Search

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, 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 discriminate patients eligible or not eligible for emergency surgery among elderly patients.

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.

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.We examined 109 patients with gastric cancer who underwent TLTG and LATG. Among these, 100 patients underwent TLTG and the rest underwent LATG.The length of resected esophageal segment in LATG patients was significantly longer than that in TLTG patients (P0.001). The length of the resected esophagus segment was inversely correlated with body mass index in cases of esophagojejunostomy by FEEA (P0.05). Multivariate analysis revealed that T factor, N factor, and severe complications were the independent factors for survival.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.

Key Clinical Message 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.

The relationship between postoperative complications and long-term survival after surgery for esophageal squamous cell carcinoma (ESCC) is controversial. 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. 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. 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.

Patients with advanced esophageal cancer frequently experience dysphagia and dyspnea, and relief of such symptoms is important. We wished to clarify the efficacy of endoscopic stent placement in patients with dysphagia or dyspnea caused by advanced esophageal cancer. A database of patients with esophageal cancer who underwent esophageal and airway stent insertion between 2005 and 2012 was analyzed retrospectively. Effects and complications of stent insertion, and survival after stent insertion, were investigated. Eighteen patients were treated by esophageal (n = 10) and/or airway (n = 9) stent placement. Marked improvements in food intake were recognized in eight patients after esophageal stenting. Marked improvements in breathing were observed in all patients after airway stenting. Dysphagia scores in the esophageal stent group as well as dyspnea grades in Common Terminology Criteria for Adverse Events v4.0 (CTCAE 4.0) in the airway stent group were significantly improved (p = 0.0078). In the esophageal stent group, major complications (CTCAE grade ≥3) occurred in seven of ten patients (70 %). In the airway stent group, major complications occurred in three of nine patients (33 %). Median survival of all 18 patients was 87.5 (range 13–1952) days after esophageal and/or airway stent placement. Stent placement is effective for the improvement of malignant dysphasia and dyspnea caused by advanced esophageal 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.

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.

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.

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.

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). 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. 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. 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.

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.

Epigenetic alterations that do not involve a change in the DNA sequence have been increasingly recognized to be important key events in the regulation of the gene expression and carcinogenesis. Major epigenetic mechanisms include the methylation of cytosine in DNA, changes in the histone and chromatin structure due to covalent posttranslational modification of histone proteins and the RNA-mediated regulation of the gene expression. Esophageal squamous cell carcinoma (ESCC) continues to be associated with a very poor prognosis, indicating that obtaining a clear understanding of the pathogenesis of ESCC is desired for improving clinical outcomes. In this review, we discuss the recent progress in research on epigenetic alterations in ESCC, with respect to the following points: (1) DNA methylation, including global hypomethylation and DNA hypermethylation at CpG islands in the promoters of tumor suppressor genes, (2) histone acetylation/deacetylation and histone methylation with the alteration of histone-modifying enzymes and (3) alterations in the expression of microRNA and the recently emerging long non-coding RNA. We then discuss the interplay among these epigenetic events and the crosstalk between epigenetic and genetic changes in ESCC. It is therefore important to understand the molecular mechanisms underlying the development and progression of ESCC to improve the treatment outcome of this devastating disease, although this information is quite complicated and confusing.

Summary Both internal and external oxidative stresses act on DNA and can induce carcinogenesis. 8-hydroxydeoxyguanosine (8-OHdG) is an indicator of oxidative stress and it leads to transversion mutations and carcinogenesis. 8-OHdG is excision-repaired by 8-OHdG DNA glycosylase (OGG1). The purpose of this study is to clarify the effect of oxidative DNA damage and repair enzymes on esophageal carcinogenesis. The levels of 8-OHdG and OGG1 were immunohistochemically evaluated in resected specimens, including squamous cell carcinoma (SCC) in 97 patients with esophageal cancer. Higher levels of 8-OHdG in normal esophageal epithelium were associated with a higher smoking index (P = 0.0464). The 8-OHdG level was higher in cancerous areas than in normal epithelia (P = 0.0061), whereas OGG1 expression was weaker in cancerous areas than in normal epithelia (P < 0.0001). An increase of OGG1 expression in normal epithelium was observed as 8-OHdG levels increased (P = 0.0011). However, this correlation was not observed in cancerous areas. High OGG1 expression in the cytoplasm was related to deeper tumors (P = 0.0023), node metastasis (P = 0.0065) and stage (P = 0.0019). Oxidative DNA damage, which is attributable to smoking as well as disturbances in DNA repair systems, appears to be closely related to esophageal carcinogenesis and its progression.

