Simple Cancer Stem Cell Markers Predict Neoadjuvant Chemotherapy Resistance of Esophageal Squamous Cell Carcinoma.

BACKGROUND/AIM: Cancer stem cells (CSCs) contribute to resistance against neoadjuvant chemotherapy (NAC) in esophageal squamous cell carcinoma (ESCC). We conducted a retrospective observational study for the relationship between the expression levels of CSC markers in biopsy specimens prior to 5-fluorouracil plus cisplatin (FP)-NAC and the pathological responses. PATIENTS AND METHODS: We included 171 patients with ESCC who underwent the FP-NAC followed by radical resection. Biopsy specimens prior to the FP-NAC were obtained and immunochemically stained for CD44, CD133, and CD24. RESULTS: The biopsy specimens of the non-responders had the CD44high/CD24low expression at high levels, which was found as an independent predictor of not only FP-NAC resistance but also poor overall survival by multivariate analyses. CONCLUSION: CD44high/CD24low expression in the biopsy specimens prior to FP-NAC may be a predictor of FP-NAC resistance and poor prognosis of ESCC patients.

[A Case of Myeloid Sarcoma in the Small Intestine Presenting with Intussusception].

A sixty-something man presented with lower abdominal pain in early Y month 20XX, and was examined at the hospital's internal medicine outpatient clinic. An abdominal CT showed a soft tissue mass around the left hip joint, and multiple enlarged lymph nodes from inside the pelvis to the mesentery of the abdomen. We noted a small-intestinal intussusception in the lower right abdomen, and suspected malignant lymphoma. We did a CT-guided biopsy on the left hip joint soft tissue mass, and performed surgery on the small-intestinal intussusception. During surgery, we noted an approximately 30 cm ileal intussusception located about 60 cm from the terminal ileum, and enlarged lymph nodes in the nearby mesentery. We removed the ileal intussusception. The pathological diagnosis was myeloid sarcoma, and the soft tissue mass in the left hip joint was also diagnosed as myeloid sarcoma. We performed a bone-marrow biopsy at the hematology department, and diagnosed acute myeloid leukemia M2. We then started remission-induction therapy and consolidation therapy, and the patient was diagnosed as in remission in Y+5 month 20XX. We also need to keep in mind myeloid sarcoma in the intestine as a subtype of acute myeloid leukemia, as malignant tumor in the small intestine presenting with intussusception.

Meaning of C-reactive protein around esophagectomy for cStage III esophageal cancer.

PURPOSE: The prognosis of esophageal cancer is dismal, and the 3-year overall survival of cStage III does not reach 50.0%. C-reactive protein (CRP) is a well-known protein that reflects the short- and long-term operative outcomes of esophageal cancer. However, since elevated CRP levels are often observed in cStage III esophageal cancer, whether or not CRP still reflects the prognosis is unclear. METHODS: Eighty-four patients who were diagnosed with cStage III esophageal cancer and underwent R0/1 operation from January 2007 to December 2014 were retrospectively evaluated. RESULTS: The mean age was 66.8 years, and the majority of patients were male. The median preoperative and postoperative CRP levels were 0.15 and 1.47 mg/dl, respectively. A majority of the patients underwent thoracoscopic surgery, and the median blood loss and operation duration were 456 ml and 11.6 h, respectively. Forty-six patients (54.8%) died during the observation period, and the 3-year overall survival was 52.4%. A multivariate analysis showed that the preoperative CRP level, postoperative albumin level, blood loss, and complications were independent prognostic factors. A multiple linear regression analysis showed that an elevated postoperative CRP level was affected by the operation duration and preoperative CRP levels. CONCLUSIONS: These findings suggest that the preoperative CRP level is a prognostic factor for cStage III esophageal cancer and that postoperative elevation in the CRP level is affected by the operation duration.

Application of iNKT Cell-targeted Active Immunotherapy in Cancer Treatment.

