RAD51 Expression as a Biomarker to Predict Efficacy of Preoperative Therapy and Survival for Esophageal Squamous Cell Carcinoma: A Large-cohort Observational Study (KSCC1307).

OBJECTIVE: The aim of this study is to identify biomarkers that predict efficacy of preoperative therapy and survival for esophageal squamous cell carcinoma (ESCC). BACKGROUND: It is essential to improve the accuracy of preoperative molecular diagnostics to identify specific patients who will benefit from the treatment; thus, this issue should be resolved with a large-cohort, retrospective observational study. METHODS: A total of 656 patients with ESCC who received surgery after preoperative CDDP + 5-FU therapy, docetaxel + CDDP + 5-FU therapy or chemoradiotherapy (CRT) were enrolled. Immunohistochemical analysis of TP53, CDKN1A, RAD51, MutT-homolog 1, and programmed death-ligand 1 was performed with biopsy samples obtained before preoperative therapy, and expression was measured by immunohistochemistry. RESULTS: In all therapy groups, overall survival was statistically separated by pathological effect (grade 3 > grade 2 > grade 0, 1, P < 0.0001). There was no correlation between TP53, CDKN1A, MutT-homolog 1, programmed death-ligand 1 expression, and pathological effect, whereas the proportion of positive RAD51 expression (≥50%) in cases with grade 3 was lower than that with grade 0, 1, and 2 (P = 0.022). In the CRT group, the survival of patients with RAD51-positive tumor was significantly worse than RAD51-negative expressors (P = 0.0119). Subgroup analysis of overall survival with respect to positive RAD51 expression indicated preoperative chemotherapy (CDDP + 5-FU or docetaxel + CDDP + 5-FU) was superior to CRT. CONCLUSIONS: In ESCC, positive RAD51 expression was identified as a useful biomarker to predict resistance to preoperative therapy and poor prognosis in patients who received preoperative CRT. Administration of preoperative chemotherapy may be warranted for patients with positive RAD51 expression.

The survival impact of postoperative complications after curative resection in patients with esophageal squamous cell carcinoma: propensity score-matching analysis.

PURPOSE: The relationship between postoperative complications and long-term survival after surgery for esophageal squamous cell carcinoma (ESCC) is controversial. METHOD: A total of 210 patients with ESCC who underwent subtotal esophagectomy with a reconstructed gastric tube were investigated according to the development of postoperative complications. The associations of age, gender, T and N factors, and pStage with grade 0-2 complications (NSC) and grade 3 and higher complications (SC) were compared by propensity score-matching analysis. Fifty-one pairs of NSC and SC groups were selected for the final analysis. We divided 102 patients between the NSC and SC groups or between the no pulmonary complication (NPC) and the pulmonary complication (PC) groups. The overall survival (OS) and disease-free survival (DFS) were determined by the Kaplan-Meier method and were compared by log-rank tests. Possible predictors of OS and DFS were subjected to univariate analysis and multivariate Cox proportional hazard regression analysis. RESULTS: The propensity score matching revealed that the 5-year OS and DFS of the NSC group were not different from those of the SC group. However, the 5-year OS of the PC group was significantly worse than that of the NPC group, while no significant differences were observed in the DFS between the PC and NPC groups. In the multivariate analysis, UICC pStage, pulmonary complication, and American Heart Association (AHA) classification for OS and UICC pStage for DFS were significant prognostic factors. CONCLUSION: The OS and DFS did not differ in patients with or without severe postoperative complications. However, postoperative pulmonary complications were independent predictors of poorer OS, but not DFS, in patients who underwent R0 resection for ESCC.

Sarcopenia discriminates poor prognosis in elderly patients following emergency surgery for perforation panperitonitis.