Long-term dialysis often causes physiological and metabolic problems that may affect the outcomes of surgery. The aim of this study was to elucidate whether emergency surgery for acute abdomen yields similar outcomes in dialysis patients versus non-dialysis patients. The subjects were 126 patients who underwent emergency surgery for acute abdomen between January, 2007 and November, 2011 in our hospital. They were divided into a dialysis group (HD group; n = 9) and a non-dialysis group (non-HD group; n = 117) and their postoperative morbidity and mortality were compared. Postoperative morbidity and mortality were significantly worse in the HD group. All 9 of these patients succumbed to postoperative complications versus only 5 of the 117 patients in the non-HD group. The outcomes of emergency surgery for acute abdomen were significantly worse for dialysis patients than for non-dialysis patients. Prompt diagnosis, initiation of the most suitable surgical procedure, and meticulous postoperative cares are imperative to improving the surgical outcomes of dialysis patients.

Alterations in the regulation of gene expression that do not involve a change in the DNA sequence have been increasingly recognized as an important key event of carcinogenesis, referred to as "epigenetic" changes. Major epigenetic mechanisms include the methylation of cytosines in DNA, changes of histone and chromatin structure by covalent posttranslational modifications of histone proteins and alterations in the expression of microRNAs. These epigenetic alterations have also been identified in esophageal squamous cell carcinoma (ESCC). In this brief review, we will discuss DNA hypermethylation of the tumor suppressor gene promoters, histone modifications including histone acetylation/deacetylation and histone methylation and microRNAs in ESCC. Clinical implications of these epigenetic alterations in ESCC will be also discussed.

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.

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.

Esophageal cancer is frequently associated with head-and-neck cancer. It is difficult to select treatment modalities for synchronous multiple cancers in the upper aerodigestive tract. A 58-year-old woman had synchronous quintuple cancer of the upper aerodigestive tract and was in a poor nutritional state due to oral pain and dysphagia. Clinical stages of cancer in the oral cavity, hypopharynx, cervical esophagus, middle thoracic esophagus, and lower thoracic esophagus were IVA (cT4a N2b M0), I (cT1 N0 M0), IA (cT1 N0 M0), IA (cT1 N0 M0), and IIA (cT3 N0 M0), respectively. After preoperative chemoradiotherapy, curative resection of oral cavity cancer and a tube jejunostomy were performed. Then, pharyngolaryngectomy, total esophagectomy, and pharyngostomy were performed. Finally, after additional radiotherapy to the oral cavity, pharyngogastrostomy with gastric tube and microvascular anastomosis were performed. The patient achieved oral intake and is in good condition and has at this writing remained recurrence free for 26 months. This report suggests that even if there are multiple cancers, adopting multimodal treatment strategies for controlling each cancer may lead to a chance to obtain a complete cure.

Replacing the thoracic esophagus with the colon is one mode of reconstruction after esophagectomy for esophageal cancer. There is, however, a high incidence of postoperative necrosis of the transposed colon. This study evaluated the outcomes of colon interposition with the routine use of superdrainage by microvascular surgery. Twenty-one patients underwent colon interposition from 2004 to 2009. The strategy for colon interposition was to: (i) use the right hemicolon; (ii) reconstruct via the subcutaneous route; (iii) perform a microvascular venous anastomosis for all patients; and (iv) perform a microvascular arterial anastomosis when the arterial blood flow was insufficient. The clinicopathologic features, surgical findings, and outcomes were investigated. The colon was used because of a previous gastrectomy in 18 patients (85.7%) and synchronous gastric cancer in three patients (14.3%). Eight patients (38.1%) underwent preoperative chemoradiotherapy including three (14.3%) treated with definitive chemoradiotherapy. Seven patients (33.3%) underwent microvascular arterial anastomosis to supplement the right colon blood supply. Pneumonia occurred in four patients (19.0%). Anastomotic leakage was observed in five patients (23.8%); however, no colon necrosis was observed. The 3-year and 5-year overall survival rates were both 50.6%. Colon interposition with superdrainage results in successful treatment outcomes. This technique is one option for colon interposition employing the right hemicolon.

