High-signal venous sinuses on MR angiography: discrimination between reversal of venous flow and arteriovenous shunting using arterial spin labeling.

PURPOSE: It is sometimes difficult to differentiate between high signals originating from a reverse flow on magnetic resonance angiography (MRA) and occult arteriovenous shunting. We attempted to determine whether arterial spin labeling (ASL) can be used to discriminate reversal of venous flow from arteriovenous shunting for high-signal venous sinuses on MR angiography. METHODS: Two radiologists evaluated the signals of the venous sinus on MRA and ASL obtained from 364 cases without arteriovenous shunting. In addition, the findings on MRA were compared with those on ASL in an additional 13 patients who had dural arteriovenous fistula (DAVF). RESULTS: In the 364 cases (728 sides) without arteriovenous shunting, a high signal due to reverse flow in the cavernous sinuses (CS) was observed on 99 sides (13.6%) on MRA and none on ASL. Of these cases, a high signal in the sigmoid sinus, transverse sinus, and internal jugular vein was seen on 3, 3, and 8 sides, respectively. All of these venous sinuses showed a high signal from the reverse flow on MRA images. CONCLUSION: ASL is a simple and useful MR imaging sequence for differentiating between reversal of venous flow and CS DAVF. In the sigmoid and transverse sinus, ASL showed false-positives due to the reverse flow from the jugular vein, which may be a limitation of which radiologists should be aware.

[A feasibility study on cervical screening in non-attenders invited to undergo HPV self-sampling with cytology triage versus repeat invitation for cytology screening in Hokkaido].

Objectives　We investigated the participation and detection rates of cervical lesions in cervical screening non-attenders offered HPV (human papillomavirus) self-sampling with cytology triage.Methods　From 2016 to 2018, HPV self-sampling was routinely offered as an option, along with cytology, to all non-attenders in Ebetsu City, Japan. The primary endpoints were ≥CIN2 and ≥CIN3 detection rates, and secondary endpoints were abnormal cytology rates and follow-up compliance.Results　Overall, recall invitations were mailed to 6,116 non-attenders, with a response rate of 15.9% (cytology: 6.5%, HPV testing: 9.4%). Of the responders to undergo HPV self-sampling, 11.7% had a positive result and were referred to cytology triage. Moreover, ≥CIN2 and ≥CIN3 detection rates were 1.7% and 0.9%, respectively, in the HPV self-sampling group, and 1.0% and 0.8%, respectively, in the cytology group, showing no statistically significant differences. In those who underwent cytology triage following an HPV positive test, ≥CIN2 and ≥CIN3 detection rates were 23.8% and 11.9%, respectively, which was significantly higher than those who only underwent cytology alone.Conclusion　HPV self-sampling followed by cytology triage is highly effective at detecting high grade disease in non-attenders. Thus, multi-municipality-based studies to standardize processes involving this method are warranted. Furthermore, HPV self-sampling could be a promising method for inviting non-attenders who have difficulty undergoing cervical screening in the COVID-19 pandemic era.

Oxygen reserve index (ORi™) contributes to prediction of hypoxemia and patient safety during tracheal stent insertion using rigid bronchoscopy: a case report.

The oxygen reserve index (ORi™) is a new noninvasive and continuous variable, which represents a moderate hyperoxygenation status, with a unitless scale between 0.00 and 1.00. When percutaneous oxygen saturation (SpO2) exceeds 100%, arterial blood oxygen partial pressure cannot be evaluated without performing arterial blood gas analysis. Because of significant air leakage during rigid bronchoscopy, it is difficult to monitor respiration using capnography, which does not measure end-tidal carbon dioxide (ETCO2) accurately. A 66-year-old man (175 cm, 76.8 kg) with a chief complaint of difficulty in breathing was diagnosed with a thyroid tumor. Computed tomography revealed tracheal stenosis due to direct invasion of the thyroid tumor; therefore, tracheal stenting was planned immediately. After supplying 6 L/min oxygen with a face mask and administering 180 mg of propofol intravenously, the supraglottic airway was intubated. General anesthesia (total intravenous anesthesia) through continuous administration of 6-10 mg/kg/h of propofol and intermittent administration of 50 µg of fentanyl (total 200 µg) preserved spontaneous breathing. During tracheal stent insertion, disconnection between the oxygen supply system and rigid bronchoscopy, and tracheal stent expansion, the ORi tended to decrease before SpO2 decreased. Thus, measuring ORi could prevent hypoxemia during tracheal stent insertion using rigid bronchoscopy.