In tumor immunity, invariant natural killer T (iNKT) cells play a pivotal role as a link between the innate and adaptive immune systems. With a precisely regulated activation mechanism, iNKT cells have the ability to respond quickly to antigenic stimulation and rapidly produce cytokines and chemokines, and subsequently an effective antitumor immune response. The development of iNKT cell-targeted active immunotherapy enables, not only an antitumor immune response through innate and acquired immunity, but also the conversion of an immunosuppressive into an immunogenic microenvironment. This review is focused on the activation mechanism and the role of iNKT cells after therapeutic active immunization. The therapeutic strategy targeting iNKT cells is expected to be applied to clinical practice in combination with surgery and chemotherapy.

The Surgical Apgar Score Predicts Not Only Short-Term Complications But Also Long-Term Prognosis After Esophagectomy.

BACKGROUND: The surgical Apgar score (SAS) quantifies three intraoperative factors and predicts postoperative complications, but few reports describe its usefulness in esophagectomy, and no studies to date show its correlation with long-term prognosis after esophagectomy. METHODS: This study investigated 400 cases in which esophagectomy was performed on esophageal malignant tumors at the authors' hospital from January 2007 to January 2017. In this study, SAS was defined as the sum of the scores of three parameters, namely, estimated blood loss, lowest mean arterial pressure, and lowest heart rate, with values extracted from medical records. Postoperative complications classified as Clavien-Dindo grade 3 or higher were also extracted. The study retrospectively compared the relationship of SAS to postoperative complications and survival. RESULTS: Univariate analysis showed that postoperative complications were significantly associated with hypertension (p = 0.017), thoracotomy (p = 0.012), and SAS ≤ 5 (p < 0.0001), and multivariate analysis showed that hypertension (p = 0.049) and SAS ≤ 5 (p < 0.0001) were significant predictive factors for complications. In the prognostic analysis, log-rank analysis showed that patients with an SAS ≤ 5 had a significantly poorer prognosis than those with a SAS > 5 (p = 0.043), especially for complications classified as clinical stage 2 or higher (p = 0.027). In the multivariate analysis, SAS ≤ 5 was identified as a significantly poor prognostic factor for complications classified as clinical stage 2 or higher (p = 0.029). CONCLUSION: In this study, SAS was useful not only for predicting short-term complications, but also as a long-term prognostic factor after esophagectomy.

Genetic structure of a population of Potato virus Y inducing potato tuber necrotic ringspot disease in Japan; comparison with North American and European populations.

The structure of Potato virus Y (PVY) populations causing potato tuber necrotic ringspot disease (PTNRD) was analysed. The full-length sequences of the genomic RNAs of five geographically distinct isolates from Japan were determined. Recombination and phylogenetic analyses of European, North American and Japanese isolates of PVY showed that the world PVY population has three major lineages and two sublineages. Most recombinants were interlineage, and one isolate from Europe was identified as an intralineage recombinant. No recombinants were found among Japanese PTNRD isolates, which were most closely related to PTNRD isolates previously found in North America. Comparison of the within- and between population nucleotide diversities in the N lineage sequences from Japan, Europe and North America showed that Japanese population was distinct from the European and North American populations. The nucleotide sequences of the protein 1 and coat protein genes of a further 18 isolates were determined. One Japanese clade had radiated in a star burst as shown by its deviation from the neutral equilibrium model and its small nucleotide diversity. Our results suggest that PVY PTNRD was recently introduced into Japan more than once, and has expanded throughout Japan from founder populations.

Comparison of different microprocessor controlled knee joints on the energy consumption during walking in trans-femoral amputees: intelligent knee prosthesis (IP) versus C-leg.