Both squamous cell carcinomas and adenocarcinomas can develop in the esophagogastric junction. To clarify the appropriate lymph node dissection range, lymph node metastases from cancers in the esophagogastric junction were investigated.The nodal metastases were analyzed in 64 patients with squamous cell carcinoma and 129 with adenocarcinoma according to Siewert's classification, which is based on topographic anatomical criteria for adenocarcinoma.The squamous cell carcinomas located above the esophagocardial junction had more frequent metastasis to the lower and middle mediastinal lymph nodes in proportion to the depth of the tumor. Nodal metastasis was also often detected in the abdominal lymph nodes. In contrast, adenocarcinomas metastasized less frequently to the mediastinal lymph nodes, and the metastatic rates in the abdominal nodes were higher than those from squamous cell carcinoma.Esophagectomy with mediastinal and abdominal lymph node dissection is considered to be an appropriate approach for surgical resection of squamous cell carcinomas, whereas transhiatally extended gastrectomy with lower mediastinal and abdominal lymph node dissection is recommended for the treatment of adenocarcinomas.

This multicenter phase II study was designed to determine the efficacy and tolerability of oxaliplatin, levoforinate, and infusional 5-fluorouracil (FOLFOX4) as a second-line therapy for Japanese patients with unresectable advanced or metastatic colorectal cancer. A total of 53 patients with progressive disease after first-line chemotherapy were enrolled in the study. The treatment was repeated every 2 weeks until disease progression or unacceptable toxicity occurred, or the patient chose to discontinue the treatment. Four patients were ineligible and one did not receive the protocol therapy. Therefore, the response rate, overall survival (OS), and progression-free survival (PFS) were evaluated in 48 patients; toxicity was evaluated in 52 patients, excluding the patient who had not received the protocol therapy. A partial response was observed in 10 patients. The overall response rate was 20.8% (95% confidence interval [CI], 10.5%–35.0%). The median PFS was 5.6 months (95% CI, 4.1–7.0 months) and the median OS was 19.6 months (95% CI, 11.4–24.3 months). The most frequently encountered grade 3/4 hematological symptom was neutropenia (43.1%). The toxicity profile was generally predictable and manageable. The results showed good tolerability and efficacy for second-line FOLFOX4 in patients with advanced colorectal cancer, thus indicating the promise of this regimen as an effective second-line therapy for advanced colorectal cancer in the Japanese population.

The purpose of this study was to clarify the effect of preoperative chemoradiotherapy (CRT) for esophageal cancer on the postoperative course, and to determine the clinical significance of salvage esophagectomy after definitive CRT. Based on their preoperative treatment, 477 patients with esophageal cancer were classified into three groups: 253 patients who received surgery alone (Group I), 197 who received planned CRT (30–45 Gy, Group II), and 27 who received a salvage esophagectomy (radiation ≥60 Gy, Group III). Postoperative complications developed in 25, 40, and 59% of the patients in Groups I, II, and III, respectively, with pulmonary complications developing in 10, 15, and 30%, and anastomotic leakage developing in 13, 23, and 37%, respectively. Mortality rates were 2.4, 2.0, and 7.4%, respectively. Multivariate analysis revealed preoperative therapy to be an independent factor associated with postoperative risks: the odds ratios (ORs) of Groups II and III compared to Group I were 1.8 and 4.0 for pulmonary complications, while they were 1.9 and 2.8, respectively, for anastomotic leakage. No critical complications developed in the 14 patients who received salvage surgery performed with strict surgical indications after 2005. The survival of Group III was not significantly different from that of Groups I and II. Most patients who received an R1/R2 resection after definitive CRT died within 2 years after salvage surgery. Preoperative CRT is associated with postoperative complications especially in patients with R2 resection, while long-term survival can be achieved after R0 resections. Salvage surgery should be considered for carefully selected patients in whom R0 resection can be achieved.

