A Final Report on the Real Impact of the COVID-19 Pandemic on the Diagnosis of Gastrointestinal Cancer in Akita Prefecture, Japan in 2022.

The long-term impact of the coronavirus disease 2019 (COVID-19) pandemic on the disruption of gastrointestinal cancer diagnoses remains unclear. This study investigated the actual impact on esophagogastric cancer (EGC) and colorectal cancer (CRC) diagnoses up to the third year of the pandemic in Akita Prefecture, Japan, using population-based registry data. We collected data on the annual number of EGC and CRC diagnoses using a database from the collaborative Akita Prefecture hospital-based registration. The net number of cancers diagnosed in the first three years of the pandemic (2020-2022) were compared with those diagnosed in the three years before the pandemic (2017-2019). Changes in the proportion of cancer stage and initial treatment for diagnosed EGC and CRC after the pandemic were then compared. The total number of EGCs was 9.3% lower in the first three years of the pandemic than in the three years before, probably due to its long-term declining trend. The total number of CRCs in the first three years of the pandemic exceeded that in the three years before, suggesting successful recovery of the diagnostic procedure. The proportion of cancer stages and initial treatment for EGCs and CRCs remained largely unchanged after the onset of the pandemic. Based on the population-based registry data from the first three years of the pandemic, the disruption of gastrointestinal cancer diagnoses caused by the pandemic is settling down without any substantial disease progression, even in Akita Prefecture, the area with the highest incidence of cancer in all of Japan.

A Follow-up Report on the Diagnosis of Gastrointestinal Cancer during the COVID-19 Pandemic in Akita Prefecture, Japan in 2021.

We recently reported the decrease in the number of gastrointestinal (GI) cancer diagnoses in 2020 due to disturbance of the healthcare system by the coronavirus disease 2019 (COVID-19) pandemic, using a hospital-based cancer registration system in Akita prefecture, Japan. In this study, we extended the research by showing the latest data (2021) on the number of cancers and examinations. Information on the occurrence and stage of esophageal, gastric, and colorectal cancers was collected from the same database. The number of GI examinations (cancer screening procedures and endoscopic examinations) was also investigated. Following the immediate decrease in the numbers of both GI examinations and GI cancer diagnoses in 2020, a rebound increase in the numbers of GI cancer diagnoses-especially colorectal cancers-was observed in 2021, resulting from an increased number of GI examinations i.e., the total number of colorectal cancers in 2021 increased by 9.0% and 6.8% in comparison to 2020 and pre-pandemic era, respectively. However, the rebound increase in 2021 was largely due to an increase in early-stage cancers, and there was no apparent trend toward the increased predominance of more advanced cancers. It therefore seems that we managed to escape from the worst-case scenario of disturbance of the healthcare system due to pandemic (i.e., an increase in the number of more advanced cancers due to delayed diagnoses). We need to continue to watch the trends in Akita prefecture, which has the highest rate of mortality from the 3 major GI cancers in Japan.

Disturbance of Gastrointestinal Cancers Diagnoses by the COVID-19 Pandemic in a Depopulated Area of Japan: A Population-Based Study in Akita Prefecture.

Disruption of cancer screening programs and diagnoses of gastrointestinal cancers by the COVID-19 pandemic has been reported; however, little attention has been paid to the situation in depopulated areas with low infection rates. Akita Prefecture is one of the most depopulated areas of Japan and has the lowest COVID-19 infection rate per capita; at the same time, the prefecture has been top-ranked for mortality due to gastrointestinal cancer for years. In this population-based study in Akita Prefecture, we investigated the occurrence of gastrointestinal cancers and the number of cancer screening procedures over the five-year period of 2016-2020, employing a database from the collaborative Akita Prefecture hospital-based registration system of cancers. The occurrence of gastrointestinal cancers, especially esophago-gastric cancers, declined by 11.0% in 2020, when the COVID-19 pandemic affected the overall healthcare system, compared with the average of 2016-2019. Nonetheless, the occurrence of advanced-stage (stage IV) esophago-gastric cancers increased by 7.2% in 2020. The decrease in the gastrointestinal cancer diagnosis rate in 2020 coincided with a 30% decline in the total number of regular population-based screening programs. Under the ongoing COVID-19 pandemic, cancer screening was uniformly suspended throughout Japan. Accordingly, the COVID-19 pandemic has substantially disrupted the cancer screening system, leading to delays in diagnoses of gastrointestinal cancer, even in depopulated areas (Akita Prefecture) of Japan with a low prevalence of infection. Suspension of cancer screening procedures during an infectious disease pandemic should be thoroughly considered for each region based on the cancer incidence and infection status in that area.

