Videofluorographic Analysis of Swallowing Function after Total Glossolaryngectomy.

SUMMARY: Surgeons have traditionally believed that swallowing is mainly dependent on gravity after total glossolaryngectomy. However, swallowing function after total glossolaryngectomy varies widely among patients, and a thorough analysis is lacking. The authors aimed to clarify the swallowing function after total glossolaryngectomy and determine whether it is primarily dependent on gravity. The authors retrospectively analyzed videofluorographic examinations of patients who underwent total glossolaryngectomy and free or pedicle flap reconstruction. The authors enrolled 20 patients (12 male; mean age, 61 years; age range, 43 to 89 years). All patients demonstrated constriction of the reconstructed pharynx to some degree, and no patient's ability to swallow was dependent on gravity alone. Videofluorography showed excellent barium clearance in eight patients and poor clearance in 12. All patients with excellent clearance showed strong constriction of the posterior pharyngeal wall, whereas only 8.3 percent of the patients with poor clearance showed adequate constriction, which was significantly different ( p = 0.0007). Velopharyngeal closure and lip closure also contributed significantly to excellent clearance ( p = 0.041). The shape of the reconstructed pharynx (depressed, flat, protuberant) showed no statistically significant association with excellent clearance. Contrary to previous understanding, constriction of the remnant posterior pharyngeal wall played an important role in swallowing after total glossolaryngectomy, and gravity played a secondary role. Dynamic posterior pharyngeal wall movement might result from the increased power of the pharyngeal constrictor muscle and compensate for the immobility of the transferred flap. A well-functioning pharyngeal constrictor muscle and complete velopharyngeal and lip closures can contribute to excellent barium clearance in patients after total glossolaryngectomy. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

[A case of granulocyte-colony stimulating factor-producing gallbladder adenosquamous carcinoma with rapidly-growing recurrence of liver metastasis in early postoperative period].

An 82-year-old male with a gallbladder mass was diagnosed with gallbladder carcinoma through various examinations. Cholecystectomy, gallbladder bed resection, and lymph node dissection were performed. The histological examination revealed a gallbladder adenosquamous carcinoma, and this tumor showed positive staining for granulocyte-colony stimulating factor (G-CSF). Recurrence of multiple liver metastases was detected on 25th day postoperatively. Unfortunately, the patient died on 97th day postoperatively. Here, we report a case of G-CSF-producing adenosquamous carcinoma of the gallbladder with rapid recurrence of liver metastases in the early postoperative period.

A patient with cystic duct remnant calculus treated by laparoscopic surgery combined with near-infrared fluorescence cholangiography.

BACKGROUND: The recurrence of symptoms present before cholecystectomy may be caused by a cystic duct remnant. The resolution of cystic duct remnant syndrome may require surgical resection, but identification of the duct remnant during laparoscopic surgery may be difficult because of adhesions following the previous procedure. Open surgery, which is more invasive than laparoscopic surgery, is frequently chosen to avoid bile duct injury. CASE PRESENTATION: The patient was a 24-year-old woman with previous laparoscopic cholecystectomy for chronic cholecystitis and repeated attacks of biliary colic. The postoperative course was uneventful, but computed tomography revealed a remnant cystic duct calculus. Ten months after surgery, the patient returned to our department for right hypochondriac pain. Laparoscopic remnant cystic duct resection was performed with intraoperative near-infrared (NIR) fluorescence cholangiography to visualize the common bile duct and remnant cystic duct. The postoperative course was uneventful and the patient was discharged on day 3 after surgery. At the 6-month follow-up, she had no recurrence of pain. CONCLUSION: Laparoscopic surgery with NIR cholangiography is a safe and effective alternative for the removal of a cystic duct remnant calculus after cholecystectomy.

Utility of negative-pressure wound therapy for orocutaneous and pharyngocutaneous fistula following head and neck surgery.

