Effect of goal-directed haemodynamic therapy in free flap reconstruction for head and neck cancer.

BACKGROUND: In free flap reconstruction for head and neck cancer, achieving a haemodynamic target using excessive fluid infusion is associated with decreased flap survival rates and extended hospital stays. We hypothesized that goal-directed haemodynamic therapy would improve flap survival rates and shorten hospitalization periods. METHODS: Patients scheduled for free flap reconstruction were randomly assigned to a goal-directed haemodynamic therapy group (n = 31) or a conventional haemodynamic therapy control group (n = 31). The control group received extra bolus fluid and ephedrine or norepinephrine to maintain a mean arterial pressure ≥ 65 mmHg. The goal-directed haemodynamic therapy group received a colloid solution as the extra bolus fluid to maintain a stroke volume variation < 12%; dobutamine, ephedrine, or norepinephrine was administered to maintain a cardiac index ≥ 2.5 l/min/m2 and mean arterial pressure ≥ 65 mmHg. Enhanced recovery after surgery protocols were not used except for fluid therapy. An otolaryngologist blinded to group assignments assessed flap outcomes and classified them as 'survival,' 'at risk' or 'failure.' RESULTS: The hospitalization period was not significantly different between the groups. The goal-directed haemodynamic therapy group had significantly shorter intensive care unit stays and a higher flap survival rate. The crystalloid volume was significantly lower in goal-directed haemodynamic therapy group. Reoperation rates, post-operative complications, and laboratory data including inflammatory markers were similar between the groups. CONCLUSION: Compared to conventional haemodynamic therapy, goal-directed haemodynamic therapy does not reduce hospitalization periods; it may, however, reduce the length of intensive care unit stays and increase flap survival rates. Further studies including multi-centre trials with larger sample sizes are warranted.

Preoperative imaging evaluation of head and neck cancer: comparison of 2D spin-echo and 3D THRIVE MRI techniques with resected tumours.

AIM: To evaluate the usefulness of contrast-enhanced three-dimensional (3D) T1-weighted high-resolution isotropic volume examination (THRIVE) for the preoperative assessment of head and neck cancer, by comparison with spin-echo (SE) T1-weighted sequences and the pathology specimen. MATERIALS AND METHODS: Thirty-seven consecutive patients who were diagnosed with oral cavity, oropharyngeal, and hypopharyngeal cancer and received surgical excision with preoperative magnetic resonance imaging (MRI) using both SE and 3D THRIVE sequences after gadolinium injection were studied. Tumour conspicuity, motion- and flow-related artefacts were evaluated, and the tumour size was measured based on both sequences, which were correlated with the surgical specimen. The population correlation coefficient (r(g)(2)) and Bland-Altman plots were used to assess measurement agreement. RESULTS: There was no statistical difference between SE and THRIVE in terms of tumour conspicuity and motion-related artefacts, however, flow-related artefacts significantly decreased with THRIVE. The measurement agreement of tumour size estimated on both SE and THRIVE was good (r(g)(2) = 0.87 for SE and 0.93 for THRIVE), and the difference was statistically significant. CONCLUSION: The 3D THRIVE sequence provided satisfactory image quality for the accurate measurement of tumour size with fewer artefacts and could be an acceptable alternative for SE T1-weighted images for preoperative staging in patients with head and neck cancer.

Prognostic significance of lymphovascular invasion in patients with salivary duct cell carcinoma of the head and neck.

The purpose of this study was to evaluate the treatment outcomes of patients who underwent surgery with curative intention after the diagnosis of salivary duct cell carcinoma (SDC) in the head and neck area and to analyse the prognostic factors and treatment failure pattern. Fifty-nine patients treated between March 2003 and December 2018 were enrolled in the study. The mean follow-up period was 45.5 months (range 12-189 months). The 5-year overall survival rate was 54.7% and the 5-year disease-free survival rate was 56.8%. Nineteen recurrences occurred during the study period: four loco-regional recurrences and 15 distant metastases. During the study period, 10 patients died of disease relapse and 5 patients died of other medical caused. On univariate analysis, lymphovascular invasion (LVI) (P=0.031) showed the most significant correlation with mortality. On multivariate Cox regression analysis, LVI showed the most significant correlation with patient survival (P = 0.027). LVI was the most significant prognostic factor related to the 5-year overall survival rate of SDC patients. The development of novel therapeutic agents is necessary to improve the survival rate of these patients with LVI.