AIM: Sarcopenia has been reported as a prognostic predictor in various conditions; however, it has not been examined in patients with perforation panperitonitis. METHODS: A total of 103 consecutive patients with perforation panperitonitis who underwent emergency surgery from 2008 to 2016 were retrospectively evaluated. Skeletal muscle index (SMI) was measured as the cross-sectional area (cm2) of skeletal muscle in the L3 region on computed tomography images normalized for height (cm2/m2). Sarcopenia was defined as an SMI of ≤43.75 and ≤41.10 cm2/m2 in men and women, respectively. The impact of sarcopenia on postoperative outcomes was investigated. RESULTS: Sarcopenia was present in 50 (48.5%) patients. Severe complications (Clavien-Dindo grade ≥IIIb) and in-hospital mortality were more frequently observed in patients with than without sarcopenia (28.0% vs 9.4%, P = .015) (20.0% vs 5.7%, P = .029) respectively. Multivariate analysis showed that age, sarcopenia, and renal dysfunction were independent risk factors for severe complications and in-hospital mortality. The optimal cut-off levels of age and SMI for predicting these were ≥79 years and SMI <38 cm2/m2, respectively. Among the patients aged ≥79 years, those with SMI <38 cm2/m2 had a severe complication rate of 71% and an in-hospital mortality rate of 57%, whereas the rate of those with SMI ≥38 cm2/m2 was 22% (P = .011) and 11% (P = .008), respectively. CONCLUSION: Sarcopenia is a predictive factor of severe complications and in-hospital mortality following emergency surgery for perforation panperitonitis, especially in elderly patients. Estimation of sarcopenia may identify patients eligible or not eligible for emergency surgery among elderly patients.

Long-Term Outcome of Definitive Chemoradiotherapy and Induction Chemoradiotherapy Followed by Surgery for T4 Esophageal Cancer with Tracheobronchial Invasion.

BACKGROUND: T4 esophageal cancer (EC) that invades the trachea or bronchus often has poorer prognosis than other T4 ECs. We investigated the long-term results of definitive chemoradiotherapy (dCRT) or induction chemoradiotherapy followed by surgery (iCRT-S) in patients with T4 EC with tracheobronchial invasion (TBI). PATIENTS AND METHODS: From 2003 to 2013, 71 patients with T4 EC with TBI were treated in our institution; 58 underwent dCRT, and 13 underwent iCRT-S. The long-term results associated with survival were retrospectively analyzed, and prognostic factors were examined by univariable and multivariable analysis. RESULTS: The 1-, 2-, and 5-year overall survival for all patients with T4 EC with TBI treated by dCRT or iCRT-S was 57, 29, and 19%, respectively. Multivariable analysis revealed that clinical lymph node (LN) metastasis and the treatment period were significant prognostic factors. Clinical LN positivity had significantly poorer prognosis than LN negativity. The treatment outcome in the later period was significantly better than that in the earlier period. In particular, the outcome after dCRT revealed significantly better prognosis in the later compared with the earlier period, whereas the outcome after iCRT-S did not show such a difference. With respect to treatment modality, no significant difference in survival was observed between dCRT and iCRT-S. CONCLUSIONS: Clinical LN negativity and later treatment period were significantly good prognostic factors for T4 EC with TBI. The recent improvements in dCRT outcomes may help to achieve survival comparable to that of iCRT-S.

Therapeutic Strategy for Incarcerated Obturator Hernia Using Preoperative Manual Reduction and Laparoscopic Repair.

BACKGROUND: Obturator hernia (OH) is a rare but serious disease associated with high morbidity and mortality due to advanced patient age and comorbidities. This study evaluated the feasibility of a laparoscopic approach to OH. STUDY DESIGN: We retrospectively reviewed the records of 32 patients (median age 84 years; 31 women) with OH treated between 2003 and 2016. RESULTS: Five patients with incidental OH underwent total extraperitoneal (TEP) repair. Of 27 patients with incarcerated OH, 18 patients underwent laparotomy, 13 of which required bowel resection, and the remaining 9 patients underwent preoperative ultrasound-guided manual OH reduction. Of 6 patients with successful OH release, 3 and 2 patients underwent TEP and transabdominal preperitoneal repair, respectively, and 1 patient declined the operation. Three patients with failure underwent laparoscopic exploration and conversion to open operation for bowel resection. Comparing the open and laparoscopic groups, the median operation times were 67.5 minutes vs 124 minutes, respectively (p = 0.004); median postoperative stay was 19 vs 11 days, respectively (p = 0.028); and Clavien-Dindo grade II or higher complications tended to be lower (28% vs 8%, respectively; p = 0.359). Even in patients without bowel resection, the median postoperative stay was significantly shorter in the laparoscopic group compared with the open group (7.5 vs 15 days, respectively; p = 0.032). During a mean follow-up of 24.5 months, the 3-year recurrence rate for OH was 25% for non-mesh repair and 0% for mesh repair (p = 0.335). Three- and 5-year cumulative survival rates were 83% and 71%, respectively. CONCLUSIONS: Laparoscopic operations after ultrasound-guided manual reduction can be an alternative to emergent laparotomy in select OH patients.

