Presentation of oropharyngeal dysphagia and rehabilitative intervention following esophagectomy: a systematic review.

No study has systematically reviewed the evidence on presentation of oropharyngeal dysphagia and swallowing rehabilitation following esophagectomy. The purposes of this systematic review are to 1) qualitatively synthesize the current findings on oropharyngeal swallowing abnormalities identified by instrumental swallowing evaluations, 2) describe the reported health-related outcomes in relation to swallowing abnormality following esophagectomy, and 3) examine the efficacy of reported rehabilitative interventions for oropharyngeal dysphagia in patients who underwent esophagectomy. Publications were searched using five electronic databases. No language or publication date restrictions were imposed. Two authors performed a blind review for published or unpublished studies that reported swallowing biomechanics and dysphagic symptoms using instrumental evaluation of swallowing, specifically the videofluoroscopic swallowing study and fiberoptic endoscopic evaluation of swallowing, and/or health-related outcomes in relation to swallowing abnormalities, and/or therapeutic interventions for oropharyngeal dysphagia following esophagectomy. Twelve studies out of 2,193 studies including 458 patients met the inclusion criteria. Reported abnormal swallowing biomechanics included vocal fold immobility, delayed onset of swallowing, reduced hyolaryngeal elevation, and reduced opening of the upper esophageal sphincter. Aspiration (0-81%) and pharyngeal residue (22-100%) were prevalent. Those abnormal swallowing biomechanics and swallowing symptoms were commonly reported following both transhiatal and transthoracic esophagectomy. Pneumonia presented in 5-25% of the study patients. One quasi-experimental study examined the effectiveness of swallowing exercises for postoperative oropharyngeal dysphagia; three case series reported a benefit of the chin-tuck maneuver in reducing aspiration and residue. This review revealed distinct swallowing impairments and increased pneumonia risks following esophagectomy. This review also found that evidence on the efficacy of therapeutic interventions was limited. Future studies are warranted to develop effective rehabilitative interventions for postesophagectomy patients with oropharyngeal dysphagia.

ACVR1 (587T>C) mutation in a variant form of fibrodysplasia ossificans progressiva: second report.

Fibrodysplasia ossificans progressiva (FOP) is a rare, congenital disorder caused by heterozygous mutation of the bone morphogenetic protein type I receptor ACVR1. Various forms of atypical FOP have recently been identified, and a novel mutation, ACVR1 (587T>C), was reported in 2011. We report on the second patient worldwide with ACVR1 (587T>C) mutation. A 22-year-old Japanese male with no family history of heterotopic ossification did not show any malformation of the great toes and showed normal development from birth to the age of 17 years, when heterotopic ossification appeared in the lumbar area. The clinical symptoms were similar to those reported previously: the delayed onset with a slower and mild clinical course and little finger camptodactyly. Gene analysis revealed that the patient was heterozygous for ACVR1 (587T>C) mutation, the same one as reported in 2011, suggesting a correlation between the location of the mutation and the clinical symptoms. This second report of ACVR1 (587T>C) mutation worldwide is particularly meaningful in that it highlights the difference between clinical symptoms of the first reported patient with ACVR1 (587T>C) mutation and those of classic FOP.

Self-monitoring has potential for home exercise programmes in patients with haemophilia.

Haemophiliacs who have had to keep a physically inactive lifestyle due to bleeding during childhood are likely to have little motivation for exercise. The purpose of this study is to clarify the effectiveness of the self-monitoring of home exercise for haemophiliacs. A randomized controlled trial was conducted with intervention over 8 weeks at four hospitals in Japan. Subjects included 32 male outpatients aged 26-64 years without an inhibitor who were randomly allocated to a self-monitoring group and a control group. Individual exercise guidance with physical activity for improvement of their knee functions was given to both groups. The self-monitoring materials included an activity monitor and a feedback system so that the self-monitoring group could send feedback via the Internet and cellular phone. The self-monitoring was performed by checking exercise adherence and physical activity levels, bleeding history and injection of a coagulation factor. Both groups showed significant improvements in exercise adherence (P < 0.001) and physical function such as the strength of knee extension (P < 0.001), range of knee extension (P < 0.001), range of ankle dorsiflexion (P < 0.01), a modified Functional Reach (P < 0.05) and 10 metre gait time (P < 0.01). In particular, improvements in exercise adherence (P < 0.05), self-efficacy (P < 0.05), and strength of knee extension (P < 0.05) were significant in the self-monitoring group compared with those in the control group. No increase in bleeding frequency and pain scale was noted. The self-monitoring of home exercise for haemophilic patients is useful for the improvement of exercise adherence, self-efficacy and knee extension strength.

