Development of UTX-143, a selective sodium-hydrogen exchange subtype 5 inhibitor, using amiloride as a lead compound.

NHE5, an isoform of the Na+/H+ exchanger (NHE) protein, is an ion-transporting membrane protein that regulates intracellular pH and is highly expressed in colorectal adenocarcinoma. Therefore, we hypothesized that NHE5 inhibitors can be used as anticancer drugs. However, because NHE1 is ubiquitously expressed in all cells, it is extremely important to demonstrate its selective inhibitory activity against NHE5. We used amiloride, an NHE non-selective inhibitor, as a lead compound and created UTX-143, which has NHE5-selective inhibitory activity, using a structure-activity relationship approach. UTX-143 showed selective cytotoxic effects on cancer cells and reduced the migratory and invasive abilities of cancer cells. These results suggest a new concept wherein drugs exhibit cancer-specific cytotoxic effects through selective inhibition of NHE5 and the possibility of UTX-143 as a lead NHE5-selective inhibitor.

Analysis of factors associated with operative difficulty in thoracoscopic esophageal cancer surgery in the left-decubitus position: a single-center retrospective study.

BACKGROUND: The degree of difficulty in the overall procedure and forceps handling encountered by surgeons is greatly influenced by the positional relationship of intrathoracic organs in minimally invasive esophagectomy. This study aimed to identify the anatomical factors associated with the difficulty of minimally invasive esophagectomy assessed by intraoperative injuries and postoperative outcomes. METHODS: Minimally invasive esophagectomy in the left-decubitus position was performed in 258 patients. We defined α (mm) as the anteroposterior distance between the front of the vertebral body and aorta, ß (mm) as the distance between the center of the vertebral body and center of the aorta, and γ (degree) as the angle formed at surgeon's right-hand port site by insertion of lines from the front of aorta and from the front of vertebrae in the computed tomography slice at the operator's right-hand forceps hole level. We retrospectively analyzed the correlations among clinico-anatomical factors, surgeon- or assistant-caused intraoperative organ injuries, and postoperative complications. RESULTS: Intraoperative injuries significantly correlated with shorter α (0.2 vs. 3.9), longer ß (33.0 vs. 30.5), smaller γ (3.0 vs. 4.3), R1 resection (18.5% vs. 8.3%), and the presence of intrathoracic adhesion (46% vs. 26%) compared with the non-injured group. Division of the median values into two groups showed that shorter α and smaller γ were significantly associated with organ injury. Longer ß was significantly associated with postoperative tachycardia onset, respiratory complications, and mediastinal recurrence. Furthermore, the occurrence of intraoperative injuries was significantly associated with the onset of postoperative pulmonary complications. CONCLUSIONS: Intrathoracic anatomical features greatly affected the procedural difficulty of minimally invasive esophagectomy, suggesting that preoperative computed tomography simulation and appropriate port settings may improve surgical outcomes.

Dynamic switch of immunity and antitumor effects of metformin in rat spontaneous esophageal carcinogenesis.

Chronic inflammation contributes to tumor development by creating a local microenvironment that facilitates neoplastic transformation and potentiates the progression of cancer. Esophageal cancer (EC) is an inflammation-associated malignancy with a poor prognosis. The nature of the switch between chronic inflammation of the esophagus and EC-related immunological changes remains unclear. Here, we examined the dynamic alterations of immune cells at different stages of chronic esophagitis, Barrett's esophagus (BE) and EC using an esophageal spontaneous carcinogenesis rat model. We also investigated the anticancer effects of metformin. To stimulate EC carcinogenesis, chronic gastroduodenal reflux esophagitis via esophagojejunostomy was induced in 120 rats in metformin-treated and non-treated (control) groups. After 40 weeks, BE and EC developed in 96.7% and 63.3% of the control group, and in 66.7% and 23.3% of the metformin-treated group, respectively. Flow cytometric analysis demonstrated that the balance of M1/M2-polarized or phospho-Stat3-positive macrophages, regulatory T, cytotoxic T, natural killer (NK), NK T cells, and Th17 T cells was dynamically changed at each stage of the disease and were resolved by metformin treatment. These findings clarify the immunity in esophageal carcinogenesis and suggest that metformin could suppress this disease by improving the immunosuppressive tumor microenvironment and immune evasion.

