Coagulopathy Induced by Antibiotics Usage and Bowel Obstruction With Colon Cancer: Report of a Rare Case.

This case report presents a rare occurrence of coagulopathy induced by antibiotics in a woman in her 90s with chronic bowel obstruction and massive colon cancer. The patient developed vitamin K deficiency-related coagulopathy following antibiotic administration, resulting in bleeding complications. Despite initial consideration of disseminated intravascular coagulation, further investigations revealed antibiotic-induced vitamin K deficiency. Prompt discontinuation of antibiotics and IV vitamin K2 administration led to the resolution of coagulopathy. The case emphasizes the importance of cautious antibiotic use in patients with chronic bowel obstruction and prolonged fasting. The protein induced by vitamin K absence-II (PIVKA-II) proved valuable in diagnosing vitamin K deficiency. The learning points include the potential for coagulopathy with antibiotics in prolonged bowel obstruction and the utility of PIVKA-II in assessing vitamin K deficiency. Healthcare providers should exercise caution when administering antibiotics in similar clinical scenarios.

Identifying the Hernial Orifice in Superior Lumbar Hernia Repair by Utilizing Anatomical Landmarks on Preoperative CT.

Superior lumbar hernias are extremely rare, and surgical repair is essential for their treatment. However, the direct observation of the hernial orifice is frequently difficult because the hernia disappears in prone or lateral positions, which is an issue when using the open approach. Therefore, using anatomical landmarks to detect the hernial orifice on preoperative CT scans may be useful for correct identification and visualization. Here, we report two cases of superior lumbar hernias successfully treated using the abovementioned method.

Torsion of the Greater Omentum: A Mimicker of Acute Appendicitis.

Torsion of the greater omentum is rare and difficult to diagnose preoperatively. There are operative or non-operative treatment options. Operative management is often done for patients with abdominal pain in the right lower quadrant because omental torsion is misdiagnosed as appendicitis. If omental torsion is accurately diagnosed, previous reports suggest that symptoms may improve 12-120 hours after non-operative management of a primary omental torsion. Here, we report a successful case of surgical treatment for torsion of the greater omentum after non-operative treatment was ineffective. Thus, considering the severity of the pain and operative risk, a laparoscopic omentectomy may be feasible to relieve the severe abdominal pain promptly.

MMR markers correlate with clinical outcome in patients with esophageal squamous cell carcinoma.

BACKGROUND: The DNA mismatch repair system is one of the defense mechanisms in the body, and the inactivation of mismatch repair plays a pivotal role in secondary carcinogenesis and progression. However, the significance of mismatch repair in esophageal squamous cell carcinoma (ESCC) has not been established. In this study, we explored the diagnostic and prognostic significance of mismatch repair markers, mutL homologue 1 (MLH1), post-meiotic segregation increased 2 (PMS2), mutS homologue 2 (MSH2), and mutS homologue 6 (MSH6), in patients with ESCC. METHODS: We used a notation based on the proportion of immunoreactivity/expression for immunohistochemistry (PRIME notation), which allows the comparison of mismatch repair expression by assigning a score to PRIME notation. MLH1, PMS2, MSH2, and MSH6 were examined immunohistochemically in 189 surgically resected ESCC specimens. RESULTS: A total of 100/189 patients with ESCC (53%) received preoperative chemotherapy. The rates of ESCC cases with decreased mismatch repair status were 13.2%, 15.3%, 24.8%, and 12.6% for MLH1, PMS2, MSH2, and MSH6, respectively. The decreased status of individual mismatch repair markers was significantly correlated with worse prognosis in patients with ESCC. Additionally, MSH2, MSH6, and PMS2 were significantly associated with response to preoperative chemotherapy. Multivariate analysis revealed that MLH1, PMS2, and MSH2 are independent prognostic factors. CONCLUSION: Our results suggest that mismatch repair is a prognostic biomarker for ESCC and could contribute to the selection of appropriate adjuvant therapy for patients with ESCC.

Sclerosing Encapsulating Peritonitis: Abdominal Cocoon.

Sclerosing encapsulating peritonitis is a rare chronic inflammatory condition often with unknown origins. We report a case of an abdominal cocoon or sclerosing encapsulating peritonitis, which was suspected to be a result of bowel obstruction. Tuberculosis peritonitis was also suspected. However, the exact diagnosis was unclear, and it was diagnosed as an idiopathic abdominal cocoon. The patient's history is of clear relevance in this diagnosis, and this report will be of interest to clinicians attending to cases of bowel obstruction.