Comparison of human papillomavirus genotyping and cytology triage, COMPACT Study: Design, methods and baseline results in 14 642 women.

Although cytology-based screening programs have significantly reduced mortality and morbidity from cervical cancer, the global consensus is that primary human papillomavirus (HPV) testing for cervical screening increases detection of high-grade cervical intraepithelial neoplasia (CIN) and invasive cancer. However, the optimal triage strategy for HPV-positive women to avoid over-referral to colposcopy may be setting specific. As Japan requires data that have been generated domestically to modify screening guidelines, we conducted a 3-year prospective study, COMparison of HPV genotyping And Cytology Triage (COMPACT), to evaluate the potential role of HPV16/18 partial genotyping and cytology for primary HPV screening. In total, 14 642 women aged 20 to 69 years undergoing routine screening at 3 centers in Hokkaido were enrolled. Conventional cytology and HPV testing were carried out. Women with abnormal cytology or HPV16/18 positivity underwent colposcopy. Those with 12 other high-risk (hr) HPV types underwent repeat cytology after 6 months. Primary study endpoints were detection of high-grade cervical disease defined as CIN2/CIN3 or greater as determined by consensus pathology. Prevalence of cytological abnormalities was 2.4%. hrHPV, HPV 16, and HPV 18 were detected in 4.6%, 0.9%, and 0.3% of women, respectively. HPV16/18 were detected in all (8/8) invasive cervical cancers and in all (2/2) adenocarcinomas in situ. Both cytological abnormalities and hrHPV positivity declined with increasing age. This is the first Japanese study to investigate the role of partial genotyping and cytology in an HPV-based screening program. Results should help policy-makers develop guidelines for future cervical screening programs and management of cervical abnormalities based on HPV genotype.

Measurement of endometrial thickness in premenopausal women in office gynecology.

Purpose: To define the median endometrial thickness (ET) in office gynecology is thought to be important for clinical practice. However, there are few reports about ET that have included the general female population on a large scale. The median ET was determined prospectively in premenopausal women who attended office gynecology for cervical cancer screening. Methods: In total, 849 women were enrolled. The median ET was determined by using transvaginal ultrasound and the relationships between the ET and various clinical factors were analyzed. Results: The participants' median age was 38.5 years. The median ET was 8.6 mm (90% and 95% quantiles: 13.8 and 15.8 mm). The ET was not related to their age, symptoms, obstetric history, geographical location, or risk factors for endometrial cancer. In the women with a menstrual cycle length of 28-30 days, the ET was 7 mm on days 1-6, but it increased from 5.4 mm immediately after menstruation (day 7 or 8) to 9.2 mm on days 13-14. Subsequently, the ET increased further to 11.1 mm on day 18. Conclusion: In all the women, the upper limit of the ET was 13.8 mm and 15.8 mm in the 90% and 95% quantile, respectively, in office gynecology.

Tumoricidal effect and pain relief after concurrent therapy by strontium-89 chloride and zoledronic acid for bone metastases.

OBJECTIVE: The purpose of this study was to investigate the palliative and tumoricidal effects of concurrent therapy of strontium-89 chloride (89SrCl2) and zoledronic acid (ZA) for painful bone metastases. SUBJECTS AND METHODS: Fifty-one patients with painful bone metastases prostate cancer (n=17), lung cancer (n=13), breast cancer (n=12), other cancers (n=9) were treated. Bone metastases was confirmed in all patients by technetium-99m hydroxymethylene diphosphonate (99mTc-HMDP) bone scintigraphy. The numeric rating scale (NRS) and performance status (PS) were used to assess the degree of pain and patients' physical condition. The extent of bone metastases was assessed with imaging modalities including CT, MRI and/or 99mTc bone scintigraphy before treatment and 2 or 3 months after. RESULTS: The pain relief response of 89SrCl2 with ZA for bone metastases was 94% (48/51) from 1 to 3 months after treatment. The tumoricidal effect of concurrent therapy by 89SrCl2 with ZA for painful bone metastases was 8/22 as shown by imaging modalities and the rate of non-progressive disease (non-PD) was 19/22. Pain due to bone metastases assessed with the NRS was significantly improved (P<0.001) in many types of primary cancer, including prostate, breast and lung cancers. CONCLUSION: Concurrent therapy of 89SrCl2 with ZA may offer not only pain relief, but also a tumoricidal effect for painful bone metastases.