Prognostic value of tumor-infiltrating CD163+macrophage in patients with metastatic gastric cancer undergoing multidisciplinary treatment.

BACKGROUND: The multidisciplinary treatment including induction chemotherapy plus conversion surgery (CS) has attracted attention as a new strategy to improve the outcome of metastatic gastric cancer (MGC). However, it is unclear which patients achieve a good response to chemotherapy and successful CS. Tumor-infiltrating immune cells (TIICs) have been reported to be both prognostic and predictive biomarkers not only in immunotherapy but also in chemotherapy in many cancer types. However, there have been no reports on the usefulness of TIICs as biomarkers in conversion surgery for MGC. The aim of the present study was to evaluate the association between the TIICs and treatment outcome for the multidisciplinary treatment in MGC. METHODS: We retrospectively analyzed 68 MGC patients who received docetaxel plus cisplatin plus S-1 (DCS) therapy between April 2006 and March 2019 in our institute. The number of tumor-infiltrating CD4+, CD8+, Foxp3+lymphocytes, CD68+, CD163+macrophages in pre-treatment endoscopic biopsy samples were evaluated to investigate their predictive value for multidisciplinary treatment. RESULTS: Fifty patients underwent CS following DCS therapy (CS group), whereas 18 patients underwent DCS therapy alone (non-CS group). The median survival time (MST) of CS group was 33.3 months, which was significantly longer than the MST of 9.0 months in non-CS group (p < 0.01). The number of CD163+macrophages was extracted as an independent prognostic factor for overall survival in all patients. There were more cases of high infiltration of CD163+macrophages in non-CS group than in CS group. Furthermore, in CS group, pathological responders to DCS therapy showed low infiltration of CD163+ macrophages, and high infiltration of CD8+lymphocyte. CD163 low group showed a significant prolonged survival compared with CD163 high group in patients who underwent CS (p = 0.02). CONCLUSIONS: The pre-treatment CD163+macrophages infiltration would be a pivotal biomarker for predicting prognosis and pathological response to multidisciplinary treatment among TIICs in MGC. Thus, for patients with low CD163+macrophage infiltration in pre-treatment biopsy sample, diagnostic imaging should be performed frequently during chemotherapy to avoid missing the optimal timing for CS, and CS should be aggressively considered as a treatment option if curative resection is deemed feasible.

Interleukin-17A derived from mast cells contributes to fibrosis in gastric cancer with peritoneal dissemination.

OBJECTIVES: Interleukin-17A (IL-17A) is pro-inflammatory cytokine and acts as profibrotic factor in the fibrosis of various organs. Fibrosis tumor-like peritoneal dissemination of gastric cancer interferes with drug delivery and immune cell infiltration because of its high internal pressure. In this study, we examined the relationship between IL-17A and tissue fibrosis in peritoneal dissemination and elucidated the mechanism of fibrosis induced by IL-17A using human peritoneal mesothelial cells (HPMCs) and a mouse xenograft model. METHODS: Seventy gastric cancer patients with peritoneal dissemination were evaluated. The correlation between IL-17A and fibrosis was examined by immunofluorescence and immunohistochemistry. A fibrosis tumor model was developed based on subcutaneous transplantation of co-cultured cells (HPMCs and human gastric cancer cell line MKN-45) into the dorsal side of nude mice. Mice were subsequently treated with or without IL-17A. We also examined the effect of IL-17A on HPMCs in vitro. RESULTS: There was a significant correlation between IL-17A expression, the number of mast cell tryptase (MCT)-positive cells, and the degree of fibrosis (r = 0.417, P < 0.01). In the mouse model, IL-17A enhanced tumor progression and fibrosis. HPMCs treated with IL-17A revealed changes to a spindle-like morphology, decreased E-cadherin expression, and increased α-SMA expression through STAT3 phosphorylation. Moreover, HPMCs treated with IL-17A showed increased migration. CONCLUSIONS: IL-17A derived from mast cells contributes to tumor fibrosis in peritoneal dissemination of gastric cancer. Inhibiting degranulation of mast cells might be a promising treatment strategy to control organ fibrosis.

