence or metastasis in the primary lesion or other organs, we performed bilateral cervical lymph node dissection. There were 3 lymph node metastases among the dissected cervical lymph nodes pathologically. After the surgery, no relapses have occurred without the adjuvant chemotherapy.

[Laparoscopic Endoscopic Cooperative Surgery(LECS)for Duodenal Tumors].

We report 2 cases of superficial non-ampullary duodenal tumor resected using laparoscopic endoscopic cooperative surgery( LECS). A man in his5 0's underwent screening esophagogastroduodenoscopy. Endoscopy revealed a 0-Ⅱc lesion at the anal side of the papilla of Vater that measured 5 mm. We performed LECS, and pathologic examination revealed tubular adenoma with no tumor cellsat the edge of the specimen. A man in his 80's underwent screening esophagogastroduodenoscopy. Endoscopy revealed a 0-Ⅱc lesion at the posterior wall above the papilla of Vater that measured 10 mm. The biopsy showed a well-differentiated adenocarcinoma. We performed LECS, and the pathological examination revealed a tubular adenocarcinoma in the mucosal layer with no carcinoma cells at the edge of the specimen. As the treatment strategy for superficial duodenal tumors has not established yet, further accumulation of cases and investigation are necessary.

[Two Cases of Unresectable Advanced Rectal Cancer with a Long-Term Survival for Which Pathological Complete Response Was Achieved through Neoadjuvant Effective Chemotherapy].

We report 2 unusual cases of Stage IV rectal cancer for which pathological complete response was achieved with neoadjuvant chemotherapy(NAC)consisting of a combination of 5-fluorouracil(5-FU), oxaliplatin, Leucovorin(mFOLFOX6)or irinotecan(FOLFIRI), and bevacizumab, without radiotherapy. Case 1: A 65-year-old man was diagnosed as having rectal cancer with an invasive carcinoma of the prostate and lymph node metastasis. He refused to undergo surgery and received NAC instead. After NAC with mFOLFOX6 and FOLFIRI was performed, CT scan and colonoscopy revealed no evidence of disease. The subsequent result was compatible with a complete pathological response. The patient is currently alive 4 years after the first chemotherapy, without evidence of recurrence and adjuvant chemotherapy. Case 2: A 75-year-old man was diagnosed as having rectal cancer with an invasive carcinoma of the bladder and lymph node metastasis. After providing neoadjuvant bevacizumab-containing chemotherapy, low anterior resection of the rectum was performed. Operative findings showed that the tumor was only ulcer and the lymph nodes were not enlarged. The subsequent results indicated that pathological findings revealed no cancer and a complete pathological response. In conclusion, the survival benefits from NAC are still unclear for patients with an initially unresectable rectal cancer. We report 2 rare cases of rectal cancer with long survival and a complete pathological response after neoadjuvant chemotherapy.

[Three Cases of High-Grade Malignant Cancer of Unknown Primary with a Long-Term Survival].

We report 3unusual cases of cancer of unknown primary(CUP)with a long-term survival after chemotherapy. A 56-yearold man was diagnosed as having CUP with invasion of an enlarged carcinoma 20 cm in size to the pancreas and peritoneal dissemination. He received chemotherapy with paclitaxel, carboplatin, and gemcitabine. After the chemotherapy, CT scan and PET-CT revealed no evidence of disease, so tumor resection was performed. The subsequent pathological findings revealed no cancer and a complete pathological response. The patient is currently alive 4 years after the first surgery, without evidence of recurrence and adjuvant chemotherapy. A 60-year-old man was diagnosed as having CUP with an undifferentiated carcinoma and lymph node metastasis. He received chemotherapy with paclitaxel, carboplatin, and gemcitabine. However, unanticipated adverse events(finger ulcer)occurred. Thus, the chemotherapy was changed to paclitaxel, carboplatin, and etoposide. The patient is currently alive 4.2 years after the first chemotherapy, without evidence of recurrence. A 59-year-old man was diagnosed as having CUP with neuroendocrine carcinoma(NEC)and lymph node metastasis. He received chemotherapy with irinotecan and cisplatin. The lymph node metastases disappeared, but bone metastasis was found. The chemotherapy was changed to paclitaxel, carboplatin, and etoposide. The patient is currently alive 3.5 years after the first chemotherapy, without evidence of recurrence. We report 3rare cases of high-grade malignant CUP with complete pathological response, partial response, stable disease, and long-term survival after chemotherapy.

