Traumatic sigmoid colon rupture due to breast cancer metastasis: a case report.

The metastasis of breast cancer to the gastrointestinal tract is rare. Herein, we presented the case of an 85-year-old woman who had a history of invasive lobular carcinoma and experienced complete colon rupture due to relatively low-energy trauma. The patient underwent bilateral total mastectomy and axillary dissection following preoperative chemotherapy 6 years ago. She had a local recurrence 2 years after the surgery and underwent chemotherapy. Subsequently, the cancer metastasized to the thoracolumbar area and retroperitoneum. In addition, the patient fell from a height of 30 cm while hanging laundry and her abdomen hit a hose reel. Emergency surgery was performed, and the entire circumference of the sigmoid colon was ruptured. The ruptured colon lesion was resected, and the stump was closed. A double-barrel transverse colostomy was created as it was impossible to lift the stump up to the abdominal wall. Histopathological examination revealed the invasive lobular carcinoma metastasis and a linitis plastica-like change of the colon wall, which probably consequently weakened. In addition, minimal trauma can damage the gastrointestinal tract that had invasive lobular carcinoma metastasis.

Field carcinogenesis and biological significance of the potential of the bystander effect: carcinogenesis, therapeutic response, and tissue regeneration.

The "bystander effect" is a transmission phenomenon mediating communication from target to non-target cells, as well as cell-to-cell interactions between neighboring and distantly located cells. In this narrative review, we describe the fundamental and clinical significance of the bystander effect with respect to cell-to-cell interactions in carcinogenesis, therapeutic response, and tissue regeneration. In carcinogenesis, the bystander effect mediates communications between tumor microenvironments and non-malignant epithelial cells and has been suggested to impact heterogeneous tumorigenic cells in tumors and cancerized fields. In therapeutic response, the bystander effect mediates communications between drug-sensitive and drug-resistant cells and may transmit both drug efficacy and resistance. Therefore, control of therapeutic response transmission via the bystander effect might offer a promising future cancer treatment. Finally, in tissue regeneration, circulating cells and stromal cells may differentiate into various cells for the purpose of tissue regeneration under direction of the bystander effect arising from surrounding cells in a defective space. We hope that the findings we present will promote the development of innovative cancer therapies and tissue regeneration methodologies from the viewpoint of cell-to-cell interactions through the bystander effect.

A case of spontaneous esophageal submucosal hematoma.

A 78-year-old man visited a nearby hospital owing to chest pain triggered by vomiting. As computed tomography revealed suspected esophageal perforation, he was referred to our hospital. Upper gastrointestinal endoscopy showed blood coagula extending from the middle intra-thoracic to the esophago-cardiac junction (ECJ), and it was diagnosed as an esophageal submucosal hematoma. Conservative therapy was initiated by fasting and discontinuing oral anticoagulants. The lesion was monitored by upper gastrointestinal endoscopy. On day 12 of the symptom appearance, the hematoma had completely disappeared and on day 22, the patient was discharged from the hospital. In most cases, esophageal submucosal hematoma has a favorable course with preservative treatment. Esophageal submucosal hematoma should be considered as one of the differential diagnoses for chest pain triggered by vomiting.

Coexistence of superficial carcinogenesis of resident epithelium besides neuroendocrine neoplasm of the digestive tract.

BACKGROUND & AIMS: Mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) is a rare neuroendocrine neoplasm (NEN) comprising dual neuroendocrine and non-neuroendocrine components. Although the coexistence pattern of neuroendocrine and non-neuroendocrine components in definitive MiNEN is thought to overlap, there may be a coexistent pattern of both components, such as superficial carcinoma adjacent to NEN. The present study evaluated the histopathological findings of the coexistence pattern of superficial carcinomas adjacent to NENs in the esophagogastrointestinal tract. METHODS: From 2000 to 2019, 35 serial NEN resections of the esophagus (n = 9), stomach (n = 3), and large intestine (n = 23), respectively, were performed at Gunma University Hospital. Borderline areas between NEN and resident superficial epithelium were observed in the 35 serial NEN cases as well as two additional cases from affiliated hospitals. RESULTS: Among the 35 serial NEN samples, squamous cell carcinomatous/dysplastic components were identified 77.8% (7/9 cases) of esophageal NENs, and adenocarcinomatous areas were seen in 66.7% (2/3 cases) of gastric NENs and 26% (6/23 cases) of colorectal NENs. Thus, all superficial carcinomatous components adjacent to NENs were observed as squamous cell carcinoma/dysplasia in esophagus and adenocarcinoma in stomach and large intestine, which showed histological characteristics as the resident epithelial pattern in each organ. CONCLUSIONS: These findings suggested a potential "paratransformation" or "bystander effect" in resident epithelium by NENs. Thus, "bystander carcinogenesis" could be a pathogenic mechanism of resident epithelium transformation adjacent to NENs in the esophagogastrointestinal tract.