Esophageal perforation with mediastinal abscess formation is a potentially life-threatening complication after chemoradiotherapy (CRT) in patients with esophageal cancer. We present the case of a 64-year-old woman with cervico-thoracic esophageal cancer who had previously undergone distal gastrectomy. Definitive CRT was initially performed since the patient refused laryngectomy. However, she developed an esophageal fistula and a subsequent cervico-mediastinal abscess, which made oral intake impossible. In order to address the fistula, abscess, and cancer, we decided to perform a staged operation. The patient first underwent total pharyngo-laryngo-esophagectomy and abscess drainage. She next underwent esophageal reconstruction with an ileocolonic conduit through a subcutaneous route. The patient is currently alive and well after surgery. This case suggests that surgical resection may be performed in high-risk patients with cervico-thoracic esophageal cancer via a two-stage operation.

An esophagectomy followed by reconstruction for esophageal cancer is a highly aggressive operation. The purpose of this study was to justify a two-stage operation for high-risk patients with esophageal cancer. The clinical results of 27 patients who underwent two-stage operation were compared with 118 patients who underwent a simultaneous resection and reconstruction (control subjects). The reasons for the selection of the two-stage operation were underlying general disease in 13 patients (liver dysfunction, n = 6; pulmonary disease, n = 3; poor performance status, n = 2; diabetes and renal failure, n = 1 each) and high-risk operation in 14 other patients (colon interposition, n = 7; salvage operation after definitive chemoradiotherapy, n = 4; and intraoperative events, n = 3). The patients initially underwent an esophagectomy and a cervical esophagostomy. Reconstruction was usually performed 2–3 weeks later. The patients in the two-stage group were older than the control patients (mean 67.8 vs. 61.6 years old). The morbidity rate of the two-stage operation was 29.6%, which was not statistically different than control patients (32.2%). Postoperative complications in the two-stage operation were anastomotic leakage in 5 patients, and pneumonia and wound infection in 1 patient each. No patient experienced in-hospital death. The survival rates were not statistically different between the two groups. A two-stage operation is a safe operation that prevents the occurrence of critical postoperative complications, and it thus may be considered an important treatment strategy for high-risk patients with esophageal cancer.

Background Anastomotic leakage with an intractable cutaneous fistula frequently develops after an esophagectomy and reconstruction via the subcutaneous route. Methods A pectoralis major muscle (PMM) flap was used for the treatment of 6 patients with esophageal cancer who developed anastomotic leakage with fistula after reconstruction via the subcutaneous route. A gastric tube and colon had been used for reconstruction in 2 and 4 patients, respectively. A trimming and repair of the leakage site was initially performed and the anastomotic site was then covered with a muscle flap. Results Recurrent anastomotic leakage did not develop in 5 patients. Among these patients, oral intake was initiated from 11–15 days after the repair operation in 4 patients. A patient having recurrent anastomotic leakage after a repair operation recovered well with conservative therapy. Conclusion The coverage with a PMM flap over the repair site is a simple method for preventing the development of recurrent leakage after a repair operation. Even when recurrent anastomotic leakage has occurred after this operation, healing is normally expected by means of conservative treatment. We, therefore, recommend this method for the repair of intractable anastomotic leakage after reconstruction via the subcutaneous route for esophageal cancer.

Objective: This phase II study evaluated the toxicity and efficacy of a novel dosing schedule of docetaxel and S-1 as treatment for advanced gastric cancer. Methods: Patients with measurable advanced or recurrent gastric cancer and no prior exposure to the investigational drugs were treated with intravenous docetaxel 35 mg/m2 on days 1 and 15, and oral S-1 80 mg/m2/day on days 1–14 every 4 weeks. The primary endpoint was objective response. Results: Thirty-five eligible patients were enrolled and received a total of 151 cycles of treatment (median 3, range 1–19). One complete response and 13 partial responses were observed, with an overall response rate of 40% (95% CI: 24–56%). Median progression-free survival and median overall survival times were 4.5 and 14.2 months, respectively. The most common grade 3–4 toxicities were neutropenia (23%) and leukocytopenia (15%). Conclusion: Biweekly docetaxel combined with S-1 is active in advanced or recurrent gastric cancer, and can be administered with proper management of adverse events in an outpatient clinic.