Risk Factors Linking Esophageal Squamous Cell Carcinoma With Head and Neck Cancer or Gastric Cancer.

GOALS: To investigate retrospectively the risk factors for synchronous and metachronous cancers in the upper gastrointestinal tract in patients with superficial esophageal squamous cell carcinoma (ESCC). BACKGROUND: In patients who have received endoscopic resection (ER) for ESCC, synchronous and metachronous cancers are frequently detected not only in the esophagus but also in the head and neck area and the stomach. STUDY: A total of 285 patients who received ER for superficial ESCC were enrolled in this analysis. These patients were periodically followed-up endoscopically. Cumulative occurrence rates of the metachronous second primary cancers were determined by Kaplan-Meier method. Risk factors for synchronous and metachronous cancers in the head and neck area and the stomach were determined by logistic regression analyses. RESULTS: During a mean follow-up period of 76 months, the 5-year cumulative occurrence of metachronous esophageal, head and neck, and stomach cancer was 14.0%, 2.8%, and 4.1%, respectively. Although the presence of multiple lugol-voiding lesions in the esophagus was a significant risk factor for synchronous and metachronous head and neck cancers (odds ratio, 3.8; 95% confidence interval, 1.7-9.0), older age (>65 y) was a significant risk factor for synchronous and metachronous gastric cancer (odds ratio, 3.1; 95% confidence interval, 1.2-9.3). CONCLUSIONS: The risk factors for the cooccurrence of head and neck cancer and that of gastric cancer in patients with ESCC differ. This information will likely be useful for managing patients who have been treated with ER for ESCC and who possess carcinogenic potential throughout the upper gastrointestinal tract.

Short-term outcomes of multicenter prospective cohort study of gastric endoscopic resection: 'Real-world evidence' in Japan.

OBJECTIVES: A Japanese multicenter prospective cohort study examining endoscopic resection (ER) for early gastric cancer (EGC) has been conducted using a Web registry developed to determine the short-term and long-term outcomes based on absolute and expanded indications. We hereby present the short-term outcomes of this study. METHODS: All consecutive patients with EGC or suspected EGC undergoing ER at 41 participating institutions between July 2010 and June 2012 were enrolled and prospectively registered into the Web registry. The baseline characteristics were entered before ER, and the short-term outcomes were collected at 6 months following ER. RESULTS: Nine thousand six hundred and sixteen patients with 10 821 lesions underwent ER (endoscopic submucosal dissection [ESD]: 99.4%). The median procedure time was 76 min, and R0 resections were achieved for 91.6% of the lesions. Postoperative bleeding and intraoperative perforation occurred in 4.4% and 2.3% of the patients, respectively. Significant independent factors correlated with a longer procedure time (120 min or longer) were as follows: tumor size >20 mm, upper-third location, middle-third location, local recurrent lesion, ulcer findings, gastric tube, male gender, and submucosa. Histopathologically, 10 031 lesions were identified as common-type gastric cancers. The median tumor size was 15 mm. Noncurative resections were diagnosed for 18.3% of the lesions. Additional surgery was performed for 48.6% (824 lesions) of the 1695 noncurative ER lesions with a possible risk of lymph node (LN) metastasis. Among them, 64 (7.8%) exhibited LN metastasis. CONCLUSIONS: This multicenter prospective study showed favorable short-term outcomes for gastric ESD.

Phlegmonous Gastritis: A Report of Three Cases with Clinical and Imaging Features.

Phlegmonous gastritis is a rare but often fatal acute pyogenic infection of the stomach. We herein report three cases of phlegmonous gastritis with different causes: the long-term placement of a nasogastric feeding tube, bacteremia associated with cellulitis in a diabetic patient, and an adverse reaction to paclitaxel/carboplatin chemotherapy for cancer of unknown primary cause, which were classified as primary, secondary, and idiopathic types, respectively. Coping with the increasing morbidity rate associated with the diverse background of such patients requires a thorough understanding of the clinical features and image findings associated with this entity.

A case of esophageal actinomycosis with a unique morphology presenting as a refractory ulcer.