[Breast Cancer with Microinvasion and Lymph Node Metastasis Diagnosed by Microdochectomy - Report of a Case].

We report a case of breast cancer with microinvasion and lymph node metastasis. The patient was a 72-year-old woman who had spontaneous nipple discharge from her left breast. There was no detectable lesion on mammographyor duct endoscopy. Ultrasonography showed a low echoic lesion, 23×15mm in diameter, in the CD area of her left breast. Contrastenhanced MRI showed a high intensityarea, 25mm in diameter, in her left breast, so microdochectomywas performed. The histopathological diagnosis was invasive ductal carcinoma(invasion of 2mm)and the surgical margin was positive. Therefore, she underwent breast conserving surgeryplus axillaryly mph node dissection. The pathological diagnosis from the resected surgical specimen was invasive ductal carcinoma with micro lymph node metastasis, positive for ER and PgR and negative for HER2/neu protein expression. The Ki-67 labeling index was 10% and the surgical margins were negative. She was treated with radiation and endocrine therapy as adjuvant therapy. One year and 6 months after surgery, she was well without metastasis.

[Difficult Decision about a Surgical Margin for a Non-Invasive Apocrine Carcinoma in the Breast - Report of a Case].

We report a case of non-invasive apocrine carcinoma. In this case, we could not identifythe surgical margin. The patient was 39-year-old woman. Micro calcifications were discovered on her right breast during breast cancer screening. Stereotactic vacuum assisted core needle biopsywas performed and the pathological diagnosis was sclerosing adenosis. A low echoic lesion, 26mm in diameter, was discovered in the CDE area of her left breast byultrasonography . A contrast enhanced MRI showed a high intensityarea, 26mm in diameter, on her left breast. Ultrasonographyguided vacuum assisted core needle biopsywas conducted on the low echoic area. The pathological diagnosis was non-invasive ductal carcinoma. We checked her whole bodyand found no metastatic lesion. She underwent breast conserving surgeryplus sentinel lymph node biopsy. We had great difficultyin classifying the surgical margin. The pathological diagnosis from the resected surgical specimen was non-invasive apocrine carcinoma, negative for ER and PgR, and positive for HER2/neu protein expression. The Ki-67 labeling index was 20%, the surgical margins were negative, and the clinical Stage was 0(Tis, N0, M0). She was administered radiation therapy and endocrine therapy as adjuvant therapy. Two years and 6 months after surgery, she is well without metastasis.

[Axillary Lymph Node Dissection and Chemotherapy were Useful for Occult Cancer - Report of a Case].

We report a case of occult cancer. In this case, axillaryly mph node dissection and chemotherapywere useful treatments. The patient was a 71-year-old woman who had left axillaryly mph node swelling. Mammographyshowed the swollen axillary lymph nodes, but there was no lesion in either breast. Ultrasonographyalso showed the swollen axillaryly mph nodes, but there was no malignant lesion in her breasts. CT showed swollen axillaryand mediastinal lymph nodes. We checked her entire body, but could not find a malignant lesion, so we diagnosed an occult cancer. She underwent axillary lymph node dissection. The pathological diagnosis from the resected surgical specimen was metastatic carcinoma, negative for ER and PgR, and negative for HER2/neu protein expression. She was given TC chemotherapyand her CEA value decreased. After 8 cycles of TC chemotherapy, she was well without metastasis.

[Indoleamine 2,3-Dioxygenase Activity during Fulvestrant Therapy for Multiple Metastatic Breast Cancer Patients].

We evaluated the clinical significance of indoleamine 2,3-dioxygenase(IDO)during fulvestrant therapyfor multiple metastatic breast cancer patients. IDO activitycan be measured using the tryptophan(Trp)/kynurenine(Kyn)ratio. Trp and Kyn were measured using high-performance liquid chromatography(HPLC). The serum Trp/Kyn level in patients with multiple metastatic breast cancer was lower than in patients without metastases. IDO activityincreased after breast cancer metastases developed. IDO activitywas correlated with the number of metastatic lesions during toremifene and fulvestrant therapy. These results suggested that measurement of the Trp/Kyn ratio is useful to evaluate immunological metastatic status during endocrine therapy.

[Study of the Immunological Stress Caused by Breast Surgery Methods].

