Aquaporin 1 expression is associated with response to adjuvant chemotherapy in stage II and III colorectal cancer.

Aquaporin 1 (AQP1), which functions as a water transporter, is associated with cancer cell proliferation, invasion, metastasis and angiogenesis in numerous types of solid cancer, including colorectal cancer (CRC). The focus of the present study was to address the potential clinical use of AQP1 expression in CRC as a prognostic and predictive biomarker for disease recurrence and therapeutic outcomes. The current study investigated the expression of AQP1 in surgically resected specimens from 268 patients with stage 0-IV CRC. AQP1 expression was positive in 112 (41.8%) patients, and was significantly associated with left-sided tumors (P<0.01) and with aggressive tumor phenotypes, including depth of invasion (P=0.03), lymph node metastasis (P=0.03), lymphatic invasion (P<0.01) and venous invasion (P<0.01). However, AQP1 expression had no significant prognostic effect on disease-free survival (DFS) in patients with stage II and III CRC following curative surgery. In 84 stage II and III patients who were administered 5-fluorouracil-based adjuvant chemotherapy, positive AQP1 expression was associated with an increased DFS rate compared with that of AQP1-negative patients (P=0.05). Additionally, these results identified that receiving adjuvant chemotherapy was not beneficial to patients with AQP1-negative tumors. This suggests that the expression of AQP1 may be a candidate biomarker predictive of response to 5-fluorouracil-based adjuvant chemotherapy following surgery in patients with stage II and III CRC.

Descending Necrotizing Mediastinitis Treated with Tooth Extractions following Mediastinal and Cervical Drainage.

Descending necrotizing mediastinitis (DNM) is a rare condition in which oropharyngeal infection spreads to the mediastinum via the cervical fascia. Delayed diagnosis and surgery result in a high mortality rate among patients with DNM. We present a case of DNM resulting from odontogenic infection treated successfully with tooth extraction following mediastinal and cervical drainage. A 43-year-old, previously healthy Japanese man was admitted to our hospital for treatment of acute mediastinitis. Computed tomography revealed gas collection around the mid-thoracic esophagus and bilateral pleural effusion. We performed mediastinal drainage via right thoracotomy. Cervicotomy was performed on postoperative day 14 to drain a residual cervical abscess. The patient required the extraction of ten teeth over three procedures to address primary odontogenic infection before his fever resolved on postoperative day 40. Prompt diagnosis, aggressive drainage and removal of the source of infection can improve survival among patients with this life-threatening disease.

Recent trend of acute appendicitis during pregnancy.

PURPOSE: We report the clinical presentation, management and outcomes of 33 patients who underwent surgery for acute appendicitis during pregnancy between April 1997 and March 2011. METHODS: Several variables were compared between these 33 patients (pregnant group, n = 33) and non-pregnant females aged 20-40 years who underwent an acute appendectomy during the same period (control group, n = 124). RESULTS: No significant differences were found between the two groups in terms of the type of anesthesia, operative method, duration of surgery, pathology, duration of antibiotic use, and incidence of surgical site infection, except for a higher frequency of pararectal incision performed and higher leukocyte counts in the pregnant group (P < 0.01). Tocolytic agents were administered to 17 patients (52%). Preterm labor occurred in 10 patients (30%), one of whom experienced preterm delivery. CONCLUSIONS: These results suggest that acute appendicitis during pregnancy can be managed successfully without fetal loss.

Factors predicting recurrence in patients with Siewert type II carcinoma treated with curative resection.

AIM: To evaluate the recurrence risk for Siewert type II esophagogastric junction carcinoma treated with curative resection. PATIENTS AND METHODS: We retrospectively analyzed clinicopathological and recurrence-free survival (RFS) data of 52 patients after curative resection for Siewert type II carcinoma focusing on the role of lymph node metastasis around the greater curvature or parapyloric area. RESULTS: Recurrence was observed in 21 (40%) patients; the median time-to-recurrence was 11 months (range=3-33 months). According to multivariate Cox proportional hazard regression analysis, involvement of nodes no. 4sa, 4sb, 4d, 5 and/or 6 (odds ratio (OR)=6.62; 95% confidence interval (CI)=1.27-41.1; p=0.04) and younger age (OR=2.10; 95% CI=1.25-3.82; p<0.01) were significant independent risk factors affecting RFS. CONCLUSION: Involvement of no. 4-6 nodes appears to predict recurrence of Siewert type II carcinoma treated with curative resection. Patients with this risk factor may benefit from effective use of perioperative chemotherapy.