BACKGROUND: Because of the difficulty of airtight sealing and risk of salivary contamination, negative-pressure wound therapy (NPWT) has rarely been applied for postoperative fistula following head and neck surgery; thus, its utility remains unclear. METHODS: We applied NPWT in 34 patients who developed orocutaneous and pharyngocutaneous fistula after head and neck surgery. Here we retrospectively analyzed the utility of NPWT for managing those fistulas. RESULTS: Thirty-two patients (94.1%) underwent NPWT as scheduled without adverse events. In 28 patients (82.4%), fistula closure was completed only by NPWT, and the mean period to fistula closure was 30.4 days. The mean period to closure did not differ significantly between fistulas with (21.7 days) and without (39.1 days) previous irradiation. CONCLUSIONS: Airtight sealing can be maintained and postoperative fistula can be closed by NPWT with a high success rate, even after previous irradiation. NPWT is an effective and minimally invasive treatment for postoperative fistula.

Larynx-preserving reconstruction after extended base of the tongue resection.

BACKGROUND: As the base of the tongue (BOT) plays essential roles in speech and swallowing, surgical resection of BOT cancer is typically avoided. Moreover, standard reconstructive procedures for larynx-preserving BOT defects have not yet been established. We performed immediate flap reconstruction after wide resection of BOT cancer with laryngeal preservation. Herein, the functional and oncological results of our strategy were analysed. METHODS: We retrospectively evaluated patients who underwent extended BOT resection (including the oral tongue, upper/lateral oropharyngeal wall, epiglottis and false vocal cord) with laryngeal preservation between April 2006 and April 2016. We classified defects involving the oral tongue or upper/lateral oropharyngeal wall as the lateral extension type and those involving the epiglottis or false vocal cord as the laryngeal extension type. Lateral extension-type defects were closed primarily and filled with a deepithelialised skin or muscle flap. Laryngeal extension-type defects were reconstructed using a bulky skin flap plus hyo-thyroid-pexy to create a neo-epiglottis. Postoperative functional and oncologic outcomes were assessed. RESULTS: We enrolled 18 patients with extended BOT defects. Of them, 11 had a history of irradiation. The tracheal cannula was removed in all cases, although laryngeal extension defects were associated with a longer duration to removal. All patients achieved complete oral intake and retained intelligible speech, with preservation of laryngeal function. There was no local recurrence, and the 5-year overall survival was 88.9%. CONCLUSIONS: Following wide BOT resection, reconstruction with laryngeal preservation is feasible even in cases involving irradiated tumours with laryngeal extension.

[A Case of Primary Anal Fistula Cancer with Extensive Intrapelvic Spreading That Was Successfully Treated with Bevacizumab plus mFOLFOX6].

The patient was a 68-year-old man who had an anal fistula for>10 years. He was referred to our institution after visiting a local physician with left femoral pain as the main complaint and received a diagnosis of high inflammatory response. We then found discharge of pus in the perianal region during a medical examination. We also found an extensive intrapelvic tumor during a computed tomography(CT)/magnetic resonance imaging examination. In addition, the level ofa tumor marker and inflammatory response were high. To control the inflammation, we performed seton drainage and sigmoid colostomy. On the basis of the pathological findings from the mucus component, we confirmed a diagnosis of fistula cancer. Considering that the progressive lesion had extensively spread, we decided to initiate chemotherapy alone because ofthe absence ofan indication for radiotherapy. We administered bevacizumab plus mFOLFOX6, and partial response was observed on a CT scan. We could control the progression ofthe disease for>6 months. The present case suggests that bevacizumab plus mFOLFOX6 can be an effective regimen for unresectable advanced fistula cancers.

Successful management of recurrent adenoid cystic carcinoma in the deep infratemporal fossa by maxillo-orbito-zygomatic approach.

OBJECTIVE: In the case of deep invasion of an infratemporal fossa (ITF) tumor, surgeons find it difficult to gain sufficient visualization and working space by conventional surgical approaches. To overcome these limitations, we have developed a novel surgical technique, maxillo-orbito-zygomatic (MOZ) approach, by combining partial lateral maxillectomy with the conventional orbito-zygomatic approach. METHODS: A 63-year-old male presented with the fifth recurrent adenoid-cystic carcinoma in the right deep ITF. Using a Weber-Ferguson-type incision and partial dismasking, we elevated the skin and scalp flap, while preserving the facial nerve and orbicularis oculi muscle intact in the flap. Then, we performed MOZ osteotomy using three cut lines, the zygomatic arch, the frontozygomatic suture, and from the inferior orbital fissure to the anterolateral wall of the maxilla. Following this, we temporarily elevated the bone flap by partially opening the lateral maxillary sinus. We obtained an excellent surgical view of the ITF, middle skull base, and pterygopalatine fossa with this technique, which facilitated the safe removal of the tumor. RESULTS: The postoperative course remained almost uneventful, and we obtained favorable cosmetic results. CONCLUSIONS: Our novel MOZ approach could be a robust approach to remove deep ITF tumors.