To determine the role of immunosuppressive acidic protein(IAP)in the host defense of surgical patients, we investigated the kinetics of the post-operative elevation of IAP, as well as factors influencing the increase in serum IAP concentration, in 17 patients who underwent breast surgery. IAP was not increased in the pre-operation phase, post-operation phase, or 2 weeks after surgery, byvarious breast surgerymethods. In contrast, IL-6 was increased in the post-operation phase byall breast surgerymethods. IL-6 correlated with anesthesia time. These results suggest that breast surgical methods are less immunologicallyinvasive than other major surgery.

[Clinical Evaluation of Immunosuppressive Acidic Protein in the Serum of Patients with Locally Advanced Breast Cancer during Mohs Paste Treatment].

Locallyadvanced breast cancer lesions often compromise the patient's qualityof life(QOL). Mohs paste is a histopathological fixative containing zinc chloride as the main ingredient. It has been applied to perform chemosurgeryon skin tumors. In recent years, this paste has reportedlybeen veryeffective for controlling various symptoms of skin metastases in inoperable advanced cancer, such as pungent odor and hemorrhage, in the field of palliative care. We evaluated the clinical significance of immunosuppressive acidic protein(IAP)and C-reactive protein(CRP)in the serum of patients with locallyadvanced breast cancer duringMohs paste treatment. The tryptophan(Trp)/kynurenine(Kyn)ratio measures IDO activity. Trp and Kyn were measured byhigh performance liquid chromatography(HPLC). We took serum samples from 3 locallyadvanced breast cancer cases, in the pre-treatment phase, 2 times after the treatment phase, and 5 times after the treatment phase. Then, we measured IAP and CRP in these samples during Mohs paste treatment. Serum IAP values did not differ significantlybetween each of the phases; however, serum CRP values were decreased byMohs paste treatment. These results suggested that Mohs paste treatment for locallyadvanced breast cancer lesions was useful for enhancing the patient QOL, without immunosuppression.

[Indoleamine 2,3-Dioxygenase Activity in Intracystic Breast Tumors].

We evaluated the clinical significance of indoleamine 2,3-dioxygenase(IDO)in intra-cystic tumors of the breast. IDO activitycan be measured byusing the tryptophan(Trp)/kynurenine(Kyn)ratio. Trp and Kyn were measured by high performance liquid chromatography(HPLC). We took liquid from 3 intra-cystic papilloma cases and 5 intra-cystic breast cancer cases. Then, we measured the Trp/Kyn ratio in these samples, and we evaluated the difference in the Trp/Kyn ratio between the papilloma group and the breast cancer group. The Trp/Kyn ratio was significantly lower in the breast cancer group than in the papilloma group. These results suggest that measuring the Trp/Kyn ratio in cystic liquid from intra-cystic breast lesions is useful to distinguish benign intra-cystic lesions from malignant intra-cystic lesions.

[Usefulness of Local Therapy in Elderly Breast Cancer Patients with Distant Metastases].

We investigated the usefulness of local therapy in elderly breast cancer patients with distant metastases. Sixty-four elderly breast cancer patients were encountered during 10 years. Fifty-one patients had complications. The proportion of endocrine receptor-positive tumors was 95.2%. Patients who had metastases at the first visit represented 22.6% of the study group. Advanced-stage cancers were recognized in elderly patients than other patients. The mean observation time for all the patients was 7.4 years. The mortality from cancer was 6.5%, and the mortality from other diseases was 58.1%. We divided the patients into 2 groups, the non-metastases group (group A, n=48), and the metastases group (group B, n=14). There were no significant differences between groups A and B in the rates of endocrine receptor-positive tumors, surgery rate, and survival rate. These results suggest that endocrine therapy without surgery should be considered in elderly breast cancer patients with endocrine receptor-positive tumors.

[Interval Breast Cancer with Neuroendocrine Differentiation].

We report a case of interval breast cancer that was an invasive ductal carcinoma of the breast with neuroendocrine differentiation. The patient was a 66-year-old woman who had a breast lump. She had received breast cancer screening every other year. The last screening was 1 year and 6 months prior to diagnosis. A core needle biopsy for breast tumor led to a diagnosis of invasive ductal carcinoma. Breast conserving surgery plus sentinel lymph node biopsy was performed. The pathological diagnosis from the resected surgical specimen was invasive ductal carcinoma with neuroendocrine differentiation, positive for ER and PgR, and negative for HER2/neu protein expression. The surgical margins were negative, and there was no metastasis in the sentinel lymph node. She was administered radiation therapy and adjuvant endocrine therapy. Two years after surgery, she is well without metastasis.