[A Case of an Asymptomatic Coagulopathy after Peritoneovenous Shunt Placement for Malignant Ascites of Gastric Cancer].

The patient was a 61‒year‒old man who had an advanced gastric cancer with peritoneal dissemination. After chemotherapy, intraoperative findings during a total gastrectomy revealed the disappearance of the dissemination nodules. Although adjuvant chemotherapy was performed, the presence of massive ascites led to the recurrence of the peritoneal dissemination 5 months after the surgery. While the chemotherapy regimen was altered, we observed no reduction in malignant ascites. The patient complained of abdominal distention and was admitted to our hospital for symptom management. We performed a cell‒free and concentrated ascites reinfusion therapy(CART)several times. However, symptom management proved difficult; therefore, the patient underwent a peritoneovenous shunt(Denver shunt)placement. After the shunting, we observed no organ injury and improved abdominal distention; however, an asymptomatic coagulopathy was present in the course. Additionally, blood examinations showed increased FDP‒DD and thrombin‒antithrombin complex(TAT). However, 6 months after the shunting, coagulopathy improved and the patient reported the absence of abdominal distention. This report describes a patient with an asymptomatic coagulopathy after Denver shunt placement and evaluated the clinical course by using TAT values.

[Four Cases of Surgical Treatment for Radiation Enteritis].

Although radiation therapy for pelvic cancer leads to improved outcomes, it may cause radiation enteritis. Radiation enteritis is classified as early and late reaction. Late reaction indicate progressive and irreversible changes caused by ischemic changes of the intestinal mucosa. Severe cases require a surgical treatment, which is challenging because of severe adhesions and a high risk of suture failure. In addition, the postoperative course may be unfavorable in some cases. We performed surgery for 4 radiation enteritis cases; however, the postoperative course was unfavorable in 2 cases because of impaired absorption and ileus of the remaining short bowel. These patients could not eat adequately after discharge; therefore, we needed to explain and make them understand the benefits and disadvantages of radiation therapy.

Optimization of robot-assisted thoracoscopic esophagectomy in the lateral decubitus position.

BACKGROUND: On the introduction of robot-assisted thoracoscopic esophagectomy (RATE), we refined the robotic system application to enhance our surgical experience obtained through thoracoscopic esophagectomy (TE) in the lateral decubitus position (LDP). Herein, we evaluate our methods introduced to optimize RATE in the LDP. METHODS: We performed RATE in the LDP with camera rotation and manual hand control assignment to reproduce the surgical view and manipulation of open esophagectomy. Forty patients underwent RATE between July 2018 and August 2020. After the initial 30 cases (initial RATE group), we optimized the port arrangement and robot settings in the most recent ten cases (recent RATE group). The surgical results of RATE were compared with those of 30 patients underwent TE between April 2014 and May 2019 selected by propensity score-matched analysis based on cStage (TE group). RESULTS: Operative duration was significantly longer in the initial RATE group than the TE group and the recent RATE group. Thoracic blood loss was significantly less in the initial RATE group than the TE group. Console time was significantly shorter in the recent RATE group than the initial RATE group. There was no surgical mortality in RATE and the surgical morbidity rate was similar in the three groups. CONCLUSIONS: Camera rotation and manual hand control assignment during RATE in the LDP reproduced the surgical view and manipulation of open esophagectomy and TE in the LDP. The robotic platform enabled meticulous dissection and reduced blood loss, but was initially time-consuming. Optimization of the port arrangement minimized operative duration.

Evaluation of the efficacy and safety of salvage photodynamic therapy by talaporfin sodium for cervical esophageal cancers and lesions larger than 3 cm.