Genomic Landscape of Esophageal Squamous Cell Carcinoma in a Japanese Population.

BACKGROUND & AIMS: Esophageal squamous cell carcinoma (ESCC) is the predominant form of esophageal cancer in Japan. Smoking and drinking alcohol are environmental risk factors for ESCC, whereas single nucleotide polymorphisms in ADH1B and ALDH2, which increase harmful intermediates produced by drinking alcohol, are genetic risk factors. We conducted a large-scale genomic analysis of ESCCs from patients in Japan to determine the mutational landscape of this cancer. METHODS: We performed whole-exome sequence analysis of tumor and nontumor esophageal tissues collected from 144 patients with ESCC who underwent surgery at 5 hospitals in Japan. We also performed single-nucleotide polymorphism array-based copy number profile and germline genotype analyses of polymorphisms in ADH1B and ALDH2. Polymorphisms in CYP2A6, which increase harmful effects of smoking, were analyzed. Functions of TET2 mutants were evaluated in KYSE410 and HEK293FT cells. RESULTS: A high proportion of mutations in the 144 tumor samples were C to T substitution in CpG dinucleotides (called the CpG signature) and C to G/T substitutions with a flanking 5' thymine (called the APOBEC signature). Based on mutational signatures, patients were assigned to 3 groups, which associated with environmental (drinking and smoking) and genetic (polymorphisms in ALDH2 and CYP2A6) factors. Many tumors contained mutations in genes that regulate the cell cycle (TP53, CCND1, CDKN2A, FBXW7); epigenetic processes (MLL2, EP300, CREBBP, TET2); and the NOTCH (NOTCH1, NOTCH3), WNT (FAT1, YAP1, AJUBA) and receptor-tyrosine kinase-phosphoinositide 3-kinase signaling pathways (PIK3CA, EGFR, ERBB2). Mutations in EP300 and TET2 correlated with shorter survival times, and mutations in ZNF750 associated with an increased number of mutations of the APOBEC signature. Expression of mutant forms of TET2 did not increase cellular levels of 5-hydroxymethylcytosine in HEK293FT cells, whereas knockdown of TET2 increased the invasive activity of KYSE410 ESCC cells. Computational analyses associated the mutations in NFE2L2 we identified with transcriptional activation of its target genes. CONCLUSIONS: We associated environmental and genetic factors with base substitution patterns of somatic mutations and provide a registry of genes and pathways that are disrupted in ESCCs. These findings might be used to design specific treatments for patients with esophageal squamous cancers.

Temporal variations in stump pressure and assessment of images obtained from cone-beam computed tomography during balloon-occluded transarterial chemoembolization.

AIM: Balloon-occluded transcatheter arterial chemoembolization (B-TACE) was used to show the optimized duration of balloon occlusion to start injection of lipiodol in order to maximize lipiodol deposition in the nodule, and to reveal the endpoint of lipiodol injection. METHODS: Of 29 consecutive patients who underwent balloon-occluded TACE between November 2013 and February 2014, we were able to measure stump pressure for 219 nodules in 27 patients. Tumors were counted, measured and could be visually assessed in 20 of these patients at 26 sites. Tumors with multiple feeders were found in eight patients. Arterial blood pressure was measured before, immediately after and 5 min after balloon occlusion prior to intra-arterial injection, as well as before and after balloon deflation after intra-arterial injection. Images were assessed qualitatively by two radiologists as well as quantitatively by calculating the contrast-to-noise ratio. RESULTS: We found no significant difference in pressure between immediately after and 5 min after balloon occlusion. Mean stump pressure before balloon deflation after intra-arterial injection was 70.4 mmHg. We observed a significant increase in qualitative scores after balloon occlusion (P < 0.001), and the mean score in the third-order branch was significantly higher than that in the first-order branch (P = 0.048). CONCLUSION: Our results indicate that intra-arterial injection can be started at any time after balloon occlusion and that 70 mmHg may be considered as a possible indicator of the end-point for arterial injection.

