Clinical impact of C-reactive protein to albumin ratio of the 7th postoperative day on prognosis after laparoscopic colorectal cancer surgery.

PURPOSE: C-reactive protein to albumin ratio (CAR) has been utilized as a prognostic factor in various carcinomas. We investigated the relationship between preoperative, postoperative day (POD) 1, and POD 7 CARs and the prognosis of patients with colorectal cancer (CRC). METHODS: Three hundred twenty patients with CRC who underwent laparoscopic radical resection between May 2011 and December 2016 were enrolled. Patients were selected into 2 groups, high CAR and low CAR (n=72/group), based on preoperative, POD 1, and POD 7 CARs. The relapse-free survival (RFS) and overall survival (OS) were compared between groups using propensity score matching. RESULTS: The high CAR group had a significantly worse RFS (P<0.001) and OS (P=0.002) at POD 7 than those in the low CAR group. However, in preoperative and POD 1 analysis, no differences were observed. CONCLUSION: In patients with CRC, CAR of POD 7 was a significant prognostic factor.

Effective and safe reduction in visceral fat using a formula diet in a short period before highly invasive endoscopic surgery - Case series.

INTRODUCTION: We retrospectively assessed the efficacy and safety of use of short-term formula diet therapy to achieve preoperative reduction in visceral fat immediately prior to highly invasive endoscopic surgery. PRESENTATION OF CASE: We reviewed 5 cancer patients who underwent thoracoscopic and/or laparoscopic-assisted esophagectomy or gastrectomy. The cases were those with a BMI ≥30 kg/m2 or waist circumference ≥100 cm. Patients replaced one meal out of the three main meals with one or two sachets of formula diet (170-340 kcal). The other two meals were set to 600 kcal. The dietary therapy was implemented approximately 1 month before the operation. Weight loss achieved after dietary therapy ranged from 6.4% to 14.1% (p < 0.01). With the exception of one case, the decrease in visceral fat area ranged from 17.0%-40.7% (p = 0.03). Postoperative complications were anastomotic insufficiency in two cases. DISCUSSION: Although the decreases of the visceral fat were effectively implemented, the adverse effects on postoperative complications must be examined in the farther study. CONCLUSION: It was suggested that use of formula diet to achieve preoperative visceral fat reduction in a short period of time immediately prior to highly invasive endoscopic cancer surgery would be an effective and safe strategy.

Laparoscopic abdominal perineal rectal resection for rectal cancer with a horseshoe kidney using preoperative 3D-CT angiography: a case report.

BACKGROUND: A horseshoe kidney is a congenital malformation involving the fusion of the bilateral kidneys and is often accompanied by anomalies of the ureteropelvic and vascular systems. When performing resection of colorectal cancer in a patient with horseshoe kidney, damage to the ureter or excessive renal arteries should be avoided. To achieve this purpose, comprehensive preoperative anatomical assessments and surgical planning are important. Here, we report a case of a laparoscopic abdominal perineal rectal resection for lower rectal cancer with a horseshoe kidney. CASE PRESENTATION: A 79-year-old woman presented with bloody stool and was diagnosed with advanced lower rectal cancer, immediately above the rectal dentate line, without metastasis. A preoperative computed tomography (CT) scan revealed a horseshoe kidney, while a three-dimensional CT (3D-CT) angiography revealed aberrant excess renal artery from the aorta to the renal isthmus. The left ureter ran in front of the isthmus of the horseshoe kidney and presented calculus formation. Laparoscopic abdominal perineal rectal resection was performed with D3 lymph node dissection. During the operation, we mobilized the sigmoid colon mesentery via a medial approach and preserved the left ureter, the left gonadal vessels, and the hypogastric nerve plexus in the retroperitoneum in front of the horseshoe kidney. CONCLUSIONS: We report a rare case of rectal cancer surgery in a patient with a horseshoe kidney. We discuss the anatomical peculiarities of a horseshoe kidney, such as excess renal arteries, inferior vena cava, ureter, gonadal vessels, and nerves, that should be preserved according to the literature. We suggest that preoperative 3D-CT angiography is both useful for revealing the relationship between the vascular system and a horseshoe kidney and helpful when performing laparoscopic surgery for a left-sided colon and rectal cancer to avoid intraoperative injury.