Comparative study on recurrence pattern and treatment method after radical esophagectomy for esophageal cancer.

Background : With regard to the recurrence of esophageal cancer after surgery, the prognosis has improved with the progress of multimodal perioperative treatment. In this study, the recurrence pattern, treatment method, and prognosis of recurrent cases following esophageal cancer surgery were retrospectively examined. Materials and Methods : Three hundred seven patients with histologically proven squamous cell carcinoma, adenocarcinoma, and others were enrolled in the study. With respect to clinicopathologic factors and recurrence patterns, recurrence risk factors, recurrence period, treatment for recurrence, and prognosis were investigated.Results : Ninety two percent of all recurrent cases were observed within two years after radical esophagectomy. Locoregional recurrence, distant recurrence, and mixed recurrence were observed in 38 (35%), 56 (51%), and 16 (14%) cases, respectively. Patients with lymph node metastasis showed a significantly longer survival in comparison to those with metastasis to other organs (p = 0.0032). When analyzed using the treatment method, patients who underwent surgery (only surgery or additional postoperative chemotherapy) exhibited better survival in comparison to those who underwent other treatments. Discussion : Detailed and strict follow-up within two years are necessary in cases with deeper than muscular invasion, cases with extensive lymph node metastasis, or cases with lymphatic or vascular invasion. J. Med. Invest. 68 : 129-135, February, 2021.

Resistance to Preoperative Oral Care Is Associated With Postoperative Pneumonia After Oesophageal Cancer Surgery.

BACKGROUND/AIM: Postoperative pneumonia is a serious complication of major oesophageal surgery. We aimed to clarify the association between the degree of improvement in oral hygiene by perioperative oral care and postoperative pneumonia in oesophageal cancer patients. PATIENTS AND METHODS: Oesophageal cancer patients (n=129) who underwent esophagectomy received perioperative oral care. Their oral hygiene was evaluated using the Oral Assessment Guide (OAG). The relationship between perioperative OAG scores and postoperative complications was analysed. RESULTS: The average OAG scores before starting oral care, pre-operation, and post-operation were 11.0±1.7, 9.1±1.5, and 11.2±3.0, respectively (p<0.001). An increase in preoperative OAG scores was independently associated with postoperative pneumonia on multivariate analysis (p=0.027). CONCLUSION: Preoperative oral care improves oral hygiene in patients undergoing oesophageal cancer surgery. No improvement in oral hygiene despite preoperative oral care was an independent predictor of postoperative pneumonia.

CD36 Expression Is Associated with Cancer Aggressiveness and Energy Source in Esophageal Squamous Cell Carcinoma.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is an important cause of cancer-related death worldwide. CD36, a long-chain fatty acid (FA) receptor, can initiate metastasis in human oral squamous cell carcinoma (SCC), and its expression is associated with poor prognosis in several cancers. The clinical significance of CD36 expression and its function in ESCC remain unknown. METHODS: We examined the clinical significance of CD36 expression in 160 ESCC samples using immunohistochemical staining. Functional analysis was performed to determine the association between CD36 and ESCC characteristics (proliferative ability, invasive ability, and energy source dependency). RESULTS: Thirty (18.8%) ESCC cases showed high CD36 expression, indicating a significant association with progression. CD36 suppression inhibited proliferation and invasiveness in ESCC cells. ESCC cells with CD36 suppression used specific essential amino acids (EAAs) as energy sources. Cell viability depended on FAs under CD36 expression. The viability of ESCC cells with CD36 suppression depended on EAAs but not FAs. CONCLUSIONS: CD36 may be a good biomarker and therapeutic target in ESCC. Our data provide new insights into the basic mechanism of CD36-dependent energy utilization for ESCC survival. CD36 might be a key regulator of the dependency of FAs as energy source in ESCC cells.