A diagnostic pitfall; Small cell carcinoma-like features in basaloid squamous cell carcinoma of the esophagus.

Esophageal basaloid squamous cell carcinoma may resemble small cell carcinoma biopsy specimens and cause difficulties in pathology diagnosis. We aimed to clarify the clinicopathological significance of small cell carcinoma-like morphologies in basaloid squamous cell carcinoma. Thirty biopsy specimens of esophageal basaloid squamous cell carcinoma were reviewed and compared with 13 matched surgical specimens. Small cell carcinoma-like features, such as diffuse growth, nuclear molding, or nuclear crush artifact, were identified in 80% (24/30) of the biopsies and in 77% (10/13) of the surgery specimens, but in a proportionally much smaller area in the surgical specimens than in the biopsy samples. The presence of a small cell carcinoma-like feature had no impact on patients´ outcome. Immunohistochemically, synaptophysin and chromogranin A were consistently negative, while CD56 was expressed in 42% (10/24) of basaloid squamous cell carcinomas with small cell carcinoma-like features. p16, a highly sensitive marker for small cell carcinoma, was also expressed in 8% (2/24). p40 was expressed in all cases of basaloid squamous cell carcinoma. In conclusion, small cell carcinoma-like features are frequent and conspicuous in biopsies, which are probably caused by exogenous factors such as friction and external pressure that occur in biopsy procedure and in the tumor environment. Small cell carcinoma-like features may lead to a misinterpretation of a true small cell carcinoma, if CD56 is the only neuroendocrine marker expressed. p16 expression may also be detected in basaloid squamous cell carcinoma.

Tumor Microenvironment in Mixed Neuroendocrine Non-Neuroendocrine Neoplasms: Interaction between Tumors and Immune Cells, and Potential Effects of Neuroendocrine Differentiation on the Tumor Microenvironment.

The tumor microenvironment is considered to play a pivotal role in various human malignancies. Neuroendocrine and non-neuroendocrine neoplasms are considered to have different tumor microenvironments. However, owing to differences in the systemic and/or local immune statuses, tumor microenvironments in different patients may be difficult to compare. Mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs), although rare, could be useful for exploring the effects of neuroendocrine differentiation on the tumor microenvironment, because both neuroendocrine and non-neuroendocrine components are present in the same tumor. Here, we examined 33 cases of histologically confirmed MiNENs and evaluated the influence of neuroendocrine differentiation on the tumor microenvironment by comparing tumor-infiltrating lymphocytes, tumor-associated macrophages, and other relevant factors in the two components the same tumor. The immunoreactivity of those examined above was evaluated quantitatively. The values of vasohibin-1-positive density (p < 0.0001) and immunoreactivity (p < 0.0001) (representing the neoangiogenesis status) were significantly higher in neuroendocrine as compared to non-neuroendocrine areas of the same tumors. In addition, the Foxp3/CD8 (p = 0.0717) and the PD-1/CD8 ratios (p = 0.0176) (representing tumor immunity suppression) tend to increase in neuroendocrine carcinomas. Immunoreactivity of CD163, a marker of M2-like macrophages, was also higher in the neuroendocrine areas. Our findings indicate that neuroendocrine and non-neuroendocrine tumors differ from each other with respect to the characteristics of both tumor cells and the tumor microenvironment.

Definitive Chemoradiotherapy with Docetaxel, Cisplatin, and 5-Fluorouracil for Advanced Cervical Esophageal Cancer: A Medium-Term Outcome.