BACKGROUND: Salvage photodynamic therapy with talaporfin sodium has a high local control rate for esophageal cancer after definitive chemoradiotherapy. The eligibility criteria for photodynamic therapy include the absence of invasion to the cervical esophagus and a 3 cm maximum longitudinal lesion length. There is little evidence regarding the efficacy and safety of lesions outside the eligibility criteria. This retrospective cohort study evaluated the efficacy and safety of photodynamic therapy of such lesions. METHODS: Patients with consecutive lesions between February 2016 and May 2020 (n = 36) were enrolled. The local complete response rates and adverse events were compared between patients with cervical and non-cervical lesions and those with lesions larger and smaller than 3 cm. RESULTS: The local complete response rate was 77.8% and was significantly lower in cervical than in non-cervical lesions (20.0% vs 80.6%, p = 0.005). Esophageal stricture, laryngeal pain, and fever were significantly higher in the cervical than in the non-cervical lesion group; however, the detected adverse events were up to grade 2. Laser exposure dose was high in lesions larger than 3 cm (median, 650 vs 400 J; p < 0.001). No significant differences in local complete response rates and adverse effects were noted. One case involving a lesion larger than 3 cm needed balloon dilations for esophageal stricture. CONCLUSIONS: Although salvage esophageal photodynamic therapy was effective for local control with acceptable safety after definitive chemoradiotherapy failure, photodynamic therapy toward cervical lesions had a statistically lower local complete response rate. Lesions larger than 3 cm may be considered treatable.

Comparison of prognostic impact of anatomic location of the pancreas on postoperative pancreatic fistula in laparoscopic and open gastrectomy.

BACKGROUND: Postoperative pancreatic fistula (POPF) is a serious complication after gastric cancer surgery. The current study aimed to investigate the significance of the anatomic location of the pancreas as a predictor for POPF in both laparoscopic gastrectomy (LG) and open gastrectomy (OG). METHODS: In total, 233 patients with gastric cancer were assessed retrospectively. We measured the maximum vertical (P-L height; PLH) and horizontal length (P-L depth; PLD) between the upper border of pancreas and the root of left gastric artery on a preoperative CT in the sagittal direction. The maximum length of the vertical line between the surface of the pancreas and the aorta (P-A length), previously reported as prognostic factor of POPF, was also measured. We investigated the correlations between these parameters and the incidence of POPF in LG and OG groups. RESULTS: Among the patients in this study, 118 underwent OG and 115 underwent LG. In LG, the median PLH and P-A length in patients with POPF were significantly longer compared with those without POPF (p = 0.026, 0.034, respectively), but not in OG. There was no significant difference in the median PLD between the patients with or without POPF in both LG and OG. The multivariate analysis demonstrated that PLH (odds ratio [OR] 4.19, 95% confidence interval [CI] 1.57-11.3, P = 0.004) and P-A length (OR 4.06, 95%CI 1.05-15.7, P = 0.042] were independent factors for predicting POPF in LG. However, intraoperative blood loss (OR 2.55, 95%CI 1.05-6.18, P = 0.038) was extracted as an independent factor in OG. The median amylase level in the drained fluid (D-Amy) were significantly higher in patients with high PLH(≥12.4 mm) or high P-A length (≥45 mm) compared with those with low PLH or low P-A length in LG. However, there were no differences in the D-Amy levels by PLH or P-A length in OG patients. CONCLUSIONS: The anatomic location of the pancreas is a specific and independent predictor of POPF in LG but not in OG. PLH is a simple parameter that can evaluate the anatomic position of the pancreas, and it may be useful for preventing POPF after LG.

Pleomorphic rhabdomyosarcoma of the liver in an adult: a rare case report.

BACKGROUND: Rhabdomyosarcoma (RMS), a malignant neoplasm that normally differentiates to form striated muscle, is the most common type of childhood soft tissue sarcoma. However, it infrequently occurs in adults and is uncommon in the liver. We herein report a case of RMS of the liver in an adult. CASE PRESENTATION: A 73-year-old woman was admitted to our institution for investigation of a hepatic mass. She had been followed for primary biliary cirrhosis for the past 20 years. A contrast-enhanced computed tomography scan of the abdomen showed a 12- × 10-cm heterogeneous low-density mass lesion containing cystic and solid components. A percutaneous liver biopsy was performed, and poorly differentiated cancer containing an RMS cell-like component was observed. The patient was diagnosed with RMS of the liver, and open surgery with right hepatic lobectomy was performed. Histopathological examination confirmed a diagnosis of pleomorphic RMS of the liver. The patient died of rapid progression of the tumor 6 months after the operation. CONCLUSIONS: The tumor site in the present case is rare. The details of this case add to the current evidence base regarding establishment of the standard diagnosis and treatment of this rare condition. We recommend consideration of RMS as a differential diagnosis for hepatic tumors.