Effects of injured and dead cells of Escherichia coli on the colony-forming rate of live cells.

Osmotic stress-induced injured cells of Escherichia coli were prepared by sorting live cells onto tryptic soy agar (TSA) containing 10-50% sucrose. The time course of colony-forming rate (CFR%) was analyzed. A time delay in colony formation indicated a sublethal effect. The final CFR level at 24 h indicated the relative number of culturable cells irrespective of injury. A value of (100-CFR)% at 24 h indicated a lethal effect. When cells were grown on TSA containing 10% sucrose, the time delay was 4 h and the lethal effect was 4%. However, dead cells inhibited the growth of live cells. Physical contact with insoluble matter derived from dead cells or dead cells themselves might have caused growth inhibition. These findings highlight a novel perspective on colony count methods in practical situations, such as when sampling foods containing a high concentration of sucrose.

Uptake of positron emission tomography tracers reflects the tumor immune status in esophageal squamous cell carcinoma.

The relationship between the local immune status and cancer metabolism regarding 18 F-FDG and 18 F-FAMT uptake in esophageal squamous cell carcinoma (ESCC) remains unknown. The present study examined the correlations between tumor immune status, clinicopathological factors, and positron emission tomography (PET) tracer uptake in ESCC. Forty-one ESCC patients who underwent 18 F-FDG PET and 18 F-FAMT PET before surgery were enrolled in the study. Immunohistochemistry was conducted for programmed death 1 (PD-1), CD8, Ki-67, CD34, GLUT1 (18 F-FDG transporter) and LAT1 (18 F-FAMT transporter). ESCC specimens with high tumoral PD-L1 and high CD8-positive lymphocytes were considered to have "hot tumor immune status." High PD-L1 expression (53.7%) was significantly associated with tumor/lymphatic/venous invasion (P = 0.028, 0.032 and 0.018), stage (P = 0.041), CD8-positive lymphocytes (P < 0.001), GLUT1 (P < 0.001), LAT1 expression (P = 0.006), Ki-67 labelling index (P = 0.009) and CD34-positive vessel counts (P < 0.001). SUVmax of 18 F-FDG was significantly higher in high PD-L1 cases than in low PD-L1 cases (P = 0.009). SUVmax of 18 F-FAMT was significantly higher in high PD-L1 (P < 0.001), high CD8 (P = 0.012) and hot tumor groups (P = 0.028) than in other groups. High SUVmax of 18 F-FAMT (≥4.15) was identified as the only predictor of hot tumor immune status. High PET tracer uptake was significantly associated with cancer aggressiveness and hot tumor immune status in ESCC. PET imaging may be an effective tool to predict tumor immune status in ESCC with respect to immune checkpoint inhibitor sensitivity.

Pathophysiology of Vomiting and Esophageal Perforation in Boerhaave's Syndrome.

BACKGROUND AND AIMS: Boerhaave's syndrome, involving esophagus rupture, is considered a pathological response to vomiting that may occur just before perforation. However, the mechanism of vomiting and occurrence of this disease have not been clearly demonstrated. METHODS: We identified patients with esophageal perforation between 1995 and 2017 and reviewed endoscopic findings at retching during upper gastrointestinal endoscopy. Finally, we proposed a theory for the underlying pathological mechanism. RESULTS: We retrospectively investigated 10 patients with esophageal perforation between 1995 and 2017. All patients presented after vomiting associated with large volumes of food and alcohol intake. Nine were treated by primary closure of the perforation and drainage of the thoracic cavity, and one was conservatively treated. In all cases, the perforations were longitudinal tears (1-4 cm) and located in the left of the esophagus, just above the gastric cardia. CONCLUSIONS: We hypothesize that vomiting occurred by retrograde propagation of gastrointestinal motor contraction from the jejunum to the gastric antrum, followed by prolapse of the gastric fornix mucosal into the esophagus. Subsequent esophageal perforation probably resulted from excessive prolapse due to strong contraction and destruction of the muscularis mucosa of the left side of abdominal esophagus, with longitudinal stretching of the whole left esophageal wall due to traction. We also propose that Boerhaave's syndrome is defined as "post-emetic esophageal perforation" to ensure broader recognition and more expedient diagnosis and treatment. Remaining conditions without any definite causes may be labeled "idiopathic" or "spontaneous" rupture of the esophagus.