Thoracoscopic resection of a cystic seminoma of the mediastinum.

Mediastinal seminoma is an uncommon tumor that accounts for 25% of primary mediastinal germ cell tumors, which in turn comprise fewer than 5% of all germ cell tumors. Although CT normally shows a solid, lobulated tumor, mediastinal cystic seminoma has rarely been described. Here, we report a 24-year-old man who presented with a mediastinal cystic tumor that was resected after an 18-month delay via video-assisted thoracoscopic surgery while in the supine position; the procedure involved lifting the chest wall with a subcutaneous Kirschner wire. Pathological examination revealed a mediastinal cystic seminoma. No evidence of recurrence has been noted during 25 months of follow-up. Mediastinal cystic seminoma should be considered in the differential diagnosis of cystic lesions of the mediastinum. Moreover, video-assisted thoracoscopic resection may be an appropriate option for the diagnosis and treatment of such lesions.

A left thoracic approach in a prone position for thoracoscopic thoracic duct ligation in a patient with post-esophagectomy chylothorax: A case report.

INTRODUCTION: We debate whether or not to approach from right thorax for the left chylothorax after esophagectomy. PRESENTATION OF CASE: A 50s-year-old female underwent right-sided thoracoscopic esophagectomy with three-field lymphadenectomy for esophageal carcinoma (type 0-IIa, 3.4×2.2cm, T1bN0M0, Stage IA), followed by reconstruction with esophagogastric anastomosis through the posterior mediastinum. The thoracic duct was excised and ligated. The left thoracic drainage increased to 2115mL/day on the fifth postoperative day. Thoracic duct injury was diagnosed, and surgery was performed on sixth postoperative day. With the patient in a prone position, the thoracic duct was ligated successfully under thoracoscopy in the left thorax. The leakage point was found in the crushed duct by 8.8-mm titanium clips. Then, we performed mass ligation of the thoracic duct with 11-mm titanium clips below the leakage point after careful dissection. The surgery took 58min, with an estimated total blood loss of 0g. DISCUSSION: Although thoracic duct is anatomically located on the right side of the descending aorta, we employed a left-sided thoracoscopic approach due to the chylous leakage in the left thorax. With the patient in the prone position, surgeons can easily convert from a left thoracic approach to a right thoracic approach immediately without postural change if the thoracic duct cannot be found in the left thoracic cavity. CONCLUSION: This technique is useful and should be considered for patients with left chylothorax.

Metabolic Rather than Pathological Response to Preoperative Chemoradiotherapy Is a Stronger Predictor of Survival in cStage IIB-IV Esophageal Cancer.

AIM: We investigated which is the stronger predictor, pathological response or metabolic response, for survival outcome in patients treated with neoadjuvant chemoradiotherapy (NACRT) plus esophagectomy for thoracic esophageal squamous cell carcinoma (TESCC). PATIENTS AND METHODS: Fifty consecutive patients with cStage IIB-IV TESCC were enrolled. We analyzed the pathological response and metabolic response (fractional decrease in tumor maximum standardized uptake value) to NACRT. Independent prognostic factors predictive of 3-year survival were investigated using univariate and multivariate analyses. RESULTS: Among the 50 patients, 10 (20%) showed a pathological complete response (in both tumor and lymph nodes) and 36 (72%) showed grade 2-3 pathological response. Univariate analysis showed that age, gender, cT stage, pathological response and metabolic response to be significant prognostic factors. A subsequent multivariate analysis confirmed metabolic response and gender to be significant prognostic factors. CONCLUSION: Metabolic response for NACRT was an independent prognostic factor and a more powerful predictor of survival compared to pathological response.

[A case of rectal gastrointestinal stromal tumor in an elderly patient who was successfully treated with imatinib mesylate with no significant adverse events].

