Poly (ADP-ribose) polymerase-1 inhibition decreases proliferation through G2/M arrest in esophageal squamous cell carcinoma.

Poly (ADP-ribose) polymerase-1 (PARP1) plays a vital role in DNA repair and is expected to be an effective target in various malignancies. The aim of the present study was to investigate the clinical and biological significance of PARP1 expression in esophageal squamous cell carcinoma (ESCC). Immunohistochemical (IHC) staining was used to examine the association between PARP1 expression and the clinicopathological features of 86 patients with ESCC. The antitumor effect of small interfering RNA against PARP1 (siPARP1) was examined in a proliferation assay, and the mechanisms of this effect were investigated using western blot analysis and cell cycle assays. Cox multivariate analysis revealed that high expression of PARP1 in IHC staining was a statistically significant independent prognostic factor of poor overall survival (OS). The adjusted hazard ratio for OS in the group with high expression of PARP1 was 2.39 (95% confidence interval, 1.29-4.44; P=0.0051). In vitro assays showed that siPARP1 significantly decreased proliferation through G2/M arrest. Furthermore, western blot analysis showed that PARP1 was associated with the ataxia telangiectasia mutated-checkpoint kinase 2-cell division control 25c pathway. The present study suggests that PARP1 expression has a critical role in ESCC progression, and may be a clinical therapeutic target.

Overexpression of heat-shock factor 1 is associated with a poor prognosis in esophageal squamous cell carcinoma.

Heat-shock factor 1 (HSF1) is the primary regulator of the response to various stressors. A previous study showed that HSF1 expression is associated with a poor prognosis in breast cancer and hepatocellular carcinoma; however, the prognostic significance of HSF1 in esophageal squamous cell carcinoma (ESCC) is unknown. Therefore, the present study investigated the association between HSF1 expression and the clinicopathological parameters of patients, as well as the association between HSF1 expression, and heat shock protein (Hsp)27, Hsp70 and Hsp90 expression induced by HSF1, by cDNA microarray and immunohistochemistry analyses. HSF1 protein and mRNA expression were assessed in resected specimens from 270 patients with ESCC in two independent cohorts. Hsp27, Hsp70 and Hsp90 expression were also assessed in 55/270 patients. Patients with high HSF1 expression had a significantly worse OS than those with low HSF1 expression in both cohorts. In multivariate analyses, pathological T stage [hazard ratio (HR), 2.21; 95% confidence interval (CI), 1.38-3.65; P=0.0008], pathological N stage (HR, 1.73; 95% CI, 1.04-3.02; P=0.03) and HSF1 expression (HR, 2.29; 95% CI, 1.48-3.64; P=0.0002) were statistically significant independent prognostic factors. Furthermore, Hsp27 and Hsp90 expression were significantly correlated with HSF1 expression (P<0.0001), but Hsp70 expression was not (P=0.38). These results indicate that HSF1 is a prognostic factor for patients with ESCC, and that Hsp27 and Hsp90, but not Hsp70, may be the downstream targets of HSF1 in ESCC.

A novel locally operated master-slave robot system for single-incision laparoscopic surgery.

PURPOSE: Single-incision laparoscopic surgery (SILS) provides more cosmetic benefits than conventional laparoscopic surgery but presents operational difficulties. To overcome this technical problem, we have developed a locally operated master-slave robot system that provides operability and a visual field similar to conventional laparoscopic surgery. MATERIAL AND METHODS: A surgeon grasps the master device with the left hand, which is placed above the abdominal wall, and holds a normal instrument with the right hand. A laparoscope, a slave robot, and the right-sided instrument are inserted through one incision. The slave robot is bent in the body cavity and its length, pose, and tip angle are changed by manipulating the master device; thus the surgeon has almost the same operability as with normal laparoscopic surgery. To evaluate our proposed system, we conducted a basic task and an ex vivo experiment. RESULTS: In basic task experiments, the average object-passing task time was 9.50 sec (SILS cross), 22.25 sec (SILS parallel), and 7.23 sec (proposed SILS). The average number of instrument collisions was 3.67 (SILS cross), 14 (SILS parallel), and 0.33 (proposed SILS). In the ex vivo experiment, we confirmed the applicability of our system for single-port laparoscopic cholecystectomy. CONCLUSION: We demonstrated that our proposed robot system is useful for single-incision laparoscopic surgery.

[Complete response in a case of advanced esophageal cancer infiltrating into the main bronchus treated by chemoradiation therapy].