Treatment of Squamous Cell Carcinoma of the Esophagus Synchronously Associated with Head and Neck Cancer.

BACKGROUND/AIM: The aim of this study was to clarify the treatment strategy for synchronous squamous cell carcinoma of the esophagus (ESCC) and head and neck cancer (HNC). PATIENTS AND METHODS: Treatment outcomes of 91 patients with synchronous ESCC and HNC were evaluated. Thirty-eight patients received simultaneous definitive chemoradiotherapy (CRT) and 15 patients underwent simultaneous resection. RESULTS: Among the patients who received simultaneous CRT, adverse events (grade 3-5) were recognized in 14 patients (40%), including one case of death due to aspiration pneumonia. Complete response was observed in 22 patients with ESCC (58%) and 19 patients with HNC (50%). The five-year survival rate was 44%. There were no in-hospital deaths after simultaneous resection; however, postoperative complications were recognized in 4 patients. The five-year OS was 70%. CONCLUSION: The treatment of synchronous ESCC and HNC must be decided by adopting a strategy that is appropriate for each case. Both simultaneous CRT and simultaneous resection are feasible and effective treatment options.

Ileum preserving expanded jejunectomy and pancreaticoduodenectomy with combined resection of the superior mesenteric artery for huge retroperitoneal solitary fibrous tumor.

We encountered a patient with a large retroperitoneal solitary fibrous tumor, in whom we could preserve approximately 150 cm of the ileum even after pancreaticoduodenectomy combined with resection of the superior mesenteric artery, thus preventing short bowel syndrome.

Technical and Survival Risks Associated With Esophagojejunostomy by Laparoscopic Total Gastrectomy for Gastric Carcinoma.

BACKGROUND: We performed esophagojejunostomy after totally laparoscopic total gastrectomy (TLTG) using functional end-to-end anastomosis (FEEA) as the first choice and laparoscopic-assisted total gastrectomy (LATG) using a circular stapler with a transorally inserted anvil as the second choice. PATIENTS AND METHODS: We examined 109 patients with gastric cancer who underwent TLTG and LATG. Among these, 100 patients underwent TLTG and the rest underwent LATG. RESULTS: The length of resected esophageal segment in LATG patients was significantly longer than that in TLTG patients (P<0.001). The length of the resected esophagus segment was inversely correlated with body mass index in cases of esophagojejunostomy by FEEA (P<0.05). Multivariate analysis revealed that T factor, N factor, and severe complications were the independent factors for survival. CONCLUSIONS: Esophagojejunostomy using FEEA or a circular stapler with a transorally inserted anvil should be selected according to the length of the resected esophageal segment and/or body mass index.

Neuroendocrine carcinoma of the esophagus: Clinicopathological and immunohistochemical features of 14 cases.

BACKGROUND: Neuroendocrine carcinoma (NEC) of the esophagus is a rare and highly aggressive disease but the biological features are poorly understood. The objective of this study was to analyze the clinicopathological and immunohistochemical features of NEC of the esophagus. METHODS: Fourteen patients diagnosed with NEC of the esophagus from 1998 to 2013 were included in this study. Clinicopathologic features, therapeutic outcomes and immunohistochemical results were analyzed. RESULTS: Eleven out of 14 cases showed protruding or localized type with or without ulceration. Only three patients were negative for both lymph node and organ metastasis and seven cases were positive for metastases to distant organs and/or distant lymph nodes. Of the six patients with limited disease (LD), three patients were treated by surgery. Three patients with LD and seven patients with extensive disease (ED) were initially treated with chemotherapy, except for one who underwent concurrent chemo-radiotherapy due to passage disturbance. The median survival of patients with LD was 8.5 months, whereas that of patients with LD was 17 months. Among the 14 cases, 12 cases (83.3%), 13 cases (91.7%) and 12 cases (83.3%) showed positive immunostaining for choromogranin A, synaptophysin and CD56, respectively. Nine of 14 cases (64.2%) presented positive staining for c-kit and most (8/9, 88%) simultaneously showed p53 protein abnormality. Two cases were negative for c-kit and p53, and positive for CK20. CONCLUSION: Consistent with previous reports, the prognosis of NEC of esophagus is dismal. From the results of immunohistochemical study, NEC of esophagus might be divided into two categories due to the staining positivity of c-kit and p53. This study provides new insight into the biology of NEC of the esophagus.