History of lymphadenectomy for esophageal cancer and the future prospects for esophageal cancer surgery.

I would herein like to look back upon surgery for esophageal cancer, particularly on lymphadenectomy, and to speculate a little on the future prospects for esophageal surgery. There are two schools of thought on lymphadenectomy in esophageal cancer: one believes in en bloc esophagectomy, which is commonly performed in Western countries; the other believes in three-field lymphadenectomy, which is commonly performed in Japan. We esophageal surgeons at Kurume University have contributed to some advances in three-field lymphadenectomy. For example, we initiated functional mediastinal dissection to ensure patient safety, and we proposed the lymph node compartment theory to assess the clinical importance of regional nodes. Oncological surgery has progressed in terms of its safety, radicality and functional preservation, leading to improved quality-of-life for patients after surgery. This then evolved to the current development of multimodal and individualized tailor-made treatments. I believe that surgery for esophageal cancer will become bipolarized in the future. One strand will evolve as salvage surgery for residual or recurrent tumors, which non-surgical therapies have failed to cure, and the other strand will evolve as less invasive surgery, adjuvant surgery, for cancers at the relatively early stage, for which micro-metastasis can be cured by non-surgical therapies.

T1 squamous cell carcinoma of the esophagus: long-term outcomes and prognostic factors after esophagectomy.

BACKGROUND: Mucosal (T1a) and submucosal (T1b) squamous cell carcinoma of the esophagus (ESCC) have often been analyzed together and are staged as the same category in the UICC/TNM staging system. The difference in surgical outcomes between T1a and T1b ESCC therefore remains unclear. The purpose of this study was to examine the differences in surgical outcomes between T1a and T1b ESCC, and to investigate the prognostic factors in T1 ESCC. METHODS: A prospectively maintained database identified 145 previously untreated patients with pT1 ESCC who underwent radical transthoracic (n = 134) or transhiatal esophagectomy (n = 11). Median follow-up was 108 months. RESULTS: Of the 145 patients, 35 (24 %) had pT1a cancer and 110 (76 %) had pT1b cancer. Lymph node metastasis was present in 45 patients (31 %): 3 patients with pT1a cancer and 42 patients with pT1b cancer (P = 0.0003). The 5-year survival rate for the whole group was 77 %. The 5-year survival rate of the T1a patients was 94 % compared with 72 % for the T1b patients (P = 0.0282). In multivariate analysis, only the depth of tumor invasion (pT1a vs. pT1b) was an independent prognostic factor (hazard ratio 2.358; 95 % confidence interval 1.009­5.513; P = 0.0477). CONCLUSIONS: After esophagectomy, the prognosis of patients with pT1b ESCC is significantly worse than that of patients with pT1a ESCC. Infiltration into the submucosa is the only independent prognostic factor affecting survival. These findings suggested that T1a and T1b ESCC could be staged separately in the next version of UICC/TNM staging system.

Right Parasternal Approach for Aortic Valve Replacement After Presternal Gastropexy.

Due to bicuspid aortic valve aortic stenosis, a 78-year-old man with a history of esophagectomy and presternal gastric tube reconstruction required aortic valve replacement (AVR). AVR with a bioprosthetic valve was performed through a right parasternal thoracotomy. Despite the unfavorable conditions for conventional median sternotomy, AVR was successfully performed through an alternate approach. The right parasternal approach was excellent for AVR in patients with presternal gastric tube reconstruction for esophageal cancer (EC).

Neoadjuvant S-1 and oxaliplatin plus bevacizumab therapy for high-risk locally advanced rectal cancer: A prospective multicenter phase II study.