Impact of hepatic lymph node metastasis on survival of patients with synchronous resectable or unresectable liver metastases of colorectal cancer.

BACKGROUND: The goals of this retrospective study were to comprehensively evaluate the impact of hepatic lymph node (HLN) involvement on survival in patients with synchronous resectable or unresectable liver metastases from colorectal cancer and to highlight how to deal with such cases in the light of recent advances in chemotherapy. METHODS: The impact of HLN involvement on survival, along with various clinical, pathological, and therapeutic factors, was retrospectively evaluated in 61 patients with synchronous liver metastases from colorectal cancer (resectable, 26; unresectable, 35), undergoing resection of the primary tumor and histopathological evaluation between July 2000 and April 2008. RESULTS: The proportion with HLN metastasis was 11.5 % in resectable cases and 28.6 % in unresectable cases. On multivariate analysis using the Cox proportional hazards model, HLN metastasis (P < 0.001), along with non-resection of hepatic lesions (P < 0.001), larger metastatic tumor volume (P < 0.001), non-use of oxaliplatin-based chemotherapy (P < 0.001), involvement of 4 or more regional lymph nodes (P < 0.001), and excessive lymphatic invasion (P = 0.02), was identified as an independent risk factor for shorter survival. CONCLUSIONS: To establish a new therapeutic strategy for synchronous liver metastasis of colorectal cancer, the HLNs should be examined histologically in patients undergoing resection of their primary colon and rectal cancer.

Should isolated peritoneal carcinomatosis from colorectal cancer be sub-classified into stage IVB in era of modern chemotherapy?

BACKGROUND: According to the 7th edition of the TNM staging system, stage IV metastatic colorectal cancer (CRC) at the time of initial diagnosis is sub-classified into stage IVA or IVB disease. Peritoneal carcinomatosis (PC), considered to have a dismal prognosis, is exclusively sub-classified into stage IVB, even though other metastases to a sole organ are sub-classified into stage IVA, which is considered to be associated with better survival. This retrospective study was undertaken to investigate the overall survival in metastatic CRC patients, focusing on PC patients. METHODS: We reviewed data on patients with metastatic CRC at initial diagnosis surgically treated between January 2006 and June 2011. A survival analysis was performed paying special attention to PC and sub-classifying patients with PC into three categories according to metastatic sites. RESULTS: There were 69 stage IVA patients (IVA group) and 83 stage IVB. Among stage IVB patients, 20 had isolated PC (PC-I group), 28 had PC with one or more other sites of metastasis (PC-II group), and 35 had at least 2 metastatic without peritoneal involvement (NPC group). Of 152 stage IV patients, 132 (87 %) underwent resection of the primary tumor and 19 (12 %) underwent radical resection of metastatic disease with microscopic free margins (R0 resection) including 5/20 (25 %) patients in the PC1 group. A total of 139 patients received oxaliplatin-based chemotherapy in a palliative (n = 125), neoadjuvant (n = 3), or adjuvant setting after R0 resection (n = 11). Compared with 36.6 months in the PC-I group, median survival was 32.5 months (P = 0.48) in the IVA group, 14.7 months (P = 0.07) in the PC-II group, and 12.9 months (P < 0.01) in the NPC group. CONCLUSIONS: The sub-classification of isolated PC into stage IVA instead of IVB might be more appropriate in the era of modern chemotherapy. Further investigation is warranted.

Phase II multi-institutional prospective randomised trial comparing S-1+paclitaxel with S-1+cisplatin in patients with unresectable and/or recurrent advanced gastric cancer.