Prognostic role of gastrectomy in patients with gastric cancer with positive peritoneal cytology.

This retrospective study identified the optimal treatment strategy for patients with gastric cancer with positive peritoneal cytology. We analyzed clinicopathologic and survival data for 54 patients who had undergone gastrectomy and/or chemotherapy for treatment of gastric cancer with positive peritoneal cytology with (n = 40) or without (n = 14) metastatic disease. The median overall survival did not differ significantly between patients with gastric cancer with positive peritoneal cytology with and without metastatic disease (19 versus 13 months, respectively). Among 14 clinicopathologic variables, the lack of gastrectomy was the only significant independent unfavorable factor for survival (odds ratio, 1.64; 95% confidence interval, 1.04-2.57; P = 0.03). The median overall survival significantly differed among patients who had undergone gastrectomy plus chemotherapy, chemotherapy alone, and gastrectomy alone (25, 10, and 17 months, respectively; P < 0.01). Gastrectomy may be optimal for patients with (gastric cancer with positive peritoneal cytology), considering its favorable prognostic effect with respect to perioperative chemotherapy.

Production of intraperitoneal interleukin-6 following open or laparoscopic assisted distal gastrectomy.

The interleukin (IL)-6 concentration in plasma or serum has been considered to represent the degree of stress resulting from surgery. However, IL-6 in peritoneal fluid has rarely been considered. The aim of this study was to assess the concentration and amount of IL-6 in peritoneal fluid as indicators of surgical stress. To obtain basic data on peritoneal release of IL-6 during gastric cancer surgery, we measured IL-6 in peritoneal drainage samples, stored for up to 72 hours postoperatively, from patients who had undergone conventional open (ODG group, n = 20) and laparoscopic-assisted (LADG group, n = 19) distal gastrectomy. Within 24 hours, 61 and 77% of the IL-6 was released into the peritoneal cavity in the LADG and ODG groups, respectively. In both groups, the concentration and amount of peritoneal fluid IL-6 were significantly correlated with each other (LADG group: Spearman's rank correlation test [rS] = 0.48, P = 0.04; ODG group: rS = 0.58, P = 0.01). The concentration and amount of IL-6 in peritoneal fluid was 2.8- and 3.6-fold higher in the ODG than in the LADG group, respectively (P < 0.01). With regard to the relationship between the serum C-reactive protein (CRP) peak and the concentration or amount of peritoneal fluid IL-6 released within 24 hours, only the concentration of peritoneal fluid IL-6 in the LADG group was significantly correlated (rS = 0.60, P = 0.01) with the serum CRP peak. Our findings suggest that the amount and concentration of IL-6 released into the peritoneal cavity for up to 24 hours after surgery can each be a reliable parameter for assessment of surgical stress.

Predicting the amount of intraperitoneal fluid accumulation by computed tomography and its clinical use in patients with perforated peptic ulcer.

The correlation between the amount of peritoneal fluid and clinical parameters in patients with perforated peptic ulcer (PPU) has not been investigated. The authors' objective was to derive a reliable formula for determining the amount of peritoneal fluid in patients with PPU before surgery, and to evaluate the correlation between the estimated amount of peritoneal fluid and clinical parameters. We investigated 62 consecutive patients who underwent emergency surgery for PPU, and in whom prediction of the amount of accumulated intraperitoneal fluid was possible by computed tomography (CT) using the methods described by Oriuchi et al. We examined the relationship between the predicted amount of accumulated intraperitoneal fluid and that measured during surgery, and the relationship between the amount of fluid predicted preoperatively or measured during surgery and several clinical parameters. There was a significant positive correlation between the amount of fluid predicted by CT scan and that measured during surgery. When patients with gastric ulcer and duodenal ulcer were analyzed collectively, the predicted amount of intraperitoneal fluid and the amount measured during surgery were each associated with the period from onset until CT scan, perforation size, the Mannheim peritoneal index, and the severity of postoperative complications according to the Clavien-Dindo classification. Our present results suggest that the method of Oriuchi et al is useful for predicting the amount of accumulated intraperitoneal fluid in patients with PPU, and that this would be potentially helpful for treatment decision-making and estimating the severity of postoperative complications.