Gastric carcinosarcoma with rhabdomyosarcomatous differentiation: a case report and review.

We report an unusual case of gastric carcinosarcoma with rhabdomyosarcomatous and neudoendocrinal differentiation in a 71-year-old Japanese female. Gastric carcinosarcoma with rhabdomyosarcomatous and neuroendocrinal differentiation is a rare tumor. The tumor developed in the body of the stomach and was exophytic in appearance. By histochemical analysis, the tumor was shown a part of positive for desmin and myoglobin and a part of positive for synaphtophysin and vimentin.We conclude that, though rare, gastric carcinosarcoma with rhabdomyosarcomatous and neuroendocrinal differentiation thus is reviewed in the English literatures.

S-1 Adjuvant Chemotherapy Earlier After Surgery Clinically Correlates with Prognostic Factors for Advanced Gastric Cancer.

BACKGROUND: S-1 adjuvant chemotherapy is commonly administered postoperatively for stage II and III advanced gastric cancer. METHODS: This study included 113 patients treated with S-1 adjuvant chemotherapy after surgery for stage II and III advanced gastric cancer. These patients were divided into 4 groups: group A (n = 63), who had a longer duration (≥6 months) and earlier S-1 administration (≤6 weeks) after surgery; group B (n = 16), who had a longer and later S-1 administration (>6 weeks) after surgery; group C (n = 27), who had a shorter duration (<6 months) and earlier S-1 administration after surgery; and group D (n = 7), who had a shorter and later S-1 administration after surgery. RESULTS: The recurrence rates in groups A, B, C, and D were 15.7, 43.8, 44.4, and 57.1 %, respectively (A vs. B, p < 0.05, A vs. C and D, p < 0.01). The survival time of group A was significantly longer than that of other groups (p < 0.005). In addition, the survival time of patients with severe complications was significantly shorter than that of patients with non-severe complications (p < 0.05). An earlier S-1 administration after surgery was the only independent prognostic factor in the multivariate analysis. CONCLUSIONS: The prognosis of advanced gastric cancer was significantly related to the start of S-1 adjuvant treatment within 6 weeks after surgery.

Hepatic resection of hepatocellular carcinoma after proton beam therapy: A case report.

Despite the widespread use of proton beam therapy (PBT) as locoregional therapy, there is currently a lack of histological evidence about the therapeutic effect of PBT for hepatocellular carcinoma (HCC). We present a case of hepatectomy and histological examination of HCC initially treated by PBT. A 76-year-old man with chronic hepatitis C underwent routine ultrasound surveillance, which revealed a 22-mm HCC in segment 4 of the liver. His hepatic reserve was adequate for surgical resection of the tumor; however, he chose to undergo PBT because of his cardiac disease. The patient received 66 Gy in 10 fractions with no toxicity exceeding grade 1. Six months after completion of PBT, contrast computed tomography showed that the tumor had increased in size to 27 mm, and the marginal part of the tumor, but not the central region, was enhanced. Additionally, two new hypervascular nodules were present in segments 5 and 6. The patient underwent surgical treatment 7 months after PBT. The operation and postoperative clinical course were uneventful. Nine months later, however, computed tomography demonstrated new, small, enhanced nodules in the remnant liver (segments 3, 5 and 6) and sacrum. In conclusion, PBT is a valuable treatment for HCC; however, it is difficult to evaluate therapeutic effect of HCC during the early post-irradiation period and provide an alternative treatment if PBT is not effective, especially in HCC cases with good liver function.

Current status of and perspectives regarding neoadjuvant chemoradiotherapy for locally advanced esophageal squamous cell carcinoma.