An 89-year-old male patient was found to have a mass with a diameter of 54 mm in the pelvic cavity, connected to the rectum, and was diagnosed with a gastrointestinal stromal tumor (GIST)of the rectum by transrectal biopsy. The patient was treated continuously with 400mg/day of imatinib mesylate with no significant adverse events, and the tumor gradually reduced in size. The tumor reduced in size to a diameter of 24 mm at 57 months post-treatment, and a partial response has been maintained for 60 months. Colorectal GIST is rare, comprising 5% of all GIST cases, and surgical resection is the first choice of treatment. In this case, due to a lack of consent, we chose imatinib mesylate as the treatment. However, imatinib mesylate has been reported to induce adverse events more frequently in older patients, and thus we took care to reduce the treatment dosage. We report this case to highlight that a normal quantity of imatinib mesylate can be administered, with no significant adverse events.

Tumoral CRP expression in thoracic esophageal squamous cell cancers is associated with poor outcomes.

PURPOSE: Cancer cells reportedly produce C-reactive protein (CRP) locally within tumors. The aim of this study was to determine whether tumoral CRP is associated with clinical outcome and recurrence in thoracic esophageal squamous cell cancer. METHODS: The subjects included 73 Japanese patients with thoracic esophageal squamous cell cancer (pathological Stage IIA-IV) that had not been treated preoperatively with either chemotherapy or radiotherapy. Tumoral CRP expression in resected specimens of tumor tissue was assessed by immunohistochemistry. The survival rate following surgery, the rates and patterns of recurrence, and the serum CRP levels before treatment and at recurrence were analyzed in patients with and without tumoral CRP expression. RESULTS: Fifty-nine percent of the study participants (43/73) were positive for tumoral CRP expression, and the remaining 41% (30/73) were negative. No significant difference in clinicopathological factors was observed between the tumoral CRP-positive and CRP-negative groups; however, patients expressing tumoral CRP showed significantly poorer survival and recurrence rates. A multivariate analysis showed that tumoral CRP expression was an independent factor contributing to the likelihood of a poor outcome. CONCLUSION: Tumoral CRP is associated with a poor outcome in thoracic esophageal squamous cell cancer. Tumoral CRP could therefore be an important target for the treatment of this disease.

Estimating the need for neck lymphadenectomy in submucosal esophageal cancer using superparamagnetic iron oxide-enhanced magnetic resonance imaging: clinical validation study.

BACKGROUND: In cases of thoracic esophageal cancer, multidirectional lymphatic flow from the tumor means that lymph node metastasis can occur in an area extending from the neck to the abdomen. To validate a method for limiting the performance of three-field lymphadenectomy only to patients who need it, we carried out a prospective study in which superparamagnetic iron oxide (SPIO)-enhanced lymphatic mapping was used to determine whether to perform neck lymph node dissection in patients with submucosal thoracic esophageal cancer. METHODS: A total of 22 patients with clinically submucosal thoracic squamous cell esophageal cancer, without neck lymph node metastasis, were enrolled. SPIO was endoscopically injected into the peritumoral submucosal layer, after which its appearance in lymph nodes in the neck was evaluated using magnetic resonance imaging (MRI). Neck lymph nodes were then dissected based on the SPIO-enhanced MRI lymphatic mapping. RESULTS: Influx of SPIO into lymph nodes was detected in 21 patients (95% detection rate). SPIO flowed to the neck in 8 (36%) patients. Influx of SPIO into neck lymph nodes was unilateral in five patients and bilateral in three patients, and the lymph nodes were dissected accordingly. A cancer-involved node was identified in two of those patients. In 14 patients, we did not dissect neck nodes. Patients were followed up for 6 to 47 months. The neck lymph node recurrence rate was zero, and the overall recurrence rate was 5%. CONCLUSIONS: SPIO-enhanced lymphatic mapping may be useful for estimating the need for three-field lymphadenectomy with neck dissection.

[A case of recurrent malignant melanoma of esophagus responsive to combined chemotherapy, radiotherapy and cellular immunotherapy].