BACKGROUND: A combination of S-1 and cisplatin has been shown to be effective with acceptable safety for the first-line treatment of far-advanced gastric cancer in Japan. This is the first randomised phase II trial to compare S-1+paclitaxel with S-1+cisplatin in this setting. METHODS: Patients with unresectable and/or recurrent advanced gastric cancer were randomly assigned to receive one of the two regimens: S-1 (40 mg m(-2) twice daily) on days 1-14 plus paclitaxel (60 mg m(-2)) on days 1, 8, and 15 of a 4-week cycle (S-1+paclitaxel) or S-1 (40 mg m(-2) twice daily) on days 1-21 plus cisplatin (60 mg m(-2)) on day 8 of a 5-week cycle (S-1+cisplatin). The primary end point was the response rate (RR). Secondary end points included progression-free survival (PFS), overall survival (OS), and safety. RESULTS: A total of 83 patients were eligible for safety and efficacy analyses. In the S-1+paclitaxel and S-1+cisplatin groups, RRs (52.3% vs 48.7%; P=0.74) and median PFS (9 vs 6 months; P=0.50) were similar. The median OS was similar in the S-1+paclitaxel and S-1+cisplatin groups (16 vs 17 months; P=0.84). The incidence of grade 3 or higher haematological toxicity was 19.0% with S-1+paclitaxel and 19.5% with S-1+cisplatin. The incidence of grade 3 or higher non-haematological toxicity was 14.2% with S-1+paclitaxel and 17.1% with S-1+cisplatin. CONCLUSION: S-1+paclitaxel was suggested to be a feasible and effective non-platinum-based regimen for chemotherapy in patients with advanced gastric cancer. Our results should be confirmed in multicenter, phase III-controlled clinical trials.

Inter-observer reliability of three different radiographic scores for adult haemophilia.

To evaluate the inter-observer reliability of radiological assessment systems for haemophilic arthropathy, three senior orthopaedic surgeons with expertise in haemophilia independently evaluated a total of 527 joint radiographs of adult haemophilia patients, without any knowledge of the clinical data. This study was the largest study to evaluate the reliability of radiological assessment systems. As for the results, the Arnold-Hilgartner staging system showed moderate reliability (kappa value: κ = 0.44, P = 0.000), and the De Palma grading system and the Pettersson scoring system showed fair reliability (κ = 0.40, P = 0.000) and slight reliability (κ = 0.12, P = 0.000) respectively. As for the reliability of the eight findings in the Pettersson scoring system, three findings, which were 'narrowing of joint space' (κ = 0.70 P = 0.000), 'irregular subchondral surface' (κ = 0.58, P = 0.000) and 'erosion of joint margins' (κ = 0.56, P = 0.000), showed substantial or moderate reliability. Other findings showed fair or less reliability. The traditional radiological assessment systems showed poor inter-observer reliability. Both progressive scales showed higher reliability than the additive scale, and the three findings in the Pettersson scoring system showed good reliability. These results suggested that the progressive scale, including the three reliable radiological findings, might be a more reliable radiological assessment system.

Novel and recurrent TRPV4 mutations and their association with distinct phenotypes within the TRPV4 dysplasia family.

BACKGROUND: Mutations in TRPV4, a gene that encodes a Ca(2+) permeable non-selective cation channel, have recently been found in a spectrum of skeletal dysplasias that includes brachyolmia, spondylometaphyseal dysplasia, Kozlowski type (SMDK) and metatropic dysplasia (MD). Only a total of seven missense mutations were detected, however. The full spectrum of TRPV4 mutations and their phenotypes remained unclear. OBJECTIVES AND METHODS: To examine TRPV4 mutation spectrum and phenotype-genotype association, we searched for TRPV4 mutations by PCR-direct sequencing from genomic DNA in 22 MD and 20 SMDK probands. RESULTS: TRPV4 mutations were found in all but one MD subject. In total, 19 different heterozygous mutations were identified in 41 subjects; two were recurrent and 17 were novel. In MD, a recurrent P799L mutation was identified in nine subjects, as well as 10 novel mutations including F471del, the first deletion mutation of TRPV4. In SMDK, a recurrent R594H mutation was identified in 12 subjects and seven novel mutations. An association between the position of mutations and the disease phenotype was also observed. Thus, P799 in exon 15 is a hot codon for MD mutations, as four different amino acid substitutions have been observed at this codon; while R594 in exon 11 is a hotspot for SMDK mutations. CONCLUSION: The TRPV4 mutation spectrum in MD and SMDK, which showed genotype-phenotype correlation and potential functional significance of mutations that are non-randomly distributed over the gene, was presented in this study. The results would help diagnostic laboratories establish efficient screening strategies for genetic diagnosis of the TRPV4 dysplasia family diseases.