Central lymph node metastases in unilateral papillary thyroid microcarcinoma.

BACKGROUND: The indications for and appropriate extent of prophylactic central lymph node (CLN) dissection for clinically node-negative patients with unilateral papillary thyroid microcarcinoma (PTMC) are unknown. METHODS: The frequency, patterns and predictive factors for CLN metastases in 86 patients with unilateral PTMC and a clinically node-negative neck were analysed with respect to age and sex; metastasis, age, completeness, invasiveness, size (MACIS) score; tumour size; number and location of tumours; presence of ipsilateral CLN metastases; and presence of lymphovascular or capsular invasion. All patients underwent total thyroidectomy and CLN dissection. RESULTS: Twenty-seven (31 per cent) of 86 patients had metastatic CLNs: 18 ipsilateral and nine bilateral. Univariable analysis suggested male sex and tumour size greater than 0.5 cm to be significant factors in predicting ipsilateral CLN metastases. Only ipsilateral nodal positivity was a significant predictor of contralateral CLN metastases in multivariable analysis (P = 0.007). CONCLUSION: CLN metastases are relatively common in PTMC.

Endoscopic thyroidectomy via a unilateral axillo-breast approach without gas insufflation for unilateral benign thyroid lesions.

BACKGROUND: The usefulness of various endoscopic thyroid surgery techniques has been reviewed. Recently, the authors developed a unilateral axillo-breast approach for endoscopic hemithyroidectomy to minimize the visible scar in a natural position and to overcome the limitation of instrumentation. The feasibility and safety of endoscopic thyroid surgery was examined via a novel approach without gas insufflation. METHODS: This study enrolled 52 consecutive patients undergoing endoscopic hemithyroidectomy via a unilateral axillo-breast approach without gas insufflation. A skin incision parallel to the skin crease was made in the axillary fossa for insertion of a 10-mm 30 degrees rigid endoscope and endoscopic instruments. To create a working space, an external retractor was inserted through the skin incision in the axilla and raised using a lifting device. A second 1.0-cm skin incision was made along the upper margin of the mammary areola on the tumor side for insertion of a 12-mm trocar. RESULTS: Postoperative pathology showed 11 follicular adenomas, 1 follicular carcinoma, and 40 benign thyroid lesions. The operating time for the first 10 hemithyroidectomies was 154 +/- 64.88 min, which was 34.77 min longer than for the last 42 hemithyroidectomies (119.23 +/- 31.47 min; p = 0.1314). The amount of postoperative drainage was 236.63 +/- 118.67 ml, and the duration of drainage was 4.54 +/- 1.42 days. The postoperative hospital stay was 6.37 +/- 2.83 days. Overall, seven patients (7/52, 13.5%) experienced perioperative complications, including one transient recurrent laryngeal nerve palsy (1.9%), five seromas (9.6%), and one hematoma (1.9%), which arose from a subplatysmal skin flap. CONCLUSION: Although the aspect of invasiveness could be improved, endoscopic hemithyroidectomy via a unilateral axillo-breast approach without gas insufflation is safe and effective and appears to provide better cosmetic results and a shorter operation time than other endoscopic methods for managing selective unilateral benign thyroid lesions.

Collision metastasis of squamous carcinoma of the oral tongue and incidental thyroid papillary carcinoma to a single cervical lymph node.