Invasive myoepithelial carcinoma ex pleomorphic adenoma of the major salivary gland: two case reports.

BACKGROUND: Myoepithelial carcinoma (MEC) is a rare salivary gland tumor. Its long-term prognosis remains unknown because of the paucity of reported cases with long-term follow-up. Although some case series exist, the clinical features of MEC vary considerably depending on the site of origin. Therefore, accumulation of these rare cases is important. CASE PRESENTATION: Case 1: An 89-year-old man presented with a 10-year history of a mass originating from the right parotid gland and involving the neck. The mass grew rapidly for 3 months, reaching approximately 8 cm. There was no facial paralysis. MEC ex pleomorphic adenoma (PA) was suspected. Superficial parotid gland resection was performed in 2013; the tumor grade was pT3N0M0, and the resection margins were free of carcinoma. Because of several high-risk factors for metastasis (i.e., invasive carcinoma ex PA, high MIB1 index, and mutant p53 protein positivity), radiotherapy and chemotherapy were recommended as adjuvant therapy. Although the patient refused adjuvant therapy, he was recurrence-free at 36 months after surgery. Case 2: A 54-year-old woman presented with a >10-year history of a right submandibular mass, which grew rapidly for 1 year, reaching approximately 6 cm. Preoperative diagnosis was PA of the right submandibular gland. Submandibular gland resection was performed in 2013. Pathological analysis revealed invasive MEC ex PA, pT3N0M0; in addition, the carcinoma portion had an extra capsule and had invaded the platysma muscle close to the margin. An MIB1 index of 40 % and mutant p53 protein positivity indicated a high risk for metastasis. Additional resection and right neck dissection revealed no residual carcinoma. The patient refused adjuvant chemotherapy. One year after surgery, metastasis to the right pulmonary hilar node and both lungs were detected. Chemotherapy prevented recurrent growth of the lesion and extended survival. The patient was alive with cancer 30 months after the first surgery. CONCLUSIONS: High expression of the Ki67 labeling index might reflect prognosis of these cases. Chemotherapy for distant metastasis was effective, as expected. Further accumulation of cases and long follow-up data are needed to elucidate the pathophysiology and prognosis of MEC ex PA.

Esophageal Endoscopic Submucosal Dissection Assisted by an Overtube with a Traction Forceps: An Animal Study.

Esophageal endoscopic submucosal dissection (ESD) is technically difficult. To make it safer, we developed a novel method using overtube with a traction forceps (OTF) for countertraction during submucosal dissection. We conducted an ex vivo animal study and compared the clinical outcomes between OTF-ESD and conventional method (C-ESD). A total of 32 esophageal ESD procedures were performed by four beginner and expert endoscopists. After circumferential mucosal incision for the target lesion, structured as the isolated pig esophagus 3 cm long, either C-ESD or OTF-ESD was randomly selected for submucosal dissection. All the ESD procedures were completed as en bloc resections, while perforation only occurred in a beginner's C-ESD procedure. The dissection time for OTF-ESD was significantly shorter than that for C-ESD for both the beginner and expert endoscopists (22.8 ± 8.3 min versus 7.8 ± 4.5 min, P < 0.001, and 11.3 ± 4.4 min versus 5.9 ± 2.5 min, P = 0.01, resp.). The frequency and volume of the submucosal injections were significantly smaller for OTF-ESD than for C-ESD (1.3 ± 0.6 times versus 2.9 ± 1.5 times, P < 0.001, and 5.3 ± 2.8 mL versus 15.6 ± 7.3 mL, P < 0.001, resp.). Histologically, muscular injury was more common among the C-ESD procedures (80% versus 13%, P = 0.009). Our results indicated that the OTF-ESD technique is useful for the safe and easy completion of esophageal ESD.

