Tachycardia-Induced Cardiomyopathy in an Infant with Atrial Flutter and Prolonged Recovery of Cardiac Function.

Background: Tachycardia-induced cardiomyopathy (TIC) is caused by prolonged tachycardia, leading to left ventricular dilatation and systolic dysfunction with heart failure. Although TIC is more common in adults, it is rare in early infancy. Methods: Clinical testing was performed as part of medical evaluation and management. Next-generation sequencing (NGS) was conducted for a patient with TIC. A literature review on TIC was also conducted. Results: The case involved a 5-month-old infant referred to the hospital due to symptoms of heart failure lasting at least two months. The infant's heart rate was 200 beats per minute, the left ventricular ejection fraction fell below 14%, and electrocardiograms showed atrial flutter, suggesting TIC. After cardioversion, there was no recurrence of atrial flutter, and cardiac function improved 98 days after tachycardia arrest. The NGS did not identify any pathogenic variants. The literature review identified eight early infantile cases of TIC. However, no previous reports described a case with such a prolonged duration of TIC as ours. Conclusions: This is the first report of a case of prolonged TIC in a child with the documented time to recover normal cardiac function. The improvement of cardiac function depends on the duration of TIC. Early recognition and intervention in TIC are essential to improve outcomes for infantile patients, as timely treatment offers the potential for recovery.

Optimal Heart Rate May Improve Systolic and Diastolic Function in Patients with Fontan Circulation.

(1) Background: The optimal heart rate, at which the E-wave and A-wave stand adjacent without any overlaps in the Doppler transmitral flow echocardiography, is associated with maximum cardiac output and favorable clinical outcomes in adult patients with systolic heart failure. However, the clinical implication of the echocardiographic overlap length in patients with Fontan circulation remains unknown. We investigated the relationship between heart rate (HR) and hemodynamics in Fontan surgery patients with and without beta-blockers. (2) Methods and Results: A total of 26 patients (median age 1.8 years, 13 males) were enrolled. At baseline, the plasma N-terminal pro-B-type natriuretic peptide was 2439 ± 3483 pg/mL, the fraction area change was 33.5 ± 11.4%, the cardiac index was 3.55 ± 0.90 L/min/m2, and the overlap length was 45.2 ± 59.0 msec. Overlap length was importantly decreased after the one-year follow-up (7.60 ± 78.57 msec, p = 0.0069). Positive correlations were noted between the overlap length and A-wave and E/A ratio (p = 0.0021 and p = 0.0046, respectively). Ventricular end-diastolic pressure was significantly correlated with the overlap length in non-beta-blocker patients (p = 0.0483). (3) Conclusion: Overlap length may reflect the status of ventricular dysfunction. Hemodynamic preservation at lower HR could be critical for cardiac reverse remodeling.

Clinical Status and Outcome of Isolated Right Ventricular Hypoplasia: A Systematic Review and Pooled Analysis of Case Reports.

Background: Isolated right ventricular hypoplasia (IRVH), not associated with severe pulmonary or tricuspid valve malformation, is a rare congenital myocardial disease. This study aims to evaluate the clinical status and outcome of IRVH. Methods: A systematic search of keywords on IRVH was conducted. Studies were searched from MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Igaku Chuo Zasshi (Ichushi) published between January 1950 and August 2021. Results: Thirty studies met the inclusion criteria. All of these studies were case reports and included 54 patients (25 males and 29 females). The median age of the patients was 2.5 years old (0-15.3 years). Of the 54 patients, 13 (24.1%) reported a family history of cardiomyopathy. Moreover, 50 (92.6%), 19 (35.2%), and 17 (31.5%) patients were diagnosed with cyanosis, finger clubbing, and dyspnea, respectively. Furthermore, 53 (98.2%) patients had a patent foramen ovale or an atrial septal defect (ASD). Z-score of the tricuspid valve diameter on echocardiogram was -2.16 ± 1.53, concomitant with small right ventricular end-diastolic volume. In addition, 29 (53.7%), 21 (38.9%), 7 (13.0%), and 2 (3.7%) patients underwent surgery, ASD closure, Glenn operation, and one and a half ventricular repair, respectively. Among them, nine (20.4%) patients expired, and the multivariable logistic regression analysis showed that infancy, heart failure, and higher right ventricular end-diastolic pressure were risk factors for death. Conclusions: IRVH was diagnosed early in children with cyanosis and was associated with high mortality. This systematic review and pooled analysis provided evidence to assess the of IRVH degree in order to evaluate the clinical status and outcome of IRVH.