The incidence of collision tumor is exceedingly rare. There are only four published case reports. This is the first report of a case of collision metastasis of squamous cell carcinoma (SCC) of the oral tongue and incidental thyroid papillary carcinoma to the same cervical lymph node. A 47-year-old man with SCC of the oral tongue at clinical stage T4N1M0 was treated with total glossectomy and bilateral neck dissection. During neck dissection, concomitant secondary foci of thyroid papillary carcinoma were identified in the same cervical lymph node as SCC (collisional metastasis). The patient subsequently underwent total thyroidectomy and was alive without any recurrences at 25 months after the operation.

Combined surgery and postoperative radiotherapy for oropharyngeal squamous cell carcinoma in Korea: analysis of 110 cases.

The treatment of oropharyngeal squamous cell carcinoma (OSCC) remains controversial. This study reviews the authors' experience of treating OSCC, evaluates the oncologic outcome and assesses the factors affecting local/regional recurrence. A retrospective analysis of 110 consecutive OSCC patients treated primarily by surgery and/or postoperative radiotherapy was carried out. 82% of patients had advanced disease (stage III or IV). The 5-year overall survival and disease specific survival rates (DSSR) were 58% and 65%, respectively. The DSSR of the soft palate or posterior pharyngeal wall, tonsillar area, and base of tongue were 80%, 62%, and 51%, respectively (P<0.05). The 5-year DSSR according to the American Joint Committee on Cancer stages was 94% for early stage and 56% for advanced stage (P<0.05). The overall recurrence rate was 38% (42 patients). The most frequent site of recurrence was the neck (46%). Only 14% of patients with recurrences were treated successfully. Positive resection margins and the presence of pathologic lymph nodes influenced the recurrence at the primary lesion and in the neck, respectively, in a statistically significant manner. Surgery and postoperative radiotherapy provided a superior outcome in patients with advanced OSCC. A randomized study is required to assess the oncologic and functional superiority of surgery or chemoradiation.

Unilateral, clinically T2N0, squamous cell carcinoma of the tongue: surgical outcome analysis.

To determine the survival rate and analyse the predicting factors of recurrence in patients with unilateral, clinically T2N0 squamous cell carcinoma (SCC) of the tongue which does not cross the midline, a retrospective analysis of 32 such consecutive, previously untreated, cases was performed. All patients were initially treated by surgery between January 1992 and May 2004. All patients had neck dissections: 12 continuous, 20 discontinuous, 24 bilateral and 8 unilateral. Fourteen patients (44%) received adjunctive postoperative radiotherapy. Occult metastatic rates were 34% and 4% in ipsilateral and contralateral neck, respectively. Patients with pN0 cancer had a better 5-year disease-specific survival rate than those with pN+ cancer (85% versus 41%, P=0.005). Twelve patients (38%) had recurrences after the initial treatment. The recurrence rate was significantly higher in patients with pathologic nodal metastasis, peroral resection of the primary tumour or discontinuous neck dissection. The results suggest that the most effective surgical methods for treating unilateral T2N0 SCC of the tongue which does not cross the midline are: pull-through approach for primary lesion instead of peroral approach; continuous rather than discontinuous neck dissection and ipsilateral elective rather than bilateral routine elective neck dissection.

Feasibility of robot-assisted neck dissection followed by transoral robotic surgery.

Our aim was to evaluate the feasibility of robot-assisted neck dissection (RAND) followed by transoral robotic surgery (TORS) in treatment of cancers of the head and neck, which is expected to improve cosmesis and function. We studied 37 patients with biopsy-confirmed cNO or cN+ tumours of the oropharynx (n=22), hypopharynx (n=8), larynx (n=6), and oral cavity (n=1) who were treated by RAND then TORS from May 2010 to December 2012. Patients' characteristics and clinical details were recorded, together with operative complications and functional variables such as management of the airway and nasogastric or enterogastric feeding. All endoscopic TORS and RAND were successful, with no serious intraoperative complications or need to convert to open operation. All patients were satisfied with the cosmesis according to the answers given to a questionnaire. RAND followed by TORS in some cancers of the head and neck are feasible and showed a clear cosmetic benefit, although the longer operating time is a drawback. Studies of more patients with longer follow-up are required to evaluate long-term oncological and functional outcomes in more detail.