The purpose of this study was to investigate the characteristic differences between the IP and C-Leg by making a comparative study of energy consumption and walking speeds in trans-femoral amputees. The subjects consisted of four persons with traumatic trans-femoral amputations aged 17 - 33 years who had been using the IP and were active in society. Fourteen able-bodied persons served as controls. First the energy consumption at walking speeds of 30, 50, 70, and 90 m/min was measured when using the IP. Then the knee joint was switched to the C-Leg. The same energy consumption measurement was taken once the subjects were accustomed to using the C-Leg. The most metabolically efficient walking speed was also determined. At a walking speed of 30 m/min using the IP and C-Leg, the oxygen rate (ml/kg/ min) was, on average, 42.5% and 33.3% higher (P< 0.05) than for the able-bodied group. At 50 m/min, the equivalent figures were 56.6% and 49.5% (P< 0.05), while at 70 m/min the figures were 57.8% and 51.2% (P<0.05), and at 90m/min the figures were 61.9% and 55.2% (P<0.05%). Comparing the oxygen rates for the subjects using the IP and C-Leg at walking speeds of 30 m/min and 90 m/min it was found that subjects who used C-Leg walked somewhat more efficiently than those who used IP. However, there was no significant difference between the two types at each walking speed. It was also determined that the most energy-efficient walking speed for subjects using the IP and C-Leg was the same as for the controls. Although the subjects in this study walked with comparable speed and efficiency whether they used the IP or C-Leg, the subjects' energy consumption while walking with the IP and C-Leg at normal speeds were much lower than previously reported. This study suggested that the microprocessor controlled knee joints appeared to be valid alternative for improving walking performance of trans-femoral amputees.

Effect of tumor size on prognosis in patients with non-small cell lung cancer: the role of segmentectomy as a type of lesser resection.

OBJECTIVE: As a result of increasing discovery of small-sized lung cancer in clinical practice, tumor size has come to be considered an important variable affecting planning of treatment. Nevertheless, there have been no reports including large numbers of patients and focusing on tumor size, and controversy remains concerning the surgical management of small-sized tumors. Therefore, we investigated the relationships between tumor dimension and clinical and follow-up data, as well as surgical procedure in particular. METHODS: We reviewed the records of 1272 consecutive patients who underwent complete resection for non-small cell carcinoma of the lung. RESULTS: Fifty patients had tumors of 10 mm or less, 273 had tumors of 11 to 20 mm, 368 had tumors of 21 to 30 mm, and 581 had tumors of greater than 30 mm in diameter. The cancer-specific 5-year survivals of patients in these 4 groups were 100%, 83.5%, 76.5%, and 57.9%, respectively. For patients with pathologic stage I disease, they were 100%, 92.6%, 84.1%, and 76.4%, respectively. Multivariate analysis demonstrated that male sex, older age, larger tumor, and advanced pathologic stage adversely affected survival. Lesser resection was performed in 167 (52%) of 323 patients with a tumor of 20 mm or less in diameter but in 156 (16%) of 949 patients with a tumor of greater than 20 mm in diameter. The percentages of lesser resection among all procedures performed were 79%, 56%, 30%, and 15% in patients with pathologic stage I disease with a tumor of 10 mm or less, 11 to 20 mm, 21 to 30 mm, and greater than 30 mm in diameter, respectively. The 5-year cancer-specific survivals of patients with pathologic stage I disease with tumors of 20 mm or less and 21 to 30 mm in diameter were 92.4% and 87.4% after lobectomy, 96.7% and 84.6% after segmentectomy, and 85.7% and 39.4% after wedge resection, respectively. On the other hand, with a tumor of greater than 30 mm in diameter, survivals were 81.3% after lobectomy, 62.9% after segmentectomy, and 0% after wedge resection, respectively. CONCLUSIONS: Tumor size is an independent and significant prognostic factor and important for planning of surgical treatment. Although lobectomy should be chosen for patients with a tumor of greater than 30 mm in diameter, further investigation is required for tumors of 21 to 30 mm in diameter. Segmentectomy should, as a lesser anatomic resection, be distinguished from wedge resection and might be acceptable for patients with a tumor of 20 mm or less in diameter without nodal involvement.