Posterior Reversible Encephalopathy Syndrome During Combined Modality Therapy for Head and Neck Squamous Cell Carcinoma.

OBJECTIVES: Posterior reversible encephalopathy syndrome (PRES) is a rare and acute disease with central nervous system symptoms. Without appropriate therapy, patients may exhibit a poor prognosis. PRES should be recognized as a possible problem during therapy for head and neck squamous cell carcinoma (HNSCC). METHODS: A 56-year-old female developed PRES during combined modality therapy for HNSCC. On the fourth day after surgery and following chemoradiotherapy, PRES developed with a sudden visual disorder, followed by headache located at the back of the head and convulsions accompanied by impaired consciousness. We diagnosed PRES based on the clinical manifestations and magnetic resonance imaging data. RESULTS: The patient recovered from PRES by appropriate treatment. CONCLUSION: This is the first case report of PRES developed during treatment for HNSCC. Masked by other cerebrovascular disorders, more cases of PRES could exist than usually expected; therefore, we should consider PRES as a differential diagnosis for central nervous system disorders developing during high-intensity therapy.

TP53 mutation at early stage of colorectal cancer progression from two types of laterally spreading tumors.

Although most sporadic colorectal cancers (CRC) are thought to develop from protruded adenomas through the adenoma-carcinoma sequence, some CRC develop through flat lesions, so-called laterally spreading tumors (LST). We previously analyzed epigenetic aberrations in LST and found that LST are clearly classified into two molecular subtypes: intermediate-methylation with KRAS mutation and low-methylation with absence of oncogene mutation. Intermediate-methylation LST were mostly granular type LST (LST-G) and low-methylation LST were mostly non-granular LST (LST-NG). In the present study, we conducted a targeted exon sequencing study including 38 candidate CRC driver genes to gain insight into how these genes modulate the development of LST. We identified a mean of 11.5 suspected nonpolymorphic variants per sample, including indels and non-synonymous mutations, although there was no significant difference in the frequency of total mutations between LST-G and LST-NG. Genes associated with RTK/RAS signaling pathway were mutated more frequently in LST-G than LST-NG (P = 0.004), especially KRAS mutation occurring at 70% (30/43) of LST-G but 26% (13/50) of LST-NG (P < 0.0001). Both LST showed high frequency of APC mutation, even at adenoma stage, suggesting its involvement in the initiation stage of LST, as it is involved at early stage of colorectal carcinogenesis via adenoma-carcinoma sequence. TP53 mutation was never observed in adenomas, but was specifically detected in cancer samples. TP53 mutation occurred during development of intramucosal cancer in LST-NG, but during development of cancer with submucosal invasion in LST-G. It is suggested that TP53 mutation occurs in the early stages of cancer development from adenoma in both LST-G and LST-NG, but is involved at an earlier stage in LST-NG.

Genetic and epigenetic aberrations occurring in colorectal tumors associated with serrated pathway.

To clarify molecular alterations in serrated pathway of colorectal cancer (CRC), we performed epigenetic and genetic analyses in sessile serrated adenoma/polyps (SSA/P), traditional serrated adenomas (TSAs) and high-methylation CRC. The methylation levels of six Group-1 and 14 Group-2 markers, established in our previous studies, were analyzed quantitatively using pyrosequencing. Subsequently, we performed targeted exon sequencing analyses of 126 candidate driver genes and examined molecular alterations that are associated with cancer development. SSA/P showed high methylation levels of both Group-1 and Group-2 markers, frequent BRAF mutation and occurrence in proximal colon, which were features of high-methylation CRC. But TSA showed low-methylation levels of Group-1 markers, less frequent BRAF mutation and occurrence at distal colon. SSA/P, but not TSA, is thus considered to be precursor of high-methylation CRC. High-methylation CRC had even higher methylation levels of some genes, e.g., MLH1, than SSA/P, and significant frequency of somatic mutations in nonsynonymous mutations (p < 0.0001) and insertion/deletions (p = 0.002). MLH1-methylated SSA/P showed lower methylation level of MLH1 compared with high-methylation CRC, and rarely accompanied silencing of MLH1 expression. The mutation frequencies were not different between MLH1-methylated and MLH1-unmethylated SSA/P, suggesting that MLH1 methylation might be insufficient in SSA/P to acquire a hypermutation phenotype. Mutations of mismatch repair genes, e.g., MSH3 and MSH6, and genes in PI3K, WNT, TGF-ß and BMP signaling (but not in TP53 signaling) were significantly involved in high-methylation CRC compared with adenoma, suggesting importance of abrogation of these genes in serrated pathway.