Differential effects of annexins I, II, III, and V on cytosolic phospholipase A2 activity: specific interaction model.

Annexins (ANXs) are a family of proteins with calcium-dependent phospholipid binding properties. Although inhibition of phospholipase A2 (PLA2) by ANX-I has been reported, the mechanism is still controversial. Previously we proposed a 'specific interaction' model for the mechanism of cytosolic PLA2 (cPLA2) inhibition by ANX-I [Kim et al., FEBS Lett. 343 (1994) 251-255]. Here we have studied the cPLA2 inhibition mechanism using ANX-I, N-terminally deleted ANX-I (DeltaANX-I), ANX-II, ANX-II(2)P11(2), ANX-III, and ANX-V. Under the conditions for the specific interaction model, ANX-I, DeltaANX-I, and ANX-II(2)P11(2) inhibited cPLA2, whereas inhibition by ANX-II and ANX-III was negligible. Inhibition by ANX-V was much smaller than that by ANX-I. The protein-protein interactions between cPLA2 and ANX-I, DeltaANX-I, and ANX-II(2)P11(2) were verified by immunoprecipitation. We can therefore conclude that inhibition of cPLA2 by specific interaction is not a general function of all ANXs, and is rather a specific function of ANX-I. The results are consistent with the specific interaction model.

Inhibition ELISA for hepatitis B surface antigen (HBsAg) using monoclonal idiotype-anti-idiotype interaction.

Monoclonal anti-idiotypic antibody (Anti-Id) to the common (a) epitope of hepatitis B surface antigen (HBsAg) were raised and used to detect serum HBsAg in an inhibition enzyme-linked immunosorbent assay (inhibition ELISA). HRP-labelled Id 8D-3-6 was reacted with Anti-Id 4-8H coated on the solid phase in the presence of HBsAg. The ability of the antigen to inhibit the binding of labelled Id 8D-3-6 to anti-Id 4-8H was determined and the results correlated well with those obtained by radioimmunoassay. This assay requires only one washing step, takes 2 h and covers the range 10 ng/ml to 1 microgram HBsAg/ml. The inhibition ELISA is a more convenient, rapid and relatively sensitive assay which can be used to measure the level of a wide range of serum HBsAg.

Immunoaffinity purification of hepatitis B surface antigen using anti-idiotype as a specific eluent.

An immunoaffinity method for the purification of hepatitis B surface antigen (HBsAg) using monoclonal anti-idiotype (anti-Id) as a specific eluent is described. Ammonium sulfate fractions of HBsAg-containing plasma were absorbed on monoclonal idiotype (Id) immunoadsorbents. The bound material was eluted from the column with the anti-Id of HBsAg. The eluate containing anti-Id was further purified by gel filtration. The procedure yielded highly purified HBsAg. The final HBsAg product was free from contaminating human plasma and mouse ascites proteins. The procedure is generally applicable and particularly attractive when the antigen is unstable under commonly used elution conditions.

Combined chemotherapy and radiation versus radiation alone in the management of localized angiocentric lymphoma of the head and neck.

