Experience with chemotherapy for postoperative metastases of adenosquamous carcinoma of the esophagogastric junction and pathological study of its development.

We report here a case of postoperative recurrent adenosquamous carcinoma (ASC) of the esophagogastric junction (EGJ) treated with S-1 therapy. A 79-year-old woman was diagnosed with carcinoma of the EGJ. Thoracoscopic subtotal esophagectomy was performed, and pathological examination revealed advanced ASC with lymph node metastasis. Five months after surgery, multiple lung metastases and multiple lymph node metastases were observed, and the patient was treated with S-1 monotherapy, which showed partial response and may be effective for advanced ASC of the EGJ. On the other hand, immunohistological analysis of the tumors showed a relatively wide range of areas that could differentiate into both adenocarcinoma and squamous cell carcinoma, suggesting that tumor cells with multidifferentiation potential, or at least the ability to differentiate into both adeno-epithelial and squamous epithelial cells, were the likely source of the tumors.

[A Case of Advanced Esophagogastric Junction Adenocarcinoma with Enlarged Lymph Node Metastases of the Middle Mediastinum and Intraperitoneal That Exhibited pCR by Preoperative SOX Therapy].

A 79-year-old man was diagnosed with esophagogastric junction adenocarcinoma, cT3N3M0, cStage Ⅲ, including enlarged lymph node metastases(Bulky N)in the middle mediastinum and intraperitoneal. A total of 2 cycles of S-1 plus oxaliplatin(SOX)was administered. After neoadjuvant chemotherapy, the primary tumor and enlarged lymph nodes had greatly decreased in size. Subsequently, thoracoscopic subtotal esophagectomy and reconstruction with a gastric tube were performed. Histopathological examinations showed no residual cancer cells in the primary lesion and dissected lymph nodes (pathological complete response). Preoperative chemotherapy containing SOX could be a useful treatment strategy for patients with esophagogastric junction adenocarcinoma with enlarged lymph node metastasis.

Protein Energy Wasting and Sarcopenia in Dialysis Patients.

As the aging of the population progresses in Japan, the nutritional problems in dialysis patients are being highlighted. Frailty is a clinical concept including body weight loss, muscle weakness, fatigability, decreased walking speed, and decreased physical activity, which means an intermediate concept between healthy subjects and disability subjects, indicating that their activities of daily living are not decreased but they cannot smoothly perform housework or exercise. Morbidity of dialysis patients is known to be high, and mortality of dialysis patients with frailty is 3 times higher. Sarcopenia is one of the principal reasons for or triggers of frailty. It is a disease setting showing decreased muscle volume and quality associated with decreased physical function or quality of life. Recent mean age at dialysis therapy induction is getting near to 70 years old in Japan. Japanese dialysis patients who are elderly and present organ failure would have a double risk for sarcopenia. Patients with advanced stages of CKD are generally given protein diet, and it has been reported that a low protein intake in dialysis patients would be a significant risk for developing sarcopenia and increasing mortality. Recently, the focus has been on protein energy wasting (PEW) - an underlying disease condition in sarcopenia or frailty. PEW is an energy wasting condition occurring in dialysis patients, and the cause of PEW is principally decreased food intake and increased catabolism. It has recently been revealed that decreased protein intake would be a risk factor for increased mortality in dialysis patients. The incidence of PEW in dialysis patients is reported to be 14%. To avoid sarcopenia and PEW leading to frailty, we should pay much more attention to an appropriate protein and calorie intake rather than restriction in dialysis patients.

Down-regulation of magnesium transporting molecule, claudin-16, as a possible cause of hypermagnesiuria with the development of tubulo-interstitial nephropathy.