Roles of the hexosamine biosynthetic pathway and pentose phosphate pathway in bile acid-induced cancer development.

Esophageal squamous cell carcinomas (ESCCs) as well as adenocarcinomas (EACs) were developed in rat duodenal contents reflux models (reflux model). The present study aimed to shed light on the mechanism by which bile acid stimulation causes cancer onset and progression. Metabolomics analyses were performed on samples of neoplastic and nonneoplastic tissues from reflux models, and K14D, cultivated from a nonmetastatic, primary ESCC, and ESCC-DR, established from a metastatic thoracic lesion. ESCC-DRtca2M was prepared by treating ESCC-DR cells with taurocholic acid (TCA) to accelerate cancer progression. The lines were subjected to comprehensive genomic analyses. In addition, protein expression levels of glucose-6-phosphate dehydrogenase (G6PD), nuclear factor kappa B (NF-κB) (p65) and O-linked N-Acetylglucosamine (O-GlcNAc) were compared among lines. Cancers developed in the reflux models exhibited greater hexosamine biosynthesis pathway (HBP) activation compared with the nonneoplastic tissues. Expression of O-GlcNAc transferase (OGT) increased considerably in both ESCC and EAC compared with nonneoplastic squamous epithelium. Conversely, cell line-based experiments revealed the greater activation of the pentose phosphate pathway (PPP) at higher degrees of malignancy. G6PD overexpression in response to TCA exposure was observed. Both NF-κB (p65) and O-GlcNAc were expressed more highly in ESCC-DRtca2M than in the other cell lines. Moreover, ESCC-DRtca2M cells had additional chromosomal abnormalities in excess of ESCC-DR cells. Overall, glucose metabolism was upregulated in both esophageal cancer tissue and cell lines. While bile acids are not mutagenic, chronic exposure seems to trigger NF-κB(p65) activation, potentially inducing genetic mutations as well as facilitating carcinogenesis and cancer progression. Glucose metabolism was upregulated in both esophageal cancer tissue and cell lines, and the HBP was activated in the former. The cell line-based experiments demonstrated upregulation of the pentose phosphate pathway (PPP) at higher degrees of malignancy. While bile acids are not mutagenic, chronic exposure seems to trigger G6PD overexpression and NF-κB (p65) activation, potentially inducing genetic mutations as well as facilitating carcinogenesis and cancer progression.

Grading of Atrophic Gastritis is Useful for Risk Stratification in Endoscopic Screening for Gastric Cancer.

OBJECTIVES: In order to screen for gastric cancer effectively, its interval should be set according to the risk. This study aimed to determine whether risk stratification is possible using the data obtained from medical examination or endoscopic findings. METHODS: First, subjects who underwent both cancer screening and medical examination from 2009 to 2015 and underwent cancer screening once more by 2016 were studied. Data such as the lipid profile and history of smoking obtained during the medical examination, and the grade of atrophy and presence of peptic ulcers were studied using multivariate analysis. Next, subjects who underwent cancer screening twice or more between 2009 and 2015 with or without medical examinations were studied to analyze any correlation between the grade of atrophy and cancer occurrence using univariate analysis. In both studies, the status of Helicobacter pylori (HP) infection was determined. RESULTS: In the multivariate analysis, 9378 subjects were included. Aging, advanced atrophy, presence of ulcers, and uric acid levels were identified as risk factors. Among subjects who underwent successful HP eradication therapy, advanced atrophy and aging were observed to be crucial risk factors. In the univariate analysis, there were 12,941 subjects. Gastric cancer occurred more frequently in the more severe atrophy group (P < 0.001). The annual rate of cancer occurrence in the most severe atrophy group was 0.31%, which was approximately thrice as that in the less atrophy group. CONCLUSIONS: Risk stratification was possible based on endoscopic examination alone. The interval should be set depending on each case.

The Embryonic Stem Cell-Specific Transcription Factor ZFP57 Promotes Liver Metastasis of Colorectal Cancer.