Effect of histologic type and smoking status on interpretation of serum carcinoembryonic antigen value in non-small cell lung carcinoma.

BACKGROUND: Serum carcinoembryonic antigen (CEA) has all of the properties desired for a biologic measure to be used as a prognostic indicator in the clinical evaluation of lung cancer. Carcinoembryonic antigen value appears to be related to tumor histologic type and patients' smoking status, which has yet to be intensively analyzed as reports available thus far have consisted of a limited number of patients. This study was undertaken to determine whether the prognostic value of CEA differs according to histologic type in a large group of patients with clinical early-stage lung cancer, and how smoking influences its value. METHODS: Two series of 694 and 260 consecutive patients who underwent resection for clinical stage I lung adenocarcinoma and squamous cell carcinoma, respectively, were evaluated. We measured serum CEA before and after surgery, and analyzed its prognostic significance in relation to histologic type and its correlation with smoking status. RESULTS: We found significantly higher CEA levels in patients with adenocarcinomas than in those with squamous cell carcinomas (7.8 versus 5.5 ng/mL; p = 0.0018), but a higher percentage of CEA-positive patients among those with squamous cell carcinoma (109 of 260, 41.9%) than those with adenocarcinoma (245 of 694, 35.3%). Clinical stage I patients with a high preoperative CEA level had a poor prognosis, and for pathologically confirmed stage I patients with a high postoperative CEA level the prognosis was worse. The prognostic value of serum CEA level was thus significantly greater for adenocarcinoma than for squamous cell carcinoma. This was probably because of a much higher proportion of smokers among patients with squamous cell carcinoma. In adenocarcinoma, the growth of which was generally less influenced by smoking, the proportion of CEA-positive smokers (49.3%, 170 of 345) was greater than that of CEA-positive nonsmokers (21.5%, 75 of 349, p < 0.0001). Additionally, in patients with adenocarcinoma, survival of nonsmokers was more greatly influenced by CEA level than that of smokers. CONCLUSIONS: Although serum CEA values measured before and after surgery are important in identifying patients at high risk of poor survival, its specificity is higher for adenocarcinoma than for squamous cell carcinoma. When serum CEA levels are checked, smoking status of patients, particularly of those with squamous cell carcinoma, should be taken into account.

Sleeve segmentectomy for non-small cell lung carcinoma.

OBJECTIVE: Although sleeve segmentectomy for centrally located lung cancers was originally designed for patients unable to tolerate lobectomy, we have tried it in patients with noncompromised function as well. We evaluated the efficiency of this atypical type of bronchoplasty. METHODS: Of 202 patients for whom we performed bronchoplasty for primary non-small cell lung carcinoma, 16 underwent sleeve segmentectomy. RESULTS: Sixteen patients were classified into 4 groups according to the mode of bronchial reconstruction: type A, anastomosis between the right intermediate or left main and basal segmental bronchi with removal of the superior segment of the lower lobe (S6; n = 7); type B, anastomosis between the left main and lingular bronchi with removal of the upper division of the left upper lobe (S1+2+3; n = 3); type C, anastomosis between the left main and upper division bronchi with removal of the lingular segments (S4+5; n = 4); and type D, others (n = 2). Nine patients had pulmonary function sufficient to tolerate lobectomy. The tumors were completely resected in all patients. Combined performance of pulmonary angioplasty was carried out in 2 patients. Bronchial reconstruction was successful in all patients, with neither bronchial complications nor local recurrences. Ten patients had stage IA disease, and 6 had more advanced disease. All patients were alive, except 1 who died as a result of distant metastasis and 2 who died of noncancerous causes. Overall 3-year and 5-year survivals were 93.3% and 68.1%, respectively. CONCLUSIONS: Sleeve segmentectomy, which is technically demanding, should be considered in patients with centrally located and possibly curable early non-small cell lung cancer because the prevalence of small-sized or multiple lung tumors has been increasing and because our findings suggest that this lung-saving operation is safe and useful.