We report a case of advanced esophageal cancer infiltrating into the trachea that was treated by chemoradiation therapy. The patient was a 49-year-old man who complained of dysphagia and dyspnea. Various examinations revealed an esophageal cancer with direct invasion into the trachea( cT4b[ Tr], N2[ 106recR, 106recL, 106pre, 1], M0, cStage IIIc). He underwent radiotherapy. Simultaneously, he was administered morphine to relieve dyspnea and steroid to prevent tracheal edema. From the eight day of radiation therapy, chemotherapy was initiated( DCF; docetaxe[l DTX] +cisplatin[ CDDP] + 5-fluorouracil[ 5-FU]). This chemoradiation therapy considerably reduced the esophageal tumor size. Thereafter, the patient underwent 2 additional courses of chemotherapy( FAP; 5-FU+adriamycin[ ADM] +CDDP). The therapeutic effect was judged as complete response. The patient is still alive without recurrence for 3 years and 6 months after the first treatment. There are some reports about airway stenting and adjuvant therapy for airway obstruction caused by esophageal cancer. However, there are few reports on chemoradiotherapy for esophageal cancer invading into the trachea with administration of steroids to prevent tracheal edema. We believe that this is an effective treatment.

[Long-term survival after surgical resection of a cancer of unknown primary site-a case report].

We report a case of long-term survival after combination chemotherapy and surgical resection of a cancer of unknown primary site[ CUPs]. A septuagenarian female was identified as having high blood levels of carcinoembryonic antigen (CEA) during follow-up monitoring of asthma. Endoscopy and imaging studies including computed tomography (CT) and positron emission tomography (PET)-CT revealed a malignant lymph node adjacent to the abdominal aorta; however, no other lesion was detected. Therefore, we performed CT-guided biopsy and diagnosed the lesion to be a lymph node metastasis of poorly differentiated adenocarcinoma. As we considered this as a systemic disease, the patient received 2 courses of combination chemotherapy with 5-fluorouracil( 5-FU)/cisplatin( CDDP) and achieved a partial response (PR). Later, the patient received S-1 therapy as second-line chemotherapy and S-1/irinotecan( CPT-11) as third-line chemotherapy in an outpatient clinic. However, the tumor continued to grow, and therefore, we decided to perform surgical resection. Histopathological examination of the resected specimen yielded a diagnosis of metastatic adenocarcinoma of the lymph node. The patient has been well without any signs of recurrence for more than 9 years since surgery. As CUPs is generally associated with poor prognosis, this case raises the possibility that combination therapy might improve convalescence.

[Evaluation of hepatic arterial infusion chemotherapy using removable W-spiral catheter].

The authors analyzed the 62 patients who underwent hepatic arterial infusion (HAI) chemotherapy using W-spiral (WS) catheter. The catheter was successfully inserted into the hepatic artery without a coil fixation in 57 cases. After cessation of chemotherapy, the catheter was removed in 32 cases without difficulty, which resulted in improved patients' quality of life as well as preservation of patency of hepatic arteries. This catheter has a special shape-memory alloy in its tip, which allows preferable fixation without coils and removal of the catheter if desired. HAI using this catheter and subsequent removal of it is a reasonable strategy in the era with potent systemic chemotherapy.

[Adjuvant chemotherapy with FOLFOX4 regimen after curative resection of liver metastases from colorectal cancer].

Only a partial benefit of adjuvant chemotherapy administered after curative resection of colorectal cancer (CRC) metastases has been demonstrated. We report here our experience of 7 cases that were administered FOLFOX4 regimen as adjuvant chemotherapy after a curative resection of liver metastases from CRC. Five patients received 6 cycles of FOLFOX4 after prophylactic hepatic arterial infusion of 5-FU, and 2 remaining patients simply received 8 cycles of FOLFOX4. All patients completed the planned cycles of FOLFOX4 without any dose reduction of oxaliplatin. No patients developed a severe adverse effect greater than grade 2 except for grade 3 neutropenia observed in 4 cases. Although lung metastases occurred in 2 cases 28.1 and 21.3 months after liver resection, respectively, all patients are alive after a median follow up of 23.5 months. Our experience indicates that adjuvant chemotherapy with six to eight cycles of FOLFOX4 regimen is safe with a high dose intensity of oxaliplatin and expected to provide a survival benefit.

[A case of successfully treated lower rectal cancer with both inguinal lymph nodes by chemoradiotherapy].