[Long-term survival of a breast cancer patient with carcinomatous pleuritis and carcinomatous cardiac tamponade successfully treated by multimodality therapy].

A 69-year old woman was admitted to our hospital because of dyspnea and pain in her left breast. Computed tomography revealed a massive quantity of left pleural effusion, a tumor in the left breast(5 cm in diameter), left cervical and supraclavicular lymph node metastasis, and a large left axillary metastatic mass. Based on a core needle biopsy, her breast tumor was diagnosed pathologically as scirrhous carcinoma, which was positive for estrogen receptor/progesterone receptor and negative for HER2 using the FISH assay, and left pleural metastasis was diagnosed cytologically. The carcinomatous pleural effusion was successfully controlled using pleural instillations of pirarubicin HCl and OK-432 after pleural drainage. A near clinical complete response was achieved by EC systemic chemotherapy(6 months)followed by endocrine therapy(letrozole), but 3 months later she was diagnosed cytologically with carcinomatous cardiac tamponade. After operative pericardial drainage, intrapericardial instillations of cisplatin and OK-432 successfully prevented re-accumulation of pericardial effusion. Systemic chemotherapy(weekly paclitaxel)for 11 months and endocrine therapy(letrozole)resulted in a clinical complete response. One year and 10 months after pericardial drainage, she underwent surgery(mastectomy and axillary lymph node dissection level II)because of two small tumors in the left breast which were found to be malignant using PET-CT. One tumor(diameter 1.6 cm)was found pathologically to consist of degenerated cancer cells, and another tumor(diameter 2 cm)was diagnosed as recurrent cancer. There was no lymph node metastasis in the axilla except for a single mass(1.4×0.7×0.3 cm), which was composed of extremely degenerative and necrotic non-lymphoid cancerous tissue. Since having the surgery, she has not experienced recurrence on hormone therapy with fulvestrant, and to date she is still alive, 3 years and 5 months since the left pleural metastasis episode.

The efficacy of prophylactic administration of SBT/ABPC for preventing surgical site infection in elderly patients undergoing colorectal surgery.

BACKGROUND/AIMS: Colorectal surgery presents a high risk of surgical site infections (SSI). SSI and prolonged hospital stay were associated with being aged 75 yrs or older. The present study investigated the efficacy of sulbactam sodium/ampicillin sodium (SBT/ABPC), which is a combination drug of ampicillin and beta-lactamase inhibitor, as a prophylactic drug against SSI in elderly patient underwent colorectal surgery. METHODOLOGY: From July 2003 to November 2005, a total of 181 patients underwent colorectal surgery. Of these patients, 43 older than 75 yrs were compared with 138 who were younger. Patients were given SBT/ABPC as follows: Before anesthetic induction at surgery, 1.5 g of SBT/ABPC was administrated by intravenous drip infusion, and further doses were continued at 12-hour intervals for 2 days. We assessed SSI, postoperative stay, type of surgery, duration of operation, and amount of bleeding. RESULTS: The result was that SSI was found in none of the patients. There was no significant difference in rate of SSI and postoperative hospital stay between the two groups. Adverse reactions due to SBT/ABPC such as apparent skin symptoms or gastrointestinal symptoms were not observed. CONCLUSION: SBT/ABPC for elderly patients would be effective to prevent SSI in colorectal operations and could be used safely.