Treatment of primary malignant melanoma of the esophagus remains challenging. We treated a 53-year-old man with pT4N2M0, Stage IVa malignant melanoma of the esophagus with esophagectomy followed by adjuvant chemotherapy. Six months later, computed tomography revealed a 12 cm disseminated tumor of the mesenterium, multiple peritoneal dissemination, and a large amount of ascites. We administered chemotherapy consisting of dacarbazine combined with cisplatin and nimustine, and radiotherapy(50 Gy)was applied to the disseminated mesenteric tumor. At another clinic, the patient was administered synchronous cellular immunotherapy consisting of dendritic cells pulsed with autologous tumor lysates and lymphokine-activated killer cells. The mesenteric tumor was extremely responsive to this trimodal treatment. Because recurrence occurred later within the left orbita muscle, we added 50 Gy of radiation to prevent blindness. The patient responded to this treatment and survived another 6 months with high quality of life. It is difficult to treat advanced malignant melanoma of the esophagus, and patient prognosis is extremely poor. In this patient, the recurrent tumors responded well to trimodal therapy consisting of chemotherapy, radiotherapy and cellular immunotherapy.

Interleukin-2 -330T>G genetic polymorphism associates with prognosis following surgery for thoracic esophageal squamous cell cancer.

BACKGROUND: Key molecules in the T helper (Th)1 and Th2 pathways underlie differential responses to the progression and surgical treatment of cancer. We investigated the relationship between Th1/Th2 cytokine polymorphism and prognosis in patients with thoracic esophageal squamous cell cancer. MATERIALS AND METHODS: The study participants were 159 Japanese patients treated for thoracic esophageal squamous cell cancer with curative esophagectomy at Akita University Hospital. We determined the associations between prognosis following esophagectomy and genetic polymorphisms in Th1 cytokines (interleukin [IL]-2, Interferon-γ, IL-12ß), and Th2 cytokines (IL-4, IL-10). RESULTS: IL-2 -330T>G genetic polymorphism was significantly associated with prognosis after esophagectomy. Univariate and multivariate analyses using a Cox proportional hazards model revealed that patients carrying the IL-2 -330G/G genotype had a significantly poorer prognosis than those carrying the T/G or T/T genotype. However, IL-2 -330T>G polymorphism was not associated with preoperative serum IL-2 levels. Moreover, interferon-γ, IL-12ß, IL-4, and IL-10 genetic polymorphisms were not associated with prognosis after esophagectomy for thoracic esophageal squamous cell cancer. CONCLUSIONS: It is suggested that IL-2 -330T>G genetic polymorphism may be a predictive factor for prognosis in patients receiving esophagectomy for thoracic esophageal squamous cell cancer.

IGFBP3 and BAG1 enhance radiation-induced apoptosis in squamous esophageal cancer cells.

Identification of reliable markers of radiosensitivity and the key molecules that enhance the susceptibility of esophageal cancer cells to anticancer treatments would be highly desirable. To identify molecules that confer radiosensitivity to esophageal squamous carcinoma cells, we assessed the radiosensitivities of the TE-5, TE-9 and TE-12 cloneA1 cell lines. TE-12 cloneA1 cells showed significantly greater susceptibility to radiotherapy at 5 and 10Gy than either TE-5 or TE-9 cells. Consistent with that finding, 24h after irradiation (5Gy), TE-12 cloneA1 cells showed higher levels of caspase 3/7 activity than TE-5 or TE-9 cells. When we used DNA microarrays to compare the gene expression profiles of TE-5 and TE-12 cloneA1 cells, we found that the mRNA and protein expression of insulin-like growth factor binding protein 3 (IGFBP3) and Bcl-2-associated athanogene 1 (BAG1) was five or more times higher in TE-12 cloneA1 cells than TE-5 cells. Conversely, knocking down expression of IGFBP3 and BAG1 mRNA in TE-12 cloneA1 cells using small interfering RNA (siRNA) significantly reduced radiosensitivity. These data suggest that IGFBP3 and BAG1 may be key markers of radiosensitivity that enhance the susceptibility of squamous cell esophageal cancer to radiotherapy. IGFBP3 and BAG1 may thus be useful targets for improved and more individualized treatments for patients with esophageal squamous cell carcinoma.