In Japan, most esophageal cancers are squamous cell carcinomas, and the results of esophagectomy have improved remarkably in recent years. The object of this study was to evaluate advances in operative therapy for esophageal cancer in Japan.We evaluated mortality, morbidity, and prognosis in 1000 consecutive patients who underwent esophagectomy for esophageal cancer at a single institution in Japan. The patients were divided into 3 groups according to the period when esophagectomy was performed: Group I (n = 197), 1964-1980; group II (n = 432), 1981-1993; and group III (n = 371), 1993-2006.The incidence of squamous cell carcinoma was 94%. The morbidity rates were 62%, 38%, and 33 %, in groups I, II, and III, respectively (P0.01, groups I vs II and III), and the in-hospital mortality rates were 14.2%, 5.1%, and 2.4%, respectively (P0.01, between each group). The 5-year overall survival rate was 30% (14%, 27%, and 46% in groups I, II, and III, respectively; P0.0001). Multivariate analysis revealed age, gender, depth of invasion, node metastasis, distant metastasis, curability, extent of lymphadenectomy, resectability, and the period when the operation was performed as independent prognostic factors.Generally, esophagectomy has been performed safely without critical complications; however, the prognosis has improved remarkably with advances in surgical techniques and treatment modalities.

Acute lung injury (ALI) is one of most serious complications to occur after an esophagectomy for esophageal cancer. However, the pathogenesis of ALI is still unclear. The cytokine levels of pleural drainage fluid as well as peripheral blood were measured in 27 patients who had undergone an extended radical esophagectomy. Both the clinical factors and cytokine levels were compared between 11 patients with (group I) and 16 without ALI (group II). ALI occurred more frequently in patients who underwent colon interposition than in those who received a gastric tube reconstruction (86%vs 25%, P = 0.009). The operation time of group I was significantly longer than that of group II. A logistic regression analysis revealed colon interposition to be an independent factor associated with the ALI (P < 0.05). Postoperative anastomotic leakage and systemic inflammatory response syndrome (SIRS) occurred more frequently in group I than in group II (P < 0.01). Both the serum interleukin-6 (IL-6) and IL-8 levels of group I were significantly higher than those of group II. IL-1beta and tumor necrosis factor-alpha were undetectable in the peripheral blood, whereas they were detectable in the pleural effusion. The IL-1beta of pleural effusion was higher in group I than group II. In conclusion, greater surgical stress, such as a longer operative time, is thus considered to be associated with the first attack of ALI. The adverse events developing in the extra-thoracic site, such as necrosis and local infection around anastomosis may therefore be the second attack. Furthermore, ALI may cause not only SIRS but also other complications such as anastomotic leakage.

BACKGROUND Endoscopic mucosal resection (EMR) is a less invasive localized treatment for patients with esophageal carcinoma. However, indications for EMR use in cases of superficial esophageal carcinoma are controversial. The authors evaluated histopathologic risk factors for lymph node metastasis and recurrence. METHODS In the specimens resected, the authors examined depth, the superficial area and the area attached to or infiltrating the lamina muscularis mucosa. RESULTS The authors found that the superficial area and the attached or infiltrated area reflected the depth of the tumor. However, there was a recurrence of esophageal carcinoma even in m3 cases attached only to the lamina muscularis mucosa. CONCLUSIONS The authors concluded that m1 and m2 esophageal carcinoma had almost no risk of lymph node metastasis and recurrence no matter how extensive the superficial area. In addition, sm2 and sm3 carcinoma have a high frequency of lymph node metastasis and recurrence. M3 and sm1 carcinoma run the risk of lymph node metastasis and recurrence however small the superficial area and the area attached to or infiltrating the lamina muscularis mucosa. Treatment strategies for patients with superficial esophageal carcinoma, including EMR, should take the above findings into account. Cancer 2002;94:570–5. © 2002 American Cancer Society.