A 60-year-old man presented with odynophagia after bronchial artery infusion chemotherapy for pulmonary metastasis of hepatocellular carcinoma. Esophagogastroduodenoscopy (EGD) revealed an esophageal ulcer in the middle thoracic esophagus. An esophageal biopsy demonstrated no malignancy. However, the symptoms had not improved after a month. EGD was performed again and showed a white cord lump at the bottom of the same esophageal ulcer identified before, showing no improving tendency. A repeated biopsy of the lump revealed actinomycosis, and the symptoms were improved by the oral administration of ampicillin. We herein report a case in which esophageal actinomycosis with a unique morphology of refractory esophageal ulcer was rapidly improved by the administration of antibiotics.

Feasibility of colorectal endoscopic submucosal dissection (ESD) carried out by endoscopists with no or little experience in gastric ESD.

BACKGROUND AND AIM: Colorectal endoscopic submucosal dissection (ESD) is recommended to be carried out only by endoscopists with sufficient experience in gastric ESD. However, early gastric carcinoma is less common in Western countries than in Japan, and endoscopic maneuverability differs between the stomach and colorectum. We assessed the feasibility of colorectal ESD carried out by endoscopists with no or little experience in gastric ESD. METHODS: We analyzed en bloc resection, R0 resection and perforation rates in 180 consecutive colorectal ESD carried out by three endoscopists who had no or <5 cases of experience in gastric ESD. We also identified factors associated with R0 resection failure. RESULTS: Overall en bloc and R0 resection rates were 93.3% (168/180) and 82.2% (148/180), respectively. All 11 cases with perforation were treated endoscopically. Dividing 180 cases into three learning phases (early, middle, or late phases), the en bloc and R0 resection rates increased from 88.3% and 75.0% in the early phase to 98.3% and 88.3% in the late phase, respectively. Perforation rate also improved from 10.0% to 3.3%. Factors associated with R0 resection failure were location at junctions (odds ratio: 6.8, 95% CI: 1.9-27.5), preoperative factors reflecting fibrosis (5.8, 1.9-19.0), and late phase (0.2, 0.1-0.7). CONCLUSION: Endoscopists without experience in gastric ESD carried out colorectal ESD safely. In the early and middle phases (≤40 cases), they should treat mainly rectal lesions but may also resect lesions in the colon avoiding flexures. Lesions located at junctions and those with preoperative factors reflecting fibrosis should be resected after completing 40 procedures.

Two cases of cisplatin-induced permanent renal failure following neoadjuvant chemotherapy for esophageal cancer.

INTRODUCTION: We experienced two esophageal cancer patients who developed severe acute renal failure after neoadjuvant chemotherapy with cisplatin and 5-fluorourasil. PRESENTATION OF CASE: After administration of cisplatin, their serum creatinine increased gradually until they required hemodialysis and their renal failure was permanent. In both cases, renal biopsy examination indicated partial recovery of the proximal tubule, but renal function did not recover. After these events, one patient underwent definitive radiotherapy and the other underwent esophagectomy for their esophageal cancers, while continuing dialysis. Both patients are alive without cancer recurrence. DISCUSSION: In these two cases of cisplatin-induced renal failure, renal biopsy examination showed only slight disorder of proximal tubules and tendency to recover. CONCLUSION: Although cisplatin-related nephrotoxicity is a well-recognized complication, there have been few reports of renal failure requiring hemodialysis in cancer patients. In this report, we present their clinical courses and the pathological findings of cisplatin-related renal failure.

True Primary Enterolith Treated by Balloon-assisted Enteroscopy.

Primary enterolith is a rare condition that can induce ileus and intestinal perforation. We report the first case of a true primary enterolith treated by balloon-assisted enteroscopy. The patient presented with a small intestinal ileus. After its improvement following the insertion of an ileus tube, radiography with amidotrizoate sodium meglumine detected a round, movable defect in the ileum measuring 42 mm diameter. The patient was diagnosed with a primary enterolith based on her past history. The enterolith was fractured and removed using balloon-assisted enteroscopy. This case suggests that balloon-assisted enteroscopy may be an effective non-invasive treatment option for enteroliths.

Successful treatment with infliximab for refractory para-ileostomal ulceration in a patient with BehÒ«et's disease.