C-reactive protein -717C>T genetic polymorphism associates with esophagectomy-induced stress hyperglycemia.

BACKGROUND: Stress hyperglycemia refers to the transient hyperglycemia seen during illness and is usually restricted to patients without previous evidence of diabetes. The influence of genetics on surgery-induced hyperglycemia remains only partially understood. METHODS: The study participants were Japanese patients treated for thoracic esophageal cancer with curative esophagectomy at Akita University Hospital between 2003 and 2007. We determined the associations between esophagectomy-induced stress hyperglycemia (> or =30 mg/dl increases in blood glucose during surgery) and genetic polymorphisms for C-reactive protein (CRP), tumor necrosis factor (TNF)-alpha, -beta, interferon-gamma, transforming growth factor-beta1, interleukin (IL)-1beta, IL-2, IL-4, IL-6, IL-6 receptors, IL-10, IL-12beta, adiponectin, and peroxisome proliferator-activated receptor-gamma. RESULTS: In 28 (46%) patients, blood glucose levels increased more than 30 mg/dl during surgery. Among the genetic polymorphisms tested, CRP -717C>T was significantly associated with stress hyperglycemia during esophagectomy. Multivariate logistic regression revealed that patients with the CRP -717T/T genotype had a significantly greater risk of developing surgery-induced hyperglycemia than those with the CRP -717C/T genotype. Stress hyperglycemia was also significantly associated with postoperative infectious complications and duration of intensive care unit stay. CONCLUSIONS: It is suggested that CRP -717 C>T genetic polymorphism may be a predictive factor for stress hyperglycemia in patients receiving esophagectomy for thoracic esophageal cancer.

Regenerating gene I regulates interleukin-6 production in squamous esophageal cancer cells.

Regenerating gene (REG) I plays important roles in cancer cell biology. The purpose of this study was to determine whether REG I affects cytokine production in cancer cells. We transfected TE-5 and TE-9 squamous esophageal cancer cells with REG Ialpha and Ibeta and examined its effects on cytokine expression. We found that transfecting TE-5 and TE-9 cells with REG I Ialpha and Ibeta led to significantly increased expression of interleukin (IL)-6 mRNA and protein, but it had little or no effect on expression of IL-2, IL-4, IL-5, IL-10, IL-12, IL-13, IL-17A, interferon-gamma, tumor necrosis factor-alpha, granulocyte-colony stimulating factor or transforming growth factor-beta1. The elevated IL-6 expression seen in REG Ialpha transfectants was silenced by small interfering RNA-mediated knockdown. These finding suggest that REG I may act through IL-6 to exert effects on squamous esophageal cancer cell biology.

C-reactive protein 1059G>C genetic polymorphism influences serum C-reactive protein levels after esophagectomy in patients with thoracic esophageal cancer.

BACKGROUND: Little is known about how C-reactive protein (CRP) genetic polymorphisms influence the rise in serum CRP levels seen after surgery. The purpose of this study was to assess the association between CRP polymorphisms and acute-phase serum CRP levels after esophagectomy for thoracic esophageal cancer. STUDY DESIGN: We enrolled 110 patients who underwent curative esophagectomy without neoadjuvant treatment between 2003 and 2008. Using peripheral blood samples collected from the patients, polymorphisms for CRP, tumor necrosis factor, interferon-gamma, tumor growth factor-beta1, interleukin (IL)-1beta, IL-1 receptor antagonist, IL-2, IL-4, IL-6, IL-6 receptor, IL-10, and IL-12beta were all investigated to determine which, if any, affect postoperative serum CRP levels and clinical outcomes. RESULTS: Although preoperative serum CRP levels did not differ, 12 hours after esophagectomy, serum CRP levels were significantly higher in patients carrying the CRP 1059G/G genotype than in those with the 1059G/C genotype (111 +/- 35 mg/L versus 78 +/- 17 mg/L; p = 0.0266), and after 36 hours CRP levels remained higher in those with the 1059G/G genotype (217 +/- 63 mg/L versus 140 +/- 51 mg/L; p = 0.0020). Logistic regression models revealed that patients carrying the CRP 1059G/G genotype had a significantly higher likelihood of a postesophagectomy increase in serum CRP, although the CRP 1059G>C genetic polymorphism had no effect on clinical outcomes. None of the other cytokine genetic polymorphisms influenced postoperative serum CRP levels. CONCLUSIONS: Our findings suggest that the CRP 1059G>C genetic polymorphism is 1 determinant of serum CRP levels after major surgery.