BACKGROUND AND PURPOSE: To clarify the clinical benefit derived from the combined modality therapy (CMT) comprised of chemotherapy and involved-field radiotherapy (XRT) for stage I and II angiocentric lymphomas of the head and neck. MATERIAL AND METHODS: Of 143 patients with angiocentric lymphoma of the head and neck treated at the Yonsei Cancer Center between 1976 and 1995, 104 patients (XRT group) received involved-field XRT alone with a median dose of 50.4 Gy (range: 20-70 Gy), while 39 patients (CMT group) received a median three cycles (range: 1-6 cycles) of chemotherapy before starting involved-field XRT. The response rate, patterns of failure, complications, and survival data of the XRT group were compared with those of the CMT group. RESULTS: Despite a higher response rate, local failure was the most common pattern of failure in patients of the both groups. The patterns of failure, including the systemic relapse rate were not influenced by the addition of combination chemotherapy. Although both modalities were well tolerated by the majority of patients, aberrant immunologic disorders or medical illnesses, such as a hemophagocytic syndrome, sepsis, intractable hemorrhage, or the evolution of second primary malignancies were more frequently observed in patients of the CMT group. The prognosis of patients in the XRT group was relatively poor, with a 5-year overall actuarial survival rate of 38% and disease-free survival rate of 32%, respectively. However, their clinical outcome was not altered by the addition of systemic chemotherapy. Achieving complete remission was the most important prognostic factor on univariate and multivariate analyses, but treatment modality was not found to be a prognostic variable influencing survival. CONCLUSIONS: Involved-field XRT alone for angiocentric lymphoma of the head and neck was insufficient to achieve an improved survival rate, but the combination of chemotherapy and involved-field XRT failed to demonstrate any therapeutic advantage over involved-field XRT alone.

Perivascular-submandibular lymph node metastasis in squamous cell carcinoma of the tongue and floor of mouth.

AIMS: The goal of this study was to investigate the incidence of occult metastasis in perivascular lymph node and nodal recurrence in these nodal pads in squamous cell carcinoma (SCC) of the tongue and floor of mouth. METHODS: We performed a prospective analysis of the incidence of an occult metastasis in the perivascular lymph nodes in 55 patients (41 with an oral tongue carcinoma and 14 with a mouth floor carcinoma) who underwent an elective supraomohyoid neck dissection (SOHND) for SCC of the tongue and floor of mouth, from 1997 to 2002. 99 SOHND procedures were performed as follows: 72 in tongue carcinomas and 27 in the mouth floor carcinomas. RESULT: Clinically occult, but pathologically positive perivascular lymph nodes occurred in four of 72 of the tongue carcinomas and two of 27 of the mouth floor carcinomas. The incidence of the regional recurrence at level I was three of 45. CONCLUSIONS: This preliminary report reveals a small incidence of perivascular lymph-node metastases and the infrequent nodal recurrence in this area after SOHND in early-staged tongue and floor of mouth SCC.

Mycelial protoplast isolation and regeneration of Lentinus lepideus.

Generation of fungal protoplast is essential for fusion and transformation systems. Protoplast fusion offers great potential for the improvement of industrially important microorganisms. To establish conditions for the protoplast isolation and regeneration of the mycelia of Lentinus lepideus, various enzymes and osmotic stabilizers were examined. To investigate suitable medium for the culture of L. lepideus, the mycelia were grown in ten different media at 28 degrees C for 10 days. Among them potato dextrose agar (PDA) medium was found to be the best for colony growth. When Novozym 234, cellulase and beta-glucuronidase were added to the mycelia in combination or alone, Novozym 234 alone at the concentration of 10 mg/ml was the most effective for the protoplast yield. Purified spherical protoplasts of the mycelia were osmotically hypersensitive and further incubation of the mycelia with the lytic enzyme resulted in the older parts of the hyphae swollen. When we applied various osmotic stabilizers at the fixed concentration of 0.6 M on the protoplasts, the yields of protoplasts were increased until 4-hr incubation. However application of sucrose or MgSO4 led to further protection of protoplasts after that time and reached a plateau on 5- and 7-hr incubations, respectively. The suitable incubation time and optimal pH with the lytic enzyme for the maximum release of protoplasts were 6 hrs of incubation and pH 5, respectively. When we examined various osmotic stabilizers for the regeneration of the protoplast, the complete medium containing 0.6 M sucrose induced highest hyphal growth with regeneration frequency of 3.28%.

Neoadjuvant chemotherapy and radiation for inoperable carcinoma of the maxillary antrum: a matched-control study.