e15540 Background: Second-line chemotherapy can now be considered as a proven treatment option for metastatic or locally advanced gastric cancer (AGC). Two global randomized phase III trials (REGARD and RAINBOW) showed that survival benefit was significantly observed in patients treated with ramucirumab (RAM) alone and in combination with weekly doses of PTX, compared with placebo, respectively. The purpose of the study is to evaluate the efficacy and safety of weekly dose of PTX combined with RAM practically as the second-line treatment in Japanese patients with AGC refractory to an S-1-containing chemotherapy regimen. Methods: We conducted a retrospective review of the data of 18 patients with AGC who received more than 2 cycles of PTX/RAM combined chemotherapy as the second-line regimen following S-1-based treatment. The objective response rate (ORR), adverse events, progression-free survival (PFS) and overall survival (OS) were analyzed and compared with PTX monotherapy group. Results: Median number of courses were 5 for the PTX/RAM group and the discontinuation of treatment except for disease progression was found in 2 cases (33.3%). The rates of hematological toxicities of higher than grade 3 were 33.3% in the PTX/RAM group, which were higher than those found in the PTX groups. The tumor responses of the PTX/RAM group were 22% for the ORR and 78% for the DCR, compared with 21% and 48% in the PTX group, respectively. The dose intensities of PTX were 72.4% in the former group. The survival data showed that the MST after second-line exposure was 290 days and the median PFS was 131 days in the PTX/RAM group, compared with 159 days and 90 days in the PTX group, which were not significantly different. Conclusions: PTX/RAM might be one of the best regimens for Japanese patients with AGC as the second-line treatment following S-1-containing chemotherapy.

Primary neuroendocrine carcinoma (NEC) of the breast appears to be a rare neoplasm. Due to the limited number of the cases, a definitive therapeutic option for the disease has not yet been established. We herein report the case of a 57-year-old female patient with primary NEC of the breast who underwent a surgical resection and for whom the suitable adjuvant therapy is now being considered.

S-1 adjuvant chemotherapy is commonly administered postoperatively for stage II and III advanced gastric cancer.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.The recurrence rates in groups A, B, C, and D were 15.7, 43.8, 44.4, and 57.1 %, respectively (A vs. B, p0.05, A vs. C and D, p0.01). The survival time of group A was significantly longer than that of other groups (p0.005). In addition, the survival time of patients with severe complications was significantly shorter than that of patients with non-severe complications (p0.05). An earlier S-1 administration after surgery was the only independent prognostic factor in the multivariate analysis.The prognosis of advanced gastric cancer was significantly related to the start of S-1 adjuvant treatment within 6 weeks after surgery.

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.

BACKGROUND While there are reports that CYFRA 21-1 is a useful tumor marker, to our knowledge the clinical utility of this marker to detect recurrences for squamous cell carcinoma of the esophagus has not been addressed. METHODS By immunoradiometric assay, human serum levels of CYFRA 21-1, SCC antigen and CEA were measured in esophageal squamous cell carcinoma patients prior to their initial treatment. Monthly follow-ups of these tumor markers was done after surgery. RESULTS The diagnostic sensitivity of CYFRA 21-1 was 43.9% (18 of 41), a value superior to that for SCC antigen (26.8%) and CEA (17.0%) (P < 0.05). The positive rates of CYFRA 21-1 increased with progression of the disease, 22.2% of pTNM Stage 0-IIA and 77.8% of pTNM Stage IIB/III (P = 0.013), whereas SCC antigen and CEA rates were not related to pTNM stage. Among 13 patients with clinical evidence of a recurrence, 76.9% (10 of 13) exhibited an increase in CYFRA 21-1, and this increase was evident before clinical detection of the recurrence in 9 of these 13 patients (69.2%). Consequently, postoperative elevations of serum CYFRA 21-1 levels were indicative of a tumor recurrence 1–13 months before acquisition of clinical and radiological data. CONCLUSIONS The assay of CYFRA 21-1 is useful not only for diagnosis but also for close monitoring of patients with esophageal squamous cell carcinoma. Cancer 2000;89:1413–7. © 2000 American Cancer Society.

Some esophageal diseases such as carcinoma, esophagitis, and collagen diseases have often been reported to show a diffusely thickened esophageal wall in the roentogenogram findings. In the current report, a preoperative upper gastrointestinal series and an endoscopic examination showed a diffusely infiltrative type carcinoma, but other examinations did not suggest any diseases such as esophagitis or collagen diseases which might cause a thickening of the esophageal wall or a constriction, of the esophagus. A postoperative histological examination revealed the primary carcinoma to remain only within the mucosal layer, while a large degree of lymphatic vessel permeation reached the adventitia over a wide area. An extraordinary degree of lymphatic permeation spread through the esophageal wall, and stromal fibrosis developed as a result of such lymphatic permeation. These histological phenomena might thus have led to the macroscopic appearance of infiltrative type esophageal carcinoma.