BACKGROUND: Definitive chemoradiotherapy (dCRT) is widely considered as a treatment option for cervical esophageal squamous cell carcinoma (ESCC) toward preserving the larynx. We have reported favorable outcomes, including the treatment response rate and short-term survival of dCRT concomitant with docetaxel, cisplatin, and 5-fluorouracil (DCF-RT) for advanced cervical ESCC. The aim of this paper was to report the subsequent progress of the study. METHODS: We assessed 18 patients with advanced (clinical stage II-IV, including T4b and/or M1 lymph node) cervical ESCC at our department who received DCF-RT as the first-line treatment between December 2010 and June 2020. RESULTS: A total of 14 men and 4 women underwent the study regimen. The pretreatment clinical stage included stage II, stage III, stage IVA, and stage IVB cases (including 9 patients with T4b) [8 trachea and 2 thyroids] and 7 patients with the M1 lymph node. The complete response (CR) was achieved in 15 patients, stable disease in 2, and progressive disease in 1. Of 15 patients with CR, 7 experienced recurrence, and 8 had continued CR. Frequent cases of grade ≥3 adverse effects included leucopenia, neutropenia, febrile neutropenia, and pharyngeal pain. The 3-year overall survival rate, disease-free survival rate, and disease-specific survival rate were 44.2%, 47.7%, and 48.6%, respectively. CONCLUSION: DCF-RT for advanced cervical esophageal cancer could achieve a favorable prognosis with larynx preservation. Further observations are warranted to establish the long-term prognosis, late complications of radiotherapy, and the significance of salvage surgery.

Correlation between TXNRD1/HO-1 expression and response to neoadjuvant chemoradiation therapy in patients with esophageal squamous cell carcinoma.

BACKGROUND: Thioredoxin reductase 1 (TXNRD1) and heme oxygenase-1 (HO-1) are both involved in the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway and play key roles in antioxidant responses. In patients with esophageal squamous cell carcinoma (ESCC), the correlation between the expression of these two proteins and the therapeutic response to neoadjuvant chemoradiation therapy (NACRT), as well as the difference in their expression after chemoradiotherapy, remains unknown. METHODS: Proteins involved in the Nrf2 pathway were immunolocalized in carcinoma cells in ESCC patients on NACRT with 5-fluorouracil and cisplatin, followed by esophagectomy. The 8-hydroxydeoxyguanosine (8-OHdG) levels were used to quantify reactive oxygen species. The changes in immunoreactivity before and after NACRT (Δ) were assessed. RESULTS: Tumor reduction following NACRT was significantly attenuated in pre-therapeutic biopsy specimens associated with high HO-1 status. TXNRD1Δ, HO-1Δ, and 8-OHdGΔ were significantly different in the ineffective and effective groups. The overall survival was significantly lower in high Nrf2 and TXNRD1 groups. In addition, high TXNRD1 expression was an independent prognostic factor in the multivariate analysis of overall survival. CONCLUSIONS: The study findings indicate that HO-1 status in pre-therapeutic biopsy specimens could predict response to NACRT, and TXNRD1 status could predict overall survival of ESCC patients.

HO-1 in lymph node metastasis predicted overall survival in patients with esophageal squamous cell carcinoma receiving neoadjuvant chemoradiation therapy.

BACKGROUND: Lymph node metastasis is one of the pivotal factors of the clinical outcomes of patients with esophageal cancer receiving neoadjuvant chemoradiation therapy (NACRT). Both the nuclear factor-erythroid 2-related factor 2 (Nrf2) signaling pathway and heme oxygenase-1 (HO-1) are frequently upregulated in various human malignancies and associated with resistance to chemoradiation therapy, subsequently resulting in adverse clinical outcomes. However, the Nrf2 and HO-1 status in lymph node metastasis and their differences between primary and metastatic lesions are unknown. AIMS: To examine the levels of Nrf2 signaling proteins and HO-1 in primary and metastatic lesions of patients with esophageal squamous cell carcinoma using immunohistochemistry. METHODS AND RESULTS: We immunolocalized Nrf2 signaling proteins in 69 patients with lymph node metastases, who received NACRT with 5-fluorouracil and cisplatin before esophagectomy. We also compared the findings between primary and metastatic lesions. Residual lymph node metastases were detected in 30 patients and among them, both primary and metastatic lesions were available for evaluation in 25 patients. Subsequently, we correlated the results with patients' survival. Nrf2, HO-1, and the Ki-67 labeling index were all significantly lower in the patients with lymph node metastases than in those with primary tumors. Carcinoma cells with high HO-1 levels were significantly associated with pathological resistance to NACRT. These results suggested that overall and disease-free survival of esophageal squamous cell carcinoma were significantly associated with both pN2 and high HO-1 levels, respectively. CONCLUSIONS: Protein expression in the Nrf2 pathway was significantly lower in patients with lymph node metastases than in those with primary lesions. HO-1 levels in lymph node metastases could be used to predict the eventual clinical outcome of patients with esophageal cancer receiving NACRT.