BehÒ«et's disease (BD) is a chronic disorder involving multiple organ systems including the small and large intestines. A 46-year-old female diagnosed with intestinal BD presented with ileocecal perforation and diffuse peritonitis and subsequently underwent ileocolic resection with ileostomy. After surgery, she suffered from refractory para-ileostomal ulceration associated with BD. Most importantly, however, treatment with infliximab was significantly effective in healing the ulceration. This is the first report of para-ileostomal ulceration associated with BD successfully treated with infliximab, suggesting the possible use of infliximab as a therapeutic option for para-stomal ulcers related to BD.

Mesenteric lymph node abscess due to Yersinia enterocolitica: case report and review of the literature.

We describe the case of a 74-year-old female with a mesenteric lymph node abscess caused by a Yersinia enterocolitica infection. She had been administered an immunosuppressive drug and was admitted to the hospital due to a high fever, right lower abdominal pain and advanced leukocytosis. We initially diagnosed her with lymphadenitis based on the symptoms and the imaging studies. However, conservative treatment with antibiotics did not yield any improvement, and abscess formation was suspected. Surgical treatment was performed, and the culture from the drainage fluid grew Y. enterocolitica. The histological findings suggested that an ulcerative lesion of the terminal ileum was the entry port of Y. enterocolitica. The pathogen infected the mesenteric lymph nodes and spread along the ileocecal lymphatic vessels, resulting in the formation of an abscess. We also provide a review of the previously published literature on lymph node abscesses due to Y. enterocolitica infections.

Duodenocolic fistula caused by a peptic stomal ulcer following distal gastrectomy.

We herein describe the case of a 51-year-old man with a duodenocolic fistula (DCF) caused by a stomal ulcer. The patient complained of watery diarrhea, dysgeusia and malnutrition. His medical history included distal gastrectomy with Billroth I reconstruction for duodenal ulcer perforation. A combination study using endoscopy and contrast imaging confirmed the presence of DCF. Laparotomic fistulectomy was performed, which resulted in the patient's recovery from diarrhea and malnutrition. The histological findings suggested that the fistula had originated from a stomal ulcer. In patients with chronic watery diarrhea of obscure origin following gastrectomy, DCF is a possible cause of the diarrhea.

Outcomes of patients with stage IVA esophageal cancer (Japanese classification) treated with definitive chemoradiotherapy.

PURPOSE: To evaluate treatment outcomes of chemoradiotherapy for patients with stage IVA esophageal cancer and to estimate prognostic factors. MATERIALS AND METHODS: Patients with stage IVA esophageal cancer treated with chemoradiotherapy between April 2003 and March 2009 were evaluated. Patients received concurrent chemoradiotherapy comprising cisplatin plus 5-fluorouracil and 61.2 Gy of radiotherapy. Therapeutic response, overall survival time, and toxicity were examined and statistical evaluation was performed. RESULTS: Ninety patients were treated using chemoradiotherapy. Among these, 71 patients (78.9 %) received the complete course of chemoradiotherapy. Seventeen patients (18.9 %) showed complete response, 64 patients (71.1 %) had partial response, 7 patients (7.8 %) experienced no change, and 2 patients (2.2 %) exhibited progressive disease. Mean duration of follow-up was 16.1 months (range 2-88 months). Median overall survival was 12.8 months. Two- and 3-year overall survival rates were 35.1 and 18.6 %, respectively. Severe hematological toxicities included Grade 3 leukopenia in 33 patients (36.7 %). Treatment-related death was estimated to have occurred in 7 patients. Performance status and body weight loss were identified as significant prognostic factors. CONCLUSION: Our treatment outcomes appeared similar to those of previous studies that used chemoradiotherapy for advanced esophageal cancer. This treatment is useful for stage IVA esophageal cancer.

Functional roles of TGF-ß1 in intestinal epithelial cells through Smad-dependent and non-Smad pathways.