Interferon-gamma 874A>T genetic polymorphism is associated with infectious complications following surgery in patients with thoracic esophageal cancer.

BACKGROUND: Cytokines play a major role in the organization of orchestrated responses to infections, and there is an emerging consensus that cytokine gene polymorphisms mediate individual variations in cytokine expression. Our aim in this study was to assess whether cytokine polymorphisms were associated with infectious complications following esophagectomy in a Japanese population. METHODS: The study participants were Japanese patients treated with transthoracic esophagectomy without neoadjuvant treatment. DNA was extracted from blood samples, and genetic polymorphisms for interferon (INF)-gamma, tumor necrosis factor-alpha and -beta, transforming growth factor-beta1, interleukin (IL)-1beta, IL-1 receptor antagonist, IL-2, IL-6, IL-6 receptor, IL-10, and IL-12beta were investigated using the polymerase chain reaction-restriction fragment length polymorphism method. We then assessed the association between gene polymorphisms and postoperative infection. RESULTS: Of the 110 patients studied, 18 (16%) developed a postoperative infection (pneumonia, 14 patients; pyothorax, 5; intraabdominal abscess, 1; neck abscess, 1; sepsis, 2). Although the characteristics of patients who developed postoperative infections did not differ, analysis of the genotypes using the Fisher exact test revealed a significantly (P = .0215) greater incidence of postoperative infections among those carrying the INF-gamma 874 (rs2430561) A/A and A/T genotypes. Moreover, univariate and multivariate logistic regression models showed patients carrying the INF-gamma 874A/T genotype were significantly more likely to develop postoperative infectious complications (odds ratio>3.4). CONCLUSION: Our findings suggest that the IFN-gamma 874A>T polymorphism is potentially predictive of the likelihood that patients undergoing esophagectomy for thoracic esophageal cancer will develop postoperative infections. This polymorphism may therefore have important clinical relevance and should be considered when treatment regimens are designed.

CRP genetic polymorphism is associated with lymph node metastasis in thoracic esophageal squamous cell cancer.

BACKGROUND: Lymph node involvement is the most important prognostic factor in thoracic esophageal cancer. A more accurate molecular technique for diagnosing lymph node metastasis and a better understanding of the molecular mechanisms governing lymph node metastasis would be highly desirable. The purpose of this study is to examine the association between inflammation-related genetic polymorphisms and lymph node metastasis. METHODS: The study participants were 113 Japanese patients undergoing curative surgery for thoracic esophageal squamous cell cancer. DNA was extracted from blood samples and genetic polymorphisms in C-reactive protein (CRP), tumor necrosis factor (TNF)-alpha and -beta, interferon (IFN)-gamma, transforming growth factor (TGF)- beta, interleukin (IL)-1beta, IL-1 receptor antagonist, IL-2, IL-4, IL-6, IL-6 receptor, IL-10, and IL-12beta were investigated using the polymerase chain reaction-restriction fragment length polymorphism method. We then assessed the association between inflammation-related genes and lymph node metastasis. RESULTS: For CRP 1846C>T polymorphism, the frequency of the 1846T/T genotype was significantly higher in patients with lymph node metastasis (P = 0.0043), and the odds ratio (3.040) derived from logistic regression models indicated that the 1846T/T genotype significantly increases the likelihood of lymph node metastasis. In submucosal cancer, the utility of CRP 1846C>T polymorphism for predicting lymph node involvement was superior to usual methods (computed tomography and ultrasonography), with positive and negative predictive values of 69% and 75%, respectively. CONCLUSIONS: These findings suggest that CRP polymorphism is a potentially effective predictor of lymph node metastasis and may thus be useful for deciding on treatment strategy.