[Significant prognostic factors in stage IV gastric cancer].

The aim of this study was to evaluate clinicopathological variables, including the granulocyte-to-lymphocyte ratio(G/L ratio), as prognostic factors for Stage IV gastric cancer patients. A total of 70 patients treated for Stage IV gastric cancer were enrolled in this study. Univariate analysis indicated that age ≥70 years, performance status >2, resection not being performed, chemotherapy not being administered, high C-reactive protein(CRP)levels, and carbohydrate antigen 19-9 levels were significantly associated with poor survival. Multivariate analysis of these factors identified resection not being performed, chemotherapy not being administered, and high CRP levels as independent unfavorable factors of survival. Although the G/L ratio was not a prognostic factor for Stage IV gastric cancer patients in this study, further studies with greater number of patients are required to determine whether the G/L ratio is a significant biomarker associated with survival.

Heterotopic mesenteric ossification after a ruptured abdominal aortic aneurism: case report with a review of literatures.

Heterotopic mesenteric ossification (HMO) is a rare disease that results in intra-abdominal ossification of unknown origin. An 88-year-old man developed an intestinal obstruction 2 weeks after undergoing an operation for a ruptured abdominal aortic aneurysm, resulting in intestinal obstructions those did not improved concervatively. During relaparotomy performed 30 days after the first operation, hard adhesions of the small intestine and mesentery were found; these adhesions were difficult to separate without damaging the serosa of the small intestine. We removed 240 cm of the small intestine and performed a jejuno-ileo anastomosis. Microscopically, trabecular bone tissue had increased irregularly in the fat tissue of the nodules with fibrosis, which were partially lined with osteoblasts. Accordingly, we histopathologically diagnosed the patient as having HMO. The patient was treated with NSAIDs and cimetidine to prevent the recurrence of HMO. No signs of recurrence have occurred as of one year after the second operation.

[Outcomes of patients with small bowel carcinoma treated with appropriate chemotherapy selected on the basis of genetic analysis findings].

Small bowel carcinoma is a rare tumor, for which a standardized chemotherapy regimen has not yet been established. Further, this tumor may belong to the group of Lynch syndrome-associated tumors, which are resistant to 5-fluorouracil (5-FU) -based chemotherapy. We investigated mismatch repair protein expression and K-ras gene mutation status in 8 patients with aggressive small bowel carcinoma and determined the chemotherapy regimen used in these patients. Immunohistochemical staining indicated normal mismatch repair protein expression in all surgical specimens. Of 8 patients, 4( 50%) had K-ras codon 12 mutations. Because small bowel carcinoma is not significantly associated with Lynch syndrome, 5-FU-based chemotherapy would be appropriate for the treatment of these patients. The prevalence of K-ras codon 12 mutations was relatively similar to that in patients with sporadic colorectal carcinoma, and the usefulness of anti- epidermal growth factor receptor (EGFR) antibody for the treatment of small bowel carcinoma should be evaluated in the future.

[Clinical outcomes in refractory colorectal cancer patients with wild-type K-ras treated with bevacizumab and oxaliplatin-based chemotherapy as a first-line treatment].

The clinical outcomes, including adverse events, in 34 unresectable advanced colorectal cancer patients with wild-type K-ras, who were treated with bevacizumab and oxaliplatin-based chemotherapy as a first-line treatment, were analyzed for confirmation of the effectiveness and safety of this treatment. The response rate of the patients was 44% (complete remission, 2 patients; and partial remission, 13 patients). The median progression-free survival and overall survival in these patients was 11.1 and 25.1 months, respectively. Adverse events of greater than grade 3 were observed in 18 patients. Of these patients, 10 exhibited grade 3/4 neutropenia, and 6 had peripheral neuropathy. Our results were similar to those of randomized phase III trials from abroad, including those using anti-epidermal growth factor receptor antibody, with respect to effectiveness and safety. Furthermore, patients with liver metastasis had poor prognosis compared to those with metastasis to organs other than the liver. Further analysis will be required to better understand these results.

[Clinical differences between palliative gastrectomy and reduction surgery for gastrectomy in curatively unresectable gastric cancer].