The significance of neoadjuvant chemoradiotherapy (NACRT) for esophageal squamous cell carcinoma (ESCC) remains controversial with regard to the pathological response and long-term survival. We herein review the current status of and future perspectives regarding NACRT followed by esophagectomy for locally advanced ESCC. Some studies have suggested that a pathological complete response with NACRT is more common in patients with ESCC than in those with adenocarcinoma and that NACRT provided a survival benefit limited to patients with ESCC. However, NACRT may increase the risk of postoperative complications after esophagectomy. It is obvious that a favorable pathological response is the most important factor for obtaining a survival benefit, although no established parameters have been implemented clinically to predict the response to NACRT. Prospective clinical studies and basic research studies to identify predictive biomarkers for the response to NACRT are needed to aid in the development of NACRT treatment strategies for patients with ESCC.

Survival with Collateral Circulation after Gastrointestinal Ischemia Caused by Aortic Dissection: A Case Report.

We report a case of a 43-year-old man who presented with gradually intensifying abdominal pain of acute onset and was shown by contrast-enhanced computed tomography (CT) examination to have acute aortic dissection (Stanford type B). A diagnosis of gastrointestinal necrosis was made and he underwent emergency surgery. At laparoscopy, he was found to have no superior mesenteric arterial pulse and intestinal necrosis from the upper jejunum to the right transverse colon. Resection of the superior mesenteric artery (SMA) perfusion area was performed. Postoperatively, ischemia in the perfusion area of the celiac artery was also diagnosed, manifesting as gallbladder necrosis, portal vein gas accompanying gastric wall necrosis, perforation of the remaining upper jejunum, and hepatic and splenic infarction. However, development of a collateral circulation originating in the left colic branch of the inferior mesenteric artery (IMA) enabled retrograde provision of blood to the celiac artery through the SMA pancreaticoduodenal arcade. Thus, in this case, spontaneous development of a natural bypass created a new route for arterial perfusion, contributing to the patient's survival. When ischemia of the celiac artery and SMA perfusion areas occur, collateral circulation can develop from the IMA.

Comparison of Neoadjuvant Chemotherapy to Surgery Followed by Adjuvant Chemotherapy in Japanese Patients with Peritoneal Lavage Cytology Positive for Gastric Carcinoma.

BACKGROUND: Therapeutic strategies for positive peritoneal lavage cytology [CY(+)] findings have not yet been established. The aim of the present study was to compare the effects of neoadjuvant systemic chemotherapy and surgery followed by S-1 adjuvant chemotherapy for treating gastric carcinoma in patients with CY(+) status without peritoneal metastasis. PATIENTS AND METHODS: Twenty-three patients with CY(+) status without peritoneal metastasis who underwent curative surgery for gastric carcinoma between October 1999 and December 2014 were included in the study. Ten patients received neoadjuvant systemic chemotherapy followed by surgery, whereas 13 patients underwent surgery, in nine cases followed by S-1 adjuvant chemotherapy. RESULTS: The 5-year survival in both groups was 15%, and no significant difference was observed. However, the prognosis for patients with CY(-) status after neoadjuvant systemic chemotherapy was significantly better than that of patients who were still CY(+) after neoadjuvant systemic chemotherapy (p<0.01). Among all patients, the prognosis of those with less than clinical N2 disease was significantly better than that of patients with clinical N3 (p<0.01). In multivariate analysis, clinical lymph node metastasis was the only independent prognostic factor for CY(+) patients without peritoneal metastasis (p<0.05). CONCLUSION: The prognosis of gastric carcinoma with CY(+) without peritoneal metastasis is still stage IV disease and is dependent on the degree of clinical lymph node metastasis, in spite of therapeutic treatment.

[A Case of Laparoscopic Surgery for Early Gastric Cancer that Occurred after Coronary Artery Bypass Grafting using the Right Gastroepiploic Artery].

We herein report a case involving a 70-year-old man who was diagnosed with early gastric cancer that occurred after coronary artery bypass grafting (CABG) using the right gastroepiploic artery (RGEA) for effort-induced angina. He was successfully treated by laparoscopic surgery. Preoperative cardiac three-dimensional computed tomography and coronary angiography showed an occlusion of the RGEA graft, which could lead to ligation of the RGEA to dissect the lymph nodes along the RGEA. The laparoscopic approach helps to identify and avoid injury to the RGEA graft because of its enlarged and precise viewing field compared with laparotomy followed by retractor placement. Laparoscopic surgery is a useful method in such cases to reduce perioperative complications risk.