Necroptosis in Esophageal Squamous Cell Carcinoma: An Independent Prognostic Factor and Its Correlation with Tumor-Infiltrating Lymphocytes.

Necroptosis is a pivotal process in cancer biology; however, the clinical significance of necroptosis in esophageal squamous cell carcinoma (ESCC) has remained unknown. Therefore, in this study, we aimed to verify the potential involvement of necroptosis in the clinical outcome, chemotherapeutic resistance, and tumor microenvironment of ESCC. Mixed lineage kinase domain-like protein (MLKL) and phosphorylated MLKL (pMLKL) were immunohistochemically examined in 88 surgically resected specimens following neoadjuvant chemotherapy (NAC) and 53 pre-therapeutic biopsy specimens, respectively. Tumor-infiltrating lymphocytes (TILs) were also evaluated by immunolocalizing CD3, CD8, and forkhead box protein 3 (FOXP3) in the residual tumors after NAC. High pMLKL status in the post-NAC resected specimens was significantly correlated with worse prognosis in ESCC patients. Multivariate analysis demonstrated that a high pMLKL status was an independent prognostic factor. In pre-NAC biopsy specimens, a high pMLKL status was significantly associated with a lower therapeutic efficacy. CD8+ TILs were significantly lower in the high-pMLKL group. FOXP3+ TILs were significantly higher in both high-MLKL and high-pMLKL groups. We first demonstrated pMLKL status as an independent prognostic factor in ESCC patients. Our study revealed the possible involvement of necroptosis in the immunosuppressive microenvironment, resulting in the attenuated therapeutic efficacy of NAC and eventual adverse clinical outcomes in ESCC.

Thoracoscopic esophagectomy for esophageal carcinoma after peroral endoscopic myotomy for esophageal achalasia: a case report.

BACKGROUND: Esophageal achalasia causes dysphagia following impaired relaxation of the lower esophageal sphincter due to the degeneration of Auerbach's plexus in the esophageal smooth muscle. Recently, peroral endoscopic myotomy (POEM) has become one of the preferred treatment options for esophageal achalasia. However, pathomorphological changes after POEM have not been well examined. CASE PRESENTATION: A 65-year-old man with a history of POEM for esophageal achalasia was diagnosed with clinical stage II (cT2-N0-M0) thoracic esophageal squamous cell carcinoma and was consequently treated with neoadjuvant chemotherapy followed by thoracoscopic esophagectomy. Intraoperatively, the esophagus appeared dilated, reflecting esophageal achalasia; however, fairly slight fibrous adhesions were observed between the esophagus and the pericardial surface despite previously performed POEM via an anterior incision. Histopathological examination revealed esophageal wall thickening, edema, and fibrosis extending from the lamina propria to the submucosa. Besides, the majority of the inner layer and some proportion of the outer layer of the muscularis propria were found to be missing or atrophic at the esophagogastric junction (EGJ). No ganglion cells could be detected at the Auerbach's plexus. CONCLUSIONS: The previous history of POEM did not affect circumferential mediastinal periesophageal dissection during thoracoscopic esophagectomy. Nevertheless, a large proportion of the inner layer of the muscularis propria at the EGJ level seemed to have become lost or atrophic because of the POEM procedure.

p16 in highly malignant esophageal carcinomas: the correlation with clinicopathological factors and human papillomavirus infection.

p16 is generally considered to be a surrogate maker of human papillomavirus (HPV) infection and also a predictive marker of favorable clinical outcome of patients with squamous cell carcinoma of the oropharynx. p16 overexpression is also known to be induced by deregulation of RB1 in neuroendocrine carcinomas. In highly malignant esophageal neoplasms, however, the status of p16 has remained largely unknown. We immunolocalized p16 and Rb1 in 82 surgically resected esophageal high-grade squamous cell carcinomas (46 poorly differentiated and 36 basaloid squamous cell carcinomas) and 15 esophageal small-cell carcinomas in order to clarify the clinical and biological significance of p16. p16 immunoreactivity was detected in 7/82 (9%) high-grade squamous cell carcinomas and 15 (100%) small-cell carcinomas. p16 immunoreactivity was significantly associated with Rb1 protein loss in both groups (P < 0.001). HPV was detected in none of the p16-positive cases examined. Clinical outcome of the p16-positive high-grade squamous cell carcinomas was not different from that of the p16-negative counterparts (P = 0.687) but significantly better than those with the small-cell carcinomas (P = 0.023). p16 was therefore considered to be induced through an inactivation of the RB1 signaling pathway and not through HPV infection in highly malignant esophageal neoplasms. Nevertheless, patients' clinical outcome of these neoplasms significantly differs; therefore, small-cell carcinomas have to be carefully differentiated from other neoplasms. In addition, p16 overexpression is not predictive of favorable clinical outcome in high-grade squamous cell carcinomas of the esophagus.