Comparable Data Between Double Endoscopic Intraluminal Operation and Conventional Endoscopic Submucosal Dissection for Esophageal Cancer.

BACKGROUND: Endoscopic submucosal dissection (ESD) of superficial esophageal cancer has been used increasingly as an alternative to surgery because it is minimally invasive and has a high rate of en bloc resection. We previously reported that the double endoscopic intraluminal operation (DEILO) is a useful technique for ESD of early esophageal cancers. In the current study, we showed comparable short-term data between DEILO and conventional ESD groups to demonstrate the further advanced use of DEILO. METHODS: We studied 111 esophageal cancer patients with 111 lesions treated using endoscopic surgery between January 2010 and June 2016 at Gunma University Hospital. Of the patients, 51 underwent DEILO (DEILO group) and 60 underwent conventional ESD (ESD group). We compared the operable performance, complications, and pathological outcome between the ESD and DEILO groups. RESULTS: There was no significant difference in operable performance. However, the DEILO group showed a significantly lower rate of mediastinal emphysema compared to the ESD group (p = 0.025). Overall, the DEILO group showed a lower complication rate compared to the ESD group, although there was no apparent significance. CONCLUSION: To our knowledge, this is the first report comparing DEILO and conventional ESD for esophageal cancer. The results showed that DEILO is not inferior to conventional ESD. DEILO is an excellent endoscopic surgical method, although it has some limitations compared to conventional ESD.

Evaluation of Surgical Procedures that Affect the Hemodynamics Using the FloTrac System in Esophageal Cancer Patients.

BACKGROUND/AIM: Esophagectomy is more invasive compared to other gastrointestinal surgery types. Perioperative circulatory management is important to avoid postoperative heart complications. The FloTrac sensor along with the Vigileo monitor is a minimally invasive haemodynamic monitoring device. Here, we examined different surgical procedures affecting hemodynamics using the FloTrac system in esophageal cancer patients following esophagectomy. PATIENTS AND METHODS: Thirty-one patients undergoing postoperative monitoring with the FloTrac sensor/Vigileo monitor system following esophagectomy were included. Evaluation of cardiac index (CI) and stroke volume variation (SVV) measurements were performed by analyzing the number of aberrant values. We evaluated the correlation between the number of aberrant values of CI, SVV and surgical methods of esophagectomy and perioperative factors. RESULTS: There was no significant correlation between the number of aberrant values of CI, SVV and operative approach or fields of lymphadenectomy. Regarding the reconstruction route following esophagectomy, there was a significant correlation between the number of aberrant values of CI, SVV and retrosternal route compared with other routes. There was a significant correlation between the number of aberrant values of SVV and preoperative heart complication. CONCLUSION: Hemodynamic stability management using FloTrac/Vigileo system following esophagectomy is useful for safe performance of postoperative management of esophageal cancer patients.

Docetaxel, cisplatin, and 5-fluorouracil combination chemoradiotherapy for patients with cervical esophageal cancer: a single-center retrospective study.

BACKGROUND: To evaluate the efficacy of docetaxel, cisplatin, and 5-fluorouracil as combination chemoradiotherapy (DCF-RT) for cervical esophageal cancer (CEC), we performed a retrospective analysis of CEC patients treated by DCF-RT at a single institution. METHODS: We conducted a single-center retrospective study. Twenty-one patients with CEC who underwent DCF-RT between 1999 and 2017 at our institute were included in this study. Chemotherapy consisted of intravenous docetaxel at 50 mg/m2 on day 1, intravenous CDDP at 60 mg/m2 on day 1, and intravenous 5-FU at 600 mg/m2 on days 1-4, repeated every 4 weeks for two cycles. Among the 21 patients, six were irradiated using three-dimensional conformal RT (3D- conformal RT) and 15 were treated using intensity-modulated RT (IMRT) consisting of 60 Gy in 30 fractions. RESULTS: The median follow-up period was 49.6 months (range 4.6-97.6). The overall complete response (CR) and local CR rates were 61.9% and 81.0% for all patients, and 76.9% and 84.6% for patients without hypopharyngeal and/or thoracic esophageal invasion, respectively. The 3-year overall survival (OS), progression-free survival (PFS), and local failure-free survival (LFFS) rates were 79.6, 52.4, and 74.7%, respectively. Grade 3-4 leucopenia developed in 12 patients (70.6%), neutropenia developed in 13 patients (81.2%), and mucositis developed in 2 patients (9.5%). There were no treatment-related deaths. CONCLUSIONS: The 3-year OS and LFFS of patients who underwent DCF-RT were higher than those in the previous studies. Although the high rate of myelosuppression requires careful management, DCF-RT is a safe and effective modality for CEC.