The role of family history in the multiple occurrence of cancer in the upper aerodigestive tract (UADT) remains unclear. The family histories of close relatives were examined in 167 patients with either hypopharyngeal or cervical esophageal cancer (PhCe cancer) and in 167 control subjects with benign diseases. The odds ratio for PhCe cancer was 2.6 in relation to family history of UADT cancers. Based on the family histories of close relatives, 167 cases with PhCe cancer were divided into 3 groups (Group I, 18 cases with a family history of UADT cancer; Group II, 37 cases with a family history of other cancers; Group III, 112 cases with no family history of any cancers). The mean age of the cases in group I was 59.4, which was younger than in group III (64.2). Second primary squamous-cell carcinomas in the UADT were more frequently recognized in group I (39%) than in group III (11%). However, no differences were observed in the smoking and drinking habits of male patients between each group. These results thus suggest that a family history of UADT cancers appears to be associated with the multiple occurrence of UADT cancers as well as the development of PhCe cancer.

e15577Background: Second-line chemotherapy can now be considered as a proven treatment option for patients with metastatic or locally advanced gastric cancer (AGC). Nab-paclitaxel (nab-PTX) is a na...

The results and outcomes of surgical resection for esophageal carcinoma have improved remarkably in recent years; however, recurrence still frequently develops, even after complete resection. The purpose of this study is to clarify the characteristics of recurrence in this patient population. Among 208 patients, who underwent R0 resection for esophageal carcinoma, recurrence developed in 61. Clinical data were available for 56 of these patients, who were the subjects of this study. We evaluated the time, patterns, and treatment of recurrence in these patients. Recurrence developed within 1 and 2 years after esophagectomy in 71 and 84% of the patients, respectively, and was classified as loco-regional (54%), hematogenous (36%), or mixed type (10%). The prognosis of patients with loco-regional recurrence tended to be better than that of those with distant metastasis, although the difference was not significant (P = 0.088). Patients with recurrence treated by chemotherapy alone or multimodal therapy, such as radiation or surgery combined with systemic chemotherapy, survived significantly longer than those with untreatable recurrence (P = 0.016). These findings reinforce the importance of careful follow-up for both loco-regional and hematogenous recurrence after esophagectomy, particularly during the first 2 years.

Purpose The aim of this study was to establish a simple criterion to predict prognosis of patients with gastric carcinoma. Methods Two hundred four patients with gastric carcinoma, who had been treated with curative resection, were enrolled. One point was added for each category among four pathological factors of depth of tumor, lymph node metastasis, venous invasion, and lymphatic invasion. Pathological Prognostic Score (PPS) was determined by an aggregate of these points for each category. Results There existed a significant difference between survivals of patients with PPS 0 or 1 and 2 or 3 (P = 0.0002). Similarly, there also existed a significant difference between survivals of patients with PPS 2 or 3 and 4 (P = 0.010). Conclusions PPS can be quite simple criteria to predict prognosis of gastric carcinoma with a strict stratification. J. Surg. Oncol. 2010;102:11–17. J. Surg. Oncol. 2010;102:73–76. © 2010 Wiley-Liss, Inc.

Metachronous gastric carcinoma arising in a gastric tube used for esophageal reconstruction has been occasionally encountered in long-term survivors of esophageal cancer. This study investigated 10 cases of gastric tube cancer in order to clarify the characteristics and the outcome of these patients.Four hundred and seventy-one patients underwent a radical esophagectomy at Kyushu University Hospital between 1989 and 2003. There were 10 cases of gastric tube cancer after an esophagectomy.The interval between the esophagectomy and the development of the gastric tube cancer ranged from 1.1 to 7 years. There was no peak for the incidence of gastric tube cancer. In 6 of 10 cases of gastric tube cancer, endoscopic or surgical resection were performed for the treatment; however, chemotherapy was administered to the other 4 cases for several reasons. The prognosis of patients who underwent resection was better than that of the other patients.Frequent endoscopic examinations are therefore important even several years after performing an esophagectomy, since the risk of gastric tube cancer is higher than the risk of a recurrence of esophageal cancer several years after an esophagectomy. Only an early diagnosis permits a less invasive and appropriate approach for the treatment of gastric tube cancer.