Aim: We report the short/mid-term results of surgery for high-risk locally advanced rectal cancer (LARC) after neoadjuvant chemotherapy (NAC, four courses of S-1 + oxaliplatin+ bevacizumab) without radiotherapy with the primary aim of ypT0-2. Methods: High-risk LARC was defined as cT4b, mesorectal fascia (MRF) ≤1 mm (MRF+), or lateral lymph node metastasis (cLLN+) on high-resolution MRI. The planned 32 cases from April 2018 to December 2021 were all included. Results: There were 10 patients at cT4b (31.2%), 26 MRF+ (81.3%), and 22 cLLN+ (68.8%). Thirteen (40.6%) underwent NAC after a colostomy for stenosis. NAC was completed in 26 (81.2%) cases. Grade 3 or higher adverse events occurred in six (18.7%). One patient developed progressive disease (3.2%). Eleven were ycT0-3MRF-LLN- (34.3%). Curative-intent surgery was performed on 31, with sphincter-preserving surgery in 20, abdominoperineal resection in nine, total pelvic exenteration in two, and lateral lymph node dissection in 24. Two had R1/2 resection (6.4%). A Grade 3 or higher postoperative complication rate occurred in 3.2%. Pathological complete response and ypT0-2 rates were 12.9% and 45.1%. Three-year disease-free survival rates (3yDFS) for ypT0-2 and ypT ≥3 were 81.2%, 46.6% (p = 0.061), and 3-year local recurrence rates (3yLR) were 0%, 48.8% (p = 0.015). 3yDFS for ycT0-3MRF-LLN- and ycT4/MRF+/LLN+ were 87.5%, 48.0% (p = 0.031) and 3yLR were 0%, 42.8% (p = 0.045). Conclusion: NAC yielded a clinically significant effect in about half of high-risk LARC patients. If NAC alone is ineffective, radiotherapy should be added, even if extended surgery is intended.

Incidence risk of cervical intraepithelial neoplasia 3 or more severe lesions is a function of human papillomavirus genotypes and severity of cytological and histological abnormalities in adult Japanese women.

We examined incidence probabilities of cervical intraepithelial neoplasia 3 (CIN3) or more severe lesions (CIN3+) in 1,467 adult Japanese women with abnormal cytology in relation to seven common human papillomavirus (HPV) infections (16/18/31/33/35/52/58) between April 2000 and March 2008. Sixty-seven patients with multiple HPV infection were excluded from the risk factor analysis. Incidence of CIN3+ in 1,400 patients including 68 with ASCUS, 969 with low grade squamous intraepithelial lesion (LSIL), 132 with HSIL without histology-proven CIN2 (HSIL/CIN2(-)) and 231 with HSIL with histology-proven CIN2 (HSIL/CIN2(+)) was investigated. In both high grade squamous intraepithelial lesion (HSIL)/CIN2(-) and HSIL/CIN2(+), HPV16/18/33 was associated with a significantly earlier and higher incidence of CIN3+ than HPV31/35/52/58 (p = 0.049 and p = 0.0060, respectively). This association was also observed in LSIL (p = 0.0002). The 1-year cumulative incidence rate (CIR) of CIN3+ in HSIL/CIN2(-) and HSIL/CIN2(+) according to HPV genotypes (16/18/33 vs. 31/35/52/58) were 27.1% vs. 7.5% and 46.6% vs. 19.2%, respectively. In contrast, progression of HSIL/CIN2(+) to CIN3+ was infrequent when HPV DNA was undetected: 0% of 1-year CIR and 8.1% of 5-year CIR. All cervical cancer occurred in HSIL cases of seven high-risk HPVs (11/198) but not in cases of other HPV or undetectable/negative-HPV (0/165) (p = 0.0013). In conclusion, incidence of CIN3+ depends on HPV genotypes, severity of cytological abnormalities and histology of CIN2. HSIL/CIN2(+) associated with HPV16/18/33 may justify early therapeutic intervention, while HSIL/CIN2(-) harboring these HPV genotypes needs close observation to detect incidence of CIN3+. A therapeutic intervention is not indicated for CIN2 without HPV DNA.