A simple and safe technique for performing single-port laparoscopic resection of appendiceal mucocele.

We report a new method of performing single-port laparoscopic surgery for appendiceal mucocele. The key points of our technique are placing a 3/4 circumferential skin incision with multiple radial splits on the confine of the umbilicus, use of a "home-made" multichannel port system, and trimming the skin incision straight through the confine of the umbilicus at the time of wound closure. A 65-year-old woman with appendiceal mucocele, 80 mm in diameter, successfully underwent ileocecal resection by this procedure. She remains in good health without any wound complications 8 months postoperatively.

Curative colectomy via minilaparotomy approach without utilizing specific instruments.

BACKGROUND: This study evaluated the need for specific instruments when performing a curative resection of colon cancer via a minilaparotomy approach, which has been reported to be a minimally invasive alternative to a laparoscopic approach. METHODS: The feasibility, safety, and early oncological outcome were compared among 73 patients (first group), in whom a curative resection of colon cancer was performed via a minilaparotomy (skin incision < or =7 cm) utilizing specific instruments (North-bridge retractor system) between September 2002 and March 2005, and 94 patients (second group), in whom a similar procedure was performed without utilizing specific instruments between April 2005 and October 2007. RESULTS: The two groups did not differ significantly in terms of age, sex, body mass index, site of tumor, level of lymph node dissection, blood loss, UICC stage, number of harvested lymph nodes, incidence of postoperative complications, length of postoperative hospital days, or overall survival, although the frequency of prior abdominal surgery was higher (38.3 vs. 21.9%; P = 0.03) and the median operating time required for a standard lymph node dissection was shorter (120 vs. 135 min; P = 0.03) in the second group. CONCLUSION: With improved techniques and experience, specific instruments are not necessary for the performance of a curative colectomy via a minilaparotomy approach.

Resection of stage 0/I colon cancer via a circumferential periumbilical skin incision: relevance to single-incision laparoscopic surgery.

BACKGROUND: We have been performing curative resection of colon cancer via a minilaparotomy without utilizing any laparoscopic instruments as an alternative to laparoscopic-assisted approach. Based on our experiences and improved surgical techniques, we have devised a new method for performing resection of stage 0/I colon cancer via a circumferential periumbilical skin incision that is associated with better cosmesis than standard minilaparotomy. METHODS: The short- and long-term results of curative colectomy via a circumferential periumbilical skin incision without utilizing any laparoscopic instruments performed in selected patients with stage 0/I colon cancer between October 2003 and July 2004 were analyzed. RESULTS: There were 8 men and 2 women with a median age of 66.5 years (range 61-77 years). Their median body mass index was 22.4 kg/m(2) (range 21.1-27.7 kg/m(2)). Pathological stage according the TNM classification was stage 0 in 4 patients and stage I in 6 patients. Median operative time was 160.5 min (range 135-203 min), and median blood loss was 60 ml (range 5-330 ml). Postoperative complications consisted of seroma in two patients and small bowel obstruction in one patient. After a median follow-up period of 5.7 years, there were no recurrences or wound complications. CONCLUSION: Curative colectomy via a circumferential periumbilical skin incision seems oncologically safe, yields satisfactory cosmetic results, and may provide an alternative to single-incision laparoscopic surgery in selected patients with colon cancer.

Predicting delayed pressure ulcer healing using thermography: a prospective cohort study.