Post-esophagectomy Adjuvant Chemotherapy Benefits Esophageal Cancer Patients.

BACKGROUND/AIM: Postoperative chemotherapy is an absolutely imperative treatment for advanced esophageal cancer patients, while preoperative chemotherapy is the standard therapy for clinical stage II/III esophageal squamous cell carcinoma (ESCC) in Japan. The aim of this study was to report the effect of postoperative chemotherapy on survival after esophagectomy due to thoracic esophageal squamous cell carcinoma. PATIENTS AND METHODS: One hundred thirteen consecutive patients with esophageal carcinoma who underwent esophagectomy were included. Several regiments were performed at various times. RESULTS: Adjuvant chemotherapy brought a significantly superior overall survival (p=0.002), although there was no significant difference in cancer-specific survival (p=0.054) for clinical stage II or stage III esophageal cancer patients. Depth of invasion (p=0.003), number of lymph node metastases (p=0.048), and venous invasion (p<0.001) were risk factors for recurrence in the adjuvant-chemotherapy group with positive lymph nodes. Additionally, a not well-differentiated type, lymphatic and venous invasions were risk factors for recurrence in the surgery-alone group without positive lymph nodes. CONCLUSION: Postoperative adjuvant chemotherapy contributes to the prognosis of clinical stage II or III esophageal cancer patients.

[High-resolution Manometry for Esophageal Motility Disorders].

High-resolution manometry (HRM) has significant contribution in the field of esophageal motility disorders recently. The development of HRM has categorized various esophageal motility disorders focusing on patterns of esophageal motor function. Additionally, the Chicago classification criteria are widely used for manometric diagnosis. HRM provides functional imaging of the esophagus. HRM has closely spaced pressure sensors and displays pressure variations as pressure topography plots. In the analysis of HRM according to the Chicago classification, a hierarchical categorization of motility disorders is made after evaluation of the individual swallow patterns. First the lower esophageal sphincter (LES) function, and subsequently the esophageal pressure patterns are used to make a diagnosis. The hierarchical flow-chart has 4 groups; (1) incomplete LES relaxation( achalasia or esophagogastric junction outflow obstruction), (2) major motility disorders, (3) minor motility disorders, (4) normal esophageal motility. HRM is the gold standard for diagnosis of esophageal motility disorders.

Correlation between high FBXW7 expression in pretreatment biopsy specimens and good response to chemoradiation therapy in patients with locally advanced esophageal cancer: A retrospective study.

BACKGROUND AND OBJECTIVES: Esophageal squamous cell carcinoma (ESCC) exhibits good reactivity to chemoradiation therapy (CRT). The dysregulation of F-Box and WD Repeat Domain Containing 7 (FBXW7) is associated with therapeutic resistance in cancer cells. However, the correlation between FBXW7 expression and CRT sensitivity in patients with clinical ESCC has been investigated only in few studies. Therefore, this study aimed to elucidate the significance of FBXW7 expression in pretreatment biopsy specimens from patients with ESCC receiving CRT. METHODS: We investigated the relationship between FBXW7 expression and CRT sensitivity in 30 pretreatment biopsy specimens with histological grades of post-CRT surgically resected tumors. Furthermore, we evaluated the effects of high FBXW7 expression on the sensitivity to cytotoxic agents, including docetaxel and nedaplatin, and radiation in ESCC cells in vitro. RESULTS: High FBXW7 expression before CRT correlated with a good pathological CRT response in patients with advanced ESCC (P < .05). Further, our in vitro data showed that both chemo and radiation sensitivity increased in TE-8 and KYSE140 cells overexpressing FBXW7 compared with mock cells because of the degradation of the anti-apoptotic protein MCL1. CONCLUSIONS: The evaluation of FBXW7 expression before CRT treatment is a potential predictor of good responders among patients with ESCC receiving CRT.