[Laparoscopic-Assisted Percutaneous Endoscopic Gastrostomy--Report of Three Cases].

Laparoscopic-assisted percutaneous endoscopic gastrostomy (LAPEG) was performed in consecutive three patients for whom it was unable to place a percutaneous endoscopic gastrostomy (PEG). The mean operation time was 40.3 min, and mean blood loss was 1.3 g. Three trocars were placed, two for working and another for endoscopy, and a PEG was established by an usual Introducer method. There were no complications both intra- and post-operatively. LAPEG might be a safe alternative when the application of PEG is difficult.

Late-type port-site recurrence of unexpected gallbladder carcinoma 11 years after laparoscopic cholecystectomy.

A 55-year-old man had laparoscopic cholecystectomy for acute cholecystitis and unexpected gallbladder cancer, followed by a liver bed resection and lymph node dissection. Eleven years later, he had a port-site recurrence of gallbladder cancer requiring resection; at that time, no other site of recurrence was observed. The patient has survived for 20 months without another recurrence. Although a rare finding, clinicians should be alert to the possibility of such a recurrence even 11 years after complete cure of the primary tumor, particularly in patients who have undergone laparoscopic cholecystectomy for unexpected gallbladder cancer.

Chromosomal instability associated with global DNA hypomethylation is associated with the initiation and progression of esophageal squamous cell carcinoma.

BACKGROUND: Global DNA hypomethylation is associated with increased chromosomal instability and plays an important role in tumorigenesis. The methylation status of the long interspersed nuclear element-1 (LINE-1) element is a useful surrogate marker for global DNA methylation. Although LINE-1 hypomethylation is recognized as a poor prognostic marker, the correlation of LINE-1 methylation level with tumor suppressor gene mutation, chromosomal instability, and clinical significance in esophageal squamous cell carcinoma (ESCC) remains unclear. METHODS: Using resected tumor tissues and the corresponding normal esophageal mucosa from 105 patients with ESCC, bisulfite pyrosequencing analysis was performed to quantify the LINE-1 methylation levels. p53 mutations in exons two to ten were detected by polymerase chain reaction direct sequencing. Chromosomal instability was assessed by single nucleotide polymorphism array comparative genomic hybridization analysis. RESULTS: The LINE-1 methylation level of ESCC was significantly lower than matched normal mucosa. LINE-1 methylation levels of normal mucosa from the esophagus had a significant inverse correlation with both cigarette smoking and alcohol consumption of the study subjects. LINE-1 hypomethylation of ESCC was significantly associated with lymph node metastasis, lymphovascular invasion, the frequency of p53 mutation and poor survivability. The LINE-1 methylation levels in ESCC had a significant inverse association with the percentage of copy number alterations in the whole genome, mirroring chromosomal instability. CONCLUSIONS: Our results suggested that whole genome hypomethylation caused by chronic inflammation could initiate carcinogenesis of esophageal squamous cells through chromosomal instability. In addition, chromosomal instability associated with the global hypomethylation might correlate highly with the progression of ESCC.

Characteristic risk factors in cirrhotic patients for posthepatectomy complications: comparison with noncirrhotic patients.

There seemed to be characteristic risk factors in cirrhotic patients for posthepatectomy complications because these patients have less hepatic reserve as compared with noncirrhotic patients. The aim of the current study was to identify these characteristic risk factors in cirrhotic patients. We performed 419 primary hepatectomies for hepatocellular carcinoma. The patients were divided into the cirrhotic group (n = 198) and the noncirrhotic group (n = 221), and the risk factors for posthepatectomy complications were compared between the groups. Thirty-six cirrhotic patients (18.2%) experienced Clavien's Grade III or more complications. Tumor size, intraoperative blood loss, duration of operation, major hepatectomy (two or more segments), and necessity of blood transfusion were found to be significant risk factors in univariate analyses. Multivariate analysis revealed that major hepatectomy and intraoperative blood loss were independent risk factors for posthepatectomy complications in patients with cirrhosis. On the other hand, the duration of operation was only an independent risk factor for posthepatectomy complication in noncirrhotic patients. Cirrhotic patients should avoid a major hepatectomy and undergo a limited resection preserving as much liver tissue as possible and meticulous surgical procedures to lessen intraoperative blood loss are mandatory to prevent major posthepatectomy complications.