Tubulo-interstitial nephropathy (TIN) is a critical pathological setting for the renal prognosis, and an increase in the urine magnesium excretion is a well-known characteristic feature as one of clinical parametets for the assessment of TIN. We examined the correlation between the development of TIN and the changes in the mRNA expression of renal magnesium-transporting molecules in rats with unilateral ureter obstruction (UUO). Ureter-ligated kidney was sampled at day-0 (control), day-1 (early phase) and day-7 (late phase). The development of TIN was assessed by immunohistochemistry and the real-time PCR of fibrosis-related genes (MCP-1: 105.1 ± 14.8% on day-0, 132.9 ± 25.7% on day-1, 302.7 ± 32.7% on day-7, TGF-ß: 101.1 ± 7.6% on day-0, 93.6 ± 4.1% on day-1, 338.9 ± 20.7% on day-7) . The respective expressions of claudin-10, 14, 16, 19, and transient receptor potential (TRP) M6 as magnesium-transporting molecules were also studied. The expression of calcium sensing receptor (CaSR) as an inhibitory regulator of claudin-14 was additionally studied. The gene expression of claudin-16 was decreased in the late phase of UUO (100.2 ± 2.9% at day-0, 90.3 ± 6.3% at day-1, 36.4 ± 1.6% at day-7) which was consistent with the increased urine magnesium excretion. Immunohistochemistry showed an apparent reduction of the immunoreactivity of claudin-16 in the late phase. The expression of TRPM6 was reduced even in the early phase. The immunohistochemistry and gene expression of MCP-1 and TGF-ß showed that TIN was not apparent in the early phase but was significant in the late phase of UUO. The density of peritubular capillaries was diminished in the late phase but not in the early phase. Expression of claudin-14 and CaSR was up- and down-regulated, respectively. Our findings may indicate that the characteristic hypermagnesiuria in TIN is principally caused by the dysfunction of magnesium reabsorption in the thick ascending limb of Henle resulting from a significant decrease in the claudin-16 expression. The down-regulation might be closely related to the development of TIN.

Evaluation of the functions of the temporary catheter with various tip types.

INTRODUCTION: A temporary catheter (TC) is used short-term and for emergencies. There are some cases when we cannot withdraw blood immediately after inserting the catheter in our patients. The reason is said to be the tips of the TC sticking to the vascular walls. OBJECTIVE: We evaluated examined 3 catheters with different tip shapes in a simulation circuit to assess the effect on the blood flow. METHODS: Water was circulated in the simulation circuit at 1 L/minute. Next, we inserted each TC into the model, and the TCs were connected to the dialysis circuit at 200 mL/minute. We put gold powder into the simulation circuit. We visually observed the movement of the gold power at the head of the catheter and measured the recirculation rate. RESULT: The uplift type TC was able to perform blood removal and reinfusion with the least difficulties. All recirculation rates were less than 1%. The hindrance caused by hitting a vascular wall is believed to have been reduced. CONCLUSION: With the manipulation of the catheter tip shapes, blood was able to circulate smoothly. We expect less blood clots and a decrease in sticking to the vascular wall. We plan to study these 3 catheters at clinical tests in the future.

Right axillary lymph node metastasis of carcinoma of the cecum with histologically proven cutaneous lymphatic invasion by carcinoma cells: a case report.

Axillary lymph node metastasis from colorectal carcinoma is extremely rare, and this scarcity hinders understanding of its pathogenesis and, thus, the application of appropriate management. Here, we present a case with axillary lymph node metastasis of cecal carcinoma associated with macroscopic invasion of the skin of the abdominal wall with histological evidence of such invasion, findings which support our hypothesis that the axillary lymph node metastasis developed via the lymph channels in the skin of the abdominal wall. A 76-year-old woman with cecal carcinoma (T4N1M0), complicated with an abdominal wall abscess, underwent right hemicolectomy with partial resection of the abdominal wall. Histology demonstrated multiple sites of lymphatic invasion in the skin. Two months later, an enlarged right axillary lymph node was noticed on CT, and an excisional biopsy was obtained, which later confirmed metastatic adenocarcinoma. This is the first case report of axillary lymph node metastasis of carcinoma of the cecum with histologically proven invasion via the lymphatic system in the skin. If axillary lymph node metastasis results from aberrant lymphatics due to invasion from an adjacent organ, and not the result of systemic malignant disease, it may be considered as a surgically curable pathology. Therefore, the authors advocate that patients with axillary lymph node metastasis should be evaluated with regard to the possibility of surgical curability.

Clinical significance of fractional magnesium excretion (FEMg) as a predictor of interstitial nephropathy and its correlation with conventional parameters.

BACKGROUND: Elevated urine Mg excretion and its correlation with histological damage in tubulo-interstitial nephropathy (TIN) were reported. Here we investigated the clinical significance of the fractional excretion of Mg (FEMg) for the prediction of TIN. METHODS: We enrolled and assessed 94 adult patients with various renal diseases diagnosed principally by renal biopsy. RESULTS: Our stratified analysis based on the value of the conventional TIN parameter N-acetylglucosaminidase (NAG) excretion showed that the high-NAG index group (more than median value of NAG-to-Cr ratio, n = 47) demonstrated significantly high FEMg values (p = 0.017). A univariate analysis revealed a significant correlation between the FEMg and the NAG index (R = 0.60) but not for other parameters. A multivariate regression analysis confirmed the significance of the FEMg as an effective predictor of the NAG index. The FEMg showed a significant correlation with the estimated glomerular filtration rate (eGFR) in the patients with eGFR ≤ 30 mL/min. The correlation of FEMg with the NAG index was not observed in the primary glomerulonephritis patients but was apparent in the patients with hypertensive nephrosclerosis or interstitial nephritis. CONCLUSION: Our findings may indicate that the combination of the FEMg and the NAG index can provide a specific, sensitive assessment for TIN in patients without renal insufficiency.