OBJECTIVE: To investigate whether thermography can be used to detect latent inflammation in pressure ulcers and predict pressure ulcer prognosis in a clinical setting. METHOD: For this cohort study, we recruited 35 patients with stage II-IV pressure ulcers on the torso, who underwent thermographic assessment on discovery of their pressure ulcer. The patients were followed up for at least 3 weeks. Thermography was performed immediately after dressing removal. Pressure ulcers were classified into two groups depending on whether or not the wound site temperature was lower or higher than the periwound skin: the low temperature group and the high temperature group respectively. A generalised estimation equation was used to estimate the relative risk of delayed healing of pressure ulcers, comparing wounds with high temperatures and low temperatures. RESULTS: Of the 35 patients, 21 had 'low temperature' wounds and 14 had 'high temperature' wounds at baseline. Two patients in the high temperature group presented with overt infection, and were excluded from further analysis. Twenty-two pressure ulcers were considered to heal 'normally' (that is, the wound area reduced by 30% or more within 3 weeks) and 16 did not heal. The baseline DESIGN score (a measure of gross wound status) did not differ in any subscales between the high and low temperature groups. The relative risk for delayed healing in high temperature cases was 2.25 (95% confidence intervals; 1.13-4.47, p=0.021). Sensitivity was 0.56, specificity was 0.82, positive predictive value was 0.75, and negative predictive value was 0.67. CONCLUSION: Our results indicate that using thermography to classify pressure ulcers according to temperature could be a useful predictor of healing at 3 weeks, even though wound appearances may not differ at the point of thermographical assessment. The higher temperature in the wound site, when compared with periwound skin, may imply the presence of critical colonisation, or other factors which disturb the wound healing.

Restoration of membrane excitability in a behavioral mutant of Paramecium caudatum during conjugation and by microinjection of wild-type cytoplasm.

When cells of the behavioral mutant cnrC of Paramecium caudatum were mated with the wild type, phenotype change from CNR (no backward swinning) to wild type in the cnrC mate occurred immediately after the formation of tight pairs. No change of phenotype occurred when cells of cnrA or cnrB were mated with wild type. Phenotypic change from CNR to wild type in cells of cnrC was also induced by microinjection of wild-type cytoplasm. Microinjection of wild-type cytoplasm induced no change in cells of cnrA or cnrB. Phenotypic change in the cnrC mate during conjugation can be explained by cytoplasmic exchange during conjugation, though transfer of membrane sites for excitability through membrane fluidity cannot be ruled out.

Intra- and interspecific complementation of membrane-inexcitable mutants of Paramecium.

Membrane excitation was the basis for backward swimming of Paramecium facing stimulus. According to standard genetic tests, inexcitable mutants fell into three complementation groups for both Paramecium tetraurelia (pwA, pwB, and pwC) and Paramecium caudatum (cnrA, cnrB, and cnrC). Cytoplasm from a wild type transferred to a mutant through microinjection restored the excitability. Transfusions between genetically defined complementation groups of the same species effected curing, whereas transfusions between different mutants (alleles) of the same group or between sister cells of the same mutant clone did not. Cytoplasmic transfers of all combinations among the six groups of mutants of the two species showed that any cytoplasm, except those from the same group, was able to cure. Since the pawns and the caudatum nonreversals complement one another through transfusion, they appeared to belong to six different complementation groups. The extent of curing, the amount of transfer needed to cure, and the time course of curing were characteristic of the group that received the transfusion. Variations in these parameters further suggested that the six groups represented six different genes. Because the donor cytoplasms from either species were equally effective quantitatively in curing a given mutant, the curing factors were not species specific. These factors are discussed.

Microinjection of cytoplasm as a test of complementation in Paramecium.

Mutants in Paramecium tetraurelia, unable to generate action potentials, have been isolated as cells which show no backward swimming in response to ionic stimulation. These "pawn" mutants belong to at least three complementation groups designated pwA, pwB, and pwC. We have found that microinjection of cytoplasm from a wild-type donor into a pawn recipient of any of the three complementation groups restores the ability of the pawn to generate action potentials and hence swim backward. In addition, the cytoplasm from a pawn cannot restore a recipient of the same complementation group, but that from a pawn of a different group can. Electrophysiological analysis had demonstrated that the restoration of backward swimming is not due to a simple addition of ions but represents a profound change in the excitable membrane of the recipient pawn cells. Using known pawn mutants and those which had previously been unclassified, we have been able to establish a perfect concordance of genetic complementation and complementation by cytoplasmic transfer through microinjection. This method has been used to classify pawn mutants that are sterile or hard-to-mate and to examine the ability of cytoplasms from different species of ciliated protozoa to restore the ability to swim backward in the pawn mutants of P. tetraurelia. A cell homogenate has also been fractionated by centrifugation to further purify the active components. These results demonstrate that transfer of cytoplasm between cells by microinjection can be a valid and systematic method to classify mutants. This test is simpler to perform than the genetic complementation test and can be used under favorable conditions in mutants that are sterile and in cells of different species.