BACKGROUND AND AIMS: Transforming growth factor-ß1 (TGF-ß1) is one of the growth factors expressed in the gut, and has been shown to play an important role in intestinal mucosal healing. We investigated the effects of TGF-ß1 on the cellular functions of intestinal epithelial cells, and also evaluated its signaling pathways in these cells. METHODS: We used the rat IEC-6 intestinal epithelial cell line for these studies. The expression of TGF-ß1/Smad signaling molecules was examined. We evaluated the effect of TGF-ß1 on the proliferation and differentiation by the BrdU incorporation assay and real-time PCR. We manipulated the expression levels of Smad2 and Smad3 using an adenovirus system and small interfering RNA to examine the signaling pathways. The expression of Smad2 and Smad3 along the crypt-villus axis was also examined in the murine intestine. RESULTS: IEC-6 cells produced TGF-ß1 and expressed functional TGF-ß/Smad signaling molecules. The addition of TGF-ß1 in the culture medium suppressed the proliferation and increased the expression of a differentiation marker of enterocytes, in a dose-dependent manner. The adenovirus-mediated and small interfering RNA-mediated studies clearly showed that the growth inhibitory effect and the promotion of differentiation were exerted through a Smad3-dependent and a Smad2-dependent pathway, respectively. IEC-6 cells exhibited upregulated expression of an inhibitory Smad (Smad7) as a form of negative feedback via a non-Smad pathway. Smad2 was predominantly expressed in villi, and Smad3 in crypts. CONCLUSIONS: TGF-ß1 regulates the cellular functions of intestinal epithelial cells through both Smad-dependent and non-Smad pathways.

Outcomes of patients receiving additional esophagectomy after endoscopic resection for clinically mucosal, but pathologically submucosal, squamous cell carcinoma of the esophagus.

PURPOSE: This study investigated the actual rate or extent of lymph node metastasis or the survival outcomes among patients that underwent esophagectomy with lymph node dissection after ESD for clinical mucosal, but pathological submucosal, esophageal cancer. METHODS: Seventeen patients that received esophagectomy with two- or three-field lymph node dissection as additional treatment after ESD for clinical mucosal, but pathological submucosal, esophageal cancer between 2006 and 2010 were analyzed. The rate and extent of lymph node metastasis and the patient outcomes were determined. RESULTS: The tumor depths were diagnosed as SM1 in 8 (47 %) patients and SM2 in 9 (53 %), based on the analyses of resected specimens. Lymphatic invasion was evident in 13 (76 %) patients, while venous invasion was detected in 5 (29 %). Five (29 %) patients had pathologically detected lymph node involvement. Seven (0.8 %) of the 890 dissected nodes showed cancer involvement. Three patients had one involved node in the mediastinum or abdomen, and 2 patients had 2 involved nodes in the abdomen. The patients were followed up for 11-71 months (median 23 months), and all were alive without recurrence at the final follow-up. CONCLUSION: Twenty-nine percent of the patients diagnosed with clinically mucosal, but pathologically submucosal, thoracic squamous cell esophageal cancer after ESD had 1-2 cancer-involved lymph nodes in the lower mediastinum and abdomen. Esophagectomy with lymph node dissection is therefore considered to be a necessary and effective additional treatment for these patients.

Epimorphin protects hepatocytes from oxidative stress by inhibiting mitochondrial injury.

BACKGROUND AND AIMS: Many investigations have demonstrated that cell injuries caused by generation of reactive oxygen species (ROS) is a common mechanism of various hepatic disorders. Recently, we have demonstrated that epimorphin, originally cloned as a mesenchymal protein, protects cultured intestinal epithelial cells from ROS. We therefore examine whether epimorphin protects primary cultured hepatocytes from ROS-induced cell injury. METHODS: We explored the cell viability and the intracellular ROS levels of purified murine hepatocytes after exposure to 0.5 mM H(2)O(2) with or without pretreatment of epimorphin. Then, we observed mitochondrial permeability transition (MPT) and depolarization using confocal microscopy to make clear the mechanism that epimorphin inhibited cell injuries after exposure to H(2)O(2). In addition, to clarify the signaling pathways related to cell survival, we carried out Western blotting analysis with phosphorylated stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) polyclonal antibody to evaluate the inhibition of JNK by epimorphin. Finally, we evaluated the cell viability in hepatocytes administered JNK inhibitor. RESULTS: Epimorphin protected primary cultured hepatocytes from H(2)O(2)-induced cell injuries independent of intracellular ROS levels. Epimorphin also inhibited onset of MPT, depolarization of the mitochondrial membrane potential, and eventually cell killing. The cell protective function of epimorphin after exposure to H(2)O(2) was not dependent on Akt signaling but on JNK signaling. CONCLUSION: Epimorphin can protect hepatocytes from MPT-dependent cell injury induced by ROS. Since hepatic disorders could be caused by MPT-dependent cell injuries with excessive ROS, epimorphin might open a new therapeutic avenue for hepatic disorders.