The efficacy of prophylactic administration of SBT/ABPC for preventing surgical site infection in elderly patients undergoing colorectal surgery.

BACKGROUND/AIMS: Colorectal surgery presents a high risk of surgical site infections (SSI). SSI and prolonged hospital stay were associated with being aged 75 years or older. We investigated the efficacy of sulbactam sodium/ampicillin sodium (SBT/ABPC), which is a combination drug of ampicillin and beta-lactamase inhibitor, as a prophylactic drug against SSI in elderly patients undergoing colorectal surgery. METHODOLOGY: From July 2003 to November 2005, a total of 181 patients underwent colorectal surgery. Of these patients, 43 who were older than 75 years were compared with 138 who were younger. Patients were given SBT/ABPC as follows: Before anesthetic induction at surgery, 1.5 g of SBT/ABPC was administrated by intravenous drip infusion, and further doses were continued at 12-hour intervals for 2 days. We assessed SSI, postoperative stay, type of surgery, duration of operation, and amount of bleeding. RESULTS: The result was that SSI was found in none of the patients. There was no significant difference in rate of SSI and postoperative hospital stay between the two groups. Adverse reactions due to SBT/ABPC such as apparent skin symptoms or gastrointestinal symptoms were not observed. CONCLUSIONS: SBT/ABPC for elderly patients would be effective to prevent SSI in colorectal operations and could be used safely.

Hepatic arterial infusion combined with oral UFT/UZEL systemic chemotherapy for unresectable liver metastasis of colorectal cancer.

BACKGROUND/AIMS: Hepatic arterial infusion (HAI) chemotherapy has a number of limitations, including a low rate of complete response and frequent extrahepatic recurrence, in colorectal cancer (CRC) patients with unresectable hepatic metastases. A clinical trial was planned to assess the safety and efficacy of combination chemotherapy of HAI and oral administration of UFT and leucovorin (UZEL) in CRC patients with unresectable liver metastases. METHODOLOGY: Sixteen CRC patients with unresectable liver metastases were treated with concurrent HAI and systemic oral UFT/UZEL. Eligible patients were previously untreated (except for adjuvant therapy) CRC patients with unresectable liver metastases, with WHO performance statuses of 0 to 2. On an outpatient basis, the patients received a treatment regimen consisting of 5-fluorouracil at 1000 mg/m2 and l-Leucovorin at 50 mg/m2 for 5 hours on days 1, 8, 15, and 22 by hepatic arterial infusion plus oral UFT (300 mg/m2) and UZEL (75 mg/body) on days 2-7, 9-14, and 23-28 followed by withdrawal for one week. The cycles were repeated every 5 weeks until disease progression. RESULTS: A total of 103 cycles of HAI with the UFT/UZEL regimen were administered (median, 5 cycles; range, 6 to 9 cycles). The response rate was 87.5% (14 partial responses and 2 stable diseases). The median progression-free survival rate was 9.2 months, and the median survival time was 22 months. No treatment-related grade 3 or 4 adverse events were observed. CONCLUSIONS: This novel locoregional HAI with an oral UFT/UZEL systemic chemotherapeutic regimen is feasible in an outpatient setting and should be considered as first-line chemotherapy for CRC patients with unresectable liver metastases.

Novel sugar-cholestanols as anticancer agents against peritoneal dissemination of tumor cells.

Chemically synthesized sugar-cholestanols with mono-, di-, and tri-saccharides attached to cholestanol showed strong inhibiting activity against the proliferation of colorectal and gastric cancer cells. In contrast, cholestanol without sugar moieties was totally ineffective. Furthermore, when cancer cells were exposed to GlcNAcRbetacholestanol (R=(-) or beta1-3Gal), the compound was rapidly taken up via the lipid rafts/microdomains on the cell surface. The uptake of sugar-cholestanol in mitochondria increased gradually and was followed by the release of cytochrome c from mitochondria and the activation of apoptotic signals through the mitochondrial pathway and the caspase cascade, leading to apoptotic cell death, characterized by DNA ladder formation and nuclear fragmentation. Additionally, the examination of GlcNAcRbetacholestanol in a mouse model of peritoneal dissemination showed a dramatic reduction of tumor growth (P < 0.003) and prolonged mouse survival time (P<0.0001). Based on these observations, we believe that the sugar-cholestanols described here have clinical potential as novel anticancer agents.