Multimodality Therapy Including Proton Beam Therapy for AFP Producing Esophageal Cancer with Multiple Liver Metastases.

A 50-year-old man who presented with a fever and epigastralgia was diagnosed to have esophageal carcinoma which was identified as poorly differentiated adenocarcinoma producing alpha-fetoprotein (AFP) with Barrett's esophagus. Computed tomography revealed multiple liver metastases and lymph node metastases surrounding the stomach. We first performed chemotherapy for the systemic lesions and proton beam therapy for the local control of lesions without complete remission and we were able to successfully control the frequently recurring lesions by proton beam therapy, cryotherapy and chemotherapy. A complete response has been maintained for 16 months and the overall survival time is 4 years and 2 months. Proton beam therapy for primary esophageal cancer and metastatic lesions was thus found to be an effective therapeutic option for such cases.

High expression of carcinoembryonic antigen and telomerase reverse transcriptase in circulating tumor cells is associated with poor clinical response to the immune checkpoint inhibitor nivolumab.

The present study aimed to enrich circulating tumor cells (CTCs) from blood samples using a new size-sorting CTC chip. The present study also set out to identify a blood sensitivity marker for the immune checkpoint inhibitor nivolumab in patients with advanced, pre-treatment lung cancer. The CTC sorting efficacy of the chip was investigated and the large cell fraction of blood samples from 15 patients with pre-treatment lung cancer who were later administered nivolumab were purified. The expression levels of carcinoembryonic antigen (CEA), human Telomerase Reverse Transcriptase (hTERT), cytokeratin19 (CK19), and programmed death ligand-1 (PD-L1) were investigated to clarify the association between these CTC markers and the clinical response to nivolumab. The CTC chip effectively enriched cells from lung cancer cell line PC-9. The large cell fraction had a high expression of CEA and hTERT, with the former being significantly associated with the clinical response to nivolumab. The expression of CEA and hTERT in CTCs derived from the blood of a patient with lung cancer were also validated. The evaluation of CEA and possibly hTERT in CTCs collected by the CTC chip may represent a promising predictive blood marker for sensitivity to nivolumab. To the best of our knowledge this is the first report to describe the predictive CTC marker for nivolumab in pre-treatment patients.

Elucidation of the Anatomical Mechanism of Nodal Skip Metastasis in Superficial Thoracic Esophageal Squamous Cell Carcinoma.

BACKGROUND: Lymph node metastasis (LNM) is a standard mechanism of cancer progression in esophageal squamous cell carcinoma (ESCC). We aimed to clarify the anatomical mechanism of skip nodal metastasis to mediastinal zones by analyzing the relationship between LNM to sentinel zones and lymphatic vessel counts in the muscle layer adjacent to the outer esophagus. METHODS: We examined the surgical records of 287 patients with ESCC who underwent potentially curative surgery (three-field lymphadenectomy) and whole esophagi, including pharynges and stomachs from 10 cadavers, to determine the number of lymphatic vessels in the intra-outer longitudinal muscle layer adjacent to the outer esophagus of the cervical (Ce), upper thoracic, middle thoracic (Mt), lower thoracic (Lt), and abdominal esophagi (Ae). RESULTS: The frequency of LNM to the middle mediastinal and supraclavicular zones, including the Mt and Ce, respectively, was lower than to the upper and lower mediastinal and abdominal zone in patients with superficial and advanced thoracic ESCC. In cadavers, the lymphatic vessel counts of the intra-outer longitudinal muscle layer in the Mt and Ce were significantly lower than those of the Lt and Ae, suggesting that lymphatic flow toward the outside of the Mt and Ce was not more abundant than to other sites. CONCLUSION: Our anatomical data suggested that the absence of intra-muscle lymphatic vessels in the middle mediastinal and supraclavicular zones causes skip LNM in patients with thoracic ESCC. Thus, standard esophagectomy with lymph node dissection, including distant zones, may be appropriate for treating patients with superficial thoracic ESCC.