Expression of mesenchymal markers vimentin and fibronectin: the clinical significance in esophageal squamous cell carcinoma.

BACKGROUND: The importance of mesenchymal characteristics has not been fully elucidated in esophageal cancer. METHODS: Ten normal and 77 tumor specimens were collected. Microarray analysis was performed to analyze the expression patterns of epithelial markers, mesenchymal markers, epithelial mesenchymal transition (EMT)-related genes and stem cell markers. RT-PCR analysis was conducted to confirm the results of microarray analysis. Immunohistochemical analysis was performed to verify the level of protein expression. Statistical analysis was performed to investigate the correlation between selected genes and clinicopathological factors. RESULTS: Microarray analysis showed that epithelial markers were significantly down-regulated whereas mesenchymal markers and EMT transcription factors were up-regulated in cancer cells. Two types of gene expression patterns were found in the clustering analysis, type 1 tumors and type 2 tumors. Type 1 tumor clusters did not reveal a fixed gene expression pattern whereas type 2 tumor clusters revealed up-regulation of mesenchymal markers EMT inducers and related genes. Vimentin and fibronectin were selected to distinguish between tumor types 1 and 2. Type 2 tumors showed significantly larger tumor sizes (p < 0.0001), wider ranges of lymph node metastasis (p = 0.0057), and a more severe clinical stage (p < 0.0001) than did type 1 tumors. The prognosis of patients with type 2 tumors was significantly worse than that of patients with type 1 tumors. Univariate and multivariate analyses revealed that classification of type 2 tumors was an independent prognostic factor. CONCLUSIONS: The analysis of mesenchymal markers in esophageal cancer is useful in distinguishing patients with a poor prognosis.

Randomized controlled trial comparing antioxidant-enriched enteral nutrition with immune-enhancing enteral nutrition after esophagectomy for cancer: a pilot study.

PURPOSE: The objective of this study was to compare the effects of two types of enteral supplements, an antioxidant-enriched enteral nutrition (AeEN) and an immune-enhancing enteral nutrition (IeEN), on the nutrition, immunoinflammatory response, antioxidant capacity and clinical outcomes in patients after esophagectomy for cancer. METHODS: Patients (n = 20) undergoing esophagectomy for cancer were randomized in this single-center, open-label study. Two types of enteral supplements were used for 5 days before surgery and 7 days after surgery. The circulating levels of nutritional markers, immunoinflammatory markers, oxidative stress markers, and the antioxidant capacity were compared throughout the perioperative period, and the patients' clinical outcomes were also compared. RESULTS: The circulating levels of nutritional markers decreased after surgery, but the changes were not significantly different between the AeEN group and the IeEN group throughout the perioperative period. Surgery increased the immunoinflammatory markers, and the levels were not significantly different between the groups after surgery. Surgery also increased the levels of oxidative stress markers, but there were no significant differences between the groups throughout the study period. CONCLUSIONS: The results of this pilot study suggest that AeEN and IeEN have a similar effect on nutrition, the immunoinflammatory response, antioxidant capacity and clinical outcomes after esophagectomy for cancer. These findings, therefore, warrant further studies on a larger scale.

Changes in Acidity Levels in the Gastric Tube After Esophagectomy for Esophageal Cancer.

Reflux esophagitis and gastric tube ulcer sometimes cause severe clinical problems in patients undergoing esophagectomy with gastric tube reconstruction. We previously reported that acidity in the gastric tube was decreased for 1 year after esophagectomy, and that lower acidity levels were associated with Helicobacter pylori (H. pylori) infection. However, the long-term changes in gastric acidity remain unknown. We aimed to investigate the long-term changes in gastric acidity after surgery. Eighty-nine patients who underwent esophagectomy with gastric tube reconstruction for esophageal cancer were analyzed. They underwent 24-hour pH monitoring, serum gastrin measurement, and H. pylori infection examination before surgery, at 1 month, 1 year, and 2 years after surgery. The gastric acidity at 1 month and 1 year after surgery was significantly lower than that before surgery (p=0.003, p=0.003). However, there was no difference in gastric acidity before and 2 years after surgery. The gas tric acidity in H. pylori-infected patients was significantly lower in comparison to non-infected patients at each time point (p=0.0003, p<0.0001, p<0.0001, p<0.0001, respectively). In H. pylori-infected patients, gastric acid ity was decreased for 1 year after surgery, and recovered within 2 years after surgery. However, no significant differences were observed in the acidity levels of non-infected patients during the 2-year follow-up period. The serum gastrin level increased after esophagectomy. The acidity levels in the gastric tube recovered within 2 years after surgery. Periodic endoscopy examination is recommended for early detection of acid-related disease, such as reflux esophagitis or gastric tube ulcer, after esophagectomy with gastric tube reconstruction.