Combined transcervical and orbitozygomatic approach for the removal of a nasopharyngeal adenocarcinoma.

OBJECTIVE: In some cases, the exposure and safeguarding of the internal carotid artery (ICA) are not easy by the maxillary swing approach that is used as a mainstay for the removal of nasopharyngeal tumors. To address this issue, we have developed a new combined transcervical and orbitozygomatic approach. METHODS: A nasopharyngeal adenocarcinoma arose in a 52-year-old patient and occupied the right middle skull base extending to the ICA. We first identified and dissected the ICA from the posterolateral part of the tumor using a transcervical approach. Then, the tumor was approached and removed by an orbitozygomatic technique with hemifacial dismasking. The surgical defect was filled using a temporal muscle flap, which was divided into two parts according to the blood supply from either the anterior or the posterior deep temporal artery. RESULTS: The postoperative course was uneventful and favorable cosmetic results were obtained. The patient has been free of carcinoma for more than 40 months after the surgery. CONCLUSION: Our new combined approach might be a good option for selected patients with nasopharyngeal tumors.

Systematic stereoscopic analyses for cloacal development: The origin of anorectal malformations.

The division of the embryonic cloaca is the most essential event for the formation of digestive and urinary tracts. The defective development of the cloaca results in anorectal malformations (ARMs; 2-5 per 10,000 live births). However, the developmental and pathogenic mechanisms of ARMs are unclear. In the current study, we visualized the epithelia in the developing cloaca and nephric ducts (NDs). Systemic stereoscopic analyses revealed that the ND-cloaca connection sites shifted from the lateral-middle to dorsal-anterior part of the cloaca during cloacal division from E10.5 to E11.5 in mouse embryos. Genetic cell labeling analyses revealed that the cells in the ventral cloacal epithelium in the early stages rarely contributed to the dorsal part. Moreover, we revealed the possible morphogenetic movement of endodermal cells within the anterior part of the urogenital sinus and hindgut. These results provide the basis for understanding both cloacal development and the ARM pathogenesis.

A case of ß-catenin-positive hepatocellular adenoma with MR imaging sign of diffuse intratumoral fat deposition.

Hepatocellular adenoma (HCA) is a rare primary benign tumor of the liver, which occurs predominantly in young and middle-aged women. Recently, the subclassification of HCA was proposed by the Bordeaux group. Subsequently, characteristic radiological and clinical features have been revealed in each HCA subtype. According to the previous literature, diffuse intratumoral fat deposition is a very common finding in hepatocyte nuclear factor 1α-negative HCA, but this finding has been reported in ß-catenin-positive HCA in the literature for only one case. In this case report, we report the second case of ß-catenin-positive HCA with MR imaging sign of diffuse intratumoral fat deposition, confirmed immunohistologically on the basis of a surgical specimen. In addition, our case showed hypovascularity and isointensity on the hepatobiliary phase which have been reported as characteristic findings in ß-catenin-positive HCA. Diffuse intratumoral fat deposition can be observed in ß-catenin-positive HCA, which has a greater probability of malignant transformation than other types of HCA.

Methylation epigenotypes and genetic features in colorectal laterally spreading tumors.