The significance of the Glasgow prognostic score (GPS), an inflammation-based prognostic score, as an indicator of aggressiveness in gastric carcinoma has not been investigated fully.Two hundred thirty-two patients with gastric carcinoma were enrolled. Patients who had both an elevated C-reactive protein (1.0 mg/dL) and hypoalbuminemia (3.5 g/dL) were allocated a traditional GPS (TGPS) of 2. Patients who had one of these abnormal values were allocated a TGPS of 1, and patients who had neither were allocated a TGPS of 0.There existed a significant difference between the survival of adjacent groups of patients when examined using the TGPS (P = .05 for TGPS 0 vs 1 and P = .006 for TGPS 1 vs 2). Multivariate analysis based on TGPS demonstrated that TGPS (P = .020) and tumor stage (P = .0007) proved to be independent prognostic indicators for worse prognosis.The preoperative measurement of an inflammation-based prognostic score can demonstrate a strict stratification for the prognosis of patients with gastric carcinoma.

The purpose of this study was to clarify the indications for an esophagectomy in elderly patients (especially patients over 80 years of age) with esophageal cancer.A total of 668 patients with thoracic esophageal cancer who underwent an esophagectomy by the transthoracic approach were divided into three groups according to age, namely, groups I (80 years, n=16), II (70-79 years, n=158), and III (or=69 years, n=494). In group I, surgery was only done in patients with PS 0 or 1, as well as normal cardiac and pulmonary functions.The incidence of preoperative pulmonary risk was 16% and 7% in groups II and III, respectively (P0.01). The morbidity rates of group II and III were 42% and 32%, respectively (P0.05). Pulmonary complications occurred in 18% and 10%, respectively, and cardiovascular complications occurred in 11% and 4%, respectively (P0.01). In group I, the morbidity and 30-day mortality rates were 25% and 0%, respectively, and pulmonary and cardiovascular complications occurred only in one patient each (6%). No significant differences were observed in cause-specific survival.In the elderly, preoperative pulmonary risk is frequently present, and careful perioperative management is needed while paying special attention to pulmonary and cardiovascular complications. However, when the indications for surgery can be strictly determined, an esophagectomy is considered a viable treatment alternative with satisfactory prognosis even in patients 80 years of age and older without any increased morbidity or mortality.

Bone marrow (BM) is a prognostically relevant indicator organ of micrometastasis; however, the clinical importance of BM micrometastasis in gastric cancer patients is not yet known. In the present study, the BM of 267 consecutive patients with primary gastric cancer was examined for tumor cells using immunocytochemical techniques. Real-time quantitative RT-PCR was used to ensure that the tumor cells were detected properly. Among the 267 cases analyzed, 30 cases (11.2%) had cytokeratine-positive cells in the bone marrow. Positive findings were related to the tumor stage (P

The emergence of trastuzumab has drastically changed therapy for breast cancer. Trastuzumab (Herceptin; Genentech) is a recombinant humanized monoclonal antibody that targets an epitope in the extracellular domain of the human epidermal growth factor receptor 2 (HER2) protein. HER2 is a member of a family of four transmembrane receptor tyrosine kinases that regulate cell growth, survival, and differentiation via multiple signal transduction pathways. Overexpression of HER2 or amplification of the HER2 gene occurs in 20%–30% of human breast cancers. Preclinical models have demonstrated that this antibody has significant antitumor activity as a single agent, and it also has a synergy with certain chemotherapeutic drugs. Phase II and III clinical trials performed in women with metastatic breast cancers that overexpress HER2 have shown trastuzumab to have clinical activity when used as monotherapy, while also improving survival when used as a first-line therapy in combination with chemotherapy. At present, clinical investigations are focusing attention on the efficacy of trastuzumab in both the adjuvant and neoadjuvant setting, as well as in the metastatic setting. In this review, we describe the developments and current status of trastuzumab-based treatment for breast cancer.