BACKGROUND: The embryonic stem cell-specific transcription factor, ZFP57, has been shown to play an important role in tumor formation. In this study, we examined if ZFP57 is involved in colorectal cancer metastasis. MATERIALS AND METHODS: First, we used colorectal cancer cell lines to perform in vivo metastatic experiments with nude mice. Next, we carried out immunohistochemical analysis of clinical specimens of colorectal cancers. RESULTS: In liver metastatic experiments using human colorectal cancer HT29 and HCT116 cells, liver polymetastases occurred at high frequency in ZFP57-overexpressing HT29 and HCT116 cells, whereas both control cells only resulted in oligometastases. Next, we analyzed ZFP57 expression using clinical specimens. Liver metastasis-positive cases were more frequently associated with ZFP57 overexpression than negative cases in primary lesions of colorectal cancer, and the overexpression was particularly remarkable in tumor invasive lesions. Furthermore, ZFP57 overexpression was significantly correlated not only with liver metastasis but also with lymph node metastasis. In addition, the expression level of ZFP57 was significantly correlated with that of the metastasis-related gene NANOG. We also found that ZFP57 overexpression reduced the progression-free survival rate of patients with colorectal cancer. CONCLUSIONS: This study demonstrated that ZFP57 plays an important role in the hematogenous metastasis of colorectal cancer, suggesting that it could be used as a novel treatment target.

[Successful Treatment of Advanced Esophageal Cancer with DCF Chemotherapy and Pegfilgrastim].

Docetaxel, cisplatin, and 5-FU(DCF)chemotherapy for esophageal cancer has been reported to be highly effective, but often causes serious adverse events, including severe bone marrow suppression. We report the successful treatment of a 67- year-old man with highly advanced esophageal cancer with invasion of the left bronchus and broad lymph node metastases. He received induction chemotherapy with DCF therapy, and prophylactic administration of pegfilgrastim. He safely completed 5 courses of DCF therapy without serious adverse events, such as neutropenia and febrile neutropenia. The size of the primary tumor and lymph node metastases remarkably reduced after the third course of DCF. He underwent thoracoscopic esophagectomy with three-field lymph node dissection and reconstruction with a gastric tube. The pathological findings of the resected specimen showed no viable malignant cells in the primary lesion and the pathological effect after chemotherapy was judged as Grade 3. Viable cancer cells still remained in 10 lymph nodes in the dissected field. DCF therapy with prophylactic administration of pegfilgrastim may be an effective and safe treatment for advanced esophageal cancer.

[A Case of Stage â £Rectal Cancer with Dyskeratosis Congenita].

A 27-year-old man was diagnosed with dyskeratosis congenita from DKC1 gene mutation at 9 years of age and had been followed-up regularly.An upper gastrointestinal endoscopy performed for vomiting revealed gastric varices.Further examination resulted in a diagnosis of Stage Ⅳrectal cancer with portal hypertension, splenomegaly, liver, and lung metastasis and he was referred to our department.A laparoscopic splenectomy was performed, followed by a laparoscopic low anterior resection for rectal cancer.Subsequently, resection of the pulmonary and liver metastasis was performed, resulting in macroscopic radical resection.However, 3 months after the hepatectomy, unresectable multiple lung metastasis was detected and he received 5 courses of chemotherapy with cetuximab.A grade 3 skin rash was observed and chemotherapy was discontinued. After 5 courses, he had pneumothorax and received drainage.He had sudden respiratory failure 2 days after pleural adhesion therapy of OK-432 was performed.He was diagnosed with interstitial pneumonia induced by OK-432 and steroid pulse therapy, which resulted in his death without improvement 21 days after admission.

[A Case of Thrombotic Microangiopathy Arising from Breast Cancer Treated with Chemotherapy].

The present study reports the case of a 49-year-old woman who was diagnosed with cancer of the left breast at the age of 43 years.Following chemotherapy, the patient had undergone partial mastectomy and axillary lymphadenectomy.Postoperatively, she underwent radiotherapy and hormone therapy.Five years and 4 months after the operation, the patient developed pain in the cervical vertebrae and was diagnosed with spinal metastasis.During the period, she began experiencing fatigue and hematological investigations indicated anemia, as well as thrombocytopenia, jaundice, and schistocytes.The patient was referred to our facility for further examination and treatment.On investigation, she was diagnosed with cancer-related thrombotic microangiopathy(TMA).The patient was advised to undergo chemotherapy due to which symptoms of TMA were relieved.She continued to receive chemotherapy for the following 3 years and 2 months until her death.