Aberrant DNA methylation plays an important role in genesis of colorectal cancer (CRC). Previously, we identified Group 1 and Group 2 methylation markers through genome-wide DNA methylation analysis, and classified CRC and protruded adenoma into three distinct clusters: high-, intermediate- and low-methylation epigenotypes. High-methylation epigenotype strongly correlated with BRAF mutations and these aberrations were involved in the serrated pathway, whereas intermediate-methylation epigenotype strongly correlated with KRAS mutations. Here, we investigated laterally spreading tumors (LSTs), which are flat, early CRC lesions, through quantitative methylation analysis of six Group 1 and 14 Group 2 methylation markers using pyrosequencing. Gene mutations in BRAF, KRAS and PIK3CA, and immunostaining of TP53 and CTNNB1 as well as other clinicopathological factors were also evaluated. By hierarchical clustering using methylation information, LSTs were classified into two subtypes; intermediate-methylation epigenotype correlating with KRAS mutations (p = 9 × 10(-4)) and a granular morphology (LST-G) (p = 1 × 10(-7)), and low-methylation epigenotype correlating with CTNNB1 activation (p = 0.002) and a nongranular morphology (LST-NG) (p = 1 × 10(-7)). Group 1 marker methylation and BRAF mutations were barely detected, suggesting that high-methylation epigenotype was unlikely to be involved in LST development. TP53 mutations correlated significantly with malignant transformation, regardless of epigenotype or morphology type. Together, this may suggest that two molecular pathways, intermediate methylation associated with KRAS mutations and LST-G morphology, and low methylation associated with CTNNB1 activation and LST-NG morphology, might be involved in LST development, and that involvement of TP53 mutations could be important in both subtypes in the development from adenoma to cancer.

Laparoscopic versus open adrenalectomy for adrenal myelolipoma.

INTRODUCTION: Earlier reports of laparoscopic adrenalectomy (LA) for adrenal myelolipoma are limited. PRESENTATION OF CASE: Between June 2000 and September 2012, we performed right adrenal resections using LA and open adrenalectomy (OA) in patients with myelolipoma (n = 3 and n = 3, respectively). Then, we evaluated patients' background characteristics and short- and long-term outcomes for both groups. The median maximum diameters of tumors were 3.5 (3.0-4.4) cm and 7.1 (7.0-9.5) cm for the LA and OA groups, respectively. The median durations of the operation were 152 (117-188) min and 218 (153-230) min, and the median blood loss volumes were 50 (20-160) mL and 290 (62-1237) mL in the LA and OA groups, respectively. The median postoperative lengths of hospital stay were 4 (4-4) days and 11 (11-13) days for the LA and OA groups, respectively. Conversion from LA to an open approach during surgery was not necessary in any of the cases. Additionally, perioperative morbidity and mortality were not observed. DISCUSSION: The limitation of this study is its methodological design; it is a case series and not a matched-control study, which would be difficult to conduct owing to the rare nature of adrenal myelolipoma. However, we esteem that LA will become widespread in the future because it is feasible, cosmetic, and less invasive. CONCLUSION: LA was a safe, feasible, and effective approach to adrenal myelolipoma, assisted by advancement in preoperative imaging diagnostic techniques.

Discrimination of fibrotic staging of chronic hepatitis C using multiple fibrotic markers.

AIM: In order to evaluate and judge a fibrotic stage of patients with chronic hepatitis C, multivariate regression analysis was performed using multiple fibrotic markers. METHODS: A total of 581 patients from eight hepatology units and institutes were diagnosed by needle biopsy as having chronic liver disease caused by hepatitis C virus. Twenty-three variables and their natural logarithmic transformation were employed in the multivariate analysis. RESULTS: Multivariate regression analysis finally obtained the following function: z = 2.89 × ln (type IV collagen 7S) (ng/mL) - 0.011 × (platelet count) (×10(3) /mm(3) ) + 0.79 × ln (total bilirubin) (mg/dL) + 0.39 × ln (hyaluronic acid) (µg/L) - 1.87. Median values of the fibrotic score of F1 (n = 172), F2 (n = 80), F3 (n = 37) and F4 (n = 16) were calculated as 1.00, 1.45, 2.82 and 3.83, respectively. Multiple regression coefficient and coefficient of determination were 0.56 and 0.320, respectively. Validation with patient data from other institutions demonstrated good reproducibility of the fibrotic score for hepatitis C (FSC), showing 1.10 in F1 (n = 156), 2.35 in F2 (n = 73), 3.16 in F3 (n = 36) and 3.58 in F4 (n = 11). CONCLUSION: A concise multiple regression function using four laboratory parameters successfully predicted pathological fibrotic stage of patients with hepatitis C virus infection.