A matched-control study comparing standard radiotherapy versus neoadjuvant chemotherapy and radiation was undertaken to clarify the effects of neoadjuvant systemic chemotherapy for locally advanced squamous cell carcinoma of the maxillary antrum. Thirty-four patients with inoperable maxillary cancer were treated with neoadjuvant chemotherapy and radiotherapy (Group II). Before starting radiotherapy, all patients in Group II received two or three cycles of neoadjuvant chemotherapy consisting of cisplatin and a 5-day continuous infusion of 5-fluorouracil with or without intravenous injection of vinblastine. Radiation doses ranged from 66 Gy to 75 Gy (median, 70 Gy). The response rate, patterns of failure, toxicity, and survival for Group II were compared with those for 34 stage-matched patients treated with radiation alone (Group I). Despite a higher response rate to neoadjuvant chemotherapy, the recurrence rate and patterns of treatment failure were not influenced by the addition of neoadjuvant chemotherapy. In most cases, neoadjuvant chemotherapy did not interfere with subsequent radiotherapy, and radiation-induced late complications occurred equally in both treatment groups. After a median follow-up of 48 months, there was no significant difference in 5-year actuarial survival or disease-free survival between the two treatment groups. Radiation alone for inoperable maxillary cancer was clearly suboptimal for improving local control and survival rate, but neoadjuvant chemotherapy in addition to standard radiotherapy failed to demonstrate any therapeutic advantage over radiation alone.

Inhibition of DNA synthesis in murine tumor cells by geldanamycin, an antibiotic of the benzoquinoid ansamycin group.

The mechanism of action of geldanamycin, a benzoquinoid ansamycin, was investigated with murine lymphoblastoma L5178Y cells. The agent inhibited the cell growth at concentrations over 0.01 micrograms/ml. The antibiotic blocked DNA synthesis more markedly than RNA and protein syntheses. Mitosis was not significantly affected by the drug in the cells synchronized with demecolcine (Colcemid). The antibiotic did not interfere with in vitro assembly of tubulin. In the synchronized cells, strong inhibition of DNA synthesis was observed when geldanamycin was introduced into the culture prior to S phase of the cell cycle. The degree of inhibition was stronger with prolongation of incubation period and with increase of DNA synthesis rate. The results suggested that initiation of DNA synthesis or S phase is affected by the drug. DNA degradation was not significantly induced in vivo by the antibiotic. Geldanamycin blocked DNA polymerase alpha more markedly than beta and gamma. The degree of inhibition depended up on concentrations of enzyme but not upon those of template, suggesting a drug-enzyme interaction. IC50 for DNA polymerase alpha was 10 micrograms/ml and for DNA polymerase beta 100 micrograms/ml at low concentrations of enzyme. The inhibition of DNA polymerase alpha by the antibiotic was non-competitive and Ki was 20 microM.

In vivo and in vitro cross-resistance of kanamycin-resistant mutants of E. coli to other aminoglycoside antibiotics.

Cross resistance of kanamycin-resistant mutants of E. coli Q13 to other aminoglycosides (streptomycin, neomycin, gentamicin and dibekacin) was demonstrated in vivo (growth) and in vitro (polyphenylalanine synthesis, codon misreading and translocation on the ribosomes). Kanamycin-resistant mutants, R1-4, R2-1, R2-2, R3-3 and R3-5 showed various degrees of cross-resistance to streptomycin, gentamicin, neomycin and dibekacin in vivo. In vitro, polyphenylalanine synthesis was more resistant to kanamycin, streptomycin, neomycin and gentamicin on the ribosomes of the kanamycin-resistant mutants than on those of the parental strain. In the presence of kanamycin, neomycin or gentamicin, less degrees of [14C]isoleucine uptake with poly[U] (codon misreading) were observed on the ribosomes obtained from the resistant mutants than on the sensitive cell ribosomes. The N-acetyl-[14C]phenylalanyl-puromycin synthesis enhanced by an elongation factor, EF-G and GTP (translocation) was more resistant to kanamycin and dibekacin on the mutant ribosomes than on the parental ribosomes. The results indicate that the cross-resistance to other aminoglycoside antibiotics, as well as the kanamycin resistance, are attributed to mutational alterations of the ribosomes in these mutants.