Prognostic significance of perioperative serum carcinoembryonic antigen in non-small cell lung cancer: analysis of 1,000 consecutive resections for clinical stage I disease.

BACKGROUND: The prognostic implication of serum carcinoembryonic antigen (CEA) has yet to be comprehensively analyzed since the reports available so far have comprised small patient populations. We evaluated perioperative CEA values with regard to surgical results in a large number of patients to clarify its merit. METHODS: We measured serum CEA levels before and after surgery in 1,000 consecutive patients with clinical stage I non-small cell lung cancer who underwent resection of tumor. High CEA value was greater than 5.0 ng/mL. RESULTS: Three hundred and sixty-eight patients (36.8%) had high preoperative CEA levels. The CEA levels after surgery were normalized in 242 patients (24.2%) and persistently elevated in 126 patients (12.6%). High CEA levels were seen more frequently in patients with older age, male gender, larger size of tumor, incomplete resection, and advanced pathologic stage. Patients with a high preoperative CEA level had a poor survival. Among these patients, even worse survival was seen for those with a high postoperative CEA level. These prognostic trends were still observed for patients with pathologic stage I disease. Multivariate analysis demonstrated that both preoperative and postoperative CEA levels were independent prognostic determinants (p = 0.0243 and p < 0.0001, respectively). CONCLUSIONS: Perioperative measurement of serum CEA concentrations yields information valuable for detecting patients at high risk of poor survival. Normalization of CEA levels after surgery was a significant favorable prognostic sign in patients with an elevated CEA level before surgery. Even after apparently successful surgical therapy, patients with a high CEA level should be carefully followed up, and might represent a suitable target for neoadjuvant clinical trials.

Evolution of surgical outcomes for nonsmall cell lung cancer: time trends in 1465 consecutive patients undergoing complete resection.

BACKGROUND: Lung cancer is still the most common cause of death due to cancer. Although the 5-year survival rate of patients with lung cancer is reported to be increasing, whether the surgical results have actually been improving or not is controversial. We reviewed our experience to evaluate time trends of surgical outcomes in patients with nonsmall cell lung cancer. METHODS: We reviewed the clinical records of 1465 consecutive patients with proven primary nonsmall cell carcinoma who underwent complete removal of the primary tumor together with hilar and mediastinal lymph nodes from 1985 to 1995 (early era) and from 1996 to 2002 (late era). The clinical characteristics, surgical outcome, and overall survival of the patients were analyzed, and data from the two eras were compared. RESULTS: There were 694 patients in the early era and 771 in the late era. As for their characteristics, elder age, female sex, adenocarcinoma, earlier stage of disease and smaller size of tumor were more frequently encountered in the late era. Lobectomy was the most common procedure performed during both periods, and in the late era, the rate of segmentectomy was doubled (11% to 25%) whereas that of pneumonectomy was much less (6% to 1%). Although the frequency of operative deaths in the two eras did not differ (0.3%), that of in-hospital deaths and of postoperative complications decreased significantly in the late era (2% to 0.5% and 28% to 12%, respectively). A significant improvement in survival probability was observed in patients with pathologic stage IA (p < 0.0001), IB (p = 0.0477), and III disease (p = 0.00120) but not in those with pathologic stage II disease (p = 0.5353). Also, the multivariate analysis of patients with pathologic stage I or III demonstrated that age, sex, and size of the tumor were significant prognostic determinants, and confirmed that the recent prolonged survivals remained significant even after simultaneous adjustment for other factors. CONCLUSIONS: These data indicate a significant recent improvement in surgical outcomes after stratification of various prognostic variables although careful consideration should be given to the retrospective nature of this study.