Over-expression of 14-3-3sigma in budding colorectal cancer cells modulates cell migration in the presence of tenascin-C.

Epigenetic silencing of the 14-3-3sigma gene by CpG hypermethylation has been reported in many kinds of cancers, but has been considered inapplicable in the colorectal variety. The expression of 14-3-3sigma in colorectal cancer is located primarily in the invasive area. The interaction between tumor cells and the extracellular matrix (ECM) is involved in tumor invasion. In the current study, we investigated the correlation between 14-3-3sigma expression and the ECM, focusing especially on the presence of tenascin-C (TNC) at the invasive area of colorectal cancers. Correlations between the immunohistochemical expression of 14-3-3sigma and TNC, as well as other clinicopathological factors, were evaluated in 123 colorectal carcinoma tissues. 14-3-3sigma expression was frequently observed in budding tumor cells in the invasive area and expression was significantly correlated with budding formation (p=0.001), pTNM classification (p=0.001) and stromal TNC expression (p=0.004). Using colorectal cancer cell lines and ECMs, the up-regulation of 14-3-3sigma mRNA levels was investigated by semi-quantitative RT-PCR. TNC surrounding the tumor cells increased 14-3-3sigma mRNA expression 1.8- to 2.2-fold in HCT116 cells. The effect of 14-3-3sigma over-expression on tumor cell migration was investigated using an agarose-cell droplet migration assay. Over-expression of 14-3-3sigma up-regulated HCT116 cell migration on TNC (p<0.001). We concluded that the expression of 14-3-3sigma in the invasive area modulates tumor cell migration in certain types of colorectal cancer and thus facilitates tumor progression.

Galectin-3 expression in colorectal cancer: relation to invasion and metastasis.

BACKGROUND: Galectin-3, a beta-galactoside-binding protein, has been associated with various biological processes, such as cell adhesion, recognition, proliferation, differentiation and apoptosis. The aim of this study was to determine the relationship of galectin-3 expression to clinicopathological findings in patients with colorectal cancer. Furthermore, the correlation between the expression of galectin-3 and beta-catenin, and the Ki-67 labeling index were investigated. MATERIALS AND METHODS: Immunohistochemical assessment of galectin-3, beta-catenin and Ki-67 expression was performed on samples from 108 patients with colorectal cancer. The expression of galectin-3 was classified at the tumor surface and the invasive front, and its relationship with clinicopathological factors was considered from a statistical viewpoint. RESULTS: There was significant liver metastasis when the expression of galectin-3 was lower at the invasive front of a tumor compared to its surface (p = 0.04). There were also significant correlations between beta-catenin expression at the tumor surface and liver metastasis and tumor stage (p = 0.03, p = 0.04 respectively). CONCLUSION: The reduction of galectin-3 expression is associated with the invasion and metastasis of colorectal cancer. A possible involvement of galectin-3 expression in tumor invasion, metastasis and proliferation in patients with colorectal cancer is suggested.

Effect of basic fibroblast growth factor, trafermin, on entero-related fistulae, report of two cases.

Entero-related fistulae are often intractable. Recently, growth factors were generally in sight with the development of regenerative medicine. Basic fibroblast growth factor (bFGF) possesses potent angiogenic activity. In Japan, recombinant bFGF, also known as Trafermin, has been administered for intractable skin ulcer for its strong effect on tissue granulation. Here, we report the effect of bFGF for entero-related fistulae. Two intractable cases were treated by applying bFGF in the fistulae after performing the enterostomy. Case 1: Postoperative intractable vesicorectal fistula was treated by bFGF. 82 days later, fistula was closed. Case 2: Colonic perforation due to ischemic colitis was treated. 37 days after treatment, fistula was closed. In conclusion, in the treatment of the intractable entero-related fistulae, Trafermin was useful for healing the fistulae.