Surgical treatments for curatively unresectable gastric cancer include reduction surgery and palliative surgery(palliative gastrectomy and bypass operation). Both palliative gastrectomy and reduction surgery reduce the tumor volume. In this study, the clinical significance of these treatment methods was investigated. The subjects were 58 patients with unresectable gastric cancer for which surgery was performed as the primary treatment. Of these patients, 38 patients underwent reduction surgery and 20 patients underwent palliative surgery. On univariate analysis, age and gender were not significant. Pre-operative performance status(PS) in patients treated with reduction surgery was favorable compared to that in patients receiving palliative surgery(PS 0: 65.8 vs 40.0%, p=0.06). The administration rate of post-operative chemotherapy in patients treated with reduction surgery was higher than that in patients with palliative surgery (92.1 vs 65.0%, p<0.01). The median survival time in patients treated with reduction surgery was 18.2 months, while that in patients with palliative surgery was 11.0 months (p<0.01). These results indicated that reduction surgery was clinically different compared to palliative surgery in terms of the administration rate of post-operative chemotherapy and prognosis.

Usefulness of indocyanine green angiography for evaluation of blood supply in a reconstructed gastric tube during esophagectomy.

We report a case of necrosis of a reconstructed gastric tube in a 77-year-old male patient who had undergone esophagectomy. At the time of admission, the patient had active gastric ulcers, but these were resolved by treatment with a proton pump inhibitor. Subtotal esophagectomy with gastric tube reconstruction was performed. Visually, the reconstructed gastric tube appeared to be well perfused with blood. Using indocyanine green (ICG) fluorescence imaging the gastroepiploic vessels were well enhanced and no enhancement was visable 3 to 4 cm from the tip of the gastric tube. Four days after esophagectomy, gastric tube necrosis was confirmed, necessitating a second operation. The necrosis of the gastric tube matched the area that had been shown to lack blood perfusion by ICG angiography imaging. It seems that ICG angiography is useful for the evaluation of perfusion in a reconstructed gastric tube.

[A case of gastric cancer patient with liver metastasis treated by radiofrequency ablation therapy combined with intra-arterial chemotherapy].

We performed radio-frequency ablation (RFA) therapy combined with intra-arterial chemotherapy for a 71-year old female gastric cancer patient with liver metastasis. She underwent total gastrectomy due to advanced gastric cancer in July of 1996. Because CT scans revealed multiple liver tumors with her, she also underwent intra-arterial chemotherapy comprising of 5-fluorouracil, cis-platinum and Leucovorin. Although her liver tumors decreased in size and number, after 9 months, we had to remove the catheter because of hepatic artery obstruction. Immediately after the removal, 5 hepatic metastases appeared, which were 3.5 cm in maximum diameter. After RFA therapy, CT scans revealed homogenously attenuated lesions. Liver biopsy demonstrated a complete coagulation necrosis. She is currently alive going into 19 months after liver metastasis and 7 months after RFA.

[A case of long-term survival after chemo-radiation for postoperative local recurrence of rectal cancer].

The patient was a 64-year-old male who underwent an abdomino-perineal resection (D3) for advanced lower rectal carcinoma with a formulated vesicorectal abscess. The tumor was a well-differentiated adenocarcinoma, type 2 in the Japanese Classification of Colorectal Carcinoma, and was measured 5.5x4.3 cm in size. Histologically, the tumor was considered to be stage II (H0, P0, a2, n0 (0/86), ly0, v0). He received a postoperative chemotherapy with oral UFT-E (400 mg/day) for 1 year. After 2 years from the surgery, the patient developed a perineal pain, and pelvic CT scans revealed a 4 cm mass anterior to the sacrum. The CEA level was increased to 11 ng/ml. Consequently, a diagnosis of local recurrence was made, and radiochemotherapy was commenced. Radiotherapy was given to the pelvic region at a total dose of 70 Gy (Given 2 Gy each x 35 fragments). Chemotherapy with CDDP and 5-FU was administered via the right internal iliac artery followed by administration of 5'-DFUR (600 mg/day). After that regimen, a recurrence of the pelvic tumor caused an increase in pain, and the patient developed renal failure. He died after 4 years and 10 months from the initial detection of recurrence. This report presents a case of local recurrence of advanced rectal carcinoma, in which we were able to achieve a long-term survival and improvement in QOL by an intensive multidisciplinary therapy.