Acute esophageal necrosis with esophagus perforation treated by thoracoscopic subtotal esophagectomy and reconstructive surgery on a secondary esophageal stricture: a case report.

BACKGROUND: Acute esophageal necrosis is defined as necrosis of the esophageal mucosa causing diffuse black pigmentation of the esophagus, the so-called black esophagus from its endoscopic findings. The prevalence is only 0.001~0.2%, while its mortality rate is up to 32%. However, most of the cases are fatal by comorbidities. CASE PRESENTATION: A 67-year-old female with diabetes mellitus was transported to the emergency room with hematemesis and disordered consciousness. She had suffered from nausea and epigastralgia for 2 days. The patient's general status was shock evidenced by vital signs, and she did not respond to rehydration. After intubation, emergency endoscopic examination revealed black pigmentation of the esophageal mucosa, and the condition was diagnosed as acute esophageal necrosis. Antibiotics and plasmapheresis had been started, and the patient gradually stabilized. One week after the admission, esophagus perforation was suspected from the significant increase of the right pleural effusion and free air at the esophagus wall and the mediastinum on CT scan. Emergency thoracoscopy revealed an edematous esophagus which was colored black. Esophagectomy with esophagostomy and enterostomy was performed. On resected specimen, mucosal necrosis was found only on the squamous epithelium, with three perforating areas in the middle to lower thoracic esophagus. No signs of inflammation or ischemia were found on the gastric mucosa of the esophagogastric junction. After the operation, the patient recovered generally well, except for the severe stenosis of the cervical esophagus. Cervical esophagectomy, tracheotomy, and anterior thoracic route reconstruction with free jejunum interposition and gastric tube were performed 9 months after the first surgery. No postoperative complications occurred; on the 37th day after the operation, the patient was eating well and was transferred to continue swallowing rehabilitation. CONCLUSION: It is important to detect the esophagus perforation and mediastinitis early and thereby not to miss the chance of surgical intervention to save the patient's life. Surgery should be minimized, and reconstruction should be considered next. If the cervical esophagus is also affected, reconstruction surgery should be performed by removing cervical esophagus and anastomosing it to the hypopharynx using a gastric tube and free jejunum interposition as needed.

Amyand's hernia complicated with appendix perforation treated by two-stage surgery consisting of laparoscopic appendectomy followed by elective inguinal hernioplasty: A case report.

INTRODUCTION: An inguinal hernia with an incarcerated appendix is defined as Amyand's hernia, and it is relatively rare. Amyand's hernia complicated with appendicitis, especially perforated appendicitis, is even rarer. Postoperative surgical site infection (SSI) is a dangerous complication, especially in Amyand's hernia with appendix perforation. The selection of an appropriate surgical approach is necessary to prevent postoperative SSI. Here, we report a case of Amyand's hernia complicated with appendix perforation that was successfully managed using a two-stage surgical approach consisting of laparoscopic appendectomy followed by elective inguinal hernioplasty. PRESENTATION OF CASE: A 70-year-old male presented with fever and right lower quadrant pain from the day before. After the patient was diagnosed with acute appendicitis within a right inguinal hernia, emergency laparoscopy was performed. The appendix was incarcerated in the right internal inguinal ring and perforated at the base. We decided to take a two-stage surgical approach to avoid postoperative SSI and performed only laparoscopic appendectomy. No postoperative complications occurred. Inguinal hernioplasty was performed 1 month after the first operation. There were no adhesions in the preperitoneal space, and no adverse events occurred postoperatively. CONCLUSIONS: A two-stage surgical approach consisting of laparoscopic appendectomy followed by elective inguinal hernioplasty was used successfully to treat Amyand's hernia complicated with appendix perforation without causing postoperative SSI.