Alpha1,2fucosylation is a superior predictor of postoperative prognosis for colorectal cancer compared with blood group A, B, or sialyl Lewis X antigen generated within colorectal tumor tissues.

BACKGROUND: We have previously demonstrated tumor-specific alpha1,2fucosylation, which is associated with resistance of tumor cells to anticancer treatment in human colorectal tumor tissues. By using the YB-2 monoclonal antibody, the resulting products have been identified as Y, Le(b), and H type 2 antigens in colorectal tumor tissues. METHODS: Immunohistochemical analyses of colorectal cancer tissues (74 specimens) were performed with a newly established mouse monoclonal antibody, YB-3 specifically recognizing H disaccharide (Fucalpha1,2Galbeta) structures, and anti-A, anti-B, YB-2, and anti-sialyl Lewis X (SLX) antibodies, together with the analyses of glycosyltransferases involved in the synthesis of ABH antigens in the same tissues. RESULTS: The YB-3 antibody enabled us to detect colorectal tumors, particularly tumors in the distal large intestine and the rectum, with high sensitivity (74.3%) and specificity (100%). From immunohistochemical and enzymatic analyses of colorectal tissues, we found that once alpha1,2fucosylation had proceeded in tumor tissues, blood group A or B antigen was also synthesized in approximately half of the tissues of A or B blood type, but not in their normal tissues. A correlation of survival rate with immunostaining of tissues was found only by YB-3 antibody and not by anti-A, anti-B, or anti-SLX antibody. CONCLUSIONS: As a predictor of postoperative prognosis of patients with colorectal cancer, immunodetection of alpha1,2fucosylated antigens with the YB-3 antibody seemed to be superior to blood groups A, B, or SLX antigen in colorectal tumor tissues.

Second-line combination chemotherapy of oral S-1 with cisplatin and irinotecan for colorectal cancer resistant to 5-FU.

BACKGROUND/AIMS: A phase I clinical trial has been planned to determine the recommended dose and to assess the safety and efficacy of combination chemotherapy of S-1 with cisplatin and irinotecan (SCI regimen) as a second-line treatment in 5-fluorouracil (5-FU) resistant colorectal cancer (CRC). METHODOLOGY: Patients with unresectable recurrent or metastatic CRC were enrolled in this study for second-line treatment. On an outpatient basis, the patients received a treatment SCI regimen comprising S-1 oral administration for 28 days followed by withdrawal for 2 weeks, plus cisplatin and irinotecan were administered on days 1, 8, 15 and 22 by intravenous injection. These courses were repeated every 6 weeks. Starting doses were 70 mg/m2 S-1, 6 mg/m2 Cisplatin, and 60 mg/m2 Irinotecan. RESULTS: A total of 29 patients was enrolled. Dose-limiting toxicities were fatigue, nausea, and leucopenia. Twenty-three patients at recommended dose were evaluable for treatment response. The response rate was 21.7% (5 partial responses, 13 stable diseases, and 5 progressive diseases). The median progression-free survival rate was 4.3 months; the median survival time was 9.6 months. CONCLUSIONS: The SCI regimen is feasible in an outpatient setting and should be considered as second-line chemotherapy for patients with 5-FU resistant CRC.

Oral regimen consisting of UFT/UZEL for elderly patients with colorectal cancer.