Effect of an Intelligent Prosthesis (IP) on the walking ability of young transfemoral amputees: comparison of IP users with able-bodied people.

OBJECTIVE: To make a comparative study of energy expenditure and walking speeds between able-bodied people and young Intelligent Prosthesis (IP) users and to demonstrate the effect of IP on the walking ability of young amputees. DESIGN: The test subjects were eight young traumatic transfemoral amputees. Fourteen able-bodied persons served as controls. All amputees used an IP, and they had all undergone a prosthetic rehabilitation program for 8 wk. IP users, who had completed the rehabilitation program, were instructed to walk at speeds of 30, 50, 70, 90, and 110 m/min. Measurements of energy expenditure while walking were taken. The most metabolically efficient waking speed was also determined. RESULTS: On average, the IP users experienced an oxygen uptake that was 24.1% and 24.2% higher than those for the controls at speeds of 70 and 90 m/min, respectively. It was also determined that the most metabolically efficient walking speed for the IP users was the same as for the controls. CONCLUSIONS: This study showed that young IP users who undergo an adequate prosthetic rehabilitation program can achieve remarkably improved walking performance. Young IP users could walk at the normal speeds of able-bodied people, with only around a 24% increase in energy expenditure.

Physical fitness of lower limb amputees.

OBJECTIVE: To investigate the cardiorespiratory endurance of the physical fitness of amputees and able-bodied subjects of the same ages and to demonstrate deterioration of the physical fitness of the amputees. DESIGN: The test subjects were 31 amputees. Eighteen able-bodied persons served as controls. The incremental exercise test was performed to evaluate physical fitness. Sixteen of 31 amputees underwent endurance training by using a cycle ergometer driven by the intact leg, and their physical fitness was evaluated after completion of the endurance training program. RESULTS: The Vo2max, anaerobic threshold, and maximum workload for the amputees were significantly lower than those of the able-bodied group. The equivalent values for the endurance training group before exercise treatment were 18.0, 12.1, and 63.9, respectively. After exercise treatment, these values significantly increased, and there was no significant difference from the able-bodied subjects. CONCLUSIONS: This study showed that the physical fitness of amputees was clearly lower than that of the able-bodied subjects and that the amputees were able to recover from a poorly conditioned status after endurance training.

Potato Tuber Necrotic Ringspot Disease Occurring in Japan: Its Association with Potato virus Y Necrotic Strain.

Unfamiliar necrotic symptoms on or within potato tubers of cultivars Nishiyutaka and Dejima were observed in Nagasaki prefecture, Japan, in 1992. Symptoms were typically on the surface of the tuber, which either protruded at first and then became sunken, or showed necrotic spots, with necrosis within the tubers. Symptoms sometimes appeared at harvesting but more often appeared after storage for several months. Investigations revealed that the causal agents of the disease were isolates of Potato virus Y necrotic strain (PVYNTN) and the disease was potato tuber necrotic ringspot disease (PTNRD), previously reported in Europe and Lebanon. Five potato cultivars were inoculated with an isolate from necrotic tubers. The highest percentage of progeny tubers showing PTNRD was found in cv. Nishiyutaka (23.3%). In contrast, cvs. Shima-bara, Mayqueen, and Danshaku showed a low percentage of PTNRD. Additional potato tubers with PTNRD were also observed after storage of the tubers. To investigate the relatedness between isolates of PVYNTN and of necrotic strain PVYN, previously isolated in Japan, Nishiyu-taka was inoculated with an isolate of PVYN, which also induced PTNRD. Nucleotide sequences of coat protein (CP) genes of six PVYNTN isolates were determined. The CPs were 267 amino acids in length, with a substitution of one or no amino acid among each of the six isolates. The phylogenetic relationship based on nucleotide sequences of CP genes showed that these six PVYNTN isolates clustered together with PVYN isolates. This is the first report of PTNRD caused by PVYNTN isolates in Asia.