[A Case of Histiocytoid Breast Carcinoma Accompanied by Multiple Axillary Lymph Node Metastases].

According to previous reports in our country, histiocytoid breast carcinoma is a very rare case of its tissue type, accounting for only 0.3% of all breast cancer cases. We have neither established a diagnostic standard nor a general idea for these tumors. Previously, its inherited pathology was assumed to be a sub-form of invasive lobular carcinoma. However, some researchers indicate the presence of components that are assumed to originate from milk ducts or differentiation in the apocrine gland. In this way, origins of pathologies for these tumors seem to be complex. Previous reports suggest cases of relatively long survival times without spreading to distant sites. Recently, we encountered one case of histiocytoid breast carcinoma accompanied by multiple axillary lymph node metastases.

Survival benefit of multimodal local therapy for repeat recurrence of thoracic esophageal squamous cell carcinoma after esophagectomy.

BACKGROUND: This study was performed to clarify the optimal therapeutic strategy for recurrent disease after esophagectomy. METHODS: We investigated the prognosis of 37 patients who developed recurrence among 128 patients who underwent curative thoracoscopic esophagectomy (TE) at Kanazawa University Hospital. The prognostic factors after recurrence were examined by univariate and multivariate analyses. RESULTS: Of these 37 recurrences, 29 patients underwent local therapy (surgery, 10 patients; surgery followed by radiation, 2 patients; radiation, 17 patients). Radiation includes intensity-modulated radiation therapy, chemoradiation, and simple radiation therapy. Seventeen patients (58.6%) were considered to have undergone successful therapy by disappearance or diminishment of the targeted region without regrowth. Eleven of 17 patients (64.7%) showed repeat recurrence at another site. Multiple local therapy was performed for repeat recurrence or uncontrollable first therapy. Finally, 57 local therapies were performed. Using multimodal local therapy, 37 (64.9%) of 57 recurrences were successfully managed. The 12 patients treated by surgery as the initial therapy showed the most favorable survival. Seventeen patients who underwent successful initial therapy showed better survival than others. Multiple or miscellaneous organ metastasis, abdominal lymphatic recurrence and best supportive care at recurrence were statistically significant negative variables for survival after recurrence. Performance of surgery and successful therapy as the initial recurrence were statistically significant positive variables for survival after recurrence. Multivariate analysis showed that successful therapy at the initial recurrence was the only independent variable for survival after recurrence. CONCLUSIONS: Multimodal local therapy for repeat recurrence after TE contributes to the improvement of survival after recurrence.

Oral cryotherapy for prophylaxis of oral mucositis caused by docetaxel, cisplatin, and fluorouracil chemotherapy for esophageal cancer.

BACKGROUND: Chemotherapy, including preoperative chemotherapy, plays an important role in the treatment of esophageal cancer. However, although docetaxel, cisplatin, and fluorouracil (DCF) therapy has a powerful antitumor effect, the associated adverse events make it difficult to maintain the patient's general condition. Oral mucositis is an important adverse effect of chemotherapy, and its severity, frequency, and impact on patient quality of life should not be underestimated. This study evaluated the role of oral cryotherapy for prophylaxis of oral mucositis caused by DCF therapy. METHODS: We retrospectively examined the incidence and severity of adverse events, including mucositis, in 72 patients with esophageal cancer treated with DCF. Fifty-eight patients received cryotherapy during docetaxel administration and 14 received no cryotherapy. RESULTS: The incidence of mucositis of all grades and grade 3 was significantly lower in the cryotherapy group compared with the no-cryotherapy group (24.1% vs. 71.4%, P < 0.001 and 0% vs. 28.6%, P = 0.001, respectively). The incidence of anorexia of all grades and grade 3 was also significantly lower in the cryotherapy group (22.4% vs. 57.1%, P = 0.037 and 0% vs. 28.6%, P = 0.010, respectively). CONCLUSION: Adjunctive oral cryotherapy is effective for the prophylaxis and relief of oral mucositis and anorexia caused by chemotherapy.