BACKGROUND/AIMS: A clinical trial has been planned to assess the safety and efficacy of oral administration of UFT and leucovorin (UZEL) in elderly patients with advanced colorectal cancer (CRC). METHODOLOGY: Twenty-six patients with advanced CRC who were over 70 years and considered ineligible for combination chemotherapy received oral UFT 300 mg/day and UZEL 75mg/day were administered orally for 28 days followed by a 7-day rest period. Treatment was repeated every 5 weeks until disease progression. RESULTS: A total of 106 cycles of UFT/UZEL were administered (median, four cycles; range, one to twelve cycles). UFT/UZEL was well tolerated. The response rate was 11% (3 partial responses, 16 stable diseases, and 7 progressive diseases). The median progression-free survival rate was 3.9 months and the median survival time was 9.8 months. Treatment-related grade 3 and 4 adverse events were not observed. CONCLUSIONS: Oral regimen consisting of UFT/ UZEL is effective and well tolerated in elderly patients with advanced CRC who are considered ineligible for combination chemotherapy.

Liver metastases of a minute rectal carcinoid less than 5mm in diameter: a case report.

We report a case of liver metastases of a minute rectal carcinoid less than 5mm in diameter, which was found during the postoperative follow-up course of a stomach cancer patient. For the early stomach cancer, laparoscope-assisted distal gastrectomy with lymph node dissection was performed on August 26, 1998. Later, abdominal CT revealed space-occupying lesions in the liver (S2). Metastatic tumors of the stomach cancer were suspected, but further examination revealed that the lesions were metastatic tumors due to a rectal carcinoid tumor. Ten months later, metastatic carcinoid tumors were found in the liver (S1, S5, S6, S7, S8). Subsegmentectomy of the liver (S7) and microwave coagulation therapy (S1, S5, S6, S8) were performed. Carcinoid tumors metastatic to the lymph nodes, liver, and other areas have been reported, but all were larger than 20mm in diameter. In this case, the primary tumor was less than 5mm in diameter, which is extremely rare. This patient was successfully treated with lateral segmentectomy, subsegmentectomy (S7), microwave coagulation therapy of the liver, and transanal extirpation. She is presently in a good condition and has had no recurrence of the carcinoid tumor from ten months after the last hepatectomy.

Serum interleukin-12 and interleukin-18 levels as a tumor marker in patients with esophageal carcinoma.

Interleukin (IL)-12 and IL-18 participate in tumor immunology. Serum IL-12 and IL-18 levels were determined in patients with esophageal carcinoma, and the relationship between clinicopathologic factors and prognosis was investigated. Peripheral blood samples were obtained from 15 healthy volunteers and from 70 patients with esophageal carcinoma before curative surgery. IL-12 and IL-18 levels were determined in each serum sample by enzyme-linked immunosorbent assay. Mean serum IL-12 and IL-18 levels were significantly higher in patients with esophageal carcinoma compared with healthy volunteers (P < 0.05) and mean serum IL-12 and IL-18 levels increased in patients as the pathologic stage progressed. A positive correlation was observed between serum IL-12 and IL-18 levels (P < 0.01). In patients with esophageal carcinoma, increasing serum IL-12 and IL-18 levels correlated with tumor growth and progression. The function of these two interleukin in the host immune response remains unclear. However, this part of the host immune response did not appear to contribute to the postoperative prognosis. Serum IL-12 and IL-18 levels might correlate with a certain depth of invasion and might be useful tumor markers in patients with esophageal carcinoma.

Paraesophageal hiatus hernia, which has progressed for 8 years: report of a case.

We report a case of a paraesophageal hernia, which was successfully treated with laparoscopic surgery after a natural history of eight years. Eight years before surgery only the fundus of the stomach was included in the hernia sac. At surgery, although the gastroesophageal junction and fundus were found in their normal positions, the distal half of the stomach and the omentum were pulled into the thorax, which demonstrated an organoaxial gastric volvulus. As the omentum tightly adhered to the top of the hernia sac and there was no tight adhesion between the stomach and hernia sac, the omentum could serve as the lead point for the gastric volvulus. This patient was successfully treated with laparoscopic surgery and is presently in good condition without any recurrence of the hernia.