Esophagectomy with extended lymphadenectomy for submucosal esophageal cancer: long-term outcomes and prognostic factors.

BACKGROUND: There are controversies regarding the extent of lymphadenectomy necessary during the course of esophagectomy for submucosal esophageal cancer. The purpose of this study was to examine the long-term outcomes after esophagectomy with extended lymphadenectomy in patients with submucosal esophageal cancer and to investigate the prognostic factors in these patients. MATERIALS: A prospectively maintained database identified 105 previously untreated patients with submucosal esophageal cancer who underwent transthoracic esophagectomy with three-field or two-field lymphadenectomy. Median follow-up was 101 months. RESULTS: All patients received R0 resection. Ninety-eight patients had squamous cell carcinoma, and seven had adenocarcinoma. Lymph node metastasis was present in 38 patients (36.2%), of whom 9 patients (23.7%) had positive cervical nodes. Thirty-five patients (33.3%) had other primary malignancies. The overall 5- and 10-year survival rates were 74.4 and 57.4%, respectively. The cause of death was recurrent disease in 16 patients, other malignancy in 12, and noncancer-related disease in 18. Univariate analyses demonstrated that other primary malignancy (P = 0.0041), poor differentiation (P = 0.0203), and angiolymphatic invasion (P = 0.0347) significantly affected overall survival. There was no difference in survival between patients with lymph node metastasis and those without (P = 0.9809). Multivariate analysis found other primary malignancy to be the only independent prognostic factor (hazards ratio, 2.295; 95% confidence interval, 1.201-4.386; P = 0.0119). CONCLUSIONS: Esophagectomy with extended lymphadenectomy for submucosal esophageal cancer results in 57.4% survival at 10 years. Other primary malignancy is the only independent predictor affecting long-term survival. Patients should be examined rigorously for other primary malignancy as well as recurrent disease during long-term follow-up.

Evaluation of overall tumor cellularity after neoadjuvant chemotherapy in patient with locally advanced hypopharyngeal cancer.

The aim of this study is to clarify the prognostic value of the pathological overall tumor cellularity after neoadjuvant chemotherapy for locally advanced hypopharyngeal cancer. In consecutive series of 45 operable patients with locally advanced hypopharyngeal cancer, neoadjuvant chemotherapy by cisplatin and 5-fluorouracil was administered. Pathological image analysis was performed in 30 patients using the large cross-section specimen after total resection to evaluate the overall tumor cellularity. The chemotherapeutic responses were classified according to the pathological grading scale by dividing into four categories; more than 70% overall tumor cellularity in Grade 1, between an estimated 10 and 70% in Grade 2, less than 10% in Grade 3, and no identifiable malignant tumor cells in Grade 4. The pathological grades were taken into account for analysis of the survival. In 30 available patients, 40% had Grade 1 pathological response, 30% had Grade 2, and 30% had Grade 3. There was no Grade 4 patient. The overall 5-year survival rate for these 30 patients was 53.33%. The survival rate (61.66%) for patients with Grade 2 and 3 responses was significantly higher than that (27.78%) for patients with Grade 1 response (p = 0.009). Cox regression analysis revealed that the increasing pathological grade was an independent predictor of a better survival in patients undergoing neoadjuvant chemotherapy. We have shown that the prognosis of patients with locally advanced hypopharyngeal cancer, who had been treated by neoadjuvant chemotherapy followed by total resection, can be predicted by evaluation of pathological overall tumor cellularity from the large section specimen.