We report a case of successfully treated lower rectal cancer with both inguinal lymph nodes by chemoradiotherapy. A 59-year-old man presented with anal pain. A colonoscopy revealed primary rectal cancer. The histological diagnosis was well to moderately differentiated adenocarcinoma. A computed tomography showed metastases to pararectal, both inguinal lymph nodes and right external iliac. After a ileostomy construction was done, he was treated with intensity modulated radiotherapy (a total 50.4 Gy) and chemotherapy with FOLFOX. The primary tumor had completely disappeared, and metastases to lymph nodes showed a remarkable shrinkage after the chemoradiotherapy. Nine months after radiation therapy, however, multiple lung and liver metastases were observed by a computed tomography, which were treated by systemic chemotherapy with FOLFOX and bevacizumab. The primary tumor and metastases to lymph nodes are still controlled well for 2 years after the initial chemoradiotherapy.

[Two cases of long-term survival with CY1, stage IV gastric cancer due to surgery and postoperative chemotherapy].

The first case is a man in his 30s with gastric cancer, of which clinical finding was T3N0M0P0M0 (Stage II), underwent a distal gastrectomy with D2 lymphadenectomy. CY1 was detected during the operation and the final findings was T3N2M0H0P0CY1 (Stage IV). After the operation, we administered 120 mg/day of S-1 for 38 months and the patient remains alive for 6 years and 2 months. The second case is a man in his 20s with gastric cancer, of which clinical finding was T3N0M0P0M0 (Stage IIIa), underwent a distal gastrectomy with D2 lymphadenectomy. CY1 was detected during the operation and the final findings was T3N2M0H0P0CY1 (Stage IV). After the operation, we administered 120 mg/day of S-1 for 13 months and the patient remains alive for 6 years and 2 months. A combination gastrectomy with D2 lymphadenectomy and postoperative chemotherapy was considered to be a radical treatment for CY1, Stage IV gastric cancer.

[A complete response (CR) case of multiple lung metastases after radical lobectomy for non-small-cell-lung cancer obtained by cisplatin+vindesine].

A 69-year-old man was diagnosed with squamous cell carcinoma of the lung, and underwent right upper lobectomy in October 2000. Histological findings were as follows: 2.5 cm in diameter, moderately differentiated squamous cell carcinoma of the lung, ly0, v0, n0, pT1N0M0, stage IA. No adjuvant therapies were performed. Multiple lung metastases were detected on CT scan in June 2001, and four cycles of chemotherapy with cisplatin+vindesine (day 1: cisplatin 100 mg/body, days 1, 8 and 15: vindesine 3 mg/body) were performed. The metastases were completely disappeared on CT scan in December 2001. No relapse has been seen for six years and two months.

[A case of advanced gastric cancer responding to S-1/paclitaxel was pathologically complete response].

A 63-year-old man was found to have advanced gastric cancer and staging laparoscopy revealed positivity of peritoneal washing cytology. Since curative surgery was deemed not possible, we started chemotherapy using S-1 (80 mg/m2) orally administered for 2 weeks and paclitaxel (50 mg/m2) administered intravenously on days 1 and 8. After 3 courses of chemotherapy, the primary lesion and regional metastatic lymph node were diminished by CT. We confirmed a peritoneal washing cytology negative by laparoscopic examination. We performed a total gastrectomy and dissection of regional lymph node (D2). Pathologically, cancer cells disappeared both in the main tumor and lymph nodes, and histological efficacy was evaluated as grade 3. Adjuvant chemotherapy was done with same regimen, and he has had no recurrence as of 15 months after surgery.

[A case of AFP producing gastric cancer for which radiation therapy was effective in paraaortic lymph node recurrence].

The patient was a 75-year-old woman, who was diagnosed with type 3 gastric cancer. Total gastrectomy with D2-#10 lymph node dissection and partial hepatic resection was performed. Histological findings showed it to be stage IV (pT2N1M0P0CY0H1) and AFP producing gastric cancer. After the operation, liver metastasis was found, and RFA, partial hepatic resections, hepatic intra-arterial infusion chemotherapy (5-FU, CDDP), intravenous chemotherapy (docetaxel, paclitaxel, CPT-11) were applied. Although liver metastasis was disappeared, paraaortic lymph node recurrence appeared, and chemotherapy was not effective. Radiation therapy (2 Gy/day, total 50 Gy) for paraaortic lymph node metastasis was performed. The metastatic node underwent complete remission following a radiation therapy. Three years and six months passed since the first operation, and the patient has shown no signs of relapse. Therefore, our case suggests radiation therapy could be an effective treatment modality for the lymph node metastasis in AFP producing gastric cancer.