[A case of inverted papilloma of the renal pelvis, associated with metachronous urothelial carcinoma of the urinary bladder].

The patient visited our hospital because of macrohematuria. Cystoscopical examination did not reveal any bladder tumors but a tumor shadow in the right renal pelvis was revealed by computed tomographic scan. Urothelial carcinoma was suspected and right nephroureterectomy was performed. Pathologically the tumor was diagnosed as inverted papilloma. Four months later during the follow up of the tumor, urothelial carcinoma of the urinary bladder was detected by cystoscopy. Inverted papilloma of the renal pelvis is a rare lesion and only 39 cases to date have been reported. Because inverted papilloma of the upper urinary tract is often associated with other urothelial tumors, careful long-term follow up is advisable.

Development of a questionnaire to assess 'Hie' symptoms using an evidence-based analysis.

OBJECTIVES: Certain symptoms and signs are culturally specific. 'Hie' (chill sensation) is a major symptom experienced by Japanese people; however, it is not easily understood by Westerners. Although Hie is not life-threatening, it greatly hampers the quality of life in sufferers. To develop a remedy for Hie, valid and reliable measures are required. This is the first study aimed at developing a standardized questionnaire to quantitatively measure Hie symptom. METHODS: This was a cross-sectional study. To identify question items, we conducted a literature search using published books that mention Hie and related symptoms. The first draft of the questionnaire was prepared by selecting 31 items, including three empirically used items, using the Delphi method. A total of 744 Japanese volunteers completed the draft questionnaire. Simple correlation and factor analyses were performed to select items for the final version of Hie questionnaire and for evaluating its test-retest reliability. RESULTS: The following ten question items were ultimately selected: feeling a breeze, shivery feeling, tolerance, sensitivity to cold, Hie-like sensation in an airplane, dislike of air conditioning, use of gloves, use of an electric blanket, use of heavy clothing and need for heating devices. Of the ten Hie-related question items, five pertained to physical symptoms and the other five to daily behaviours. The internal consistency of the ten-item questionnaire was high, with a Cronbach's alpha of 0.85. The test-retest reliability of the questionnaire was preserved by the paired two-tailed t test. CONCLUSIONS: A new questionnaire was developed to evaluate the subjective symptom of Hie. This questionnaire demonstrated sufficient reliability and could be used as a tool to assess this symptom.

Induction of indefinite survival of fully mismatched cardiac allografts and generation of regulatory cells by sarpogrelate hydrochloride.

BACKGROUND: At initiation of the immunologic response, platelets rapidly release chemical mediators such as serotonin (5-hydroxytryptamine, [5-HT]) and cytokines. Sarpogrelate hydrochloride (SH), a selective 5-HT2-receptor antagonist, is used to treat patients with peripheral arterial disease. We investigated the effect of SH on the alloimmune response in a murine cardiac transplantation model. METHODS: CBA mice underwent transplantation of a C57BL/10 heart and received a short course of SH treatment. Survival of the allograft was recorded. An adoptive transfer study was performed to determine whether regulatory cells were generated. Immunohistochemistry studies of intercellular adhesion molecule 1 (ICAM-1), histological, cell-proliferation, and cytokine assessments were performed. RESULTS: Untreated CBA mice rejected C57BL/10 cardiac grafts acutely (median survival time [MST], 8 days). In mice given 10 mg/kg of SH, all allografts survived indefinitely (MST, >100 days); these mice also had significantly prolonged survival of donor-specific skin grafts but acute rejection of third-party skin grafts. Secondary CBA recipients given not only whole but also CD4 splenocytes from primary SH-treated CBA recipients with C57BL/10 cardiac allograft had indefinite survival of C57BL/10 hearts (MST, >100 days). SH inhibited upregulation of ICAM-1 on endothelial cells in the allografts. Graft acceptance and hyporesponsiveness were confirmed by the histological and cell-proliferation studies, respectively. Production of interleukin-4 and interleukin-10 from splenocytes of SH-treated transplant recipients increased compared to that from splenocytes of untreated recipients. CONCLUSION: SH induced indefinite survival of fully allogeneic cardiac allografts, generated CD4 regulatory cells, inhibited ICAM-1 expression in the allografts, and upregulated IL-4 and IL-10 production.